CE/CME

---

CE/CME No: CR-1502

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Describe the presenting signs and symptoms of atrial fibrillation (A-fib).
• Define the differential and tests for diagnosing A-fib.
• Identify the risk factors associated with A-fib.
• Discuss the anticoagulant treatment options for nonvalvular A-fib.
• List aspects of A-fib management about which patients benefit from clinician instruction.

FACULTY
Deedra Harrington, Janis R. Guilbeau, and Christy McDonald Lenahan are Assistant Professors in the College of Nursing and Allied Health Professions at the University of Louisiana at Lafayette. Dr. Harrington is also a cardiology intensivist nurse practitioner at the Heart Hospital of Lafayette. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of February 2015. 

Article begins on next page >>

 

Patients with nonvalvular atrial fibrillation (A-fib) have a fivefold greater risk for ischemic stroke than those without. Newer oral anticoagulants reduce this risk—but also increase risk for serious bleeding, including intracranial hemorrhage. Here are the evidence-based guidelines to help you make the choice that’s best for your patient.

Atrial fibrillation (A-fib) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation that results in ineffective atrial contraction; this causes inadequate ventricular rate control and variable ventricular filling.¹ A common cardiac arrhythmia that is estimated to affect between 2.7 and 6.1 million Americans,² A-fib is projected to affect as many as 12.1 million people by the year 2030.³ Incidence increases with age; while less than 1% of patients with A-fib are younger than 60, more than a third are 80 or older.¹

Morbidity and mortality associated with A-fib are significant. The risk for an embolic event is particularly profound—five times that of persons without A-fib; again, this risk increases with age. In patients ages 50 to 59, 1.5% of strokes are attributed to A-fib; this percentage increases to 23.5% for those ages 80 to 89.²

Treatment of A-fib is aimed at rate control and rhythm conversion, generally through the use of drugs or ablation procedures, and stroke risk reduction, using oral anticoagulants to prevent thrombus formation. This review will focus on the use of newer oral anticoagulants for reduction of stroke risk associated with nonvalvular A-fib.

PATIENT PRESENTATION
Patients with new-onset A-fib may present with a variety of symptoms, including palpitations, chest pain, pressure or discomfort, shortness of breath, lightheadedness, fatigue, or exercise intolerance.⁴ Patients with chest pain, palpitations, and shortness of breath in particular should be assessed immediately for myocardial infarction before evaluating for A-fib. Poor perfusion may cause a decreased level of patient consciousness; therefore, hypotension or even Alzheimer disease should be ruled out.

Continue for diagnostic evaluation >>

 

DIAGNOSTIC EVALUATION
A complete patient history and thorough review of systems will enable the clinician to identify the risk factors for A-fib and establish a diagnosis (see Table 1).^1,4,5 Evaluation should also include a detailed physical examination. Upon initial cardiovascular assessment, the patient’s apical pulse may be rapid, irregular, or disorganized during auscultation. If underlying A-fib is related to a valvular abnormality, an audible murmur may be auscultated.⁵

Workup for A-fib includes the standard 12-lead ECG, chest radiograph, thyroid function test, and echocardiogram. The 12-lead ECG is definitive for making the diagnosis of A-fib (see Figure 1). A-fib is characterized by irregular R-R intervals when atrioventricular conduction is present, absence of distinct repeating P waves, and irregular atrial activity.¹

If the patient describes episodes consistent with A-fib that is not detectable at the office visit, 24- or 48-hour ambulatory Holter monitoring may be revealing. Event monitors can be used to determine the frequency with which the patient experiences A-fib over an extended period of time (up to 30 days).⁶

As part of the differential diagnosis of A-fib, clinicians need to consider other possible atrial conduction abnormalities, including atrial flutter, atrial tachycardia, atrioventricular nodal reentry tachycardia, multifocal atrial tachycardia, and Wolff-Parkinson-White syndrome.⁵ 

To rule out other etiologies, consider performing the following examinations and tests⁴

• A chest x-ray can rule out undiagnosed lung disease (eg, chronic obstructive pulmonary disease).
• To exclude hyperthyroidism as a cause of the patient’s symptoms, thyroid function testing and a physical examination for exophthalmos, carotid bruits, and thyromegaly are needed.
• Echocardiography is useful to exclude valvular abnormalities and/or heart failure.
• A complete blood cell count will rule out any infectious process or anemic state.
• Renal function studies and a comprehensive metabolic panel will detect signs of renal failure or electrolyte imbalance.
• Cardiac enzyme measurement can help rule out the occurrence of a myocardial event.
• A brain natriuretic peptide test can identify if heart failure is a contributing factor.

Continue for A-fib classification >>

 

A-FIB CLASSIFICATION
For purposes of choosing appropriate therapy, it is necessary to determine whether the cause of A-fib is valvular or nonvalvular. Valvular A-fib is described as A-fib that occurs in the presence of valvular heart disease or defect, such as rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.¹ In the absence of these types of conditions, A-fib is considered nonvalvular. The vast majority of patients have nonvalvular A-fib; in the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study, researchers found that, among 17,974 adults with A-fib who were members of a large California health maintenance organization, only 4.9% had valvular heart disease.⁸

A-fib is commonly classified into four subcategories, based on its duration: paroxysmal, persistent, longstanding persistent, and permanent.

Paroxysmal. The occurrence of at least two episodes that have terminated in less than seven days without treatment.

Persistent. An episode lasting more than seven days or less than seven days after electric or pharmacologic conversion.

Longstanding persistent. Continuous A-fib for more than one year.

Permanent. A category for patients in whom rhythm control is no longer being pursued.

This simplified classification is often used to choose between ablative or medication therapies. To ensure accuracy, however, underlying causes, risk factors, and mechanisms should be determined.⁹

Stroke risk calculation
Once nonvalvular A-fib is confirmed, the next step is to control the ventricular rate and attempt to convert the A-fib rhythm. To accomplish this, the patient’s risk for stroke must be estimated and the need for oral anticoagulation determined.

The CHADS₂ risk stratification system for calculating an individual’s risk for ischemic stroke in A-fib was developed in 2001. The risk criteria used in the calculation are Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, prior Stroke, transient ischemic attack, or thromboembolism.¹⁰

Recent additions to the criteria account for advanced age, gender, and known vascular disease.^1,5 Known as the CHA₂DS₂-VASc, this scoring system is outlined in Table 2. If the patient’s score is 0, risk for stroke is low and anticoagulation therapy is not recommended. If the score is 1, the risk is intermediate, and the patient may be treated with aspirin therapy or anticoagulation. With a CHA₂DS₂-VASc score of 2 or greater, anticoagulation treatment is recommended to reduce the risk for stroke.¹

While the expanded CHA₂DS₂-VASc criteria more clearly define the basis for an anticoagulation recommendation—particularly in older patients, women, and those with a vascular history—the superiority of one over the other is undetermined.¹¹ However, the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with A-fib recommend use of the CHA₂DS₂-VASc.¹

Continue for anticoagulation therapy >>

 

ANTICOAGULATION THERAPY
The choice of anticoagulation treatment requires weighing the risks and benefits of oral anticoagulation therapy. Stroke and bleeding risks, cost, tolerability, potential for drug interactions, likelihood of patient adherence to the anticoagulation regimen, and patient preferences should be considered.¹

The three oral anticoagulants recently approved by the FDA for the reduction of stroke and systemic embolism risks in nonvalvular A-fib are dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors.^12-14

The clinical trials upon which the FDA’s approval of these anticoagulants was based included only patients with nonvalvular A-fib. For patients with valvular disease, warfarin, a vitamin-K–dependent inhibitor, is currently recommended.^1,15 It is also recommended for patients with both end-stage renal disease (ESRD) and either nonvalvular or valvular A-fib.¹

A-fib and chronic kidney disease
It is estimated that one-third of patients with A-fib are also diagnosed with chronic kidney disease (CKD).¹⁶  Because patients with CKD have a greater risk for bleeding, anticoagulant therapy for these ­patients requires reduced dosing and close monitoring for bleeding.

The 2014 ACC/AHA/HRS practice guidelines include guidance for selection of oral anticoagulants for patients with nonvalvular A-fib and CKD (see Table 3).^1,12-14,17 Dosing of dabigatran and rivaroxaban require evaluation of creatinine clearance before treatment is initiated.

When warfarin is indicated, dose adjustments for renal impairment are based on the prothrombin time/international normalized ratio (INR) value.¹ Current guidelines recommend maintaining a therapeutic INR between 2.0 and 3.0 for nonvalvular A-fib in patients with CKD.¹ Patients with difficulty maintaining therapeutic INR levels may benefit from alternate therapy with Xa inhibitors or a direct thrombin inhibitor except in the presence of ESRD.¹

Continue for patient adherence >>

 

PATIENT ADHERENCE
Recent studies have indicated that adherence to anticoagulation therapy among A-fib patients drops by as much as 50% after one year of therapy.¹⁸ Causes are multifactorial and include complexity of treatment regimen, missed doses, patient unawareness of stroke risk, and fear of bleeding.¹⁹ Educating both patients and caregivers has been associated with significant improvements in medication compliance in these patients.¹⁹

Complex regimens
Treatment requirements, such as the serial laboratory testing and dosage adjustments associated with warfarin therapy, can be a major contributing factor to anticoagulation nonadherence.^18,20  In this regard, the newer once-daily medications that require limited follow-up may be good alternatives to warfarin.²¹

In patients for whom warfarin therapy is indicated, educational interventions may include

• Written information for patients and caregivers about medication regimens and dosage scheduling
• Reinforcement of treatment goals and outcomes
• Use of dosing aids such as dated and timed pill dispensers
• Incorporating caregiver support to help patients adhere to the medication regimen.

These interventions have been shown to improve adherence with complex treatment regimens.²²

Missed doses
Missing anticoagulant doses is not an uncommon occurrence, and patients should be advised of appropriate catch-up strategies when this occurs.

For dabigatran, the missed dose should be taken as soon as the patient remembers, but only if the next scheduled dose is more than six hours away.¹² For rivaroxaban, missed doses should be taken as soon as the patient remembers, and the next dose should resume as scheduled.¹³ For apixaban, a missed dose should be taken as soon as possible but not in combination with any other doses.¹⁴

For patients taking warfarin, a missed dose should be taken as soon as possible on the same day.²³ If more than 24 hours have elapsed, the patient should contact his or her health care provider before taking any medication.²³

Stroke risk
Adherence to anticoagulation therapy significantly reduces the risk for stroke among A-fib patients. Estimates suggest that anticoagulants can reduce stroke risk by as much as 68% in patients with A-fib.²⁴

Even with optimal anticoagulation therapy, however, stroke remains a major complication.²⁵ Through group sessions or patient education pamphlets, patients and caregivers should be informed about the high risk for stroke associated with A-fib and should know its early symptoms.²⁶ These include sudden onset of one or more of the following: confusion or difficulty understanding speech; numbness or weakness of the face or extremities, limited to one side of the body; severe headache; dizziness, loss of balance, or difficulty ambulating; and/or visual disturbances in one or both eyes.²⁶

Next page: Bleeding risk >>

 

Bleeding risk
Patients should be advised of the major risk for bleeding associated with all anticoagulant therapies.²⁷ Screening for bleeding includes assessment of Hypertension, Abnormal renal and/or liver function, previous Stroke, Bleeding history, Labile INR, being Elderly, and currently prescribed Drugs and/or excessive use of alcohol (known as HAS-BLED) (see Table 4).^1,28  Use of a bleeding risk assessment tool such as HAS-BLED may help identify the patient’s risk but cannot be the basis for treatment decisions.^1,29 

Despite efforts to decrease bleeding risks, patients should understand that hemorrhagic complications can still occur. Patients taking anticoagulants should be familiar with early signs and symptoms of bleeding (eg, sudden, severe headache; melena; hematemesis; nosebleeds) and should notify their health care provider immediately if any of these symptoms occur.^12-14,23

If bleeding occurs, it is recommended that anticoagulant treatment be stopped. In addition, depending on the severity of the bleeding, the clinician may elect to administer activated prothrombin complex concentrates, recombinant factor VIIa, or concentrates of factors II, IX, or X to reverse the effects of newer oral anticoagulants.¹ Vitamin K, the antidote for warfarin, is not effective on direct thrombin inhibitors or factor Xa inhibitors. Currently, there is no established means of reversing the anticoagulant effects of the newer oral anticoagulants.^12-14

FOLLOW-UP
Since optimal utilization of cardiovascular medication occurs in only 50% of the patient population, appropriate follow-up must be implemented to ­improve overall outcomes of pharmacologic therapy.³⁰ Follow-up protocols depend on multiple factors, including type of anticoagulation therapy, patient response to therapy, and patient comorbidities.³¹ Monitoring warfarin use is time-consuming and resource-intensive; laboratory monitoring requirements for the newer oral anticoagulants have not been established.³²

Patients taking warfarin should be vigilant in follow-up with serial laboratory measurements and dosage adjustments.²³ Once therapy is initiated, INR is monitored every two to four days until two therapeutic INR levels are obtained.^31,33 Monitoring can then be changed to once weekly until two more therapeutic levels are obtained.³¹ The INR monitoring interval can then be increased to every two to four weeks, with two weeks being a more conservative strategy.³³ The practitioner may want to consider advancing to four-week monitoring intervals once four therapeutic INR levels have been obtained.³¹ It may be necessary to return to two-to-four day monitoring of INR if a nontherapeutic INR is obtained, the patient becomes ill, a medication is changed, or the patient makes a significant dietary change.³¹

When to refer
Primary care practitioners can manage anticoagulation therapy safely and efficiently, but cardiology referral may be warranted in certain situations. For example, patients with complex cardiac disease may benefit from cardiology referral.⁷ Considerations for referral to a cardiologist for further evaluation may include

• Abnormal exercise stress test results
• Abnormal echocardiogram results
• 12-lead ECG that reveals rapid, irregular wide pre-excited QRS complexes⁵

Patients who are drug intolerant or who remain symptomatic on pharmacologic rate control should also be referred to cardiology.⁷ In addition, patients who may require a pacemaker or defibrillator or who may be candidates for ablation should also be referred to an electrophysiology specialist.⁷

Continue for conclusion >>

 

CONCLUSION
Nonvalvular A-fib is a common arrhythmia that contributes significantly to morbidity among older adults. Use of the most current clinical practice guidelines coupled with patient education will improve overall patient outcomes.

* Editor's note: At press time, the FDA had announced approval of another oral anticoagulant, edoxaban, for the reduction of stroke and systemic embolism risks in nonvalvular A-fib.

---

CE/CME No: CR-1502

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Describe the presenting signs and symptoms of atrial fibrillation (A-fib).
• Define the differential and tests for diagnosing A-fib.
• Identify the risk factors associated with A-fib.
• Discuss the anticoagulant treatment options for nonvalvular A-fib.
• List aspects of A-fib management about which patients benefit from clinician instruction.

FACULTY
Deedra Harrington, Janis R. Guilbeau, and Christy McDonald Lenahan are Assistant Professors in the College of Nursing and Allied Health Professions at the University of Louisiana at Lafayette. Dr. Harrington is also a cardiology intensivist nurse practitioner at the Heart Hospital of Lafayette. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of February 2015. 

Article begins on next page >>

 

Patients with nonvalvular atrial fibrillation (A-fib) have a fivefold greater risk for ischemic stroke than those without. Newer oral anticoagulants reduce this risk—but also increase risk for serious bleeding, including intracranial hemorrhage. Here are the evidence-based guidelines to help you make the choice that’s best for your patient.

Atrial fibrillation (A-fib) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation that results in ineffective atrial contraction; this causes inadequate ventricular rate control and variable ventricular filling.¹ A common cardiac arrhythmia that is estimated to affect between 2.7 and 6.1 million Americans,² A-fib is projected to affect as many as 12.1 million people by the year 2030.³ Incidence increases with age; while less than 1% of patients with A-fib are younger than 60, more than a third are 80 or older.¹

Morbidity and mortality associated with A-fib are significant. The risk for an embolic event is particularly profound—five times that of persons without A-fib; again, this risk increases with age. In patients ages 50 to 59, 1.5% of strokes are attributed to A-fib; this percentage increases to 23.5% for those ages 80 to 89.²

Treatment of A-fib is aimed at rate control and rhythm conversion, generally through the use of drugs or ablation procedures, and stroke risk reduction, using oral anticoagulants to prevent thrombus formation. This review will focus on the use of newer oral anticoagulants for reduction of stroke risk associated with nonvalvular A-fib.

PATIENT PRESENTATION
Patients with new-onset A-fib may present with a variety of symptoms, including palpitations, chest pain, pressure or discomfort, shortness of breath, lightheadedness, fatigue, or exercise intolerance.⁴ Patients with chest pain, palpitations, and shortness of breath in particular should be assessed immediately for myocardial infarction before evaluating for A-fib. Poor perfusion may cause a decreased level of patient consciousness; therefore, hypotension or even Alzheimer disease should be ruled out.

Continue for diagnostic evaluation >>

 

DIAGNOSTIC EVALUATION
A complete patient history and thorough review of systems will enable the clinician to identify the risk factors for A-fib and establish a diagnosis (see Table 1).^1,4,5 Evaluation should also include a detailed physical examination. Upon initial cardiovascular assessment, the patient’s apical pulse may be rapid, irregular, or disorganized during auscultation. If underlying A-fib is related to a valvular abnormality, an audible murmur may be auscultated.⁵

Workup for A-fib includes the standard 12-lead ECG, chest radiograph, thyroid function test, and echocardiogram. The 12-lead ECG is definitive for making the diagnosis of A-fib (see Figure 1). A-fib is characterized by irregular R-R intervals when atrioventricular conduction is present, absence of distinct repeating P waves, and irregular atrial activity.¹

If the patient describes episodes consistent with A-fib that is not detectable at the office visit, 24- or 48-hour ambulatory Holter monitoring may be revealing. Event monitors can be used to determine the frequency with which the patient experiences A-fib over an extended period of time (up to 30 days).⁶

As part of the differential diagnosis of A-fib, clinicians need to consider other possible atrial conduction abnormalities, including atrial flutter, atrial tachycardia, atrioventricular nodal reentry tachycardia, multifocal atrial tachycardia, and Wolff-Parkinson-White syndrome.⁵ 

To rule out other etiologies, consider performing the following examinations and tests⁴

• A chest x-ray can rule out undiagnosed lung disease (eg, chronic obstructive pulmonary disease).
• To exclude hyperthyroidism as a cause of the patient’s symptoms, thyroid function testing and a physical examination for exophthalmos, carotid bruits, and thyromegaly are needed.
• Echocardiography is useful to exclude valvular abnormalities and/or heart failure.
• A complete blood cell count will rule out any infectious process or anemic state.
• Renal function studies and a comprehensive metabolic panel will detect signs of renal failure or electrolyte imbalance.
• Cardiac enzyme measurement can help rule out the occurrence of a myocardial event.
• A brain natriuretic peptide test can identify if heart failure is a contributing factor.

Continue for A-fib classification >>

 

A-FIB CLASSIFICATION
For purposes of choosing appropriate therapy, it is necessary to determine whether the cause of A-fib is valvular or nonvalvular. Valvular A-fib is described as A-fib that occurs in the presence of valvular heart disease or defect, such as rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.¹ In the absence of these types of conditions, A-fib is considered nonvalvular. The vast majority of patients have nonvalvular A-fib; in the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study, researchers found that, among 17,974 adults with A-fib who were members of a large California health maintenance organization, only 4.9% had valvular heart disease.⁸

A-fib is commonly classified into four subcategories, based on its duration: paroxysmal, persistent, longstanding persistent, and permanent.

Paroxysmal. The occurrence of at least two episodes that have terminated in less than seven days without treatment.

Persistent. An episode lasting more than seven days or less than seven days after electric or pharmacologic conversion.

Longstanding persistent. Continuous A-fib for more than one year.

Permanent. A category for patients in whom rhythm control is no longer being pursued.

This simplified classification is often used to choose between ablative or medication therapies. To ensure accuracy, however, underlying causes, risk factors, and mechanisms should be determined.⁹

Stroke risk calculation
Once nonvalvular A-fib is confirmed, the next step is to control the ventricular rate and attempt to convert the A-fib rhythm. To accomplish this, the patient’s risk for stroke must be estimated and the need for oral anticoagulation determined.

The CHADS₂ risk stratification system for calculating an individual’s risk for ischemic stroke in A-fib was developed in 2001. The risk criteria used in the calculation are Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, prior Stroke, transient ischemic attack, or thromboembolism.¹⁰

Recent additions to the criteria account for advanced age, gender, and known vascular disease.^1,5 Known as the CHA₂DS₂-VASc, this scoring system is outlined in Table 2. If the patient’s score is 0, risk for stroke is low and anticoagulation therapy is not recommended. If the score is 1, the risk is intermediate, and the patient may be treated with aspirin therapy or anticoagulation. With a CHA₂DS₂-VASc score of 2 or greater, anticoagulation treatment is recommended to reduce the risk for stroke.¹

While the expanded CHA₂DS₂-VASc criteria more clearly define the basis for an anticoagulation recommendation—particularly in older patients, women, and those with a vascular history—the superiority of one over the other is undetermined.¹¹ However, the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with A-fib recommend use of the CHA₂DS₂-VASc.¹

Continue for anticoagulation therapy >>

 

ANTICOAGULATION THERAPY
The choice of anticoagulation treatment requires weighing the risks and benefits of oral anticoagulation therapy. Stroke and bleeding risks, cost, tolerability, potential for drug interactions, likelihood of patient adherence to the anticoagulation regimen, and patient preferences should be considered.¹

The three oral anticoagulants recently approved by the FDA for the reduction of stroke and systemic embolism risks in nonvalvular A-fib are dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors.^12-14

The clinical trials upon which the FDA’s approval of these anticoagulants was based included only patients with nonvalvular A-fib. For patients with valvular disease, warfarin, a vitamin-K–dependent inhibitor, is currently recommended.^1,15 It is also recommended for patients with both end-stage renal disease (ESRD) and either nonvalvular or valvular A-fib.¹

A-fib and chronic kidney disease
It is estimated that one-third of patients with A-fib are also diagnosed with chronic kidney disease (CKD).¹⁶  Because patients with CKD have a greater risk for bleeding, anticoagulant therapy for these ­patients requires reduced dosing and close monitoring for bleeding.

The 2014 ACC/AHA/HRS practice guidelines include guidance for selection of oral anticoagulants for patients with nonvalvular A-fib and CKD (see Table 3).^1,12-14,17 Dosing of dabigatran and rivaroxaban require evaluation of creatinine clearance before treatment is initiated.

When warfarin is indicated, dose adjustments for renal impairment are based on the prothrombin time/international normalized ratio (INR) value.¹ Current guidelines recommend maintaining a therapeutic INR between 2.0 and 3.0 for nonvalvular A-fib in patients with CKD.¹ Patients with difficulty maintaining therapeutic INR levels may benefit from alternate therapy with Xa inhibitors or a direct thrombin inhibitor except in the presence of ESRD.¹

Continue for patient adherence >>

 

PATIENT ADHERENCE
Recent studies have indicated that adherence to anticoagulation therapy among A-fib patients drops by as much as 50% after one year of therapy.¹⁸ Causes are multifactorial and include complexity of treatment regimen, missed doses, patient unawareness of stroke risk, and fear of bleeding.¹⁹ Educating both patients and caregivers has been associated with significant improvements in medication compliance in these patients.¹⁹

Complex regimens
Treatment requirements, such as the serial laboratory testing and dosage adjustments associated with warfarin therapy, can be a major contributing factor to anticoagulation nonadherence.^18,20  In this regard, the newer once-daily medications that require limited follow-up may be good alternatives to warfarin.²¹

In patients for whom warfarin therapy is indicated, educational interventions may include

• Written information for patients and caregivers about medication regimens and dosage scheduling
• Reinforcement of treatment goals and outcomes
• Use of dosing aids such as dated and timed pill dispensers
• Incorporating caregiver support to help patients adhere to the medication regimen.

These interventions have been shown to improve adherence with complex treatment regimens.²²

Missed doses
Missing anticoagulant doses is not an uncommon occurrence, and patients should be advised of appropriate catch-up strategies when this occurs.

For dabigatran, the missed dose should be taken as soon as the patient remembers, but only if the next scheduled dose is more than six hours away.¹² For rivaroxaban, missed doses should be taken as soon as the patient remembers, and the next dose should resume as scheduled.¹³ For apixaban, a missed dose should be taken as soon as possible but not in combination with any other doses.¹⁴

For patients taking warfarin, a missed dose should be taken as soon as possible on the same day.²³ If more than 24 hours have elapsed, the patient should contact his or her health care provider before taking any medication.²³

Stroke risk
Adherence to anticoagulation therapy significantly reduces the risk for stroke among A-fib patients. Estimates suggest that anticoagulants can reduce stroke risk by as much as 68% in patients with A-fib.²⁴

Even with optimal anticoagulation therapy, however, stroke remains a major complication.²⁵ Through group sessions or patient education pamphlets, patients and caregivers should be informed about the high risk for stroke associated with A-fib and should know its early symptoms.²⁶ These include sudden onset of one or more of the following: confusion or difficulty understanding speech; numbness or weakness of the face or extremities, limited to one side of the body; severe headache; dizziness, loss of balance, or difficulty ambulating; and/or visual disturbances in one or both eyes.²⁶

Next page: Bleeding risk >>

 

Bleeding risk
Patients should be advised of the major risk for bleeding associated with all anticoagulant therapies.²⁷ Screening for bleeding includes assessment of Hypertension, Abnormal renal and/or liver function, previous Stroke, Bleeding history, Labile INR, being Elderly, and currently prescribed Drugs and/or excessive use of alcohol (known as HAS-BLED) (see Table 4).^1,28  Use of a bleeding risk assessment tool such as HAS-BLED may help identify the patient’s risk but cannot be the basis for treatment decisions.^1,29 

Despite efforts to decrease bleeding risks, patients should understand that hemorrhagic complications can still occur. Patients taking anticoagulants should be familiar with early signs and symptoms of bleeding (eg, sudden, severe headache; melena; hematemesis; nosebleeds) and should notify their health care provider immediately if any of these symptoms occur.^12-14,23

If bleeding occurs, it is recommended that anticoagulant treatment be stopped. In addition, depending on the severity of the bleeding, the clinician may elect to administer activated prothrombin complex concentrates, recombinant factor VIIa, or concentrates of factors II, IX, or X to reverse the effects of newer oral anticoagulants.¹ Vitamin K, the antidote for warfarin, is not effective on direct thrombin inhibitors or factor Xa inhibitors. Currently, there is no established means of reversing the anticoagulant effects of the newer oral anticoagulants.^12-14

FOLLOW-UP
Since optimal utilization of cardiovascular medication occurs in only 50% of the patient population, appropriate follow-up must be implemented to ­improve overall outcomes of pharmacologic therapy.³⁰ Follow-up protocols depend on multiple factors, including type of anticoagulation therapy, patient response to therapy, and patient comorbidities.³¹ Monitoring warfarin use is time-consuming and resource-intensive; laboratory monitoring requirements for the newer oral anticoagulants have not been established.³²

Patients taking warfarin should be vigilant in follow-up with serial laboratory measurements and dosage adjustments.²³ Once therapy is initiated, INR is monitored every two to four days until two therapeutic INR levels are obtained.^31,33 Monitoring can then be changed to once weekly until two more therapeutic levels are obtained.³¹ The INR monitoring interval can then be increased to every two to four weeks, with two weeks being a more conservative strategy.³³ The practitioner may want to consider advancing to four-week monitoring intervals once four therapeutic INR levels have been obtained.³¹ It may be necessary to return to two-to-four day monitoring of INR if a nontherapeutic INR is obtained, the patient becomes ill, a medication is changed, or the patient makes a significant dietary change.³¹

When to refer
Primary care practitioners can manage anticoagulation therapy safely and efficiently, but cardiology referral may be warranted in certain situations. For example, patients with complex cardiac disease may benefit from cardiology referral.⁷ Considerations for referral to a cardiologist for further evaluation may include

• Abnormal exercise stress test results
• Abnormal echocardiogram results
• 12-lead ECG that reveals rapid, irregular wide pre-excited QRS complexes⁵

Patients who are drug intolerant or who remain symptomatic on pharmacologic rate control should also be referred to cardiology.⁷ In addition, patients who may require a pacemaker or defibrillator or who may be candidates for ablation should also be referred to an electrophysiology specialist.⁷

Continue for conclusion >>

 

CONCLUSION
Nonvalvular A-fib is a common arrhythmia that contributes significantly to morbidity among older adults. Use of the most current clinical practice guidelines coupled with patient education will improve overall patient outcomes.

* Editor's note: At press time, the FDA had announced approval of another oral anticoagulant, edoxaban, for the reduction of stroke and systemic embolism risks in nonvalvular A-fib.

---

CE/CME No: CR-1502

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Describe the presenting signs and symptoms of atrial fibrillation (A-fib).
• Define the differential and tests for diagnosing A-fib.
• Identify the risk factors associated with A-fib.
• Discuss the anticoagulant treatment options for nonvalvular A-fib.
• List aspects of A-fib management about which patients benefit from clinician instruction.

FACULTY
Deedra Harrington, Janis R. Guilbeau, and Christy McDonald Lenahan are Assistant Professors in the College of Nursing and Allied Health Professions at the University of Louisiana at Lafayette. Dr. Harrington is also a cardiology intensivist nurse practitioner at the Heart Hospital of Lafayette. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of February 2015. 

Article begins on next page >>

 

Patients with nonvalvular atrial fibrillation (A-fib) have a fivefold greater risk for ischemic stroke than those without. Newer oral anticoagulants reduce this risk—but also increase risk for serious bleeding, including intracranial hemorrhage. Here are the evidence-based guidelines to help you make the choice that’s best for your patient.

Atrial fibrillation (A-fib) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation that results in ineffective atrial contraction; this causes inadequate ventricular rate control and variable ventricular filling.¹ A common cardiac arrhythmia that is estimated to affect between 2.7 and 6.1 million Americans,² A-fib is projected to affect as many as 12.1 million people by the year 2030.³ Incidence increases with age; while less than 1% of patients with A-fib are younger than 60, more than a third are 80 or older.¹

Morbidity and mortality associated with A-fib are significant. The risk for an embolic event is particularly profound—five times that of persons without A-fib; again, this risk increases with age. In patients ages 50 to 59, 1.5% of strokes are attributed to A-fib; this percentage increases to 23.5% for those ages 80 to 89.²

Treatment of A-fib is aimed at rate control and rhythm conversion, generally through the use of drugs or ablation procedures, and stroke risk reduction, using oral anticoagulants to prevent thrombus formation. This review will focus on the use of newer oral anticoagulants for reduction of stroke risk associated with nonvalvular A-fib.

PATIENT PRESENTATION
Patients with new-onset A-fib may present with a variety of symptoms, including palpitations, chest pain, pressure or discomfort, shortness of breath, lightheadedness, fatigue, or exercise intolerance.⁴ Patients with chest pain, palpitations, and shortness of breath in particular should be assessed immediately for myocardial infarction before evaluating for A-fib. Poor perfusion may cause a decreased level of patient consciousness; therefore, hypotension or even Alzheimer disease should be ruled out.

Continue for diagnostic evaluation >>

 

DIAGNOSTIC EVALUATION
A complete patient history and thorough review of systems will enable the clinician to identify the risk factors for A-fib and establish a diagnosis (see Table 1).^1,4,5 Evaluation should also include a detailed physical examination. Upon initial cardiovascular assessment, the patient’s apical pulse may be rapid, irregular, or disorganized during auscultation. If underlying A-fib is related to a valvular abnormality, an audible murmur may be auscultated.⁵

Workup for A-fib includes the standard 12-lead ECG, chest radiograph, thyroid function test, and echocardiogram. The 12-lead ECG is definitive for making the diagnosis of A-fib (see Figure 1). A-fib is characterized by irregular R-R intervals when atrioventricular conduction is present, absence of distinct repeating P waves, and irregular atrial activity.¹

If the patient describes episodes consistent with A-fib that is not detectable at the office visit, 24- or 48-hour ambulatory Holter monitoring may be revealing. Event monitors can be used to determine the frequency with which the patient experiences A-fib over an extended period of time (up to 30 days).⁶

As part of the differential diagnosis of A-fib, clinicians need to consider other possible atrial conduction abnormalities, including atrial flutter, atrial tachycardia, atrioventricular nodal reentry tachycardia, multifocal atrial tachycardia, and Wolff-Parkinson-White syndrome.⁵ 

To rule out other etiologies, consider performing the following examinations and tests⁴

• A chest x-ray can rule out undiagnosed lung disease (eg, chronic obstructive pulmonary disease).
• To exclude hyperthyroidism as a cause of the patient’s symptoms, thyroid function testing and a physical examination for exophthalmos, carotid bruits, and thyromegaly are needed.
• Echocardiography is useful to exclude valvular abnormalities and/or heart failure.
• A complete blood cell count will rule out any infectious process or anemic state.
• Renal function studies and a comprehensive metabolic panel will detect signs of renal failure or electrolyte imbalance.
• Cardiac enzyme measurement can help rule out the occurrence of a myocardial event.
• A brain natriuretic peptide test can identify if heart failure is a contributing factor.

Continue for A-fib classification >>

 

A-FIB CLASSIFICATION
For purposes of choosing appropriate therapy, it is necessary to determine whether the cause of A-fib is valvular or nonvalvular. Valvular A-fib is described as A-fib that occurs in the presence of valvular heart disease or defect, such as rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.¹ In the absence of these types of conditions, A-fib is considered nonvalvular. The vast majority of patients have nonvalvular A-fib; in the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study, researchers found that, among 17,974 adults with A-fib who were members of a large California health maintenance organization, only 4.9% had valvular heart disease.⁸

A-fib is commonly classified into four subcategories, based on its duration: paroxysmal, persistent, longstanding persistent, and permanent.

Paroxysmal. The occurrence of at least two episodes that have terminated in less than seven days without treatment.

Persistent. An episode lasting more than seven days or less than seven days after electric or pharmacologic conversion.

Longstanding persistent. Continuous A-fib for more than one year.

Permanent. A category for patients in whom rhythm control is no longer being pursued.

This simplified classification is often used to choose between ablative or medication therapies. To ensure accuracy, however, underlying causes, risk factors, and mechanisms should be determined.⁹

Stroke risk calculation
Once nonvalvular A-fib is confirmed, the next step is to control the ventricular rate and attempt to convert the A-fib rhythm. To accomplish this, the patient’s risk for stroke must be estimated and the need for oral anticoagulation determined.

The CHADS₂ risk stratification system for calculating an individual’s risk for ischemic stroke in A-fib was developed in 2001. The risk criteria used in the calculation are Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, prior Stroke, transient ischemic attack, or thromboembolism.¹⁰

Recent additions to the criteria account for advanced age, gender, and known vascular disease.^1,5 Known as the CHA₂DS₂-VASc, this scoring system is outlined in Table 2. If the patient’s score is 0, risk for stroke is low and anticoagulation therapy is not recommended. If the score is 1, the risk is intermediate, and the patient may be treated with aspirin therapy or anticoagulation. With a CHA₂DS₂-VASc score of 2 or greater, anticoagulation treatment is recommended to reduce the risk for stroke.¹

While the expanded CHA₂DS₂-VASc criteria more clearly define the basis for an anticoagulation recommendation—particularly in older patients, women, and those with a vascular history—the superiority of one over the other is undetermined.¹¹ However, the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with A-fib recommend use of the CHA₂DS₂-VASc.¹

Continue for anticoagulation therapy >>

 

ANTICOAGULATION THERAPY
The choice of anticoagulation treatment requires weighing the risks and benefits of oral anticoagulation therapy. Stroke and bleeding risks, cost, tolerability, potential for drug interactions, likelihood of patient adherence to the anticoagulation regimen, and patient preferences should be considered.¹

The three oral anticoagulants recently approved by the FDA for the reduction of stroke and systemic embolism risks in nonvalvular A-fib are dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors.^12-14

The clinical trials upon which the FDA’s approval of these anticoagulants was based included only patients with nonvalvular A-fib. For patients with valvular disease, warfarin, a vitamin-K–dependent inhibitor, is currently recommended.^1,15 It is also recommended for patients with both end-stage renal disease (ESRD) and either nonvalvular or valvular A-fib.¹

A-fib and chronic kidney disease
It is estimated that one-third of patients with A-fib are also diagnosed with chronic kidney disease (CKD).¹⁶  Because patients with CKD have a greater risk for bleeding, anticoagulant therapy for these ­patients requires reduced dosing and close monitoring for bleeding.

The 2014 ACC/AHA/HRS practice guidelines include guidance for selection of oral anticoagulants for patients with nonvalvular A-fib and CKD (see Table 3).^1,12-14,17 Dosing of dabigatran and rivaroxaban require evaluation of creatinine clearance before treatment is initiated.

When warfarin is indicated, dose adjustments for renal impairment are based on the prothrombin time/international normalized ratio (INR) value.¹ Current guidelines recommend maintaining a therapeutic INR between 2.0 and 3.0 for nonvalvular A-fib in patients with CKD.¹ Patients with difficulty maintaining therapeutic INR levels may benefit from alternate therapy with Xa inhibitors or a direct thrombin inhibitor except in the presence of ESRD.¹

Continue for patient adherence >>

 

PATIENT ADHERENCE
Recent studies have indicated that adherence to anticoagulation therapy among A-fib patients drops by as much as 50% after one year of therapy.¹⁸ Causes are multifactorial and include complexity of treatment regimen, missed doses, patient unawareness of stroke risk, and fear of bleeding.¹⁹ Educating both patients and caregivers has been associated with significant improvements in medication compliance in these patients.¹⁹

Complex regimens
Treatment requirements, such as the serial laboratory testing and dosage adjustments associated with warfarin therapy, can be a major contributing factor to anticoagulation nonadherence.^18,20  In this regard, the newer once-daily medications that require limited follow-up may be good alternatives to warfarin.²¹

In patients for whom warfarin therapy is indicated, educational interventions may include

• Written information for patients and caregivers about medication regimens and dosage scheduling
• Reinforcement of treatment goals and outcomes
• Use of dosing aids such as dated and timed pill dispensers
• Incorporating caregiver support to help patients adhere to the medication regimen.

These interventions have been shown to improve adherence with complex treatment regimens.²²

Missed doses
Missing anticoagulant doses is not an uncommon occurrence, and patients should be advised of appropriate catch-up strategies when this occurs.

For dabigatran, the missed dose should be taken as soon as the patient remembers, but only if the next scheduled dose is more than six hours away.¹² For rivaroxaban, missed doses should be taken as soon as the patient remembers, and the next dose should resume as scheduled.¹³ For apixaban, a missed dose should be taken as soon as possible but not in combination with any other doses.¹⁴

For patients taking warfarin, a missed dose should be taken as soon as possible on the same day.²³ If more than 24 hours have elapsed, the patient should contact his or her health care provider before taking any medication.²³

Stroke risk
Adherence to anticoagulation therapy significantly reduces the risk for stroke among A-fib patients. Estimates suggest that anticoagulants can reduce stroke risk by as much as 68% in patients with A-fib.²⁴

Even with optimal anticoagulation therapy, however, stroke remains a major complication.²⁵ Through group sessions or patient education pamphlets, patients and caregivers should be informed about the high risk for stroke associated with A-fib and should know its early symptoms.²⁶ These include sudden onset of one or more of the following: confusion or difficulty understanding speech; numbness or weakness of the face or extremities, limited to one side of the body; severe headache; dizziness, loss of balance, or difficulty ambulating; and/or visual disturbances in one or both eyes.²⁶

Next page: Bleeding risk >>

 

Bleeding risk
Patients should be advised of the major risk for bleeding associated with all anticoagulant therapies.²⁷ Screening for bleeding includes assessment of Hypertension, Abnormal renal and/or liver function, previous Stroke, Bleeding history, Labile INR, being Elderly, and currently prescribed Drugs and/or excessive use of alcohol (known as HAS-BLED) (see Table 4).^1,28  Use of a bleeding risk assessment tool such as HAS-BLED may help identify the patient’s risk but cannot be the basis for treatment decisions.^1,29 

Despite efforts to decrease bleeding risks, patients should understand that hemorrhagic complications can still occur. Patients taking anticoagulants should be familiar with early signs and symptoms of bleeding (eg, sudden, severe headache; melena; hematemesis; nosebleeds) and should notify their health care provider immediately if any of these symptoms occur.^12-14,23

If bleeding occurs, it is recommended that anticoagulant treatment be stopped. In addition, depending on the severity of the bleeding, the clinician may elect to administer activated prothrombin complex concentrates, recombinant factor VIIa, or concentrates of factors II, IX, or X to reverse the effects of newer oral anticoagulants.¹ Vitamin K, the antidote for warfarin, is not effective on direct thrombin inhibitors or factor Xa inhibitors. Currently, there is no established means of reversing the anticoagulant effects of the newer oral anticoagulants.^12-14

FOLLOW-UP
Since optimal utilization of cardiovascular medication occurs in only 50% of the patient population, appropriate follow-up must be implemented to ­improve overall outcomes of pharmacologic therapy.³⁰ Follow-up protocols depend on multiple factors, including type of anticoagulation therapy, patient response to therapy, and patient comorbidities.³¹ Monitoring warfarin use is time-consuming and resource-intensive; laboratory monitoring requirements for the newer oral anticoagulants have not been established.³²

Patients taking warfarin should be vigilant in follow-up with serial laboratory measurements and dosage adjustments.²³ Once therapy is initiated, INR is monitored every two to four days until two therapeutic INR levels are obtained.^31,33 Monitoring can then be changed to once weekly until two more therapeutic levels are obtained.³¹ The INR monitoring interval can then be increased to every two to four weeks, with two weeks being a more conservative strategy.³³ The practitioner may want to consider advancing to four-week monitoring intervals once four therapeutic INR levels have been obtained.³¹ It may be necessary to return to two-to-four day monitoring of INR if a nontherapeutic INR is obtained, the patient becomes ill, a medication is changed, or the patient makes a significant dietary change.³¹

When to refer
Primary care practitioners can manage anticoagulation therapy safely and efficiently, but cardiology referral may be warranted in certain situations. For example, patients with complex cardiac disease may benefit from cardiology referral.⁷ Considerations for referral to a cardiologist for further evaluation may include

• Abnormal exercise stress test results
• Abnormal echocardiogram results
• 12-lead ECG that reveals rapid, irregular wide pre-excited QRS complexes⁵

Patients who are drug intolerant or who remain symptomatic on pharmacologic rate control should also be referred to cardiology.⁷ In addition, patients who may require a pacemaker or defibrillator or who may be candidates for ablation should also be referred to an electrophysiology specialist.⁷

Continue for conclusion >>

 

CONCLUSION
Nonvalvular A-fib is a common arrhythmia that contributes significantly to morbidity among older adults. Use of the most current clinical practice guidelines coupled with patient education will improve overall patient outcomes.

* Editor's note: At press time, the FDA had announced approval of another oral anticoagulant, edoxaban, for the reduction of stroke and systemic embolism risks in nonvalvular A-fib.

---

CE/CME No: CR-1501

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Explain the attention-deficit/hyperactivity disorder (ADHD) diagnostic criteria of inattention, hyperactivity, and/or impulsivity as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), and the DSM-5 update.
• Discuss the American Academy of Pediatrics clinical practice guideline for evaluation, diagnosis, treatment, and monitoring of children and adolescents with ADHD.
• Describe the classes of medications available to treat ADHD, the indications for each, and the forms available (eg, short- versus long-acting, tablets, capsules, patches, liquids).
• Identify environmental factors at home and in school that can affect a child’s ADHD and know how to address them.
• Understand and provide support for the parent’s role in managing a child’s ADHD. 

FACULTY
Amy Chandler is a family nurse practitioner at Peninsula Surgical Group in Salisbury, Maryland. Mary Parsons is an Assistant Professor at the University of Maryland School of Nursing in Baltimore. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.25 hours of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of January 2015. 

Article begins on next page >>

 

Hyperactivity, impulsivity, disruptive behavior, lack of focus—the symptoms of attention-deficit/hyperactivity disorder can negatively impact children and their families. Primary care providers have the opportunity to bring a semblance of order to chaos, and improve quality of life for all involved, by identifying affected patients and providing effective treatment options. Here is everything you need to know.

Attention-deficit/hyperactivity disorder (ADHD) is a diagnosis on the rise. In 2011, approximately 11% of school-aged children had ever been diagnosed with ADHD—an increase of 2 million children since 2003.¹ Another analysis found that, while more children ages 8 to 15 years were diagnosed with ADHD than with any other mental health disorder, only about half had received treatment for it.² Since the majority of children—65% to 85%—are diagnosed in the primary care setting,³ there is a clear need for primary care clinicians to be up-to-date on the diagnosis and treatment of this disorder.

To enhance both evidence-based practice and quality outcomes for the child and family dealing with this chronic and challenging disorder, an overview of the latest information about ADHD is presented here. In addition to diagnostic criteria, clinical presentation, screening methods, and treatment options, a discussion of the parental role in ADHD management and a medication reference guide are also provided (the latter to facilitate appropriate selection of initial pharmacologic therapy).

INTRODUCTION
ADHD is characterized by persistent patterns of hyperactivity-impulsivity and/or inattention⁴ and is diagnosed about twice as often in boys as in girls.² The hyperactive-impulsive form usually manifests before age 7, while the inattentive form may not be apparent until age 8 or 9.⁵ Although symptoms may wane with maturity, they persist into adulthood for about 50% of patients.⁶

ADHD can impair academic performance, disrupt familial and interpersonal relationships, and lead to social isolation and low self-esteem.⁴ Clinicians should be mindful of the potential negative long-term effects of ADHD, which include increased risk for substance abuse and other antisocial activities and fewer vocational opportunities.⁷

The economic impact of ADHD is also significant. An often-cited 2007 cost-of-illness analysis estimated a minimum annual societal cost of $42.5 billion for pediatric ADHD. A more likely estimate is twice that and highlights the public health importance of ADHD to health care practitioners, families, and society.⁸

ETIOLOGY
Currently, a single cause for ADHD has not been established, although research supports a genetic basis, with secondary factors (eg, environmental influences) also involved.⁹ Ongoing studies have identified numerous genes that contribute to ADHD.¹⁰ The disorder has also been seen in children with brain damage, including perinatal brain damage, fetal alcohol syndrome, and Down syndrome.¹¹

MRI studies have shown brain patterns that link ADHD with decreased functioning in the cingulo-frontal-parietal (CFP) cognitive-attention network. Specifically, impairment in the dorsal anterior midcingulate cortex, termed the daMCC, is responsible for inappropriate or excessive motor behavior, while alterations in the dorsolateral prefrontal cortex, or DLPFC, have adverse effects on the ability to think ahead, plan, and reason.¹² With this knowledge, clinicians can choose medications that target specific areas of the brain, if appropriate.

Environmental influences
Two factors hypothesized to influence ADHD symptoms are nutrition and the home environment. Many studies have examined the effects of refined sugar, additives, and preservatives on ADHD symptoms. Results indicate that, while monitoring a child’s intake of these ingredients may be beneficial from a nutritional standpoint, it is unlikely that they significantly affect ADHD symptoms.^10,13,14

Given ADHD’s genetic component, parents may have ADHD themselves—making it more difficult for them to provide consistency and structure in the home environment.^15,16 Chaotic living situations can exacerbate ADHD symptoms,¹¹ and research indicates that mothers with ADHD are more likely to engage in negative parenting, with higher demands and little praise, than mothers without the disorder.¹⁵ They may exhibit less patience and feel the need to control the child’s environment, even during playtime.¹⁷ Preschool hyperactivity has been identified in children whose parents exhibit coercive, overstimulating, negative, or inconsistent parenting.¹⁸

Next page: Making the Diagnosis >>

 

MAKING THE DIAGNOSIS
Presenting behaviors
Symptoms of ADHD typically manifest in academic settings. The greater frequency of ADHD diagnosis and treatment in boys may derive from differences in how the genders externalize behaviors.¹⁹ While boys often exhibit more impulsive and aggressive behavior, girls internalize symptoms and are more likely to be inattentive. As a result, girls are less likely to be disruptive in the classroom and may not be ­referred for evaluation. Boys, on the other hand, may be overdiagnosed due to their disruptive behaviors.¹⁹ Daley indicates that inattention (eg, daydreaming) and hyperactivity (eg, fidgeting) symptoms become more apparent in structured settings, such as a ­classroom.¹⁵

Any child who requires a mental health assessment should also be screened for ADHD; if the results of the screening suggest ADHD, a full evaluation is warranted.²⁰

Diagnostic criteria
According to the American Psychiatric Association’s criteria—outlined in the Diagnostic and Statistical Manual of Mental Disorders–IV (Text Revision) (DSM-IV-TR) and the subsequent DSM-5—the diagnosis of ADHD requires that the patient have at least six symptoms of inattention, hyperactivity, and/or impulsivity.^4,21,22 For patients ages 17 or older, the DSM-5 requires five symptoms of inattention or hyperactivity-impulsivity.²¹

Children are usually unable to complete one task prior to starting another and are easily distracted by noises otherwise ignored by others (eg, lawnmowing, background conversation).⁴ They may also exhibit excessive fidgeting and interrupt formal conversations or lectures.⁴ Inappropriate behavior relative to the child’s developmental level must have been present for at least six months prior to age 7 (according to DSM-IV-TR)⁴ or age 12 (DSM-5).²¹

In addition to exhibiting the above symptoms for a minimum of six months, impairment must be observed in at least two settings (home, school, or work), with obvious clinical impairment in social, academic, or occupational functioning.⁴ ADHD symptoms can vary depending on the setting; the child may have more difficulty paying attention and following directions in a classroom filled with children than in an environment with less stimuli (eg, one-on-one home situations).¹¹

Children who exhibit ADHD symptoms in only one setting may actually have problems secondary to cognition, emotional maturity, or feelings of well-­being in a particular setting.¹¹ Therefore, the clinician must rely on multiple sources of information (eg, parents, teachers, other caregivers) in order to make the diagnosis of ADHD.²³ A teacher should have had regular contact with the child for at least four to six months in order to provide an accurate evaluation of symptoms and their persistence.⁵

Assessment scales
Validated parent and teacher instruments, along with the DSM-IV-TR criteria, can be used to obtain data to support a diagnosis of ADHD.^5,24

The Conners Comprehensive Behavior Rating Scales and the ADHD Rating Scale IV (DSM-IV) can be used by teachers and parents to document behaviors of preschool-aged children.⁵

The Vanderbilt Assessment Scales, which have been validated in both primary care and referral settings, may be used for children older than 4.⁵

More information about rating scales is available at the National Resource Center on ADHD website (www.help4adhd.org/en/treatment/scales).

In addition to parent- or teacher-reported data, further evidence of functional impairment may be gleaned through a review of report cards, standardized testing, and school records (eg, attendance or disciplinary actions).²⁴ 

Differential diagnosis
The differential diagnosis should include other mental health conditions, sleep disorders, and any possible underlying medical or developmental problems.²⁴ Hyperthyroidism and lead toxicity, as examples, could elicit symptoms consistent with ADHD.¹¹ When the diagnosis is in doubt, coexisting conditions are present, or treatment options are in question, the primary care clinician should refer the patient to a pediatric or mental health specialist for further evaluation.²³

BEFORE TREATMENT
After the diagnosis is made but before treatment commences, a complete review of systems, physical and psychologic evaluation, cardiac and sleep history, thorough family history pertaining to mental health and medical conditions, and an age-appropriate interview are required.²⁴ The exam results assist in identifying other concerns that would indicate the need for appropriate diagnostic testing and/or referral (see Table 1).

Although stimulant treatment for ADHD has not been shown to increase cardiovascular events in otherwise healthy young people,²⁵ experts differ in their opinions about the need for screening ECG prior to treatment initiation. The American Heart Association recommends a screening ECG before stimulant therapy is initiated,²⁶ while the American Academy of Pediatrics (AAP) does not, as long as the history and exam results yield no cardiac findings.²⁷ Since the Prescribing Information for most ADHD medications cautions against use in patients with known serious cardiac abnormalities, if exam findings suggest the possibility of cardiovascular disease, further evaluation with ECG and referral to a pediatric cardiologist are indicated.^26,28

In the interview, the clinician should explore the patient’s perception of his or her behavior in response to family and social relationships and academic performance (eg, parent-teacher communication, report cards, detentions, suspensions). The psychosocial history may provide an explanation for acute onset of symptoms or coexisting disorders. Family history provides valuable insight regarding the health and cognitive abilities of family members, as well as the possibility of genetic influences on the child.²⁴ 

Parents should be advised that ADHD is a chronic condition that requires a long-term treatment approach for symptoms that may last into adulthood. Identification of goals and treatment success depend on collaborative efforts with parents, teachers, clinicians, caregivers, and mental health clinicians.²⁴

Continue for parents and ADHD >>

 

PARENTS AND ADHD
Stress
Caregivers for a child with ADHD are burdened with the ongoing challenges of the child’s inability to follow rules and his or her continual struggles with academics and peer relationships.²⁹ These hardships stress parents’ patience, often resulting in parental impulsive reactivity (eg, physical punishment of the child).

In addition, social isolation for both children and parents is common because of the judgmental scrutiny of other parents whose children are not affected by ADHD.³⁰ Parents’ career and social activities may be interrupted, adding to the sense of guilt, blame, burnout, and depression often associated with parenting a child with ADHD.²⁹

While some parenting stress is expected, those who are unable to cope with everyday events are more likely to experience conflict and anger, further increasing the child’s anxiety and emotional state.³¹ This dysfunctional environment prohibits the adoption of positive parenting techniques and ultimately contributes to more psychologic distress and harm to the parent-child relationship.³¹

Support
Once a child is diagnosed with ADHD, parents require adequate education to bolster their understanding of how to manage their child’s symptoms.²⁹ Establishing effective support systems—whether a spouse, family member, friend, or another parent whose child has ADHD—is imperative to enable parents to cope with the stress and to promote positive parenting, which has been shown to decrease symptomatic behavior.³²

Furthermore, understanding the individual child’s traits will help the parents channel his or her energy into personal areas of interest, such as sports or creative outlets (art, dance, theater).³²

Training
Parenting styles may play a role in the management of a child’s ADHD.^9,11 Encouraging parents to learn how to change their responses to their child’s behavior through evidence-based behavioral training can be one of the most effective interventions for both parents and children.³³ Parents who participate in this training gain greater behavioral understanding and treatment satisfaction, and their children experience significant improvement in conduct and other symptoms.²³

TREATMENT OPTIONS
Choice of treatment depends on patient age, the severity of functional impairment, and the individual needs of the child. Treatment may include behavioral therapy, medication administration, or a combination of the two.²³

Behavioral therapy
Behavioral therapists can provide parents and teachers with evidence-based training to understand and manage ADHD conduct.³⁴ Parents and teachers are taught to recognize the effects of environmental factors on behavior and then to modify environments and daily schedules and set appropriate limits. They learn how to reinforce positive behavior, identify triggers, and decrease inappropriate behavior, using calm disciplinary approaches that lead to positive parent-child and teacher-student relationships.^23,34

Collaborative efforts between parents and teachers are crucial to the child’s treatment plan, and individualized educational plans should be implemented to enhance academic performance, social skills, and self-esteem. For example, teachers can send home daily report cards to assist parents with monitoring core symptoms and treatment efficacy.³⁵

Behavioral therapy classes for both parent and child, or for parents only, usually meet weekly for eight to 20 weeks. Parents learn how to build positive relationships, set limits, and respond consistently with rewards or punishments (eg, consequences, time-outs). Less effective outcomes were noted when such interventions were tried by parents without adequate training.^14,24,33

Medications have been found to be more effective to treat ADHD symptoms than behavioral therapy alone, and parents and teachers report higher satisfaction with treatment plans that combine behavior modification with pharmacologic therapy.²³

Next: Medication recommendations >>

 

MEDICATION RECOMMENDATIONS
AAP medication recommendations are age-specific and should be used only if the patient meets DSM-IV-TR criteria.²⁴ An overview of both stimulant and nonstimulant treatment options for ADHD is provided in the Figure.

When an ADHD treatment regimen does not result in improved symptoms and functioning, the clinician should revisit the treatment plan and differential diagnosis. After reevaluation, the clinician may choose to add or change medication type or dose, adjust behavioral therapy, or consider the possibility of language or learning disabilities, mental health disorders, other psychosocial stressors, or poor adherence to the treatment plan.²⁴

Parents may refuse stimulant therapy for their child, fearing future drug use (or abuse) in adolescence.²⁴ Clinicians should respect parents’ decisions to defer stimulant therapy, while at the same time clarifying concerns or misunderstandings in order to provide optimal care for the child.²⁴ Studies have demonstrated that stimulant treatment for ADHD has a protective effect, with outcomes suggesting significantly decreased risk for drug or alcohol dependence.³⁶

Clinician-provided anticipatory education about dose titration, expected treatment results, and potential adverse effects will help prepare parents for the ADHD medication management process.²³ The length of time needed for dose titration varies by class of ADHD medication (see Table 2). For stimulants, effects on core symptoms may be seen within the first week. Nonstimulants take longer: up to six weeks for atomoxetine and up to four weeks for the a₂-adrenergic agonists.²⁴

Stimulants
Evidence strongly supports stimulants as first-line treatment for ADHD in children ages 6 and older.²³ Stimulants are safe and efficacious in reducing the core symptoms of inattention, hyperactivity, and impulsivity.²³ The initial choice of stimulant depends on the individual child’s needs. It should be noted that, although decreased growth rates have been observed in children taking stimulants, this effect ends by the third year of treatment.³⁸ If maximum doses are reached and desired effects are not achieved with the first stimulant, choosing an alternate drug in the stimulant class may be an effective option.²⁴ Clinicians may also consider other drug classes based on the comprehensive exam, adverse effects profile, contraindications, and individual responses.

Nonstimulants
Nonstimulant medications include atomoxetine and the a₂-adrenergic agonists extended-release clonidine and extended-release guanfacine.²⁴ 

Atomoxetine. Atomoxetine is a selective norepinephrine-reuptake inhibitor that may be prescribed if substance abuse or diversion is suspected or if stimulant therapy is contraindicated, undesirable, or unsuccessful.^24,39 Using weight-based dosing for titration,³⁷ the first week of therapy should begin with a half-dose to minimize sedation or gastrointestinal symptoms.²⁴ While atomoxetine can be quite effective, caution should be used when prescribing this agent, as it carries a black box warning for suicidal ideation.²⁴   

α₂-Adrenergic agonists. Both extended-release clonidine and extended-release guanfacine are α₂-adrenergic agonists that may be beneficial when stimulants and atomoxetine have failed or when there are coexisting conditions.³⁷ Either clonidine or guanfacine can be given in combination with a stimulant, if stimulant or atomoxetine treatment alone is unsuccessful or if adverse effects are unacceptable.^24,39 Sedative effects and withdrawal irritability are more common with clonidine than with guanfacine, and when discontinued, these medications should be tapered to avoid blood pressure changes.^24,40 

Age-specific recommendations
Medications should be selected based on age ranges. In preschool-age children (ages 4 to 5), methylphenidate is recommended when target behaviors and impaired functioning persist for nine months in both home and day care/school settings, despite behavioral therapy.^23,24 As examples, medication may be warranted if the child poses a significant risk of injury to other children or caregivers and/or faces expulsion from preschool or day care because of his or her behaviors.³⁴

Risks and benefits should be considered carefully before medical therapy is initiated in this group. Further, the lowest possible starting dose of methylphenidate is preferred for preschoolers due to their slower metabolism.²⁴ While dextroamphetamine is FDA approved for children younger than 6, efficacy and safety have not been proven in this age group and the AAP does not recommend it.²³

For children ages 6 to 18, the AAP recommends combined treatment with medication and evidence-based behavioral training for the patient, parent, and teacher. In the adolescent population, evidence supports use of stimulants as first-line therapy, but with close monitoring for medication misuse.²³ Misuse may become apparent through increased prescription refills; if identified, ADHD medication should be discontinued and substance abuse treatment initiated before ADHD therapy recommences.²⁴

Continue for dosing and special considerations >>

 

Dosing and special considerations
Initiation of ADHD medication is usually begun over the weekend to allow parents time to observe for adverse effects, to better manage the drug titration process, and to minimize academic disruptions.⁴¹ Although more expensive, the extended-release formulas are often selected to eliminate the need for multiple doses and to decrease perceived stigma associated with medication administration at school.²⁴ Longer-acting formulations have also been shown to increase treatment adherence. Adding shorter-acting doses in late afternoon, however, may be helpful if the child experiences difficulty concentrating (eg, on homework, sports, driving).²⁴

Although drug holidays are not usually recommended, children can be evaluated for this individually. For example, a child whose ADHD symptoms primarily involve inattention may only require medication on school days.³⁷

Follow-up
During the titration process, which can take up to three months, weekly clinician contacts—some by phone—to monitor effectiveness, adherence, and adverse effects are recommended (see Table 3). Blood pressure and heart rate should be monitored carefully and titration continued as needed until optimal response to treatment has been achieved.²⁴ Monitoring should continue every three months for the first year of treatment and biannually thereafter.²⁴ After several years, it is reasonable to consider a closely monitored drug-free trial period to determine if medication is still necessary.²⁴ Finally, clinicians should remain cognizant of the potential cardiovascular effects of longer-term stimulant use and adhere to clinical guidelines.⁴²

If coexisting conditions such as severe mood or anxiety disorders are present and improvement is not noted in core ADHD symptoms after three months of treatment, the patient should be referred to a mental health specialist.²³

CONCLUSION
Primary care providers must be knowledgeable about ADHD and offer appropriate evidence-based interventions, treatments, and supportive measures to patients and families dealing with this disorder. Clinicians should know what resources are available for parents of children with ADHD. Psychoeducation for parents, families, and teachers is imperative to ensure positive home and school environments. Each treatment plan requires an individual approach, and optimal use of all available resources is desirable. Implementing evidence-based recommendations will increase the overall quality of life for children and families dealing with ADHD and optimize behavioral outcomes.

The authors would like to thank Laurie Rockelli, PhD, RN, PMHCNS-BC, and William Campbell, EdD, RN, for their revisions and support in the completion of this article.

---

CE/CME No: CR-1501

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Explain the attention-deficit/hyperactivity disorder (ADHD) diagnostic criteria of inattention, hyperactivity, and/or impulsivity as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), and the DSM-5 update.
• Discuss the American Academy of Pediatrics clinical practice guideline for evaluation, diagnosis, treatment, and monitoring of children and adolescents with ADHD.
• Describe the classes of medications available to treat ADHD, the indications for each, and the forms available (eg, short- versus long-acting, tablets, capsules, patches, liquids).
• Identify environmental factors at home and in school that can affect a child’s ADHD and know how to address them.
• Understand and provide support for the parent’s role in managing a child’s ADHD. 

FACULTY
Amy Chandler is a family nurse practitioner at Peninsula Surgical Group in Salisbury, Maryland. Mary Parsons is an Assistant Professor at the University of Maryland School of Nursing in Baltimore. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.25 hours of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of January 2015. 

Article begins on next page >>

 

Hyperactivity, impulsivity, disruptive behavior, lack of focus—the symptoms of attention-deficit/hyperactivity disorder can negatively impact children and their families. Primary care providers have the opportunity to bring a semblance of order to chaos, and improve quality of life for all involved, by identifying affected patients and providing effective treatment options. Here is everything you need to know.

Attention-deficit/hyperactivity disorder (ADHD) is a diagnosis on the rise. In 2011, approximately 11% of school-aged children had ever been diagnosed with ADHD—an increase of 2 million children since 2003.¹ Another analysis found that, while more children ages 8 to 15 years were diagnosed with ADHD than with any other mental health disorder, only about half had received treatment for it.² Since the majority of children—65% to 85%—are diagnosed in the primary care setting,³ there is a clear need for primary care clinicians to be up-to-date on the diagnosis and treatment of this disorder.

To enhance both evidence-based practice and quality outcomes for the child and family dealing with this chronic and challenging disorder, an overview of the latest information about ADHD is presented here. In addition to diagnostic criteria, clinical presentation, screening methods, and treatment options, a discussion of the parental role in ADHD management and a medication reference guide are also provided (the latter to facilitate appropriate selection of initial pharmacologic therapy).

INTRODUCTION
ADHD is characterized by persistent patterns of hyperactivity-impulsivity and/or inattention⁴ and is diagnosed about twice as often in boys as in girls.² The hyperactive-impulsive form usually manifests before age 7, while the inattentive form may not be apparent until age 8 or 9.⁵ Although symptoms may wane with maturity, they persist into adulthood for about 50% of patients.⁶

ADHD can impair academic performance, disrupt familial and interpersonal relationships, and lead to social isolation and low self-esteem.⁴ Clinicians should be mindful of the potential negative long-term effects of ADHD, which include increased risk for substance abuse and other antisocial activities and fewer vocational opportunities.⁷

The economic impact of ADHD is also significant. An often-cited 2007 cost-of-illness analysis estimated a minimum annual societal cost of $42.5 billion for pediatric ADHD. A more likely estimate is twice that and highlights the public health importance of ADHD to health care practitioners, families, and society.⁸

ETIOLOGY
Currently, a single cause for ADHD has not been established, although research supports a genetic basis, with secondary factors (eg, environmental influences) also involved.⁹ Ongoing studies have identified numerous genes that contribute to ADHD.¹⁰ The disorder has also been seen in children with brain damage, including perinatal brain damage, fetal alcohol syndrome, and Down syndrome.¹¹

MRI studies have shown brain patterns that link ADHD with decreased functioning in the cingulo-frontal-parietal (CFP) cognitive-attention network. Specifically, impairment in the dorsal anterior midcingulate cortex, termed the daMCC, is responsible for inappropriate or excessive motor behavior, while alterations in the dorsolateral prefrontal cortex, or DLPFC, have adverse effects on the ability to think ahead, plan, and reason.¹² With this knowledge, clinicians can choose medications that target specific areas of the brain, if appropriate.

Environmental influences
Two factors hypothesized to influence ADHD symptoms are nutrition and the home environment. Many studies have examined the effects of refined sugar, additives, and preservatives on ADHD symptoms. Results indicate that, while monitoring a child’s intake of these ingredients may be beneficial from a nutritional standpoint, it is unlikely that they significantly affect ADHD symptoms.^10,13,14

Given ADHD’s genetic component, parents may have ADHD themselves—making it more difficult for them to provide consistency and structure in the home environment.^15,16 Chaotic living situations can exacerbate ADHD symptoms,¹¹ and research indicates that mothers with ADHD are more likely to engage in negative parenting, with higher demands and little praise, than mothers without the disorder.¹⁵ They may exhibit less patience and feel the need to control the child’s environment, even during playtime.¹⁷ Preschool hyperactivity has been identified in children whose parents exhibit coercive, overstimulating, negative, or inconsistent parenting.¹⁸

Next page: Making the Diagnosis >>

 

MAKING THE DIAGNOSIS
Presenting behaviors
Symptoms of ADHD typically manifest in academic settings. The greater frequency of ADHD diagnosis and treatment in boys may derive from differences in how the genders externalize behaviors.¹⁹ While boys often exhibit more impulsive and aggressive behavior, girls internalize symptoms and are more likely to be inattentive. As a result, girls are less likely to be disruptive in the classroom and may not be ­referred for evaluation. Boys, on the other hand, may be overdiagnosed due to their disruptive behaviors.¹⁹ Daley indicates that inattention (eg, daydreaming) and hyperactivity (eg, fidgeting) symptoms become more apparent in structured settings, such as a ­classroom.¹⁵

Any child who requires a mental health assessment should also be screened for ADHD; if the results of the screening suggest ADHD, a full evaluation is warranted.²⁰

Diagnostic criteria
According to the American Psychiatric Association’s criteria—outlined in the Diagnostic and Statistical Manual of Mental Disorders–IV (Text Revision) (DSM-IV-TR) and the subsequent DSM-5—the diagnosis of ADHD requires that the patient have at least six symptoms of inattention, hyperactivity, and/or impulsivity.^4,21,22 For patients ages 17 or older, the DSM-5 requires five symptoms of inattention or hyperactivity-impulsivity.²¹

Children are usually unable to complete one task prior to starting another and are easily distracted by noises otherwise ignored by others (eg, lawnmowing, background conversation).⁴ They may also exhibit excessive fidgeting and interrupt formal conversations or lectures.⁴ Inappropriate behavior relative to the child’s developmental level must have been present for at least six months prior to age 7 (according to DSM-IV-TR)⁴ or age 12 (DSM-5).²¹

In addition to exhibiting the above symptoms for a minimum of six months, impairment must be observed in at least two settings (home, school, or work), with obvious clinical impairment in social, academic, or occupational functioning.⁴ ADHD symptoms can vary depending on the setting; the child may have more difficulty paying attention and following directions in a classroom filled with children than in an environment with less stimuli (eg, one-on-one home situations).¹¹

Children who exhibit ADHD symptoms in only one setting may actually have problems secondary to cognition, emotional maturity, or feelings of well-­being in a particular setting.¹¹ Therefore, the clinician must rely on multiple sources of information (eg, parents, teachers, other caregivers) in order to make the diagnosis of ADHD.²³ A teacher should have had regular contact with the child for at least four to six months in order to provide an accurate evaluation of symptoms and their persistence.⁵

Assessment scales
Validated parent and teacher instruments, along with the DSM-IV-TR criteria, can be used to obtain data to support a diagnosis of ADHD.^5,24

The Conners Comprehensive Behavior Rating Scales and the ADHD Rating Scale IV (DSM-IV) can be used by teachers and parents to document behaviors of preschool-aged children.⁵

The Vanderbilt Assessment Scales, which have been validated in both primary care and referral settings, may be used for children older than 4.⁵

More information about rating scales is available at the National Resource Center on ADHD website (www.help4adhd.org/en/treatment/scales).

In addition to parent- or teacher-reported data, further evidence of functional impairment may be gleaned through a review of report cards, standardized testing, and school records (eg, attendance or disciplinary actions).²⁴ 

Differential diagnosis
The differential diagnosis should include other mental health conditions, sleep disorders, and any possible underlying medical or developmental problems.²⁴ Hyperthyroidism and lead toxicity, as examples, could elicit symptoms consistent with ADHD.¹¹ When the diagnosis is in doubt, coexisting conditions are present, or treatment options are in question, the primary care clinician should refer the patient to a pediatric or mental health specialist for further evaluation.²³

BEFORE TREATMENT
After the diagnosis is made but before treatment commences, a complete review of systems, physical and psychologic evaluation, cardiac and sleep history, thorough family history pertaining to mental health and medical conditions, and an age-appropriate interview are required.²⁴ The exam results assist in identifying other concerns that would indicate the need for appropriate diagnostic testing and/or referral (see Table 1).

Although stimulant treatment for ADHD has not been shown to increase cardiovascular events in otherwise healthy young people,²⁵ experts differ in their opinions about the need for screening ECG prior to treatment initiation. The American Heart Association recommends a screening ECG before stimulant therapy is initiated,²⁶ while the American Academy of Pediatrics (AAP) does not, as long as the history and exam results yield no cardiac findings.²⁷ Since the Prescribing Information for most ADHD medications cautions against use in patients with known serious cardiac abnormalities, if exam findings suggest the possibility of cardiovascular disease, further evaluation with ECG and referral to a pediatric cardiologist are indicated.^26,28

In the interview, the clinician should explore the patient’s perception of his or her behavior in response to family and social relationships and academic performance (eg, parent-teacher communication, report cards, detentions, suspensions). The psychosocial history may provide an explanation for acute onset of symptoms or coexisting disorders. Family history provides valuable insight regarding the health and cognitive abilities of family members, as well as the possibility of genetic influences on the child.²⁴ 

Parents should be advised that ADHD is a chronic condition that requires a long-term treatment approach for symptoms that may last into adulthood. Identification of goals and treatment success depend on collaborative efforts with parents, teachers, clinicians, caregivers, and mental health clinicians.²⁴

Continue for parents and ADHD >>

 

PARENTS AND ADHD
Stress
Caregivers for a child with ADHD are burdened with the ongoing challenges of the child’s inability to follow rules and his or her continual struggles with academics and peer relationships.²⁹ These hardships stress parents’ patience, often resulting in parental impulsive reactivity (eg, physical punishment of the child).

In addition, social isolation for both children and parents is common because of the judgmental scrutiny of other parents whose children are not affected by ADHD.³⁰ Parents’ career and social activities may be interrupted, adding to the sense of guilt, blame, burnout, and depression often associated with parenting a child with ADHD.²⁹

While some parenting stress is expected, those who are unable to cope with everyday events are more likely to experience conflict and anger, further increasing the child’s anxiety and emotional state.³¹ This dysfunctional environment prohibits the adoption of positive parenting techniques and ultimately contributes to more psychologic distress and harm to the parent-child relationship.³¹

Support
Once a child is diagnosed with ADHD, parents require adequate education to bolster their understanding of how to manage their child’s symptoms.²⁹ Establishing effective support systems—whether a spouse, family member, friend, or another parent whose child has ADHD—is imperative to enable parents to cope with the stress and to promote positive parenting, which has been shown to decrease symptomatic behavior.³²

Furthermore, understanding the individual child’s traits will help the parents channel his or her energy into personal areas of interest, such as sports or creative outlets (art, dance, theater).³²

Training
Parenting styles may play a role in the management of a child’s ADHD.^9,11 Encouraging parents to learn how to change their responses to their child’s behavior through evidence-based behavioral training can be one of the most effective interventions for both parents and children.³³ Parents who participate in this training gain greater behavioral understanding and treatment satisfaction, and their children experience significant improvement in conduct and other symptoms.²³

TREATMENT OPTIONS
Choice of treatment depends on patient age, the severity of functional impairment, and the individual needs of the child. Treatment may include behavioral therapy, medication administration, or a combination of the two.²³

Behavioral therapy
Behavioral therapists can provide parents and teachers with evidence-based training to understand and manage ADHD conduct.³⁴ Parents and teachers are taught to recognize the effects of environmental factors on behavior and then to modify environments and daily schedules and set appropriate limits. They learn how to reinforce positive behavior, identify triggers, and decrease inappropriate behavior, using calm disciplinary approaches that lead to positive parent-child and teacher-student relationships.^23,34

Collaborative efforts between parents and teachers are crucial to the child’s treatment plan, and individualized educational plans should be implemented to enhance academic performance, social skills, and self-esteem. For example, teachers can send home daily report cards to assist parents with monitoring core symptoms and treatment efficacy.³⁵

Behavioral therapy classes for both parent and child, or for parents only, usually meet weekly for eight to 20 weeks. Parents learn how to build positive relationships, set limits, and respond consistently with rewards or punishments (eg, consequences, time-outs). Less effective outcomes were noted when such interventions were tried by parents without adequate training.^14,24,33

Medications have been found to be more effective to treat ADHD symptoms than behavioral therapy alone, and parents and teachers report higher satisfaction with treatment plans that combine behavior modification with pharmacologic therapy.²³

Next: Medication recommendations >>

 

MEDICATION RECOMMENDATIONS
AAP medication recommendations are age-specific and should be used only if the patient meets DSM-IV-TR criteria.²⁴ An overview of both stimulant and nonstimulant treatment options for ADHD is provided in the Figure.

When an ADHD treatment regimen does not result in improved symptoms and functioning, the clinician should revisit the treatment plan and differential diagnosis. After reevaluation, the clinician may choose to add or change medication type or dose, adjust behavioral therapy, or consider the possibility of language or learning disabilities, mental health disorders, other psychosocial stressors, or poor adherence to the treatment plan.²⁴

Parents may refuse stimulant therapy for their child, fearing future drug use (or abuse) in adolescence.²⁴ Clinicians should respect parents’ decisions to defer stimulant therapy, while at the same time clarifying concerns or misunderstandings in order to provide optimal care for the child.²⁴ Studies have demonstrated that stimulant treatment for ADHD has a protective effect, with outcomes suggesting significantly decreased risk for drug or alcohol dependence.³⁶

Clinician-provided anticipatory education about dose titration, expected treatment results, and potential adverse effects will help prepare parents for the ADHD medication management process.²³ The length of time needed for dose titration varies by class of ADHD medication (see Table 2). For stimulants, effects on core symptoms may be seen within the first week. Nonstimulants take longer: up to six weeks for atomoxetine and up to four weeks for the a₂-adrenergic agonists.²⁴

Stimulants
Evidence strongly supports stimulants as first-line treatment for ADHD in children ages 6 and older.²³ Stimulants are safe and efficacious in reducing the core symptoms of inattention, hyperactivity, and impulsivity.²³ The initial choice of stimulant depends on the individual child’s needs. It should be noted that, although decreased growth rates have been observed in children taking stimulants, this effect ends by the third year of treatment.³⁸ If maximum doses are reached and desired effects are not achieved with the first stimulant, choosing an alternate drug in the stimulant class may be an effective option.²⁴ Clinicians may also consider other drug classes based on the comprehensive exam, adverse effects profile, contraindications, and individual responses.

Nonstimulants
Nonstimulant medications include atomoxetine and the a₂-adrenergic agonists extended-release clonidine and extended-release guanfacine.²⁴ 

Atomoxetine. Atomoxetine is a selective norepinephrine-reuptake inhibitor that may be prescribed if substance abuse or diversion is suspected or if stimulant therapy is contraindicated, undesirable, or unsuccessful.^24,39 Using weight-based dosing for titration,³⁷ the first week of therapy should begin with a half-dose to minimize sedation or gastrointestinal symptoms.²⁴ While atomoxetine can be quite effective, caution should be used when prescribing this agent, as it carries a black box warning for suicidal ideation.²⁴   

α₂-Adrenergic agonists. Both extended-release clonidine and extended-release guanfacine are α₂-adrenergic agonists that may be beneficial when stimulants and atomoxetine have failed or when there are coexisting conditions.³⁷ Either clonidine or guanfacine can be given in combination with a stimulant, if stimulant or atomoxetine treatment alone is unsuccessful or if adverse effects are unacceptable.^24,39 Sedative effects and withdrawal irritability are more common with clonidine than with guanfacine, and when discontinued, these medications should be tapered to avoid blood pressure changes.^24,40 

Age-specific recommendations
Medications should be selected based on age ranges. In preschool-age children (ages 4 to 5), methylphenidate is recommended when target behaviors and impaired functioning persist for nine months in both home and day care/school settings, despite behavioral therapy.^23,24 As examples, medication may be warranted if the child poses a significant risk of injury to other children or caregivers and/or faces expulsion from preschool or day care because of his or her behaviors.³⁴

Risks and benefits should be considered carefully before medical therapy is initiated in this group. Further, the lowest possible starting dose of methylphenidate is preferred for preschoolers due to their slower metabolism.²⁴ While dextroamphetamine is FDA approved for children younger than 6, efficacy and safety have not been proven in this age group and the AAP does not recommend it.²³

For children ages 6 to 18, the AAP recommends combined treatment with medication and evidence-based behavioral training for the patient, parent, and teacher. In the adolescent population, evidence supports use of stimulants as first-line therapy, but with close monitoring for medication misuse.²³ Misuse may become apparent through increased prescription refills; if identified, ADHD medication should be discontinued and substance abuse treatment initiated before ADHD therapy recommences.²⁴

Continue for dosing and special considerations >>

 

Dosing and special considerations
Initiation of ADHD medication is usually begun over the weekend to allow parents time to observe for adverse effects, to better manage the drug titration process, and to minimize academic disruptions.⁴¹ Although more expensive, the extended-release formulas are often selected to eliminate the need for multiple doses and to decrease perceived stigma associated with medication administration at school.²⁴ Longer-acting formulations have also been shown to increase treatment adherence. Adding shorter-acting doses in late afternoon, however, may be helpful if the child experiences difficulty concentrating (eg, on homework, sports, driving).²⁴

Although drug holidays are not usually recommended, children can be evaluated for this individually. For example, a child whose ADHD symptoms primarily involve inattention may only require medication on school days.³⁷

Follow-up
During the titration process, which can take up to three months, weekly clinician contacts—some by phone—to monitor effectiveness, adherence, and adverse effects are recommended (see Table 3). Blood pressure and heart rate should be monitored carefully and titration continued as needed until optimal response to treatment has been achieved.²⁴ Monitoring should continue every three months for the first year of treatment and biannually thereafter.²⁴ After several years, it is reasonable to consider a closely monitored drug-free trial period to determine if medication is still necessary.²⁴ Finally, clinicians should remain cognizant of the potential cardiovascular effects of longer-term stimulant use and adhere to clinical guidelines.⁴²

If coexisting conditions such as severe mood or anxiety disorders are present and improvement is not noted in core ADHD symptoms after three months of treatment, the patient should be referred to a mental health specialist.²³

CONCLUSION
Primary care providers must be knowledgeable about ADHD and offer appropriate evidence-based interventions, treatments, and supportive measures to patients and families dealing with this disorder. Clinicians should know what resources are available for parents of children with ADHD. Psychoeducation for parents, families, and teachers is imperative to ensure positive home and school environments. Each treatment plan requires an individual approach, and optimal use of all available resources is desirable. Implementing evidence-based recommendations will increase the overall quality of life for children and families dealing with ADHD and optimize behavioral outcomes.

The authors would like to thank Laurie Rockelli, PhD, RN, PMHCNS-BC, and William Campbell, EdD, RN, for their revisions and support in the completion of this article.

---

CE/CME No: CR-1501

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Explain the attention-deficit/hyperactivity disorder (ADHD) diagnostic criteria of inattention, hyperactivity, and/or impulsivity as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), and the DSM-5 update.
• Discuss the American Academy of Pediatrics clinical practice guideline for evaluation, diagnosis, treatment, and monitoring of children and adolescents with ADHD.
• Describe the classes of medications available to treat ADHD, the indications for each, and the forms available (eg, short- versus long-acting, tablets, capsules, patches, liquids).
• Identify environmental factors at home and in school that can affect a child’s ADHD and know how to address them.
• Understand and provide support for the parent’s role in managing a child’s ADHD. 

FACULTY
Amy Chandler is a family nurse practitioner at Peninsula Surgical Group in Salisbury, Maryland. Mary Parsons is an Assistant Professor at the University of Maryland School of Nursing in Baltimore. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.25 hours of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of January 2015. 

Article begins on next page >>

 

Hyperactivity, impulsivity, disruptive behavior, lack of focus—the symptoms of attention-deficit/hyperactivity disorder can negatively impact children and their families. Primary care providers have the opportunity to bring a semblance of order to chaos, and improve quality of life for all involved, by identifying affected patients and providing effective treatment options. Here is everything you need to know.

Attention-deficit/hyperactivity disorder (ADHD) is a diagnosis on the rise. In 2011, approximately 11% of school-aged children had ever been diagnosed with ADHD—an increase of 2 million children since 2003.¹ Another analysis found that, while more children ages 8 to 15 years were diagnosed with ADHD than with any other mental health disorder, only about half had received treatment for it.² Since the majority of children—65% to 85%—are diagnosed in the primary care setting,³ there is a clear need for primary care clinicians to be up-to-date on the diagnosis and treatment of this disorder.

To enhance both evidence-based practice and quality outcomes for the child and family dealing with this chronic and challenging disorder, an overview of the latest information about ADHD is presented here. In addition to diagnostic criteria, clinical presentation, screening methods, and treatment options, a discussion of the parental role in ADHD management and a medication reference guide are also provided (the latter to facilitate appropriate selection of initial pharmacologic therapy).

INTRODUCTION
ADHD is characterized by persistent patterns of hyperactivity-impulsivity and/or inattention⁴ and is diagnosed about twice as often in boys as in girls.² The hyperactive-impulsive form usually manifests before age 7, while the inattentive form may not be apparent until age 8 or 9.⁵ Although symptoms may wane with maturity, they persist into adulthood for about 50% of patients.⁶

ADHD can impair academic performance, disrupt familial and interpersonal relationships, and lead to social isolation and low self-esteem.⁴ Clinicians should be mindful of the potential negative long-term effects of ADHD, which include increased risk for substance abuse and other antisocial activities and fewer vocational opportunities.⁷

The economic impact of ADHD is also significant. An often-cited 2007 cost-of-illness analysis estimated a minimum annual societal cost of $42.5 billion for pediatric ADHD. A more likely estimate is twice that and highlights the public health importance of ADHD to health care practitioners, families, and society.⁸

ETIOLOGY
Currently, a single cause for ADHD has not been established, although research supports a genetic basis, with secondary factors (eg, environmental influences) also involved.⁹ Ongoing studies have identified numerous genes that contribute to ADHD.¹⁰ The disorder has also been seen in children with brain damage, including perinatal brain damage, fetal alcohol syndrome, and Down syndrome.¹¹

MRI studies have shown brain patterns that link ADHD with decreased functioning in the cingulo-frontal-parietal (CFP) cognitive-attention network. Specifically, impairment in the dorsal anterior midcingulate cortex, termed the daMCC, is responsible for inappropriate or excessive motor behavior, while alterations in the dorsolateral prefrontal cortex, or DLPFC, have adverse effects on the ability to think ahead, plan, and reason.¹² With this knowledge, clinicians can choose medications that target specific areas of the brain, if appropriate.

Environmental influences
Two factors hypothesized to influence ADHD symptoms are nutrition and the home environment. Many studies have examined the effects of refined sugar, additives, and preservatives on ADHD symptoms. Results indicate that, while monitoring a child’s intake of these ingredients may be beneficial from a nutritional standpoint, it is unlikely that they significantly affect ADHD symptoms.^10,13,14

Given ADHD’s genetic component, parents may have ADHD themselves—making it more difficult for them to provide consistency and structure in the home environment.^15,16 Chaotic living situations can exacerbate ADHD symptoms,¹¹ and research indicates that mothers with ADHD are more likely to engage in negative parenting, with higher demands and little praise, than mothers without the disorder.¹⁵ They may exhibit less patience and feel the need to control the child’s environment, even during playtime.¹⁷ Preschool hyperactivity has been identified in children whose parents exhibit coercive, overstimulating, negative, or inconsistent parenting.¹⁸

Next page: Making the Diagnosis >>

 

MAKING THE DIAGNOSIS
Presenting behaviors
Symptoms of ADHD typically manifest in academic settings. The greater frequency of ADHD diagnosis and treatment in boys may derive from differences in how the genders externalize behaviors.¹⁹ While boys often exhibit more impulsive and aggressive behavior, girls internalize symptoms and are more likely to be inattentive. As a result, girls are less likely to be disruptive in the classroom and may not be ­referred for evaluation. Boys, on the other hand, may be overdiagnosed due to their disruptive behaviors.¹⁹ Daley indicates that inattention (eg, daydreaming) and hyperactivity (eg, fidgeting) symptoms become more apparent in structured settings, such as a ­classroom.¹⁵

Any child who requires a mental health assessment should also be screened for ADHD; if the results of the screening suggest ADHD, a full evaluation is warranted.²⁰

Diagnostic criteria
According to the American Psychiatric Association’s criteria—outlined in the Diagnostic and Statistical Manual of Mental Disorders–IV (Text Revision) (DSM-IV-TR) and the subsequent DSM-5—the diagnosis of ADHD requires that the patient have at least six symptoms of inattention, hyperactivity, and/or impulsivity.^4,21,22 For patients ages 17 or older, the DSM-5 requires five symptoms of inattention or hyperactivity-impulsivity.²¹

Children are usually unable to complete one task prior to starting another and are easily distracted by noises otherwise ignored by others (eg, lawnmowing, background conversation).⁴ They may also exhibit excessive fidgeting and interrupt formal conversations or lectures.⁴ Inappropriate behavior relative to the child’s developmental level must have been present for at least six months prior to age 7 (according to DSM-IV-TR)⁴ or age 12 (DSM-5).²¹

In addition to exhibiting the above symptoms for a minimum of six months, impairment must be observed in at least two settings (home, school, or work), with obvious clinical impairment in social, academic, or occupational functioning.⁴ ADHD symptoms can vary depending on the setting; the child may have more difficulty paying attention and following directions in a classroom filled with children than in an environment with less stimuli (eg, one-on-one home situations).¹¹

Children who exhibit ADHD symptoms in only one setting may actually have problems secondary to cognition, emotional maturity, or feelings of well-­being in a particular setting.¹¹ Therefore, the clinician must rely on multiple sources of information (eg, parents, teachers, other caregivers) in order to make the diagnosis of ADHD.²³ A teacher should have had regular contact with the child for at least four to six months in order to provide an accurate evaluation of symptoms and their persistence.⁵

Assessment scales
Validated parent and teacher instruments, along with the DSM-IV-TR criteria, can be used to obtain data to support a diagnosis of ADHD.^5,24

The Conners Comprehensive Behavior Rating Scales and the ADHD Rating Scale IV (DSM-IV) can be used by teachers and parents to document behaviors of preschool-aged children.⁵

The Vanderbilt Assessment Scales, which have been validated in both primary care and referral settings, may be used for children older than 4.⁵

More information about rating scales is available at the National Resource Center on ADHD website (www.help4adhd.org/en/treatment/scales).

In addition to parent- or teacher-reported data, further evidence of functional impairment may be gleaned through a review of report cards, standardized testing, and school records (eg, attendance or disciplinary actions).²⁴ 

Differential diagnosis
The differential diagnosis should include other mental health conditions, sleep disorders, and any possible underlying medical or developmental problems.²⁴ Hyperthyroidism and lead toxicity, as examples, could elicit symptoms consistent with ADHD.¹¹ When the diagnosis is in doubt, coexisting conditions are present, or treatment options are in question, the primary care clinician should refer the patient to a pediatric or mental health specialist for further evaluation.²³

BEFORE TREATMENT
After the diagnosis is made but before treatment commences, a complete review of systems, physical and psychologic evaluation, cardiac and sleep history, thorough family history pertaining to mental health and medical conditions, and an age-appropriate interview are required.²⁴ The exam results assist in identifying other concerns that would indicate the need for appropriate diagnostic testing and/or referral (see Table 1).

Although stimulant treatment for ADHD has not been shown to increase cardiovascular events in otherwise healthy young people,²⁵ experts differ in their opinions about the need for screening ECG prior to treatment initiation. The American Heart Association recommends a screening ECG before stimulant therapy is initiated,²⁶ while the American Academy of Pediatrics (AAP) does not, as long as the history and exam results yield no cardiac findings.²⁷ Since the Prescribing Information for most ADHD medications cautions against use in patients with known serious cardiac abnormalities, if exam findings suggest the possibility of cardiovascular disease, further evaluation with ECG and referral to a pediatric cardiologist are indicated.^26,28

In the interview, the clinician should explore the patient’s perception of his or her behavior in response to family and social relationships and academic performance (eg, parent-teacher communication, report cards, detentions, suspensions). The psychosocial history may provide an explanation for acute onset of symptoms or coexisting disorders. Family history provides valuable insight regarding the health and cognitive abilities of family members, as well as the possibility of genetic influences on the child.²⁴ 

Parents should be advised that ADHD is a chronic condition that requires a long-term treatment approach for symptoms that may last into adulthood. Identification of goals and treatment success depend on collaborative efforts with parents, teachers, clinicians, caregivers, and mental health clinicians.²⁴

Continue for parents and ADHD >>

 

PARENTS AND ADHD
Stress
Caregivers for a child with ADHD are burdened with the ongoing challenges of the child’s inability to follow rules and his or her continual struggles with academics and peer relationships.²⁹ These hardships stress parents’ patience, often resulting in parental impulsive reactivity (eg, physical punishment of the child).

In addition, social isolation for both children and parents is common because of the judgmental scrutiny of other parents whose children are not affected by ADHD.³⁰ Parents’ career and social activities may be interrupted, adding to the sense of guilt, blame, burnout, and depression often associated with parenting a child with ADHD.²⁹

While some parenting stress is expected, those who are unable to cope with everyday events are more likely to experience conflict and anger, further increasing the child’s anxiety and emotional state.³¹ This dysfunctional environment prohibits the adoption of positive parenting techniques and ultimately contributes to more psychologic distress and harm to the parent-child relationship.³¹

Support
Once a child is diagnosed with ADHD, parents require adequate education to bolster their understanding of how to manage their child’s symptoms.²⁹ Establishing effective support systems—whether a spouse, family member, friend, or another parent whose child has ADHD—is imperative to enable parents to cope with the stress and to promote positive parenting, which has been shown to decrease symptomatic behavior.³²

Furthermore, understanding the individual child’s traits will help the parents channel his or her energy into personal areas of interest, such as sports or creative outlets (art, dance, theater).³²

Training
Parenting styles may play a role in the management of a child’s ADHD.^9,11 Encouraging parents to learn how to change their responses to their child’s behavior through evidence-based behavioral training can be one of the most effective interventions for both parents and children.³³ Parents who participate in this training gain greater behavioral understanding and treatment satisfaction, and their children experience significant improvement in conduct and other symptoms.²³

TREATMENT OPTIONS
Choice of treatment depends on patient age, the severity of functional impairment, and the individual needs of the child. Treatment may include behavioral therapy, medication administration, or a combination of the two.²³

Behavioral therapy
Behavioral therapists can provide parents and teachers with evidence-based training to understand and manage ADHD conduct.³⁴ Parents and teachers are taught to recognize the effects of environmental factors on behavior and then to modify environments and daily schedules and set appropriate limits. They learn how to reinforce positive behavior, identify triggers, and decrease inappropriate behavior, using calm disciplinary approaches that lead to positive parent-child and teacher-student relationships.^23,34

Collaborative efforts between parents and teachers are crucial to the child’s treatment plan, and individualized educational plans should be implemented to enhance academic performance, social skills, and self-esteem. For example, teachers can send home daily report cards to assist parents with monitoring core symptoms and treatment efficacy.³⁵

Behavioral therapy classes for both parent and child, or for parents only, usually meet weekly for eight to 20 weeks. Parents learn how to build positive relationships, set limits, and respond consistently with rewards or punishments (eg, consequences, time-outs). Less effective outcomes were noted when such interventions were tried by parents without adequate training.^14,24,33

Medications have been found to be more effective to treat ADHD symptoms than behavioral therapy alone, and parents and teachers report higher satisfaction with treatment plans that combine behavior modification with pharmacologic therapy.²³

Next: Medication recommendations >>

 

MEDICATION RECOMMENDATIONS
AAP medication recommendations are age-specific and should be used only if the patient meets DSM-IV-TR criteria.²⁴ An overview of both stimulant and nonstimulant treatment options for ADHD is provided in the Figure.

When an ADHD treatment regimen does not result in improved symptoms and functioning, the clinician should revisit the treatment plan and differential diagnosis. After reevaluation, the clinician may choose to add or change medication type or dose, adjust behavioral therapy, or consider the possibility of language or learning disabilities, mental health disorders, other psychosocial stressors, or poor adherence to the treatment plan.²⁴

Parents may refuse stimulant therapy for their child, fearing future drug use (or abuse) in adolescence.²⁴ Clinicians should respect parents’ decisions to defer stimulant therapy, while at the same time clarifying concerns or misunderstandings in order to provide optimal care for the child.²⁴ Studies have demonstrated that stimulant treatment for ADHD has a protective effect, with outcomes suggesting significantly decreased risk for drug or alcohol dependence.³⁶

Clinician-provided anticipatory education about dose titration, expected treatment results, and potential adverse effects will help prepare parents for the ADHD medication management process.²³ The length of time needed for dose titration varies by class of ADHD medication (see Table 2). For stimulants, effects on core symptoms may be seen within the first week. Nonstimulants take longer: up to six weeks for atomoxetine and up to four weeks for the a₂-adrenergic agonists.²⁴

Stimulants
Evidence strongly supports stimulants as first-line treatment for ADHD in children ages 6 and older.²³ Stimulants are safe and efficacious in reducing the core symptoms of inattention, hyperactivity, and impulsivity.²³ The initial choice of stimulant depends on the individual child’s needs. It should be noted that, although decreased growth rates have been observed in children taking stimulants, this effect ends by the third year of treatment.³⁸ If maximum doses are reached and desired effects are not achieved with the first stimulant, choosing an alternate drug in the stimulant class may be an effective option.²⁴ Clinicians may also consider other drug classes based on the comprehensive exam, adverse effects profile, contraindications, and individual responses.

Nonstimulants
Nonstimulant medications include atomoxetine and the a₂-adrenergic agonists extended-release clonidine and extended-release guanfacine.²⁴ 

Atomoxetine. Atomoxetine is a selective norepinephrine-reuptake inhibitor that may be prescribed if substance abuse or diversion is suspected or if stimulant therapy is contraindicated, undesirable, or unsuccessful.^24,39 Using weight-based dosing for titration,³⁷ the first week of therapy should begin with a half-dose to minimize sedation or gastrointestinal symptoms.²⁴ While atomoxetine can be quite effective, caution should be used when prescribing this agent, as it carries a black box warning for suicidal ideation.²⁴   

α₂-Adrenergic agonists. Both extended-release clonidine and extended-release guanfacine are α₂-adrenergic agonists that may be beneficial when stimulants and atomoxetine have failed or when there are coexisting conditions.³⁷ Either clonidine or guanfacine can be given in combination with a stimulant, if stimulant or atomoxetine treatment alone is unsuccessful or if adverse effects are unacceptable.^24,39 Sedative effects and withdrawal irritability are more common with clonidine than with guanfacine, and when discontinued, these medications should be tapered to avoid blood pressure changes.^24,40 

Age-specific recommendations
Medications should be selected based on age ranges. In preschool-age children (ages 4 to 5), methylphenidate is recommended when target behaviors and impaired functioning persist for nine months in both home and day care/school settings, despite behavioral therapy.^23,24 As examples, medication may be warranted if the child poses a significant risk of injury to other children or caregivers and/or faces expulsion from preschool or day care because of his or her behaviors.³⁴

Risks and benefits should be considered carefully before medical therapy is initiated in this group. Further, the lowest possible starting dose of methylphenidate is preferred for preschoolers due to their slower metabolism.²⁴ While dextroamphetamine is FDA approved for children younger than 6, efficacy and safety have not been proven in this age group and the AAP does not recommend it.²³

For children ages 6 to 18, the AAP recommends combined treatment with medication and evidence-based behavioral training for the patient, parent, and teacher. In the adolescent population, evidence supports use of stimulants as first-line therapy, but with close monitoring for medication misuse.²³ Misuse may become apparent through increased prescription refills; if identified, ADHD medication should be discontinued and substance abuse treatment initiated before ADHD therapy recommences.²⁴

Continue for dosing and special considerations >>

 

Dosing and special considerations
Initiation of ADHD medication is usually begun over the weekend to allow parents time to observe for adverse effects, to better manage the drug titration process, and to minimize academic disruptions.⁴¹ Although more expensive, the extended-release formulas are often selected to eliminate the need for multiple doses and to decrease perceived stigma associated with medication administration at school.²⁴ Longer-acting formulations have also been shown to increase treatment adherence. Adding shorter-acting doses in late afternoon, however, may be helpful if the child experiences difficulty concentrating (eg, on homework, sports, driving).²⁴

Although drug holidays are not usually recommended, children can be evaluated for this individually. For example, a child whose ADHD symptoms primarily involve inattention may only require medication on school days.³⁷

Follow-up
During the titration process, which can take up to three months, weekly clinician contacts—some by phone—to monitor effectiveness, adherence, and adverse effects are recommended (see Table 3). Blood pressure and heart rate should be monitored carefully and titration continued as needed until optimal response to treatment has been achieved.²⁴ Monitoring should continue every three months for the first year of treatment and biannually thereafter.²⁴ After several years, it is reasonable to consider a closely monitored drug-free trial period to determine if medication is still necessary.²⁴ Finally, clinicians should remain cognizant of the potential cardiovascular effects of longer-term stimulant use and adhere to clinical guidelines.⁴²

If coexisting conditions such as severe mood or anxiety disorders are present and improvement is not noted in core ADHD symptoms after three months of treatment, the patient should be referred to a mental health specialist.²³

CONCLUSION
Primary care providers must be knowledgeable about ADHD and offer appropriate evidence-based interventions, treatments, and supportive measures to patients and families dealing with this disorder. Clinicians should know what resources are available for parents of children with ADHD. Psychoeducation for parents, families, and teachers is imperative to ensure positive home and school environments. Each treatment plan requires an individual approach, and optimal use of all available resources is desirable. Implementing evidence-based recommendations will increase the overall quality of life for children and families dealing with ADHD and optimize behavioral outcomes.

The authors would like to thank Laurie Rockelli, PhD, RN, PMHCNS-BC, and William Campbell, EdD, RN, for their revisions and support in the completion of this article.

---

CE/CME No: CR-1412

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Discuss the evolution in thinking about the pathogenesis of and treatment for vocal cord dysfunction (VCD).
• Describe the three primary functions of the healthy vocal cords.
• List the conditions or factors that may trigger VCD.
• Explain how to differentiate VCD from asthma.
• Develop a treatment plan for VCD that addresses both patient-specific VCD triggers and management of symptomatic episodes.

FACULTY
Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies and Randy D. Danielsen is a Professor and Dean at the Arizona School of Health Sciences, AT Still University, Mesa. Ms. MacConnell is also a clinical PA affiliated with Enticare, an otolaryngology practice in Chandler, Arizona. Susan Symington is a clinical PA with the Arizona Asthma & Allergy Institute, with which Dr. Danielsen is also affiliated.
Linda MacConnell and Randy Danielsen have no significant financial relationships to disclose. Susan Symington is a member of the speaker’s bureau for Teva Respiratory and Thermo Fisher Scientific, Inc.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of December 2014.

Article begins on next page >>

 

The symptoms of vocal cord dysfunction (VCD) can be mistaken for those
of asthma or other respiratory illnesses. As a result, VCD is often misdiagnosed,
leading to unnecessary, ineffective, costly, or even dangerous treatment. Here are
the facts that will enable you to avoid making an erroneous diagnosis, choosing
potentially harmful treatment, and delaying effective treatment.

A 33-year-old oncology nurse, JD, had moved from Seattle to Phoenix about six months earlier for a job opportunity. Shortly after starting her new job, she had developed intermittent dyspnea on exertion, with a cough lasting several minutes at a time, along with a sensation of heaviness over the larynx and a choking sensation. These symptoms were precipitated by gastroesophageal reflux disease (GERD), postnasal drainage, stress, and significant environmental change (ie, Seattle to Phoenix). She noticed that, since moving to Phoenix, she frequently cleared her throat but denied any hoarseness, dysphagia, chest tightness, chest pain, or wheezing. She noted nasal congestion and clear nasal discharge on exposure to inhaled irritants (eg, woodstove smoke) and strong fragrances (eg, perfume or cologne).

On physical examination, the patient was alert, oriented, and in no acute distress. She was coughing intermittently but was able to speak in complete sentences. No stridor or dyspnea was noted, either on exertion (jogging in place) or at rest.

HEENT examination was normal, with no scalp lesions or tenderness; face, symmetric; light reflex, symmetric; conjunctivae, clear; sclera white, without lesions or redness; pupils, equal, reactive to light and accommodation; tympanic membranes and canals, clear with intact landmarks; no nasal deformities; nasal mucosa, mildly erythematous with mild engorgement of the turbinates; no nasal polyps seen; nasal septum midline without perforation; no sinus tenderness on percussion; pharynx, clear without exudate; uvula rises on phonation; and oral mucosa and gingivae, pink without lesions. Neck was supple without masses or thyromegaly, and trachea was midline. Lungs were clear to auscultation with normal respiratory movement and no accessory muscle use, with normal anteroposterior diameter. Heart examination revealed regular rate and rhythm, without murmur, clicks, or gallops.

Examination of the skin was normal, without rashes, hives, swelling, petechiae, or significant ecchymosis. There was no palpable cervical, supraclavicular, or axillary adenopathy.

Results of laboratory studies included a normal complete blood count with differential and a normal IgE level of 46.3 IU/mL. Spirometry testing revealed normal values without obstruction; however, there was a flattening of the inspiratory flow loop, with no reversibility after bronchodilator, which was highly suggestive of vocal cord dysfunction (VCD). Perennial nonallergic rhinitis (formerly called vasomotor rhinitis) was confirmed because the patient experienced fewer symptoms to perfume after nasal corticosteroid use. The patient’s GERD was generally well controlled with esomeprazole but was likely a contributing factor to her vocal cord symptoms.

On laryngoscopy, abnormal vocal cord movement toward the midline during both inspiration and expiration was visualized, confirming the diagnosis of VCD.

BACKGROUND
VCD is a partial upper airway obstruction caused by paradoxical adduction (medial movement) of the vocal cords.¹ Although it is primarily associated with inspiration, it sometimes manifests during expiration as well.

The true incidence of VCD is uncertain; different studies have found incidence rates varying from 2% to 27%, with higher rates in patients with asthma.^1,2 However, highlighting the risk for misdiagnosis, some 10% of patients evaluated for asthma unresponsive to aggressive treatment were found, in fact, to have VCD alone.²

Similarly, although VCD is generally more common in women than in men, the reported female-to-male ratio has varied from 2:1 to 4:1.^1,2,4 Some reports suggest that VCD is seen more frequently in younger women, with average ages at diagnosis of 14.5 in adolescents and 33 in adults.^2,3 Others identify a broader age range, with most patients older than 50.⁴

Historically, VCD has been known by a variety of names and has been observed clinically since 1842. In that year, Dunglison referred to it as hysteric croup, describing a disorder of the laryngeal muscles brought on by “hysteria.”⁵ Later, Mackenzie was able to visualize adduction of the vocal cords during inspiration in patients with stridor by using a laryngoscope.⁶ Osler demonstrated his understanding of the condition in 1902, stating, “Spasm of muscles may occur with violent inspiratory effort and great distress, and may even lead to cyanosis. Extraordinary cries may be produced either inspiratory or expiratory.”⁷

More recently, in 1974, Patterson et al reported finding laryngoscopic evidence of VCD, which they termed Munchausen’s stridor.⁸ They used this descriptor to report on the case of a young woman with 15 hospital admissions for this condition. At the time, the etiology of the condition was believed to be largely psychologic, and its evaluation was consigned to psychiatrists and other mental health practitioners.

As laryngoscopy became more widely available in the 1970s and 1980s, diagnosis of VCD increased, although the condition remains underrecognized.⁹ Ibrahim et al suggest that primary care clinicians may not be as aware of VCD as they should be and may not consider laryngoscopy for possible VCD in patients whose asthma is poorly controlled.²

Disagreement persists with regard to the preferred name for the condition. Because numerous disorders involve abnormal vocal cord function, Christopher proposed moving away from the broad term VCD and toward a more descriptive term: paradoxical vocal fold motion (PVFM) disorder.¹⁰ Interestingly, use of the two terms seems to be divided along specialty lines: VCD is preferred by allergy, pulmonology, and mental health specialists, while PVFM is favored by otolaryngology specialists and speech-language pathologists.¹¹

Further complicating awareness and recognition of VCD is its longstanding reputation as a psychologic disorder. In fact, the paradigm has shifted away from defining VCD as a purely psychopathologic entity to the identification of numerous functional etiologies for the disorder. This, however, has resulted in many new terms to describe the condition, including nonorganic upper airway obstruction, pseudoasthma, irritable larynx syndrome, factitious asthma, spasmodic croup, functional upper airway obstruction, episodic laryngeal dyskinesia, functional laryngeal obstruction, functional laryngeal stridor, and episodic paroxysmal laryngospasm.¹

Regardless of its name, an understanding of VCD is essential for both primary care and specialty clinicians because of its frequent misdiagnosis as asthma, allergies, or severe upper airway obstruction. When it is misdiagnosed as asthma, aggressive asthma treatments—to which VCD does not respond—may be prescribed, including high-dose inhaled and systemic corticosteroids and bronchodilators. Patients may experience multiple emergency department (ED) visits and hospitalizations and, in some cases, may be subjected to tracheostomies and intubation.

Continue for vocal cord physiology and functions >>

 

VOCAL CORD PHYSIOLOGY AND FUNCTIONS
The vocal cords are located within the larynx. Abduction, or opening, of the cords is controlled by the posterior cricoarytenoid muscle; adduction, or closing, occurs via contraction of the lateral cricoarytenoid muscle. These muscles are innervated by the recurrent laryngeal nerve to control the width of the space—the rima glottidis—between the cords. During inspiration, the glottis opens; during expiration, it narrows but remains open.¹²

The vocal cords are involved in three main functions: protection of the airway, respiration, and phonation (vocal production). These functions are at least partially controlled involuntarily by brain stem reflexes; however, only airway protection—the most important of these functions—is reflexive and involuntary.¹² Respiration may be controlled voluntarily, and phonation is primarily voluntary. Closure of the vocal cords is under the control of the laryngeal nerve branches of the vagal nerve.^12,13

The vocal cords normally abduct during inspiration to allow air to pass through them into the trachea and the lungs. Sniffing, puffing, snuffling, and panting also cause the vocal cords to abduct. The vocal cords adduct with phonation (talking, singing), coughing, clearing the throat, performing the Valsalva maneuver, and swallowing. During expiration, 10% to 40% adduction is considered normal.¹⁴

VOCAL CORD DYSFUNCTION
Pathogenesis and etiology
VCD is a nonspecific term, and a number of factors may be involved in its development.¹⁵ Although the precise cause of VCD is unknown, it is believed to result from laryngeal hyperresponsiveness. This exaggerated responsiveness may be prompted by irritant and nonirritant triggers of the sensory receptors in the larynx, trachea, and large airways that mediate cough and glottis closure reflexes.¹⁶

VCD may be among a group of airway disorders triggered by occupational exposures, including irritants and psychologic stressors. For example, occupationally triggered VCD was diagnosed in rescue, recovery, and cleanup workers at the World Trade Center disaster site.⁴

A history of childhood sexual abuse has also been associated by some researchers with the development of VCD. For example, Freedman et al reported that, of 47 patients with VCD, 14 identified such a history and five were suspected of having been sexually abused as children.¹⁷

Paradoxical movement of the vocal cords causes them to close when they should open. (Click here for a video on normal and abnormal vocal cord movement.) VCD generally occurs during inspiration, causing obstruction of the incoming air through the larynx. Symptoms of VCD frequently include dyspnea, coughing, wheezing, hoarseness, and tightness or pain in the throat.

Examination of the flow-volume loops recorded when a patient experiences “wheezing” during spirometry testing reveals a flattened inspiratory loop, indicating a decrease of airflow into the lungs (see Figure 1).^13,16 “Wheezing” is actually a misnomer in this situation because the term typically refers to sounds that occur during expiration.

Triggers
Physiologic, psychologic, and neurologic factors may all contribute to VCD.^1,15 Conditions that can trigger VCD include
• Asthma
• Postnasal drip
• Recent upper respiratory illness (URI)
• Talking, singing
• Exercise
• Cough
• Voice strain
• Stress, anxiety, tension, elevated emotions
• Common irritants (eg, strong smells)
• Airborne irritants
• Rhinosinusitis
• GERD
• Use of certain medications
Identification of a particular patient’s triggers is key to successful management of VCD.

PATIENT PRESENTATION
Although there is no “typical” patient with VCD, the condition occurs more frequently in women, with the most common age at onset between 20 and 40 years. However, VCD has been seen in very young children and in adults as old as 83, and its diagnosis in the pediatric population is increasing.¹⁸

The patient may present with complaints of atypical chest pain, throat tightness, stridor, choking, difficult vocalization, cough and sometimes dysphagia, GERD, or rhinosinusitis (see Table 1). These signs and symptoms may occur without provocation, or patients may relate a history of triggers such as anxiety, irritant exposure, or exercise. In fact, about 14% of VCD is associated with exercise, particularly in young female athletes who experience shortness of breath and even stridor with exercise.¹⁹

A characteristic finding on physical examination is inspiratory stridor, along with respiratory distress.²⁰ The stridor is best auscultated not over the anterior chest wall but over the tracheal area of the anterior neck.

Continue for differential diagnosis >>

 

DIFFERENTIAL DIAGNOSIS
Distinguishing VCD from other disorders can be challenging. Differential diagnosis should include
• Non–vocal cord adduction disorders, such as thyroid goiter, upper airway hemorrhage, caustic ingestion, neoplastic disorders, rheumatoid cricoarytenoid arthritis, pharyngeal abscess, angioedema, pulmonary embolus²¹
• Anatomic defects (eg, laryngomalacia, subglottic stenosis)
• Tracheal masses (eg, enlarged thyroid gland)
• Vocal cord polyps
• Laryngospasm
• Vocal cord paresis
• Neurologic causes (eg, brain stem compression, severe cortical injury, nuclear or lower motor neuron injury, movement disorders)
• Nonorganic causes (eg, factitious symptoms or malingering; conversion disorder)²²
• Reactive airway disease.
Some disorders are easier to distinguish from VCD than others. For example, although laryngospasm may produce similar symptoms, episodes are brief, lasting seconds to minutes; VCD episodes may last hours to days.

Asthma
Even the most astute clinician will be unable to obtain adequate information from the patient history to differentiate VCD from asthma. There is a significant overlap of symptoms—shortness of breath, cough, wheezing—and frequently, the diseases coexist. History is often negative for chest pain, but it is common for patients with VCD, when asked to describe their symptoms, to report chest tightness. The clinician therefore needs to ask the patient to point to where the tightness is felt—in the chest or in the neck over the laryngeal area—to distinguish the source.

Asthma symptoms usually increase over a few hours, days, or weeks but respond to medications that open the airway and reduce inflammation (inhaled β-agonists and corticosteroids). VCD symptoms usually occur or decrease suddenly and do not respond well to traditional asthma treatments.

Other differences between asthma and VCD symptoms include voice changes and time of day when symptoms occur. The person with VCD will experience voice changes, such as hoarseness, as well as prolonged coughing episodes. Patients with asthma may awaken at night because of breathlessness, while most patients with VCD experience symptoms only during the day.

The diagnosis is generally confirmed if VCD is seen on direct laryngoscopic visualization during a symptomatic episode. In terms of adduction, the anterior cords will appear normal, but the posterior portion of the cords will display the classic “glottis chink” (see Figure 2).⁹

If the diagnosis is in question, videostroboscopy, a technique that provides a magnified slow-motion view of vocal cord vibration, can help identify or exclude pathologic conditions of the vocal cords.²³

Convincing the patient of the validity of the diagnosis may be problematic if the patient has been previously diagnosed with and treated for another condition. The diagnosis should be explained and the patient counseled what appropriate care for VCD entails (see discussion under “Patient education and self-care”).

TREATMENT
Acute episode
During an acute VCD episode, offering the patient calm reassurance can be effective in resolving the episode. Simple breathing guidance may also be beneficial; instructing the patient to breathe rapidly and shallowly (ie, pant) can result in immediate resolution of symptoms.²⁴ The patient can be advised to utilize other techniques, such as diaphragmatic breathing, breathing through the nose, breathing through a straw, pursed-lip breathing, and exhaling with a hissing sound.²⁵

Long-term management
Although various strategies are employed in the management of VCD, well-designed studies on which to base treatment decisions have not been performed. Of course, control and management of possible underlying triggers or disorders should be implemented. Because etiology is rarely known, treatment for VCD is generally empiric.

Evidence does exist, however, to suggest that voice therapy, the treatment of choice for muscle tension dysphonia, is also effective for VCD. Speech therapy with specific voice and breathing exercises can enable the patient to manage the condition, thereby reducing ED visits, hospitalizations, and treatment costs.²⁶

Patient education and self-care
Patient education is a critical component of VCD management. The clinician should explain the functions of the larynx to the patient, including the normal functioning of the vocal cords during respiration, speaking, swallowing, coughing, throat clearing, and breath holding. It may also enhance patients’ understanding of VCD to view their diagnostic laryngoscopy or videostroboscopy films.²¹

The patient should be advised to rest the voice, hydrate, utilize sialagogues (lozenges, gum) to stimulate salivation, reduce exposure to triggers when possible, and decrease stress. She should be encouraged to track VCD triggers by documenting what she is doing, where, and when, at the time of a VCD episode.

Two exercises—“paused breathing” and “belly breathing”—can be used by patients to learn how to relax the vocal cords (see “Patient Handout”). Patients should practice these exercises three times a day so that they can be easily recalled and performed during VCD episodes.

Continue for outcomes >>

 

OUTCOMES
Little is known about long-term outcomes for patients with VCD. The current literature consists of poorly described and conflicting case reports and results of small trials. Although documentation is lacking, the authors agree that, by educating the patient about the diagnosis, teaching effective VCD management strategies, and referring patients for voice therapy, clinicians can help patients achieve signicant improvement. Further investigation is needed to enhance our knowledge of the causes of VCD and to research additional diagnostic modalities and treatments.²

CASE PATIENT
After diagnosing VCD, the clinician explained the normal functioning of the vocal cords and how certain factors may cause them to close during inspiration. The patient then understood why bronchodilator therapy had failed to relieve her symptoms. She was counseled to continue her inhaled nasal steroid and proton pump inhibitor for her perennial nonallergic rhinitis and GERD, respectively, because these conditions may trigger her VCD, and to take steps to manage her stress. She learned breathing techniques to alleviate acute episodes of VCD and was informed of the option of voice therapy with a speech therapist if needed.

At six-week follow-up, the patient reported that she was complying with her medication regimen, had made an effort to relax more, and had experienced no acute attacks of VCD since her last visit.

CONCLUSION
Patients with symptoms suggestive of VCD require a thorough evaluation, including laryngoscopic examination, to ensure accurate diagnosis and avoid a too-common misdiagnosis. Primary care clinicians should know about VCD and, if not trained in the performance of flexible laryngoscopy, should refer the symptomatic patient to a specialist for appropriate work-up.

---

CE/CME No: CR-1412

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Discuss the evolution in thinking about the pathogenesis of and treatment for vocal cord dysfunction (VCD).
• Describe the three primary functions of the healthy vocal cords.
• List the conditions or factors that may trigger VCD.
• Explain how to differentiate VCD from asthma.
• Develop a treatment plan for VCD that addresses both patient-specific VCD triggers and management of symptomatic episodes.

FACULTY
Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies and Randy D. Danielsen is a Professor and Dean at the Arizona School of Health Sciences, AT Still University, Mesa. Ms. MacConnell is also a clinical PA affiliated with Enticare, an otolaryngology practice in Chandler, Arizona. Susan Symington is a clinical PA with the Arizona Asthma & Allergy Institute, with which Dr. Danielsen is also affiliated.
Linda MacConnell and Randy Danielsen have no significant financial relationships to disclose. Susan Symington is a member of the speaker’s bureau for Teva Respiratory and Thermo Fisher Scientific, Inc.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of December 2014.

Article begins on next page >>

 

The symptoms of vocal cord dysfunction (VCD) can be mistaken for those
of asthma or other respiratory illnesses. As a result, VCD is often misdiagnosed,
leading to unnecessary, ineffective, costly, or even dangerous treatment. Here are
the facts that will enable you to avoid making an erroneous diagnosis, choosing
potentially harmful treatment, and delaying effective treatment.

A 33-year-old oncology nurse, JD, had moved from Seattle to Phoenix about six months earlier for a job opportunity. Shortly after starting her new job, she had developed intermittent dyspnea on exertion, with a cough lasting several minutes at a time, along with a sensation of heaviness over the larynx and a choking sensation. These symptoms were precipitated by gastroesophageal reflux disease (GERD), postnasal drainage, stress, and significant environmental change (ie, Seattle to Phoenix). She noticed that, since moving to Phoenix, she frequently cleared her throat but denied any hoarseness, dysphagia, chest tightness, chest pain, or wheezing. She noted nasal congestion and clear nasal discharge on exposure to inhaled irritants (eg, woodstove smoke) and strong fragrances (eg, perfume or cologne).

On physical examination, the patient was alert, oriented, and in no acute distress. She was coughing intermittently but was able to speak in complete sentences. No stridor or dyspnea was noted, either on exertion (jogging in place) or at rest.

HEENT examination was normal, with no scalp lesions or tenderness; face, symmetric; light reflex, symmetric; conjunctivae, clear; sclera white, without lesions or redness; pupils, equal, reactive to light and accommodation; tympanic membranes and canals, clear with intact landmarks; no nasal deformities; nasal mucosa, mildly erythematous with mild engorgement of the turbinates; no nasal polyps seen; nasal septum midline without perforation; no sinus tenderness on percussion; pharynx, clear without exudate; uvula rises on phonation; and oral mucosa and gingivae, pink without lesions. Neck was supple without masses or thyromegaly, and trachea was midline. Lungs were clear to auscultation with normal respiratory movement and no accessory muscle use, with normal anteroposterior diameter. Heart examination revealed regular rate and rhythm, without murmur, clicks, or gallops.

Examination of the skin was normal, without rashes, hives, swelling, petechiae, or significant ecchymosis. There was no palpable cervical, supraclavicular, or axillary adenopathy.

Results of laboratory studies included a normal complete blood count with differential and a normal IgE level of 46.3 IU/mL. Spirometry testing revealed normal values without obstruction; however, there was a flattening of the inspiratory flow loop, with no reversibility after bronchodilator, which was highly suggestive of vocal cord dysfunction (VCD). Perennial nonallergic rhinitis (formerly called vasomotor rhinitis) was confirmed because the patient experienced fewer symptoms to perfume after nasal corticosteroid use. The patient’s GERD was generally well controlled with esomeprazole but was likely a contributing factor to her vocal cord symptoms.

On laryngoscopy, abnormal vocal cord movement toward the midline during both inspiration and expiration was visualized, confirming the diagnosis of VCD.

BACKGROUND
VCD is a partial upper airway obstruction caused by paradoxical adduction (medial movement) of the vocal cords.¹ Although it is primarily associated with inspiration, it sometimes manifests during expiration as well.

The true incidence of VCD is uncertain; different studies have found incidence rates varying from 2% to 27%, with higher rates in patients with asthma.^1,2 However, highlighting the risk for misdiagnosis, some 10% of patients evaluated for asthma unresponsive to aggressive treatment were found, in fact, to have VCD alone.²

Similarly, although VCD is generally more common in women than in men, the reported female-to-male ratio has varied from 2:1 to 4:1.^1,2,4 Some reports suggest that VCD is seen more frequently in younger women, with average ages at diagnosis of 14.5 in adolescents and 33 in adults.^2,3 Others identify a broader age range, with most patients older than 50.⁴

Historically, VCD has been known by a variety of names and has been observed clinically since 1842. In that year, Dunglison referred to it as hysteric croup, describing a disorder of the laryngeal muscles brought on by “hysteria.”⁵ Later, Mackenzie was able to visualize adduction of the vocal cords during inspiration in patients with stridor by using a laryngoscope.⁶ Osler demonstrated his understanding of the condition in 1902, stating, “Spasm of muscles may occur with violent inspiratory effort and great distress, and may even lead to cyanosis. Extraordinary cries may be produced either inspiratory or expiratory.”⁷

More recently, in 1974, Patterson et al reported finding laryngoscopic evidence of VCD, which they termed Munchausen’s stridor.⁸ They used this descriptor to report on the case of a young woman with 15 hospital admissions for this condition. At the time, the etiology of the condition was believed to be largely psychologic, and its evaluation was consigned to psychiatrists and other mental health practitioners.

As laryngoscopy became more widely available in the 1970s and 1980s, diagnosis of VCD increased, although the condition remains underrecognized.⁹ Ibrahim et al suggest that primary care clinicians may not be as aware of VCD as they should be and may not consider laryngoscopy for possible VCD in patients whose asthma is poorly controlled.²

Disagreement persists with regard to the preferred name for the condition. Because numerous disorders involve abnormal vocal cord function, Christopher proposed moving away from the broad term VCD and toward a more descriptive term: paradoxical vocal fold motion (PVFM) disorder.¹⁰ Interestingly, use of the two terms seems to be divided along specialty lines: VCD is preferred by allergy, pulmonology, and mental health specialists, while PVFM is favored by otolaryngology specialists and speech-language pathologists.¹¹

Further complicating awareness and recognition of VCD is its longstanding reputation as a psychologic disorder. In fact, the paradigm has shifted away from defining VCD as a purely psychopathologic entity to the identification of numerous functional etiologies for the disorder. This, however, has resulted in many new terms to describe the condition, including nonorganic upper airway obstruction, pseudoasthma, irritable larynx syndrome, factitious asthma, spasmodic croup, functional upper airway obstruction, episodic laryngeal dyskinesia, functional laryngeal obstruction, functional laryngeal stridor, and episodic paroxysmal laryngospasm.¹

Regardless of its name, an understanding of VCD is essential for both primary care and specialty clinicians because of its frequent misdiagnosis as asthma, allergies, or severe upper airway obstruction. When it is misdiagnosed as asthma, aggressive asthma treatments—to which VCD does not respond—may be prescribed, including high-dose inhaled and systemic corticosteroids and bronchodilators. Patients may experience multiple emergency department (ED) visits and hospitalizations and, in some cases, may be subjected to tracheostomies and intubation.

Continue for vocal cord physiology and functions >>

 

VOCAL CORD PHYSIOLOGY AND FUNCTIONS
The vocal cords are located within the larynx. Abduction, or opening, of the cords is controlled by the posterior cricoarytenoid muscle; adduction, or closing, occurs via contraction of the lateral cricoarytenoid muscle. These muscles are innervated by the recurrent laryngeal nerve to control the width of the space—the rima glottidis—between the cords. During inspiration, the glottis opens; during expiration, it narrows but remains open.¹²

The vocal cords are involved in three main functions: protection of the airway, respiration, and phonation (vocal production). These functions are at least partially controlled involuntarily by brain stem reflexes; however, only airway protection—the most important of these functions—is reflexive and involuntary.¹² Respiration may be controlled voluntarily, and phonation is primarily voluntary. Closure of the vocal cords is under the control of the laryngeal nerve branches of the vagal nerve.^12,13

The vocal cords normally abduct during inspiration to allow air to pass through them into the trachea and the lungs. Sniffing, puffing, snuffling, and panting also cause the vocal cords to abduct. The vocal cords adduct with phonation (talking, singing), coughing, clearing the throat, performing the Valsalva maneuver, and swallowing. During expiration, 10% to 40% adduction is considered normal.¹⁴

VOCAL CORD DYSFUNCTION
Pathogenesis and etiology
VCD is a nonspecific term, and a number of factors may be involved in its development.¹⁵ Although the precise cause of VCD is unknown, it is believed to result from laryngeal hyperresponsiveness. This exaggerated responsiveness may be prompted by irritant and nonirritant triggers of the sensory receptors in the larynx, trachea, and large airways that mediate cough and glottis closure reflexes.¹⁶

VCD may be among a group of airway disorders triggered by occupational exposures, including irritants and psychologic stressors. For example, occupationally triggered VCD was diagnosed in rescue, recovery, and cleanup workers at the World Trade Center disaster site.⁴

A history of childhood sexual abuse has also been associated by some researchers with the development of VCD. For example, Freedman et al reported that, of 47 patients with VCD, 14 identified such a history and five were suspected of having been sexually abused as children.¹⁷

Paradoxical movement of the vocal cords causes them to close when they should open. (Click here for a video on normal and abnormal vocal cord movement.) VCD generally occurs during inspiration, causing obstruction of the incoming air through the larynx. Symptoms of VCD frequently include dyspnea, coughing, wheezing, hoarseness, and tightness or pain in the throat.

Examination of the flow-volume loops recorded when a patient experiences “wheezing” during spirometry testing reveals a flattened inspiratory loop, indicating a decrease of airflow into the lungs (see Figure 1).^13,16 “Wheezing” is actually a misnomer in this situation because the term typically refers to sounds that occur during expiration.

Triggers
Physiologic, psychologic, and neurologic factors may all contribute to VCD.^1,15 Conditions that can trigger VCD include
• Asthma
• Postnasal drip
• Recent upper respiratory illness (URI)
• Talking, singing
• Exercise
• Cough
• Voice strain
• Stress, anxiety, tension, elevated emotions
• Common irritants (eg, strong smells)
• Airborne irritants
• Rhinosinusitis
• GERD
• Use of certain medications
Identification of a particular patient’s triggers is key to successful management of VCD.

PATIENT PRESENTATION
Although there is no “typical” patient with VCD, the condition occurs more frequently in women, with the most common age at onset between 20 and 40 years. However, VCD has been seen in very young children and in adults as old as 83, and its diagnosis in the pediatric population is increasing.¹⁸

The patient may present with complaints of atypical chest pain, throat tightness, stridor, choking, difficult vocalization, cough and sometimes dysphagia, GERD, or rhinosinusitis (see Table 1). These signs and symptoms may occur without provocation, or patients may relate a history of triggers such as anxiety, irritant exposure, or exercise. In fact, about 14% of VCD is associated with exercise, particularly in young female athletes who experience shortness of breath and even stridor with exercise.¹⁹

A characteristic finding on physical examination is inspiratory stridor, along with respiratory distress.²⁰ The stridor is best auscultated not over the anterior chest wall but over the tracheal area of the anterior neck.

Continue for differential diagnosis >>

 

DIFFERENTIAL DIAGNOSIS
Distinguishing VCD from other disorders can be challenging. Differential diagnosis should include
• Non–vocal cord adduction disorders, such as thyroid goiter, upper airway hemorrhage, caustic ingestion, neoplastic disorders, rheumatoid cricoarytenoid arthritis, pharyngeal abscess, angioedema, pulmonary embolus²¹
• Anatomic defects (eg, laryngomalacia, subglottic stenosis)
• Tracheal masses (eg, enlarged thyroid gland)
• Vocal cord polyps
• Laryngospasm
• Vocal cord paresis
• Neurologic causes (eg, brain stem compression, severe cortical injury, nuclear or lower motor neuron injury, movement disorders)
• Nonorganic causes (eg, factitious symptoms or malingering; conversion disorder)²²
• Reactive airway disease.
Some disorders are easier to distinguish from VCD than others. For example, although laryngospasm may produce similar symptoms, episodes are brief, lasting seconds to minutes; VCD episodes may last hours to days.

Asthma
Even the most astute clinician will be unable to obtain adequate information from the patient history to differentiate VCD from asthma. There is a significant overlap of symptoms—shortness of breath, cough, wheezing—and frequently, the diseases coexist. History is often negative for chest pain, but it is common for patients with VCD, when asked to describe their symptoms, to report chest tightness. The clinician therefore needs to ask the patient to point to where the tightness is felt—in the chest or in the neck over the laryngeal area—to distinguish the source.

Asthma symptoms usually increase over a few hours, days, or weeks but respond to medications that open the airway and reduce inflammation (inhaled β-agonists and corticosteroids). VCD symptoms usually occur or decrease suddenly and do not respond well to traditional asthma treatments.

Other differences between asthma and VCD symptoms include voice changes and time of day when symptoms occur. The person with VCD will experience voice changes, such as hoarseness, as well as prolonged coughing episodes. Patients with asthma may awaken at night because of breathlessness, while most patients with VCD experience symptoms only during the day.

The diagnosis is generally confirmed if VCD is seen on direct laryngoscopic visualization during a symptomatic episode. In terms of adduction, the anterior cords will appear normal, but the posterior portion of the cords will display the classic “glottis chink” (see Figure 2).⁹

If the diagnosis is in question, videostroboscopy, a technique that provides a magnified slow-motion view of vocal cord vibration, can help identify or exclude pathologic conditions of the vocal cords.²³

Convincing the patient of the validity of the diagnosis may be problematic if the patient has been previously diagnosed with and treated for another condition. The diagnosis should be explained and the patient counseled what appropriate care for VCD entails (see discussion under “Patient education and self-care”).

TREATMENT
Acute episode
During an acute VCD episode, offering the patient calm reassurance can be effective in resolving the episode. Simple breathing guidance may also be beneficial; instructing the patient to breathe rapidly and shallowly (ie, pant) can result in immediate resolution of symptoms.²⁴ The patient can be advised to utilize other techniques, such as diaphragmatic breathing, breathing through the nose, breathing through a straw, pursed-lip breathing, and exhaling with a hissing sound.²⁵

Long-term management
Although various strategies are employed in the management of VCD, well-designed studies on which to base treatment decisions have not been performed. Of course, control and management of possible underlying triggers or disorders should be implemented. Because etiology is rarely known, treatment for VCD is generally empiric.

Evidence does exist, however, to suggest that voice therapy, the treatment of choice for muscle tension dysphonia, is also effective for VCD. Speech therapy with specific voice and breathing exercises can enable the patient to manage the condition, thereby reducing ED visits, hospitalizations, and treatment costs.²⁶

Patient education and self-care
Patient education is a critical component of VCD management. The clinician should explain the functions of the larynx to the patient, including the normal functioning of the vocal cords during respiration, speaking, swallowing, coughing, throat clearing, and breath holding. It may also enhance patients’ understanding of VCD to view their diagnostic laryngoscopy or videostroboscopy films.²¹

The patient should be advised to rest the voice, hydrate, utilize sialagogues (lozenges, gum) to stimulate salivation, reduce exposure to triggers when possible, and decrease stress. She should be encouraged to track VCD triggers by documenting what she is doing, where, and when, at the time of a VCD episode.

Two exercises—“paused breathing” and “belly breathing”—can be used by patients to learn how to relax the vocal cords (see “Patient Handout”). Patients should practice these exercises three times a day so that they can be easily recalled and performed during VCD episodes.

Continue for outcomes >>

 

OUTCOMES
Little is known about long-term outcomes for patients with VCD. The current literature consists of poorly described and conflicting case reports and results of small trials. Although documentation is lacking, the authors agree that, by educating the patient about the diagnosis, teaching effective VCD management strategies, and referring patients for voice therapy, clinicians can help patients achieve signicant improvement. Further investigation is needed to enhance our knowledge of the causes of VCD and to research additional diagnostic modalities and treatments.²

CASE PATIENT
After diagnosing VCD, the clinician explained the normal functioning of the vocal cords and how certain factors may cause them to close during inspiration. The patient then understood why bronchodilator therapy had failed to relieve her symptoms. She was counseled to continue her inhaled nasal steroid and proton pump inhibitor for her perennial nonallergic rhinitis and GERD, respectively, because these conditions may trigger her VCD, and to take steps to manage her stress. She learned breathing techniques to alleviate acute episodes of VCD and was informed of the option of voice therapy with a speech therapist if needed.

At six-week follow-up, the patient reported that she was complying with her medication regimen, had made an effort to relax more, and had experienced no acute attacks of VCD since her last visit.

CONCLUSION
Patients with symptoms suggestive of VCD require a thorough evaluation, including laryngoscopic examination, to ensure accurate diagnosis and avoid a too-common misdiagnosis. Primary care clinicians should know about VCD and, if not trained in the performance of flexible laryngoscopy, should refer the symptomatic patient to a specialist for appropriate work-up.

---

CE/CME No: CR-1412

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Discuss the evolution in thinking about the pathogenesis of and treatment for vocal cord dysfunction (VCD).
• Describe the three primary functions of the healthy vocal cords.
• List the conditions or factors that may trigger VCD.
• Explain how to differentiate VCD from asthma.
• Develop a treatment plan for VCD that addresses both patient-specific VCD triggers and management of symptomatic episodes.

FACULTY
Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies and Randy D. Danielsen is a Professor and Dean at the Arizona School of Health Sciences, AT Still University, Mesa. Ms. MacConnell is also a clinical PA affiliated with Enticare, an otolaryngology practice in Chandler, Arizona. Susan Symington is a clinical PA with the Arizona Asthma & Allergy Institute, with which Dr. Danielsen is also affiliated.
Linda MacConnell and Randy Danielsen have no significant financial relationships to disclose. Susan Symington is a member of the speaker’s bureau for Teva Respiratory and Thermo Fisher Scientific, Inc.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of December 2014.

Article begins on next page >>

 

The symptoms of vocal cord dysfunction (VCD) can be mistaken for those
of asthma or other respiratory illnesses. As a result, VCD is often misdiagnosed,
leading to unnecessary, ineffective, costly, or even dangerous treatment. Here are
the facts that will enable you to avoid making an erroneous diagnosis, choosing
potentially harmful treatment, and delaying effective treatment.

A 33-year-old oncology nurse, JD, had moved from Seattle to Phoenix about six months earlier for a job opportunity. Shortly after starting her new job, she had developed intermittent dyspnea on exertion, with a cough lasting several minutes at a time, along with a sensation of heaviness over the larynx and a choking sensation. These symptoms were precipitated by gastroesophageal reflux disease (GERD), postnasal drainage, stress, and significant environmental change (ie, Seattle to Phoenix). She noticed that, since moving to Phoenix, she frequently cleared her throat but denied any hoarseness, dysphagia, chest tightness, chest pain, or wheezing. She noted nasal congestion and clear nasal discharge on exposure to inhaled irritants (eg, woodstove smoke) and strong fragrances (eg, perfume or cologne).

On physical examination, the patient was alert, oriented, and in no acute distress. She was coughing intermittently but was able to speak in complete sentences. No stridor or dyspnea was noted, either on exertion (jogging in place) or at rest.

HEENT examination was normal, with no scalp lesions or tenderness; face, symmetric; light reflex, symmetric; conjunctivae, clear; sclera white, without lesions or redness; pupils, equal, reactive to light and accommodation; tympanic membranes and canals, clear with intact landmarks; no nasal deformities; nasal mucosa, mildly erythematous with mild engorgement of the turbinates; no nasal polyps seen; nasal septum midline without perforation; no sinus tenderness on percussion; pharynx, clear without exudate; uvula rises on phonation; and oral mucosa and gingivae, pink without lesions. Neck was supple without masses or thyromegaly, and trachea was midline. Lungs were clear to auscultation with normal respiratory movement and no accessory muscle use, with normal anteroposterior diameter. Heart examination revealed regular rate and rhythm, without murmur, clicks, or gallops.

Examination of the skin was normal, without rashes, hives, swelling, petechiae, or significant ecchymosis. There was no palpable cervical, supraclavicular, or axillary adenopathy.

Results of laboratory studies included a normal complete blood count with differential and a normal IgE level of 46.3 IU/mL. Spirometry testing revealed normal values without obstruction; however, there was a flattening of the inspiratory flow loop, with no reversibility after bronchodilator, which was highly suggestive of vocal cord dysfunction (VCD). Perennial nonallergic rhinitis (formerly called vasomotor rhinitis) was confirmed because the patient experienced fewer symptoms to perfume after nasal corticosteroid use. The patient’s GERD was generally well controlled with esomeprazole but was likely a contributing factor to her vocal cord symptoms.

On laryngoscopy, abnormal vocal cord movement toward the midline during both inspiration and expiration was visualized, confirming the diagnosis of VCD.

BACKGROUND
VCD is a partial upper airway obstruction caused by paradoxical adduction (medial movement) of the vocal cords.¹ Although it is primarily associated with inspiration, it sometimes manifests during expiration as well.

The true incidence of VCD is uncertain; different studies have found incidence rates varying from 2% to 27%, with higher rates in patients with asthma.^1,2 However, highlighting the risk for misdiagnosis, some 10% of patients evaluated for asthma unresponsive to aggressive treatment were found, in fact, to have VCD alone.²

Similarly, although VCD is generally more common in women than in men, the reported female-to-male ratio has varied from 2:1 to 4:1.^1,2,4 Some reports suggest that VCD is seen more frequently in younger women, with average ages at diagnosis of 14.5 in adolescents and 33 in adults.^2,3 Others identify a broader age range, with most patients older than 50.⁴

Historically, VCD has been known by a variety of names and has been observed clinically since 1842. In that year, Dunglison referred to it as hysteric croup, describing a disorder of the laryngeal muscles brought on by “hysteria.”⁵ Later, Mackenzie was able to visualize adduction of the vocal cords during inspiration in patients with stridor by using a laryngoscope.⁶ Osler demonstrated his understanding of the condition in 1902, stating, “Spasm of muscles may occur with violent inspiratory effort and great distress, and may even lead to cyanosis. Extraordinary cries may be produced either inspiratory or expiratory.”⁷

More recently, in 1974, Patterson et al reported finding laryngoscopic evidence of VCD, which they termed Munchausen’s stridor.⁸ They used this descriptor to report on the case of a young woman with 15 hospital admissions for this condition. At the time, the etiology of the condition was believed to be largely psychologic, and its evaluation was consigned to psychiatrists and other mental health practitioners.

As laryngoscopy became more widely available in the 1970s and 1980s, diagnosis of VCD increased, although the condition remains underrecognized.⁹ Ibrahim et al suggest that primary care clinicians may not be as aware of VCD as they should be and may not consider laryngoscopy for possible VCD in patients whose asthma is poorly controlled.²

Disagreement persists with regard to the preferred name for the condition. Because numerous disorders involve abnormal vocal cord function, Christopher proposed moving away from the broad term VCD and toward a more descriptive term: paradoxical vocal fold motion (PVFM) disorder.¹⁰ Interestingly, use of the two terms seems to be divided along specialty lines: VCD is preferred by allergy, pulmonology, and mental health specialists, while PVFM is favored by otolaryngology specialists and speech-language pathologists.¹¹

Further complicating awareness and recognition of VCD is its longstanding reputation as a psychologic disorder. In fact, the paradigm has shifted away from defining VCD as a purely psychopathologic entity to the identification of numerous functional etiologies for the disorder. This, however, has resulted in many new terms to describe the condition, including nonorganic upper airway obstruction, pseudoasthma, irritable larynx syndrome, factitious asthma, spasmodic croup, functional upper airway obstruction, episodic laryngeal dyskinesia, functional laryngeal obstruction, functional laryngeal stridor, and episodic paroxysmal laryngospasm.¹

Regardless of its name, an understanding of VCD is essential for both primary care and specialty clinicians because of its frequent misdiagnosis as asthma, allergies, or severe upper airway obstruction. When it is misdiagnosed as asthma, aggressive asthma treatments—to which VCD does not respond—may be prescribed, including high-dose inhaled and systemic corticosteroids and bronchodilators. Patients may experience multiple emergency department (ED) visits and hospitalizations and, in some cases, may be subjected to tracheostomies and intubation.

Continue for vocal cord physiology and functions >>

 

VOCAL CORD PHYSIOLOGY AND FUNCTIONS
The vocal cords are located within the larynx. Abduction, or opening, of the cords is controlled by the posterior cricoarytenoid muscle; adduction, or closing, occurs via contraction of the lateral cricoarytenoid muscle. These muscles are innervated by the recurrent laryngeal nerve to control the width of the space—the rima glottidis—between the cords. During inspiration, the glottis opens; during expiration, it narrows but remains open.¹²

The vocal cords are involved in three main functions: protection of the airway, respiration, and phonation (vocal production). These functions are at least partially controlled involuntarily by brain stem reflexes; however, only airway protection—the most important of these functions—is reflexive and involuntary.¹² Respiration may be controlled voluntarily, and phonation is primarily voluntary. Closure of the vocal cords is under the control of the laryngeal nerve branches of the vagal nerve.^12,13

The vocal cords normally abduct during inspiration to allow air to pass through them into the trachea and the lungs. Sniffing, puffing, snuffling, and panting also cause the vocal cords to abduct. The vocal cords adduct with phonation (talking, singing), coughing, clearing the throat, performing the Valsalva maneuver, and swallowing. During expiration, 10% to 40% adduction is considered normal.¹⁴

VOCAL CORD DYSFUNCTION
Pathogenesis and etiology
VCD is a nonspecific term, and a number of factors may be involved in its development.¹⁵ Although the precise cause of VCD is unknown, it is believed to result from laryngeal hyperresponsiveness. This exaggerated responsiveness may be prompted by irritant and nonirritant triggers of the sensory receptors in the larynx, trachea, and large airways that mediate cough and glottis closure reflexes.¹⁶

VCD may be among a group of airway disorders triggered by occupational exposures, including irritants and psychologic stressors. For example, occupationally triggered VCD was diagnosed in rescue, recovery, and cleanup workers at the World Trade Center disaster site.⁴

A history of childhood sexual abuse has also been associated by some researchers with the development of VCD. For example, Freedman et al reported that, of 47 patients with VCD, 14 identified such a history and five were suspected of having been sexually abused as children.¹⁷

Paradoxical movement of the vocal cords causes them to close when they should open. (Click here for a video on normal and abnormal vocal cord movement.) VCD generally occurs during inspiration, causing obstruction of the incoming air through the larynx. Symptoms of VCD frequently include dyspnea, coughing, wheezing, hoarseness, and tightness or pain in the throat.

Examination of the flow-volume loops recorded when a patient experiences “wheezing” during spirometry testing reveals a flattened inspiratory loop, indicating a decrease of airflow into the lungs (see Figure 1).^13,16 “Wheezing” is actually a misnomer in this situation because the term typically refers to sounds that occur during expiration.

Triggers
Physiologic, psychologic, and neurologic factors may all contribute to VCD.^1,15 Conditions that can trigger VCD include
• Asthma
• Postnasal drip
• Recent upper respiratory illness (URI)
• Talking, singing
• Exercise
• Cough
• Voice strain
• Stress, anxiety, tension, elevated emotions
• Common irritants (eg, strong smells)
• Airborne irritants
• Rhinosinusitis
• GERD
• Use of certain medications
Identification of a particular patient’s triggers is key to successful management of VCD.

PATIENT PRESENTATION
Although there is no “typical” patient with VCD, the condition occurs more frequently in women, with the most common age at onset between 20 and 40 years. However, VCD has been seen in very young children and in adults as old as 83, and its diagnosis in the pediatric population is increasing.¹⁸

The patient may present with complaints of atypical chest pain, throat tightness, stridor, choking, difficult vocalization, cough and sometimes dysphagia, GERD, or rhinosinusitis (see Table 1). These signs and symptoms may occur without provocation, or patients may relate a history of triggers such as anxiety, irritant exposure, or exercise. In fact, about 14% of VCD is associated with exercise, particularly in young female athletes who experience shortness of breath and even stridor with exercise.¹⁹

A characteristic finding on physical examination is inspiratory stridor, along with respiratory distress.²⁰ The stridor is best auscultated not over the anterior chest wall but over the tracheal area of the anterior neck.

Continue for differential diagnosis >>

 

DIFFERENTIAL DIAGNOSIS
Distinguishing VCD from other disorders can be challenging. Differential diagnosis should include
• Non–vocal cord adduction disorders, such as thyroid goiter, upper airway hemorrhage, caustic ingestion, neoplastic disorders, rheumatoid cricoarytenoid arthritis, pharyngeal abscess, angioedema, pulmonary embolus²¹
• Anatomic defects (eg, laryngomalacia, subglottic stenosis)
• Tracheal masses (eg, enlarged thyroid gland)
• Vocal cord polyps
• Laryngospasm
• Vocal cord paresis
• Neurologic causes (eg, brain stem compression, severe cortical injury, nuclear or lower motor neuron injury, movement disorders)
• Nonorganic causes (eg, factitious symptoms or malingering; conversion disorder)²²
• Reactive airway disease.
Some disorders are easier to distinguish from VCD than others. For example, although laryngospasm may produce similar symptoms, episodes are brief, lasting seconds to minutes; VCD episodes may last hours to days.

Asthma
Even the most astute clinician will be unable to obtain adequate information from the patient history to differentiate VCD from asthma. There is a significant overlap of symptoms—shortness of breath, cough, wheezing—and frequently, the diseases coexist. History is often negative for chest pain, but it is common for patients with VCD, when asked to describe their symptoms, to report chest tightness. The clinician therefore needs to ask the patient to point to where the tightness is felt—in the chest or in the neck over the laryngeal area—to distinguish the source.

Asthma symptoms usually increase over a few hours, days, or weeks but respond to medications that open the airway and reduce inflammation (inhaled β-agonists and corticosteroids). VCD symptoms usually occur or decrease suddenly and do not respond well to traditional asthma treatments.

Other differences between asthma and VCD symptoms include voice changes and time of day when symptoms occur. The person with VCD will experience voice changes, such as hoarseness, as well as prolonged coughing episodes. Patients with asthma may awaken at night because of breathlessness, while most patients with VCD experience symptoms only during the day.

The diagnosis is generally confirmed if VCD is seen on direct laryngoscopic visualization during a symptomatic episode. In terms of adduction, the anterior cords will appear normal, but the posterior portion of the cords will display the classic “glottis chink” (see Figure 2).⁹

If the diagnosis is in question, videostroboscopy, a technique that provides a magnified slow-motion view of vocal cord vibration, can help identify or exclude pathologic conditions of the vocal cords.²³

Convincing the patient of the validity of the diagnosis may be problematic if the patient has been previously diagnosed with and treated for another condition. The diagnosis should be explained and the patient counseled what appropriate care for VCD entails (see discussion under “Patient education and self-care”).

TREATMENT
Acute episode
During an acute VCD episode, offering the patient calm reassurance can be effective in resolving the episode. Simple breathing guidance may also be beneficial; instructing the patient to breathe rapidly and shallowly (ie, pant) can result in immediate resolution of symptoms.²⁴ The patient can be advised to utilize other techniques, such as diaphragmatic breathing, breathing through the nose, breathing through a straw, pursed-lip breathing, and exhaling with a hissing sound.²⁵

Long-term management
Although various strategies are employed in the management of VCD, well-designed studies on which to base treatment decisions have not been performed. Of course, control and management of possible underlying triggers or disorders should be implemented. Because etiology is rarely known, treatment for VCD is generally empiric.

Evidence does exist, however, to suggest that voice therapy, the treatment of choice for muscle tension dysphonia, is also effective for VCD. Speech therapy with specific voice and breathing exercises can enable the patient to manage the condition, thereby reducing ED visits, hospitalizations, and treatment costs.²⁶

Patient education and self-care
Patient education is a critical component of VCD management. The clinician should explain the functions of the larynx to the patient, including the normal functioning of the vocal cords during respiration, speaking, swallowing, coughing, throat clearing, and breath holding. It may also enhance patients’ understanding of VCD to view their diagnostic laryngoscopy or videostroboscopy films.²¹

The patient should be advised to rest the voice, hydrate, utilize sialagogues (lozenges, gum) to stimulate salivation, reduce exposure to triggers when possible, and decrease stress. She should be encouraged to track VCD triggers by documenting what she is doing, where, and when, at the time of a VCD episode.

Two exercises—“paused breathing” and “belly breathing”—can be used by patients to learn how to relax the vocal cords (see “Patient Handout”). Patients should practice these exercises three times a day so that they can be easily recalled and performed during VCD episodes.

Continue for outcomes >>

 

OUTCOMES
Little is known about long-term outcomes for patients with VCD. The current literature consists of poorly described and conflicting case reports and results of small trials. Although documentation is lacking, the authors agree that, by educating the patient about the diagnosis, teaching effective VCD management strategies, and referring patients for voice therapy, clinicians can help patients achieve signicant improvement. Further investigation is needed to enhance our knowledge of the causes of VCD and to research additional diagnostic modalities and treatments.²

CASE PATIENT
After diagnosing VCD, the clinician explained the normal functioning of the vocal cords and how certain factors may cause them to close during inspiration. The patient then understood why bronchodilator therapy had failed to relieve her symptoms. She was counseled to continue her inhaled nasal steroid and proton pump inhibitor for her perennial nonallergic rhinitis and GERD, respectively, because these conditions may trigger her VCD, and to take steps to manage her stress. She learned breathing techniques to alleviate acute episodes of VCD and was informed of the option of voice therapy with a speech therapist if needed.

At six-week follow-up, the patient reported that she was complying with her medication regimen, had made an effort to relax more, and had experienced no acute attacks of VCD since her last visit.

CONCLUSION
Patients with symptoms suggestive of VCD require a thorough evaluation, including laryngoscopic examination, to ensure accurate diagnosis and avoid a too-common misdiagnosis. Primary care clinicians should know about VCD and, if not trained in the performance of flexible laryngoscopy, should refer the symptomatic patient to a specialist for appropriate work-up.

---

CE/CME No: CR-1411

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• List the risk factors for HCV infection.
• Identify who should be screened for HCV infection.
• Discuss the symptoms, clinical course, diagnosis, and complications of chronic HCV infection.
• Differentiate between the treatment of acute and chronic HCV infection.
• Describe the challenges of treating HCV infection in patients who are coinfected with HIV. 

FACULTY
Daniel Sturm and Samuel L. Gurevitz are Assistant Professors in the Physician Assistant Program, College of Pharmacy and Health Sciences, at Butler University in Indianapolis. Cassidy Davidson, Abigail Fritchley, and Audrey Wagaman are students in the PA Program at Butler University. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of November 2014.

Article begins on next page >>

 

Several million Americans, primarily those in their fifties and sixties, contracted hepatitis C virus (HCV) many years ago and are unaware of their infection and their risk for HCV-related liver disease. Screening at-risk patients is important because newer treatment regimens are curative and can reduce associated morbidity and mortality.

Chronic infection with hepatitis C virus (HCV) is a major cause of liver disease in the United States. National Health and Nutrition Examination Survey data indicates that 2.7 million people have chronic HCV infection; the CDC estimates 3.2 million.^1-3 Yet these individuals may be asymptomatic for years, despite slow progression of sequelae (eg, chronic liver disease, cirrhosis, hepatocellular carcinoma [HCC]) that may silently unfold. Left untreated, chronic HCV infection is associated with a 15% to 30% risk for cirrhosis within 20 years, which subsequently confers an annual risk for HCC of 2% to 4%.⁴ Additionally, chronic HCV infection is now the leading indication for liver transplantation.³

Of note, 70% of those with chronic HCV infection were born between 1945 and 1965.² This is believed to be attributable to viral transmission via contaminated blood, blood products, and organ transplants prior to the implementation of universal precautions for blood supply screening in 1992; and to past injection drug use, even if it occurred only once.³

In a recent analysis, it was determined that the clinical and economic burdens of chronic HCV infection increased in the past decade, and this trend is likely to continue during the next decade.⁵ For example, HCV was responsible for 15,106 US deaths in 2007, surpassing deaths caused by HIV for the first time.⁶ Since then, the number of HCV-related deaths has continued to increase, to 17,721 in 2011.⁷ Economic costs solely attributable to HCV infection are difficult to calculate, but estimates range from several hundred million dollars to $30 billion annually.⁵ The World Health Organization (WHO) estimates that more than 185 million people worldwide are infected with HCV and that HCV is responsible for 350,000 deaths annually.⁴

The main goal of treatment is to achieve a sustained virologic response (SVR), defined as undetectable HCV RNA in serum 12 to 24 weeks after completion of treatment and thereby prevent or reduce the complications of HCV infection.³ Proactive screening, diagnosis, monitoring, and treatment of HCV infection can significantly reduce long-term morbidity and mortality.

INDICATIONS FOR HCV SCREENING
Recommendations for HCV screening have been developed by numerous organizations, including the WHO, CDC, US Preventive Services Task Force (USPSTF), American Association for the Study of Liver Diseases (AASLD), and the Infectious Diseases Society of America (IDSA) (see Table 1).^3,4,8,9-11 Screening should be offered to all individuals meeting one or more of the criteria. A 2012 CDC update calls for one-time testing for all persons born between 1945 and 1965 because of the disproportionately high prevalence of HCV infection in this cohort, which is five times greater than in the general population.¹¹

The initial screening tool for HCV infection is an HCV antibody test. A positive or reactive anti-HCV antibody result can signify either current or resolved infection, so a positive result should be followed with an HCV ribonucleic acid (RNA) test to determine if active infection is present.^4,8-10 See Figure on previous page for an HCV screening algorithm, which includes the points at which referrals to specialists are indicated.

A rapid HCV antibody test was approved by the FDA in 2011 and is favored because of its widespread availability, ease of use, rapid results, and low cost. Point-of-care testing is comparable in sensitivity and specificity to laboratory-based HCV assays and can utilize blood obtained via fingerstick or venipuncture.⁸ This form of testing facilitates HCV screening in a variety of settings, such as health fairs and emergency departments, as well as in high-risk settings such as methadone clinics.

Populations at increased risk for HCV infection are also at increased risk for hepatitis B virus (HBV), HIV, and tuberculosis infections; therefore, screening for these may also be warranted.⁴

PROGRESSION OF UNTREATED INFECTION
Just as with chronic HCV infection, patients newly infected with HCV are typically asymptomatic; the illness manifests with clinical symptoms in only 20% to 30% of cases.³ If symptoms do appear, they include fever, fatigue, dark urine, clay-colored stool, abdominal pain, loss of appetite, nausea, vomiting, joint pain, and jaundice. These acute phase symptoms may last two to 12 weeks.¹²

Spontaneous clearance of the virus occurs in only 15% to 25% of cases (see further discussion under “Acute HCV.”).^2,3 Even if a patient clears an HCV infection, if he or she falls within one of the at-risk categories (see Table 1), then periodic screening should continue because prior HCV infection does not protect against future infection.³

The progression of chronic HCV is indolent and often subclinical, with fatigue being the most common complaint. Other nonspecific symptoms may include nausea, anorexia, myalgia, arthralgia, weakness, and weight loss. One study noted that symptoms do not correlate with disease severity.¹³ In a 10-year prospective study, chronic HCV infection increased mortality when the infection was acquired at an early age (younger than 50) and/or when cirrhosis developed.¹⁴ Patients with cirrhosis progress to liver decompensation at a rate of 3% to 6% annually.15
In addition to liver disease, HCV infection is associated with an increased risk for non-Hodgkin lymphoma.³ HCV may also induce insulin resistance, which increases the risk for hepatic fibrosis. Other studies document HCV-induced cognitive impairment, but little scientific data is yet available as to its pathogenesis.¹⁶

DIAGNOSIS
Diagnostic testing for suspected HCV infection begins with an antibody test.⁸ A positive antibody test indicates one of three possibilities: active infection, resolved infection, or a false-positive result. Two drawbacks of HCV antibody testing are that immunocompromised patients may falsely test negative and that antibodies cannot be detected until eight to 12 weeks after the infection is acquired.¹¹ A positive antibody test should be confirmed with an HCV polymerase chain reaction (PCR) RNA test.^8,10

HCV RNA testing can detect the virus earlier than antibody testing—as early as two weeks after infection. Although a positive HCV RNA test confirms current HCV infection, its higher cost precludes its use as an initial diagnostic test for lower-risk patients.

In patients who test negative but for whom there is a high index of suspicion for HCV infection (eg, jaundiced patient with an elevated alanine aminotransferase level [ALT]), or for a health care worker with a recent bloodborne HCV exposure, testing for HCV antibodies, HCV RNA, and ALT levels should be ordered at regular intervals for a period of six months.¹⁰

Acute versus chronic infection
Distinguishing acute and chronic HCV is difficult. A determination that HCV is newly acquired requires a documented negative baseline antibody test, followed by laboratory evidence of seroconversion. This is typically only seen in cases where there has been a recent, known exposure to the virus.

Both HCV antibody and RNA testing are recommended when screening high-risk patients, including those who are immunocompromised, on hemodialysis, or have had a recent exposure to HCV-positive blood.¹⁰ Rapid PCR HCV RNA tests can assess both viral load and genotype (see discussion of HCV genotypes under “Chronic HCV”).¹⁷ This information helps guide and measure patient response to treatment.

Liver disease severity
Liver fibrosis and cirrhosis are serious complications of HCV; hepatomegaly or splenomegaly may or may not be present on physical examination and patients may require liver biopsies to evaluate disease stage.¹⁸ An assessment of the severity of liver damage can determine the urgency of treatment and predict treatment efficacy.

Biopsy results permit the grading of inflammation and nodularity and the staging of septal fibrosis, which can reliably predict future progression of the patient’s disease.¹⁹ However, liver biopsy is invasive, painful, and may contain sampling errors; complications may include bleeding, infection, and occasionally accidental injury to a nearby organ. An initial noninvasive assessment may be performed using vibration-controlled transient liver elastography, an ultrasound-based technology that measures liver stiffness, which correlates well with the degree of fibrosis or cirrhosis. Elastography, along with measurement of direct serum biomarkers that are produced by activated hepatic stellate cells involved in fibrosis, affords an accurate, noninvasive means of assessing liver damage.¹⁰

Continue for treatment options >>

 

TREATMENT
Acute HCV
To prevent progression of disease from acute to chronic infection, patients diagnosed with acute disease should be treated if
• They are likely to adhere to the treatment plan
• They have no contraindications to pegylated interferon a  (PEG-IFN a) treatment.

Contraindications to PEG-IFN a treatment include uncontrolled depression, psychosis, or epilepsy; pregnancy; couples' unwillingness to use effective contraception during treatment; severe concurrent medical disease; and decompensated liver disease.²⁰

For acute HCV infection, treatment with PEG-IFN a-2a 180 µg/wk or PEG-IFN a-2b 1.5 µg/kg/wk for 24 weeks is recommended.²⁰ Treatment results in an SVR greater than 80%.²¹ Combination therapy with ribavirin (RBV) does not increase SVR in the treatment of acute HCV infection.²²

The appropriate time to begin treatment has not been firmly established because, as previously noted, 15% to 25% of those infected will spontaneously clear the virus. The European Association for the Study of the Liver (EASL) suggests that patients who remain HCV positive at 12 weeks from the time of suspected infection should be treated.²³

Chronic HCV
Treatment of chronic HCV is based on multiple considerations, many of them patient-specific (see Table 2). One key element in treatment choice is the HCV genotype with which the patient is infected.

The most prevalent in the US are genotypes 1 through 6; further, genotype 1 has two subtypes: 1a and 1b. In the US, genotype 1 is most common, infecting about 70% of patients; genotype 2, 16%; genotype 3, 12%; genotype 4, 1%; genotype 5, < 1%; and genotype 6, 1%.²⁴ Infection with one genotype does not protect an individual from future infection with the same or a different HCV genotype.³

Other factors influencing treatment include viral load, ALT levels, coinfection (eg, HIV, HBV), comorbidities, and treatment contraindications.²¹ Treatment is recommended for those who have detectable HCV RNA levels, elevated ALT levels, progressive liver disease on biopsy, and the absence of any serious comorbid conditions or contraindications. ALT levels, however, can fluctuate and do not always correlate with disease severity.

For years, the standard treatment for chronic HCV infection has been PEG-IFN a/RBV for 48 weeks. This combination produced an SVR of 50% to 80%, depending on genotype.^3,25 Recently, however, treatment protocols have changed considerably with the introduction of two new and very effective direct-acting antiviral agents (DAAs): simeprevir, an HCV NS3/4A protease inhibitor, and sofosbuvir, an HCV NS5B polymerase inhibitor.

Simeprevir was approved by the FDA in October 2013 for use in combination with PEG-IFN/RBV for treatment of chronic HCV genotype 1 infection in adults with compensated liver disease.²⁷ Because the efficacy of simeprevir is reduced in patients with HCV genotype 1a with an NS3 Q80K polymorphism, screening for NS3 Q80K is recommended; alternative therapy should be considered when this mutation is present.²⁷

Sofosbuvir received FDA approval in December 2013 for use in combination with other antiviral drugs for treatment of chronic HCV infection, with established efficacy for treatment of genotypes 1, 2, 3, and 4 and for HCV/HIV coinfection.²⁸ For genotype 1, simeprevir and sofosbuvir achieve SVRs of 80% and 90%, respectively.^27,28

Table 3 lists the current medications for treatment of chronic HCV, including their adverse effects, contraindications, and drug interactions.

Updated treatment guidelines
AASLD, IDSA, EASL, WHO, and the Department of Veterans Affairs National Hepatitis C Resource Center Program recently issued updated evidence-based recommendations for the treatment of chronic HCV.^4,10,23,26 Highlights of the changes to the guidelines include
• With the introduction of simeprevir and sofosbuvir, the guidelines no longer recommend combination PEG-IFN a/RBV for 48 weeks as the standard treatment for chronic HCV infection^11,23,26
• Treatment regimens utilizing the protease inhibitors telaprevir and boceprevir are no longer recommended (with the exception of the WHO guidelines, which include them in a “conditional” recommendation).⁴

Regimens that include telaprevir and boceprevir are associated with higher rates of serious adverse effects, such as skin reactions and anemia, and involve longer treatment duration, higher pill burden, several drug interactions, frequent dosing, intensive monitoring, and the need to be taken with food (for telaprevir, high-fat food).^10,23,26

Finally, the EASL recommends an additional agent, daclatasvir, an NS5A replication complex inhibitor, as an option for treating HCV genotype 1, 3, and 4.²³ At this time, it is approved for use in Europe but has not been approved by the FDA.

Regardless of the treatment regimen, all patients receiving HCV antiviral therapy should be tested regularly to assess effectiveness of treatment and to monitor for the occurrence of adverse effects. Recommended periodic laboratory testing should include HCV RNA, complete blood count with differential, liver function, TSH level, renal function, comprehensive metabolic panel, bilirubin level, and pregnancy.²⁹

SPECIAL POPULATIONS
Patients with HIV/HCV coinfection, a history of injection drug use, and renal impairment require management tailored to their individual circumstances.^4,23,29

HIV/HCV-coinfected patients
Approximately 25% to 33% of patients infected with HIV are coinfected with HCV. HCV infection progresses more rapidly in HIV-infected patients, and coinfected patients are at greater risk for cirrhosis, liver cancer, and liver failure.³⁰

For patients with HIV/HCV coinfection, the decision to start treatment is more complex because of the high pill burden, overlapping toxicities, and interactions among the drugs used to treat HIV and HCV infections.⁴ HIV antiviral therapy should be started before HCV treatment to improve immune function, thereby decreasing the risks for both further infections and HIV transmission. This also allows the patient to adjust gradually to each regimen.

One exception to this is when an HIV treatment–naïve patient has a CD4 count > 500 cells/mL.³⁰ In this situation, HCV treatment is sometimes completed prior to the start of HIV treatment.

Recommended treatment for HIV/HCV coinfection, by HCV genotype, is outlined below. For all regimens, the weight-based RBV dosage is calculated as follows:
• Weight < 75 kg, 1,000 mg/d
• Weight ≥ 75 kg, 1,200 mg/d^10,30
• Genotypes 1 and 4 (IFN eligible): Sofosbuvir 400 mg/d and weight-based RBV plus weekly PEG-IFN a for 12 weeks
• Genotypes 1 and 4 (IFN ineligible): Sofosbuvir 400 mg/d and weight-based RBV for 24 weeks
• Genotypes 2 and 3 (regardless of IFN eligibility): Sofosbuvir 400 mg/d and weight-based RBV for 12 weeks for genotype 2 and 24 weeks for genotype 3
• Genotypes 5 and 6 (IFN eligible): Sofosbuvir 400 mg/d plus weight-based RBV plus weekly PEG-IFN a for 12 weeks.

Injection drug users
HCV infection among young injection drug users (IDUs) is an emerging epidemic that must be addressed by recognizing at-risk populations, screening for early disease, and providing treatment and education. Globally, it is estimated that approximately 67% of IDUs—approximately 10 million people—are infected with HCV.³¹ Treatment of HCV in IDUs requires integration of many services and health care professionals, including addiction specialists. Dependence on opiates, alcohol, or other substances is common in this patient population. Patients should be counseled on the importance of abstaining from alcohol. IDUs are at risk for hepatitis A (HAV) and HBV infections and should be vaccinated against these diseases.⁴

Treatment decisions should be based on an individualized evaluation of the patient’s social, lifestyle, and clinical factors.^4,23,29 Consideration must also be given to potential drug interactions.^4,23,29 In IDUs, treatment with PEG-IFN a/RBV should be considered because DAA studies have excluded active users.²⁰ Evaluation of the safety and efficacy of new regimens containing PEG-IFN a, as well as PEG-IFN-a–free regimens, in IDUs is needed.²⁰

Renal impairment
Both PEG-IFN a and RBV require dose adjustments in patients with a creatinine clearance less than 30 mL/min.^4,10,23,26 Further, simeprevir and sofosbuvir have not been studied in HCV patients with creatinine clearance less than 30 mL/min.^10,26

On the next page: Barriers to therapy >>

 

BARRIERS TO THERAPY
Patient-related
Barriers to treatment include lack of acceptance of treatment due to the absence of symptoms; lengthy duration of treatment; adverse effects of HCV drugs; and treatment costs.¹⁰ Potential strategies to overcome such obstacles include patient education; simplified dosing; better-tolerated treatments; and collaboration with pharmaceutical companies that offer patient assistance programs.

Drugs for HCV treatment can cause unpleasant adverse effects. Clinicians should encourage ad­herence for the entire duration of treatment and provide practical advice for coping with adverse effects such as fatigue, headache and other flulike symptoms, injection site reactions, cough, bad taste in mouth, oral ulcers, dry mouth, anorexia, nausea or vomiting, skin reactions, hair thinning or hair loss, and insomnia.^10,32

Strategies that may help alleviate these undesirable effects include regular low-impact exercise; drinking plenty of fluids; eating a well-balanced diet; maintaining good sleep hygiene; taking acetaminophen or ibuprofen for myalgias or headaches; and rotating PEG-IFN a injection sites.

Substance abuse and psychiatric disorders are common in patients with HCV infection. These patients should be referred to mental health or substance abuse services.¹⁰

Clinician-related
Obstacles to successfully treating patients with chronic HCV infection include patient-related barriers; lack of expertise in HCV management; practitioner bias against or resistance to treating patients who use illicit drugs or abuse alcohol; and concerns about the costs of treatment.

Potential strategies to overcome clinician barriers include collaboration with specialists (eg, hepatologists), utilizing telemedicine if necessary; availability of accessible, clear HCV treatment guidelines; and use of computer-based clinical decision support tools (eg, pop-up reminders and standing orders).¹⁰

PATIENT COUNSELING
Patients undergoing treatment for chronic HCV ­infection should be counseled on the following ­topics³³
• Risk for transmission to sex partners
• Not sharing personal items that might have blood on them, such as toothbrushes or razors, and covering any bleeding wounds to keep from spreading infectious blood or secretions
• Need for vaccinations against HAV and HBV if not immune
• Not donating blood, organs, tissue, or semen
• Stop using illicit drugs
• If continuing to inject drugs, avoid reusing or sharing syringes, needles, water, or drug preparation equipment
• Clean the injection site with a new swab prior to injection
• Safely dispose of syringes after one use
• Consider the benefits of joining a support group
• Avoid alcohol because it can accelerate cirrhosis and end-stage liver disease
• Not to start any new medicines, including OTC and herbal medicines, without checking with their health care professional.

FUTURE TREATMENTS
Treatments for HCV infection are evolving rapidly, and IFN-free options with excellent SVRs are emerging. Below are brief summaries of some of the current research that is focused on the study of IFN-free options. Other new regimens are awaiting approval by the FDA. These include
• The combination of sofosbuvir plus ledipasvir (an NS5A inhibitor) with and without RBV, for HCV genotype 1 infection for 8 or 12 weeks. The SVR in both groups was 93% to 95%. RBV had no effect on SVR.³³
• An all-oral combination therapy of daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir, with or without RBV, for HCV genotypes 1, 2, and 3 for 24 weeks. The SVR varied from 98% with genotype 1, 92% with genotype 2, and 89% for genotype 3. Patients who received RBV had an SVR of 94%; those who did not achieved an SVR of 98%.³⁴
• The combination of ABT-450 (a protease inhibitor boosted with ritonavir), ombitasvir (NS5A inhibitor), and dasabuvir (a nonnucleoside inhibitor) with RBV in patients with HCV genotype 1 and no cirrhosis. At 12 weeks, an SVR of 96% was achieved.³⁵

Despite years of research, a vaccine to prevent HCV infection has not yet been developed, although research continues. The major challenge is the number of genotypes and subtypes of HCV. A vaccine to prevent HCV infection will need to induce immunity to all genotypes and subtypes.³⁶

CONCLUSION
Patients with chronic HCV infection are frequently unaware of this fact, even though the majority of them acquired the liver disease decades ago. Because of the potentially serious consequences of untreated chronic HCV, it is critical that primary care clinicians identify and screen patients who are at risk for having or acquiring the disease. Identification of infected patients enables treatment initiation and, in most cases, cure of the infection. All patients at risk for infection should be counseled about risk reduction and screened periodically.

Thanks to newer, more effective treatment options, patients with HCV have an excellent chance today of clearing the virus and ultimately being cured. This could lead to a dramatic reduction in future HCV-associated morbidity and mortality. Since most of those infected today have never been treated, screening of at-risk patients is essential.

* Editor's note: At press time, the FDA had announced approval of a combination pill (ledipasvir/sofosbuvir) for the treatment of patients with chronic HCV.

---

CE/CME No: CR-1411

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• List the risk factors for HCV infection.
• Identify who should be screened for HCV infection.
• Discuss the symptoms, clinical course, diagnosis, and complications of chronic HCV infection.
• Differentiate between the treatment of acute and chronic HCV infection.
• Describe the challenges of treating HCV infection in patients who are coinfected with HIV. 

FACULTY
Daniel Sturm and Samuel L. Gurevitz are Assistant Professors in the Physician Assistant Program, College of Pharmacy and Health Sciences, at Butler University in Indianapolis. Cassidy Davidson, Abigail Fritchley, and Audrey Wagaman are students in the PA Program at Butler University. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of November 2014.

Article begins on next page >>

 

Several million Americans, primarily those in their fifties and sixties, contracted hepatitis C virus (HCV) many years ago and are unaware of their infection and their risk for HCV-related liver disease. Screening at-risk patients is important because newer treatment regimens are curative and can reduce associated morbidity and mortality.

Chronic infection with hepatitis C virus (HCV) is a major cause of liver disease in the United States. National Health and Nutrition Examination Survey data indicates that 2.7 million people have chronic HCV infection; the CDC estimates 3.2 million.^1-3 Yet these individuals may be asymptomatic for years, despite slow progression of sequelae (eg, chronic liver disease, cirrhosis, hepatocellular carcinoma [HCC]) that may silently unfold. Left untreated, chronic HCV infection is associated with a 15% to 30% risk for cirrhosis within 20 years, which subsequently confers an annual risk for HCC of 2% to 4%.⁴ Additionally, chronic HCV infection is now the leading indication for liver transplantation.³

Of note, 70% of those with chronic HCV infection were born between 1945 and 1965.² This is believed to be attributable to viral transmission via contaminated blood, blood products, and organ transplants prior to the implementation of universal precautions for blood supply screening in 1992; and to past injection drug use, even if it occurred only once.³

In a recent analysis, it was determined that the clinical and economic burdens of chronic HCV infection increased in the past decade, and this trend is likely to continue during the next decade.⁵ For example, HCV was responsible for 15,106 US deaths in 2007, surpassing deaths caused by HIV for the first time.⁶ Since then, the number of HCV-related deaths has continued to increase, to 17,721 in 2011.⁷ Economic costs solely attributable to HCV infection are difficult to calculate, but estimates range from several hundred million dollars to $30 billion annually.⁵ The World Health Organization (WHO) estimates that more than 185 million people worldwide are infected with HCV and that HCV is responsible for 350,000 deaths annually.⁴

The main goal of treatment is to achieve a sustained virologic response (SVR), defined as undetectable HCV RNA in serum 12 to 24 weeks after completion of treatment and thereby prevent or reduce the complications of HCV infection.³ Proactive screening, diagnosis, monitoring, and treatment of HCV infection can significantly reduce long-term morbidity and mortality.

INDICATIONS FOR HCV SCREENING
Recommendations for HCV screening have been developed by numerous organizations, including the WHO, CDC, US Preventive Services Task Force (USPSTF), American Association for the Study of Liver Diseases (AASLD), and the Infectious Diseases Society of America (IDSA) (see Table 1).^3,4,8,9-11 Screening should be offered to all individuals meeting one or more of the criteria. A 2012 CDC update calls for one-time testing for all persons born between 1945 and 1965 because of the disproportionately high prevalence of HCV infection in this cohort, which is five times greater than in the general population.¹¹

The initial screening tool for HCV infection is an HCV antibody test. A positive or reactive anti-HCV antibody result can signify either current or resolved infection, so a positive result should be followed with an HCV ribonucleic acid (RNA) test to determine if active infection is present.^4,8-10 See Figure on previous page for an HCV screening algorithm, which includes the points at which referrals to specialists are indicated.

A rapid HCV antibody test was approved by the FDA in 2011 and is favored because of its widespread availability, ease of use, rapid results, and low cost. Point-of-care testing is comparable in sensitivity and specificity to laboratory-based HCV assays and can utilize blood obtained via fingerstick or venipuncture.⁸ This form of testing facilitates HCV screening in a variety of settings, such as health fairs and emergency departments, as well as in high-risk settings such as methadone clinics.

Populations at increased risk for HCV infection are also at increased risk for hepatitis B virus (HBV), HIV, and tuberculosis infections; therefore, screening for these may also be warranted.⁴

PROGRESSION OF UNTREATED INFECTION
Just as with chronic HCV infection, patients newly infected with HCV are typically asymptomatic; the illness manifests with clinical symptoms in only 20% to 30% of cases.³ If symptoms do appear, they include fever, fatigue, dark urine, clay-colored stool, abdominal pain, loss of appetite, nausea, vomiting, joint pain, and jaundice. These acute phase symptoms may last two to 12 weeks.¹²

Spontaneous clearance of the virus occurs in only 15% to 25% of cases (see further discussion under “Acute HCV.”).^2,3 Even if a patient clears an HCV infection, if he or she falls within one of the at-risk categories (see Table 1), then periodic screening should continue because prior HCV infection does not protect against future infection.³

The progression of chronic HCV is indolent and often subclinical, with fatigue being the most common complaint. Other nonspecific symptoms may include nausea, anorexia, myalgia, arthralgia, weakness, and weight loss. One study noted that symptoms do not correlate with disease severity.¹³ In a 10-year prospective study, chronic HCV infection increased mortality when the infection was acquired at an early age (younger than 50) and/or when cirrhosis developed.¹⁴ Patients with cirrhosis progress to liver decompensation at a rate of 3% to 6% annually.15
In addition to liver disease, HCV infection is associated with an increased risk for non-Hodgkin lymphoma.³ HCV may also induce insulin resistance, which increases the risk for hepatic fibrosis. Other studies document HCV-induced cognitive impairment, but little scientific data is yet available as to its pathogenesis.¹⁶

DIAGNOSIS
Diagnostic testing for suspected HCV infection begins with an antibody test.⁸ A positive antibody test indicates one of three possibilities: active infection, resolved infection, or a false-positive result. Two drawbacks of HCV antibody testing are that immunocompromised patients may falsely test negative and that antibodies cannot be detected until eight to 12 weeks after the infection is acquired.¹¹ A positive antibody test should be confirmed with an HCV polymerase chain reaction (PCR) RNA test.^8,10

HCV RNA testing can detect the virus earlier than antibody testing—as early as two weeks after infection. Although a positive HCV RNA test confirms current HCV infection, its higher cost precludes its use as an initial diagnostic test for lower-risk patients.

In patients who test negative but for whom there is a high index of suspicion for HCV infection (eg, jaundiced patient with an elevated alanine aminotransferase level [ALT]), or for a health care worker with a recent bloodborne HCV exposure, testing for HCV antibodies, HCV RNA, and ALT levels should be ordered at regular intervals for a period of six months.¹⁰

Acute versus chronic infection
Distinguishing acute and chronic HCV is difficult. A determination that HCV is newly acquired requires a documented negative baseline antibody test, followed by laboratory evidence of seroconversion. This is typically only seen in cases where there has been a recent, known exposure to the virus.

Both HCV antibody and RNA testing are recommended when screening high-risk patients, including those who are immunocompromised, on hemodialysis, or have had a recent exposure to HCV-positive blood.¹⁰ Rapid PCR HCV RNA tests can assess both viral load and genotype (see discussion of HCV genotypes under “Chronic HCV”).¹⁷ This information helps guide and measure patient response to treatment.

Liver disease severity
Liver fibrosis and cirrhosis are serious complications of HCV; hepatomegaly or splenomegaly may or may not be present on physical examination and patients may require liver biopsies to evaluate disease stage.¹⁸ An assessment of the severity of liver damage can determine the urgency of treatment and predict treatment efficacy.

Biopsy results permit the grading of inflammation and nodularity and the staging of septal fibrosis, which can reliably predict future progression of the patient’s disease.¹⁹ However, liver biopsy is invasive, painful, and may contain sampling errors; complications may include bleeding, infection, and occasionally accidental injury to a nearby organ. An initial noninvasive assessment may be performed using vibration-controlled transient liver elastography, an ultrasound-based technology that measures liver stiffness, which correlates well with the degree of fibrosis or cirrhosis. Elastography, along with measurement of direct serum biomarkers that are produced by activated hepatic stellate cells involved in fibrosis, affords an accurate, noninvasive means of assessing liver damage.¹⁰

Continue for treatment options >>

 

TREATMENT
Acute HCV
To prevent progression of disease from acute to chronic infection, patients diagnosed with acute disease should be treated if
• They are likely to adhere to the treatment plan
• They have no contraindications to pegylated interferon a  (PEG-IFN a) treatment.

Contraindications to PEG-IFN a treatment include uncontrolled depression, psychosis, or epilepsy; pregnancy; couples' unwillingness to use effective contraception during treatment; severe concurrent medical disease; and decompensated liver disease.²⁰

For acute HCV infection, treatment with PEG-IFN a-2a 180 µg/wk or PEG-IFN a-2b 1.5 µg/kg/wk for 24 weeks is recommended.²⁰ Treatment results in an SVR greater than 80%.²¹ Combination therapy with ribavirin (RBV) does not increase SVR in the treatment of acute HCV infection.²²

The appropriate time to begin treatment has not been firmly established because, as previously noted, 15% to 25% of those infected will spontaneously clear the virus. The European Association for the Study of the Liver (EASL) suggests that patients who remain HCV positive at 12 weeks from the time of suspected infection should be treated.²³

Chronic HCV
Treatment of chronic HCV is based on multiple considerations, many of them patient-specific (see Table 2). One key element in treatment choice is the HCV genotype with which the patient is infected.

The most prevalent in the US are genotypes 1 through 6; further, genotype 1 has two subtypes: 1a and 1b. In the US, genotype 1 is most common, infecting about 70% of patients; genotype 2, 16%; genotype 3, 12%; genotype 4, 1%; genotype 5, < 1%; and genotype 6, 1%.²⁴ Infection with one genotype does not protect an individual from future infection with the same or a different HCV genotype.³

Other factors influencing treatment include viral load, ALT levels, coinfection (eg, HIV, HBV), comorbidities, and treatment contraindications.²¹ Treatment is recommended for those who have detectable HCV RNA levels, elevated ALT levels, progressive liver disease on biopsy, and the absence of any serious comorbid conditions or contraindications. ALT levels, however, can fluctuate and do not always correlate with disease severity.

For years, the standard treatment for chronic HCV infection has been PEG-IFN a/RBV for 48 weeks. This combination produced an SVR of 50% to 80%, depending on genotype.^3,25 Recently, however, treatment protocols have changed considerably with the introduction of two new and very effective direct-acting antiviral agents (DAAs): simeprevir, an HCV NS3/4A protease inhibitor, and sofosbuvir, an HCV NS5B polymerase inhibitor.

Simeprevir was approved by the FDA in October 2013 for use in combination with PEG-IFN/RBV for treatment of chronic HCV genotype 1 infection in adults with compensated liver disease.²⁷ Because the efficacy of simeprevir is reduced in patients with HCV genotype 1a with an NS3 Q80K polymorphism, screening for NS3 Q80K is recommended; alternative therapy should be considered when this mutation is present.²⁷

Sofosbuvir received FDA approval in December 2013 for use in combination with other antiviral drugs for treatment of chronic HCV infection, with established efficacy for treatment of genotypes 1, 2, 3, and 4 and for HCV/HIV coinfection.²⁸ For genotype 1, simeprevir and sofosbuvir achieve SVRs of 80% and 90%, respectively.^27,28

Table 3 lists the current medications for treatment of chronic HCV, including their adverse effects, contraindications, and drug interactions.

Updated treatment guidelines
AASLD, IDSA, EASL, WHO, and the Department of Veterans Affairs National Hepatitis C Resource Center Program recently issued updated evidence-based recommendations for the treatment of chronic HCV.^4,10,23,26 Highlights of the changes to the guidelines include
• With the introduction of simeprevir and sofosbuvir, the guidelines no longer recommend combination PEG-IFN a/RBV for 48 weeks as the standard treatment for chronic HCV infection^11,23,26
• Treatment regimens utilizing the protease inhibitors telaprevir and boceprevir are no longer recommended (with the exception of the WHO guidelines, which include them in a “conditional” recommendation).⁴

Regimens that include telaprevir and boceprevir are associated with higher rates of serious adverse effects, such as skin reactions and anemia, and involve longer treatment duration, higher pill burden, several drug interactions, frequent dosing, intensive monitoring, and the need to be taken with food (for telaprevir, high-fat food).^10,23,26

Finally, the EASL recommends an additional agent, daclatasvir, an NS5A replication complex inhibitor, as an option for treating HCV genotype 1, 3, and 4.²³ At this time, it is approved for use in Europe but has not been approved by the FDA.

Regardless of the treatment regimen, all patients receiving HCV antiviral therapy should be tested regularly to assess effectiveness of treatment and to monitor for the occurrence of adverse effects. Recommended periodic laboratory testing should include HCV RNA, complete blood count with differential, liver function, TSH level, renal function, comprehensive metabolic panel, bilirubin level, and pregnancy.²⁹

SPECIAL POPULATIONS
Patients with HIV/HCV coinfection, a history of injection drug use, and renal impairment require management tailored to their individual circumstances.^4,23,29

HIV/HCV-coinfected patients
Approximately 25% to 33% of patients infected with HIV are coinfected with HCV. HCV infection progresses more rapidly in HIV-infected patients, and coinfected patients are at greater risk for cirrhosis, liver cancer, and liver failure.³⁰

For patients with HIV/HCV coinfection, the decision to start treatment is more complex because of the high pill burden, overlapping toxicities, and interactions among the drugs used to treat HIV and HCV infections.⁴ HIV antiviral therapy should be started before HCV treatment to improve immune function, thereby decreasing the risks for both further infections and HIV transmission. This also allows the patient to adjust gradually to each regimen.

One exception to this is when an HIV treatment–naïve patient has a CD4 count > 500 cells/mL.³⁰ In this situation, HCV treatment is sometimes completed prior to the start of HIV treatment.

Recommended treatment for HIV/HCV coinfection, by HCV genotype, is outlined below. For all regimens, the weight-based RBV dosage is calculated as follows:
• Weight < 75 kg, 1,000 mg/d
• Weight ≥ 75 kg, 1,200 mg/d^10,30
• Genotypes 1 and 4 (IFN eligible): Sofosbuvir 400 mg/d and weight-based RBV plus weekly PEG-IFN a for 12 weeks
• Genotypes 1 and 4 (IFN ineligible): Sofosbuvir 400 mg/d and weight-based RBV for 24 weeks
• Genotypes 2 and 3 (regardless of IFN eligibility): Sofosbuvir 400 mg/d and weight-based RBV for 12 weeks for genotype 2 and 24 weeks for genotype 3
• Genotypes 5 and 6 (IFN eligible): Sofosbuvir 400 mg/d plus weight-based RBV plus weekly PEG-IFN a for 12 weeks.

Injection drug users
HCV infection among young injection drug users (IDUs) is an emerging epidemic that must be addressed by recognizing at-risk populations, screening for early disease, and providing treatment and education. Globally, it is estimated that approximately 67% of IDUs—approximately 10 million people—are infected with HCV.³¹ Treatment of HCV in IDUs requires integration of many services and health care professionals, including addiction specialists. Dependence on opiates, alcohol, or other substances is common in this patient population. Patients should be counseled on the importance of abstaining from alcohol. IDUs are at risk for hepatitis A (HAV) and HBV infections and should be vaccinated against these diseases.⁴

Treatment decisions should be based on an individualized evaluation of the patient’s social, lifestyle, and clinical factors.^4,23,29 Consideration must also be given to potential drug interactions.^4,23,29 In IDUs, treatment with PEG-IFN a/RBV should be considered because DAA studies have excluded active users.²⁰ Evaluation of the safety and efficacy of new regimens containing PEG-IFN a, as well as PEG-IFN-a–free regimens, in IDUs is needed.²⁰

Renal impairment
Both PEG-IFN a and RBV require dose adjustments in patients with a creatinine clearance less than 30 mL/min.^4,10,23,26 Further, simeprevir and sofosbuvir have not been studied in HCV patients with creatinine clearance less than 30 mL/min.^10,26

On the next page: Barriers to therapy >>

 

BARRIERS TO THERAPY
Patient-related
Barriers to treatment include lack of acceptance of treatment due to the absence of symptoms; lengthy duration of treatment; adverse effects of HCV drugs; and treatment costs.¹⁰ Potential strategies to overcome such obstacles include patient education; simplified dosing; better-tolerated treatments; and collaboration with pharmaceutical companies that offer patient assistance programs.

Drugs for HCV treatment can cause unpleasant adverse effects. Clinicians should encourage ad­herence for the entire duration of treatment and provide practical advice for coping with adverse effects such as fatigue, headache and other flulike symptoms, injection site reactions, cough, bad taste in mouth, oral ulcers, dry mouth, anorexia, nausea or vomiting, skin reactions, hair thinning or hair loss, and insomnia.^10,32

Strategies that may help alleviate these undesirable effects include regular low-impact exercise; drinking plenty of fluids; eating a well-balanced diet; maintaining good sleep hygiene; taking acetaminophen or ibuprofen for myalgias or headaches; and rotating PEG-IFN a injection sites.

Substance abuse and psychiatric disorders are common in patients with HCV infection. These patients should be referred to mental health or substance abuse services.¹⁰

Clinician-related
Obstacles to successfully treating patients with chronic HCV infection include patient-related barriers; lack of expertise in HCV management; practitioner bias against or resistance to treating patients who use illicit drugs or abuse alcohol; and concerns about the costs of treatment.

Potential strategies to overcome clinician barriers include collaboration with specialists (eg, hepatologists), utilizing telemedicine if necessary; availability of accessible, clear HCV treatment guidelines; and use of computer-based clinical decision support tools (eg, pop-up reminders and standing orders).¹⁰

PATIENT COUNSELING
Patients undergoing treatment for chronic HCV ­infection should be counseled on the following ­topics³³
• Risk for transmission to sex partners
• Not sharing personal items that might have blood on them, such as toothbrushes or razors, and covering any bleeding wounds to keep from spreading infectious blood or secretions
• Need for vaccinations against HAV and HBV if not immune
• Not donating blood, organs, tissue, or semen
• Stop using illicit drugs
• If continuing to inject drugs, avoid reusing or sharing syringes, needles, water, or drug preparation equipment
• Clean the injection site with a new swab prior to injection
• Safely dispose of syringes after one use
• Consider the benefits of joining a support group
• Avoid alcohol because it can accelerate cirrhosis and end-stage liver disease
• Not to start any new medicines, including OTC and herbal medicines, without checking with their health care professional.

FUTURE TREATMENTS
Treatments for HCV infection are evolving rapidly, and IFN-free options with excellent SVRs are emerging. Below are brief summaries of some of the current research that is focused on the study of IFN-free options. Other new regimens are awaiting approval by the FDA. These include
• The combination of sofosbuvir plus ledipasvir (an NS5A inhibitor) with and without RBV, for HCV genotype 1 infection for 8 or 12 weeks. The SVR in both groups was 93% to 95%. RBV had no effect on SVR.³³
• An all-oral combination therapy of daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir, with or without RBV, for HCV genotypes 1, 2, and 3 for 24 weeks. The SVR varied from 98% with genotype 1, 92% with genotype 2, and 89% for genotype 3. Patients who received RBV had an SVR of 94%; those who did not achieved an SVR of 98%.³⁴
• The combination of ABT-450 (a protease inhibitor boosted with ritonavir), ombitasvir (NS5A inhibitor), and dasabuvir (a nonnucleoside inhibitor) with RBV in patients with HCV genotype 1 and no cirrhosis. At 12 weeks, an SVR of 96% was achieved.³⁵

Despite years of research, a vaccine to prevent HCV infection has not yet been developed, although research continues. The major challenge is the number of genotypes and subtypes of HCV. A vaccine to prevent HCV infection will need to induce immunity to all genotypes and subtypes.³⁶

CONCLUSION
Patients with chronic HCV infection are frequently unaware of this fact, even though the majority of them acquired the liver disease decades ago. Because of the potentially serious consequences of untreated chronic HCV, it is critical that primary care clinicians identify and screen patients who are at risk for having or acquiring the disease. Identification of infected patients enables treatment initiation and, in most cases, cure of the infection. All patients at risk for infection should be counseled about risk reduction and screened periodically.

Thanks to newer, more effective treatment options, patients with HCV have an excellent chance today of clearing the virus and ultimately being cured. This could lead to a dramatic reduction in future HCV-associated morbidity and mortality. Since most of those infected today have never been treated, screening of at-risk patients is essential.

* Editor's note: At press time, the FDA had announced approval of a combination pill (ledipasvir/sofosbuvir) for the treatment of patients with chronic HCV.

---

CE/CME No: CR-1411

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• List the risk factors for HCV infection.
• Identify who should be screened for HCV infection.
• Discuss the symptoms, clinical course, diagnosis, and complications of chronic HCV infection.
• Differentiate between the treatment of acute and chronic HCV infection.
• Describe the challenges of treating HCV infection in patients who are coinfected with HIV. 

FACULTY
Daniel Sturm and Samuel L. Gurevitz are Assistant Professors in the Physician Assistant Program, College of Pharmacy and Health Sciences, at Butler University in Indianapolis. Cassidy Davidson, Abigail Fritchley, and Audrey Wagaman are students in the PA Program at Butler University. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of November 2014.

Article begins on next page >>

 

Several million Americans, primarily those in their fifties and sixties, contracted hepatitis C virus (HCV) many years ago and are unaware of their infection and their risk for HCV-related liver disease. Screening at-risk patients is important because newer treatment regimens are curative and can reduce associated morbidity and mortality.

Chronic infection with hepatitis C virus (HCV) is a major cause of liver disease in the United States. National Health and Nutrition Examination Survey data indicates that 2.7 million people have chronic HCV infection; the CDC estimates 3.2 million.^1-3 Yet these individuals may be asymptomatic for years, despite slow progression of sequelae (eg, chronic liver disease, cirrhosis, hepatocellular carcinoma [HCC]) that may silently unfold. Left untreated, chronic HCV infection is associated with a 15% to 30% risk for cirrhosis within 20 years, which subsequently confers an annual risk for HCC of 2% to 4%.⁴ Additionally, chronic HCV infection is now the leading indication for liver transplantation.³

Of note, 70% of those with chronic HCV infection were born between 1945 and 1965.² This is believed to be attributable to viral transmission via contaminated blood, blood products, and organ transplants prior to the implementation of universal precautions for blood supply screening in 1992; and to past injection drug use, even if it occurred only once.³

In a recent analysis, it was determined that the clinical and economic burdens of chronic HCV infection increased in the past decade, and this trend is likely to continue during the next decade.⁵ For example, HCV was responsible for 15,106 US deaths in 2007, surpassing deaths caused by HIV for the first time.⁶ Since then, the number of HCV-related deaths has continued to increase, to 17,721 in 2011.⁷ Economic costs solely attributable to HCV infection are difficult to calculate, but estimates range from several hundred million dollars to $30 billion annually.⁵ The World Health Organization (WHO) estimates that more than 185 million people worldwide are infected with HCV and that HCV is responsible for 350,000 deaths annually.⁴

The main goal of treatment is to achieve a sustained virologic response (SVR), defined as undetectable HCV RNA in serum 12 to 24 weeks after completion of treatment and thereby prevent or reduce the complications of HCV infection.³ Proactive screening, diagnosis, monitoring, and treatment of HCV infection can significantly reduce long-term morbidity and mortality.

INDICATIONS FOR HCV SCREENING
Recommendations for HCV screening have been developed by numerous organizations, including the WHO, CDC, US Preventive Services Task Force (USPSTF), American Association for the Study of Liver Diseases (AASLD), and the Infectious Diseases Society of America (IDSA) (see Table 1).^3,4,8,9-11 Screening should be offered to all individuals meeting one or more of the criteria. A 2012 CDC update calls for one-time testing for all persons born between 1945 and 1965 because of the disproportionately high prevalence of HCV infection in this cohort, which is five times greater than in the general population.¹¹

The initial screening tool for HCV infection is an HCV antibody test. A positive or reactive anti-HCV antibody result can signify either current or resolved infection, so a positive result should be followed with an HCV ribonucleic acid (RNA) test to determine if active infection is present.^4,8-10 See Figure on previous page for an HCV screening algorithm, which includes the points at which referrals to specialists are indicated.

A rapid HCV antibody test was approved by the FDA in 2011 and is favored because of its widespread availability, ease of use, rapid results, and low cost. Point-of-care testing is comparable in sensitivity and specificity to laboratory-based HCV assays and can utilize blood obtained via fingerstick or venipuncture.⁸ This form of testing facilitates HCV screening in a variety of settings, such as health fairs and emergency departments, as well as in high-risk settings such as methadone clinics.

Populations at increased risk for HCV infection are also at increased risk for hepatitis B virus (HBV), HIV, and tuberculosis infections; therefore, screening for these may also be warranted.⁴

PROGRESSION OF UNTREATED INFECTION
Just as with chronic HCV infection, patients newly infected with HCV are typically asymptomatic; the illness manifests with clinical symptoms in only 20% to 30% of cases.³ If symptoms do appear, they include fever, fatigue, dark urine, clay-colored stool, abdominal pain, loss of appetite, nausea, vomiting, joint pain, and jaundice. These acute phase symptoms may last two to 12 weeks.¹²

Spontaneous clearance of the virus occurs in only 15% to 25% of cases (see further discussion under “Acute HCV.”).^2,3 Even if a patient clears an HCV infection, if he or she falls within one of the at-risk categories (see Table 1), then periodic screening should continue because prior HCV infection does not protect against future infection.³

The progression of chronic HCV is indolent and often subclinical, with fatigue being the most common complaint. Other nonspecific symptoms may include nausea, anorexia, myalgia, arthralgia, weakness, and weight loss. One study noted that symptoms do not correlate with disease severity.¹³ In a 10-year prospective study, chronic HCV infection increased mortality when the infection was acquired at an early age (younger than 50) and/or when cirrhosis developed.¹⁴ Patients with cirrhosis progress to liver decompensation at a rate of 3% to 6% annually.15
In addition to liver disease, HCV infection is associated with an increased risk for non-Hodgkin lymphoma.³ HCV may also induce insulin resistance, which increases the risk for hepatic fibrosis. Other studies document HCV-induced cognitive impairment, but little scientific data is yet available as to its pathogenesis.¹⁶

DIAGNOSIS
Diagnostic testing for suspected HCV infection begins with an antibody test.⁸ A positive antibody test indicates one of three possibilities: active infection, resolved infection, or a false-positive result. Two drawbacks of HCV antibody testing are that immunocompromised patients may falsely test negative and that antibodies cannot be detected until eight to 12 weeks after the infection is acquired.¹¹ A positive antibody test should be confirmed with an HCV polymerase chain reaction (PCR) RNA test.^8,10

HCV RNA testing can detect the virus earlier than antibody testing—as early as two weeks after infection. Although a positive HCV RNA test confirms current HCV infection, its higher cost precludes its use as an initial diagnostic test for lower-risk patients.

In patients who test negative but for whom there is a high index of suspicion for HCV infection (eg, jaundiced patient with an elevated alanine aminotransferase level [ALT]), or for a health care worker with a recent bloodborne HCV exposure, testing for HCV antibodies, HCV RNA, and ALT levels should be ordered at regular intervals for a period of six months.¹⁰

Acute versus chronic infection
Distinguishing acute and chronic HCV is difficult. A determination that HCV is newly acquired requires a documented negative baseline antibody test, followed by laboratory evidence of seroconversion. This is typically only seen in cases where there has been a recent, known exposure to the virus.

Both HCV antibody and RNA testing are recommended when screening high-risk patients, including those who are immunocompromised, on hemodialysis, or have had a recent exposure to HCV-positive blood.¹⁰ Rapid PCR HCV RNA tests can assess both viral load and genotype (see discussion of HCV genotypes under “Chronic HCV”).¹⁷ This information helps guide and measure patient response to treatment.

Liver disease severity
Liver fibrosis and cirrhosis are serious complications of HCV; hepatomegaly or splenomegaly may or may not be present on physical examination and patients may require liver biopsies to evaluate disease stage.¹⁸ An assessment of the severity of liver damage can determine the urgency of treatment and predict treatment efficacy.

Biopsy results permit the grading of inflammation and nodularity and the staging of septal fibrosis, which can reliably predict future progression of the patient’s disease.¹⁹ However, liver biopsy is invasive, painful, and may contain sampling errors; complications may include bleeding, infection, and occasionally accidental injury to a nearby organ. An initial noninvasive assessment may be performed using vibration-controlled transient liver elastography, an ultrasound-based technology that measures liver stiffness, which correlates well with the degree of fibrosis or cirrhosis. Elastography, along with measurement of direct serum biomarkers that are produced by activated hepatic stellate cells involved in fibrosis, affords an accurate, noninvasive means of assessing liver damage.¹⁰

Continue for treatment options >>

 

TREATMENT
Acute HCV
To prevent progression of disease from acute to chronic infection, patients diagnosed with acute disease should be treated if
• They are likely to adhere to the treatment plan
• They have no contraindications to pegylated interferon a  (PEG-IFN a) treatment.

Contraindications to PEG-IFN a treatment include uncontrolled depression, psychosis, or epilepsy; pregnancy; couples' unwillingness to use effective contraception during treatment; severe concurrent medical disease; and decompensated liver disease.²⁰

For acute HCV infection, treatment with PEG-IFN a-2a 180 µg/wk or PEG-IFN a-2b 1.5 µg/kg/wk for 24 weeks is recommended.²⁰ Treatment results in an SVR greater than 80%.²¹ Combination therapy with ribavirin (RBV) does not increase SVR in the treatment of acute HCV infection.²²

The appropriate time to begin treatment has not been firmly established because, as previously noted, 15% to 25% of those infected will spontaneously clear the virus. The European Association for the Study of the Liver (EASL) suggests that patients who remain HCV positive at 12 weeks from the time of suspected infection should be treated.²³

Chronic HCV
Treatment of chronic HCV is based on multiple considerations, many of them patient-specific (see Table 2). One key element in treatment choice is the HCV genotype with which the patient is infected.

The most prevalent in the US are genotypes 1 through 6; further, genotype 1 has two subtypes: 1a and 1b. In the US, genotype 1 is most common, infecting about 70% of patients; genotype 2, 16%; genotype 3, 12%; genotype 4, 1%; genotype 5, < 1%; and genotype 6, 1%.²⁴ Infection with one genotype does not protect an individual from future infection with the same or a different HCV genotype.³

Other factors influencing treatment include viral load, ALT levels, coinfection (eg, HIV, HBV), comorbidities, and treatment contraindications.²¹ Treatment is recommended for those who have detectable HCV RNA levels, elevated ALT levels, progressive liver disease on biopsy, and the absence of any serious comorbid conditions or contraindications. ALT levels, however, can fluctuate and do not always correlate with disease severity.

For years, the standard treatment for chronic HCV infection has been PEG-IFN a/RBV for 48 weeks. This combination produced an SVR of 50% to 80%, depending on genotype.^3,25 Recently, however, treatment protocols have changed considerably with the introduction of two new and very effective direct-acting antiviral agents (DAAs): simeprevir, an HCV NS3/4A protease inhibitor, and sofosbuvir, an HCV NS5B polymerase inhibitor.

Simeprevir was approved by the FDA in October 2013 for use in combination with PEG-IFN/RBV for treatment of chronic HCV genotype 1 infection in adults with compensated liver disease.²⁷ Because the efficacy of simeprevir is reduced in patients with HCV genotype 1a with an NS3 Q80K polymorphism, screening for NS3 Q80K is recommended; alternative therapy should be considered when this mutation is present.²⁷

Sofosbuvir received FDA approval in December 2013 for use in combination with other antiviral drugs for treatment of chronic HCV infection, with established efficacy for treatment of genotypes 1, 2, 3, and 4 and for HCV/HIV coinfection.²⁸ For genotype 1, simeprevir and sofosbuvir achieve SVRs of 80% and 90%, respectively.^27,28

Table 3 lists the current medications for treatment of chronic HCV, including their adverse effects, contraindications, and drug interactions.

Updated treatment guidelines
AASLD, IDSA, EASL, WHO, and the Department of Veterans Affairs National Hepatitis C Resource Center Program recently issued updated evidence-based recommendations for the treatment of chronic HCV.^4,10,23,26 Highlights of the changes to the guidelines include
• With the introduction of simeprevir and sofosbuvir, the guidelines no longer recommend combination PEG-IFN a/RBV for 48 weeks as the standard treatment for chronic HCV infection^11,23,26
• Treatment regimens utilizing the protease inhibitors telaprevir and boceprevir are no longer recommended (with the exception of the WHO guidelines, which include them in a “conditional” recommendation).⁴

Regimens that include telaprevir and boceprevir are associated with higher rates of serious adverse effects, such as skin reactions and anemia, and involve longer treatment duration, higher pill burden, several drug interactions, frequent dosing, intensive monitoring, and the need to be taken with food (for telaprevir, high-fat food).^10,23,26

Finally, the EASL recommends an additional agent, daclatasvir, an NS5A replication complex inhibitor, as an option for treating HCV genotype 1, 3, and 4.²³ At this time, it is approved for use in Europe but has not been approved by the FDA.

Regardless of the treatment regimen, all patients receiving HCV antiviral therapy should be tested regularly to assess effectiveness of treatment and to monitor for the occurrence of adverse effects. Recommended periodic laboratory testing should include HCV RNA, complete blood count with differential, liver function, TSH level, renal function, comprehensive metabolic panel, bilirubin level, and pregnancy.²⁹

SPECIAL POPULATIONS
Patients with HIV/HCV coinfection, a history of injection drug use, and renal impairment require management tailored to their individual circumstances.^4,23,29

HIV/HCV-coinfected patients
Approximately 25% to 33% of patients infected with HIV are coinfected with HCV. HCV infection progresses more rapidly in HIV-infected patients, and coinfected patients are at greater risk for cirrhosis, liver cancer, and liver failure.³⁰

For patients with HIV/HCV coinfection, the decision to start treatment is more complex because of the high pill burden, overlapping toxicities, and interactions among the drugs used to treat HIV and HCV infections.⁴ HIV antiviral therapy should be started before HCV treatment to improve immune function, thereby decreasing the risks for both further infections and HIV transmission. This also allows the patient to adjust gradually to each regimen.

One exception to this is when an HIV treatment–naïve patient has a CD4 count > 500 cells/mL.³⁰ In this situation, HCV treatment is sometimes completed prior to the start of HIV treatment.

Recommended treatment for HIV/HCV coinfection, by HCV genotype, is outlined below. For all regimens, the weight-based RBV dosage is calculated as follows:
• Weight < 75 kg, 1,000 mg/d
• Weight ≥ 75 kg, 1,200 mg/d^10,30
• Genotypes 1 and 4 (IFN eligible): Sofosbuvir 400 mg/d and weight-based RBV plus weekly PEG-IFN a for 12 weeks
• Genotypes 1 and 4 (IFN ineligible): Sofosbuvir 400 mg/d and weight-based RBV for 24 weeks
• Genotypes 2 and 3 (regardless of IFN eligibility): Sofosbuvir 400 mg/d and weight-based RBV for 12 weeks for genotype 2 and 24 weeks for genotype 3
• Genotypes 5 and 6 (IFN eligible): Sofosbuvir 400 mg/d plus weight-based RBV plus weekly PEG-IFN a for 12 weeks.

Injection drug users
HCV infection among young injection drug users (IDUs) is an emerging epidemic that must be addressed by recognizing at-risk populations, screening for early disease, and providing treatment and education. Globally, it is estimated that approximately 67% of IDUs—approximately 10 million people—are infected with HCV.³¹ Treatment of HCV in IDUs requires integration of many services and health care professionals, including addiction specialists. Dependence on opiates, alcohol, or other substances is common in this patient population. Patients should be counseled on the importance of abstaining from alcohol. IDUs are at risk for hepatitis A (HAV) and HBV infections and should be vaccinated against these diseases.⁴

Treatment decisions should be based on an individualized evaluation of the patient’s social, lifestyle, and clinical factors.^4,23,29 Consideration must also be given to potential drug interactions.^4,23,29 In IDUs, treatment with PEG-IFN a/RBV should be considered because DAA studies have excluded active users.²⁰ Evaluation of the safety and efficacy of new regimens containing PEG-IFN a, as well as PEG-IFN-a–free regimens, in IDUs is needed.²⁰

Renal impairment
Both PEG-IFN a and RBV require dose adjustments in patients with a creatinine clearance less than 30 mL/min.^4,10,23,26 Further, simeprevir and sofosbuvir have not been studied in HCV patients with creatinine clearance less than 30 mL/min.^10,26

On the next page: Barriers to therapy >>

 

BARRIERS TO THERAPY
Patient-related
Barriers to treatment include lack of acceptance of treatment due to the absence of symptoms; lengthy duration of treatment; adverse effects of HCV drugs; and treatment costs.¹⁰ Potential strategies to overcome such obstacles include patient education; simplified dosing; better-tolerated treatments; and collaboration with pharmaceutical companies that offer patient assistance programs.

Drugs for HCV treatment can cause unpleasant adverse effects. Clinicians should encourage ad­herence for the entire duration of treatment and provide practical advice for coping with adverse effects such as fatigue, headache and other flulike symptoms, injection site reactions, cough, bad taste in mouth, oral ulcers, dry mouth, anorexia, nausea or vomiting, skin reactions, hair thinning or hair loss, and insomnia.^10,32

Strategies that may help alleviate these undesirable effects include regular low-impact exercise; drinking plenty of fluids; eating a well-balanced diet; maintaining good sleep hygiene; taking acetaminophen or ibuprofen for myalgias or headaches; and rotating PEG-IFN a injection sites.

Substance abuse and psychiatric disorders are common in patients with HCV infection. These patients should be referred to mental health or substance abuse services.¹⁰

Clinician-related
Obstacles to successfully treating patients with chronic HCV infection include patient-related barriers; lack of expertise in HCV management; practitioner bias against or resistance to treating patients who use illicit drugs or abuse alcohol; and concerns about the costs of treatment.

Potential strategies to overcome clinician barriers include collaboration with specialists (eg, hepatologists), utilizing telemedicine if necessary; availability of accessible, clear HCV treatment guidelines; and use of computer-based clinical decision support tools (eg, pop-up reminders and standing orders).¹⁰

PATIENT COUNSELING
Patients undergoing treatment for chronic HCV ­infection should be counseled on the following ­topics³³
• Risk for transmission to sex partners
• Not sharing personal items that might have blood on them, such as toothbrushes or razors, and covering any bleeding wounds to keep from spreading infectious blood or secretions
• Need for vaccinations against HAV and HBV if not immune
• Not donating blood, organs, tissue, or semen
• Stop using illicit drugs
• If continuing to inject drugs, avoid reusing or sharing syringes, needles, water, or drug preparation equipment
• Clean the injection site with a new swab prior to injection
• Safely dispose of syringes after one use
• Consider the benefits of joining a support group
• Avoid alcohol because it can accelerate cirrhosis and end-stage liver disease
• Not to start any new medicines, including OTC and herbal medicines, without checking with their health care professional.

FUTURE TREATMENTS
Treatments for HCV infection are evolving rapidly, and IFN-free options with excellent SVRs are emerging. Below are brief summaries of some of the current research that is focused on the study of IFN-free options. Other new regimens are awaiting approval by the FDA. These include
• The combination of sofosbuvir plus ledipasvir (an NS5A inhibitor) with and without RBV, for HCV genotype 1 infection for 8 or 12 weeks. The SVR in both groups was 93% to 95%. RBV had no effect on SVR.³³
• An all-oral combination therapy of daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir, with or without RBV, for HCV genotypes 1, 2, and 3 for 24 weeks. The SVR varied from 98% with genotype 1, 92% with genotype 2, and 89% for genotype 3. Patients who received RBV had an SVR of 94%; those who did not achieved an SVR of 98%.³⁴
• The combination of ABT-450 (a protease inhibitor boosted with ritonavir), ombitasvir (NS5A inhibitor), and dasabuvir (a nonnucleoside inhibitor) with RBV in patients with HCV genotype 1 and no cirrhosis. At 12 weeks, an SVR of 96% was achieved.³⁵

Despite years of research, a vaccine to prevent HCV infection has not yet been developed, although research continues. The major challenge is the number of genotypes and subtypes of HCV. A vaccine to prevent HCV infection will need to induce immunity to all genotypes and subtypes.³⁶

CONCLUSION
Patients with chronic HCV infection are frequently unaware of this fact, even though the majority of them acquired the liver disease decades ago. Because of the potentially serious consequences of untreated chronic HCV, it is critical that primary care clinicians identify and screen patients who are at risk for having or acquiring the disease. Identification of infected patients enables treatment initiation and, in most cases, cure of the infection. All patients at risk for infection should be counseled about risk reduction and screened periodically.

Thanks to newer, more effective treatment options, patients with HCV have an excellent chance today of clearing the virus and ultimately being cured. This could lead to a dramatic reduction in future HCV-associated morbidity and mortality. Since most of those infected today have never been treated, screening of at-risk patients is essential.

* Editor's note: At press time, the FDA had announced approval of a combination pill (ledipasvir/sofosbuvir) for the treatment of patients with chronic HCV.

---

CE/CME No: CR-1410

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES

•  Identify risk factors for the development of spondylolysis and spondylolisthesis
•  Discuss the differential diagnoses associated with low back pain
•  Describe physical examination findings consistent with spondylolysis and spondylolisthesis
•  List the imaging modalities that may be used to confirm these diagnoses and explain the indications for each
•  Identify when a pediatric patient with low back pain should be referred to an orthopedic or neurologic specialist for further evaluation and treatment

FACULTY

Shannon P. More is a pediatric nurse practitioner in New York City. Rita Marie John is a Professor at the Columbia University School of Nursing in New York City. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of October 2014. 

Article begins on next page >>

 

The most common causes of low back pain in adolescents, spondylolysis and spondylolisthesis can be tricky to diagnose. The primary care clinician plays a key role in optimal management so that full recovery, in most cases, is achieved.

Spondylolysis, the most common cause of low back pain in adolescents, occurs in approximately 8% to 14% of adolescent athletes.1 It is estimated that 15% to 25% of patients with spondylolysis will develop spondylolisthesis.2 This article discusses the definitions, pathophysiology, risk factors, differential diagnosis, and clinical presentation of spondylolysis and spondylolisthesis, including a review of diagnostic imaging, treatment, and the primary care clinician’s role in the optimal management of affected patients.

Spondylolysis is a congenital or acquired unilateral or bilateral defect in the portion of a vertebra—usually L5—called the pars interarticularis, the bony area between the superior and inferior articulating facets (see Figure 1a). Recurrent trauma, such as repeated flexion, hyperextension, or twisting, can weaken the pars interarticularis. During these movements, the inferior articular process of the cranial (upper) vertebra can come into contact with the pars interarticularis of the caudal (lower) vertebra. When this happens repeatedly, a stress reaction may occur in the pars interarticularis, which can result in a stress or complete nonunion fracture.

The paraspinal muscles around the lumbar spine may adjust to accommodate the weakened vertebra, resulting in postural alterations. This can predispose patients to further spinal injury because normal muscular control of that portion of the spine is impaired.³

When the break in the pars interarticularis causes slippage, or forward movement, of the upper vertebra (again, usually L5) over the vertebra (ie, S1) below it, spondylolisthesis occurs (see Figure 1b, above).^2,4  This happens more frequently with bilateral spondylolysis and is often associated with an adolescent growth spurt.⁵

Spondylolisthesis can manifest anywhere in the spine but is most common in the lumbosacral region, with most (71% to 95%) cases occurring at L5 and the remainder at L4.⁶ Some patients develop these conditions spontaneously through strenuous activity or injury; others are predisposed but remain asymptomatic until the condition is exacerbated through athletic activities.

 Wiltse first described spondylolisthesis in 1962 and 10 years later published a classification system based on etiology and anatomy; his research is still used today as the basis for diagnosis.^7,8 The five types of spondylolisthesis are

• Type 1, dysplastic (congenital)
• Type 2, isthmic (defect in pars interarticularis)
• Type 3, degenerative (arthritic changes in older patients)
• Type 4, traumatic (acute injury)
• Type 5, pathologic (bone disease).⁸

Types 1 and 2 occur in pediatric patients, with 85% of such cases classified as type 2.⁴

The classification is further refined according to degree of severity, defined as the percentage of slippage of the upper over the lower vertebra. Grade 1 (first degree) entails a slippage of less than 25%; grade 2 (second degree), 26% to 50%; grade 3 (third degree), 51% to 75%; and grade 4 (fourth degree), greater than 75%.⁵

Risk Factors
In general, women are at greater risk for stress fractures than men are.⁹ Yet while pars interarticularis defects are twice as common in men as in women, women are more likely to progress to spondylolisthesis.¹⁰ Similarly, in patients with bilateral spondylolysis, women are significantly more likely than men (90.9% vs 66.2%) to develop spondylolisthesis.¹¹ In general, those who repetitively hyperextend the lower back (eg, football players, rowers, dancers, gymnasts, soccer players, swimmers) are at increased risk for both spondylolysis and spondylolisthesis.

While a patient’s activities and environmental stressors play a role in the development of spondylolysis and spondylolisthesis, a genetic predisposition is believed to be a factor as well: A five-fold increase in the incidence of defects of the pars interarticularis has been noted in near relatives of patients with spondylolisthesis.⁷ In addition, patients with conditions such as spina bifida occulta, severe scoliosis, and osteogenesis imperfecta are at increased risk for these conditions.^6,12

Differential DiagnosIs
Both spondylolysis and spondylolisthesis manifest as low back pain, for which the differential diagnosis is extensive. Pathologic causes of low back pain are much less common than causes related to structural weakness or trauma; however, carefully differentiating these is important so that pathology is identified promptly and treated appropriately.¹³

The differential diagnosis for low back pain in pediatric patients, by type of pain, includes

• Pain at night or with fever or other generalized symptoms: tumor or infection
• Acute pain: herniated disk, slipped apophysis, spondylolysis, vertebral fracture, or muscle strain
• Chronic pain: Scheuermann kyphosis, inflammatory spondyloarthropathies, or psychological problems
• Pain with spinal forward flexion: herniated disk or slipped apophysis
• Pain with spinal extension: spondylolysis, spondylolisthesis, or lesion or injury in the pedicle or lamina (posterior arch)
• Pain with recent-onset scoliosis: tumor, infection, herniated disk, syrinx, or idiopathic scoliosis
• Other pain: pyelonephritis or sickle cell crisis.¹³

Clinical Presentation
A systematic approach to a patient with a chief concern of low back pain is recommended. An initial assessment of the patient’s vital signs and growth parameters should be compared to those from previous visits to determine if there have been any changes in the usual pattern.

History
Use the standard HEEADSSS (Home, Education, Eating, Activities, Drugs, Sexuality, Suicide, Safety) adolescent psychosocial assessment as part of the patient history.¹⁴ In particular, focus on details about the physical activities and sports in which the patient participates and obtain data on the amount of time spent on each. When taking the family history, pay particular attention to any predisposition to musculoskeletal disorders. In the review of systems, note any history of traumatic injury.

Next, ask the patient to point with one finger to the location at which the pain is felt; in spondylolysis and spondylolisthesis, pain localizes to the waist. Obtain a detailed history of the pain, including onset, duration, frequency, location, and all alleviating or exacerbating factors.¹⁵

Physical examination
A brief summary of key features to assess during the physical examination is presented in Table 1. When completing the physical assessment, follow the typical head-to-toe approach, with special attention to evaluation of the presenting back pain.

Visual inspection. A visual inspection of the spine for scoliosis and kyphosis is key; also be sure to examine posture, assess symmetry, and observe for any midline defects.¹³ Hemangiomas, a line of hairy patches, or other abnormal markings along the body’s vertical axis may suggest an intraspinal anomaly.

Palpation. The entire spine should be palpated to confirm the location of the pain as identified by the patient. In particular, note if tenderness is felt over bony structures of the spine or in the paraspinal musculature.

Range of motion. After the locus of the pain is confirmed, instruct the patient to flex and extend the spine to assess for worsening pain. If noted, this finding is pathognomonic for spondylolysis and spondylolisthesis.¹³

Also useful for making the diagnosis is the one-leg hyperextension test, in which the patient is asked to raise one leg off the ground and lean backward. Pain elicited during this movement is indicative of back injury, including spondylolysis or spondylolisthesis. A positive result with the one-leg hyperextension test alone, however, is not a clinical marker for spondylolysis. Not only may the test elicit pain stemming from other pathologies, but the results are dependent on the patient’s subjective reporting of pain.¹⁶

Muscular signs and symptoms. Hamstring tightness is present in 80% of symptomatic patients.⁵ Consequently, the patient may have a somewhat waddling gait due to the inability to flex the hips and extend the knee simultaneously. For this reason, physical examination for spondylolysis and spondylolisthesis includes gait assessment. Other clinical signs of spondylolisthesis include a weak and drooping abdominal wall, paravertebral muscle hypertrophy, increased lumbar lordosis, hamstring muscle spasm, and pain during lateral trunk flexion/extension and double leg raising.¹⁷

Motor and sensory function. It is important to assess motor and sensory function to differentiate neurologic from orthopedic conditions. Deep tendon reflexes and lower extremity motor strength and sensory capabilities also need careful assessment.¹³ Sensation in the region of the cauda equinus requires further evaluation due to the possibility of cauda equinus compression. Hyperreflexia indicates an upper motor lesion, whereas hyporeflexia indicates a lower motor lesion—neither of which would be expected in spondylolisthesis or spondylolysis.

A patient with any positive neurologic signs should be referred to a neurologic specialist.

Diagnostic TESTING
Unfortunately, rigorous comparative research is lacking on which to base clinical practice guidelines for diagnosis (as well as treatment) of spondylolysis and spondylolisthesis.¹⁸ Nevertheless, current standards call for a detailed physical examination as an effective diagnostic tool and recommend radiologic evaluation for a definitive diagnosis.^17,18 Lateral radiographs are also useful for identifying the degree of vertebral slippage when spondylolisthesis is diagnosed.¹⁷ The specialist may choose to utilize such diagnostic modalities as CT, single-photon-emission CT (SPECT), or MRI.

Radiologic evaluation
For complete radiologic evaluation, four x-ray views of the spine are necessary: anterior-posterior (AP), lateral, and bilateral oblique views. A fracture seen in the pars interarticularis is called the Scotty dog sign because it looks like a collar around the neck of a Scottish terrier (see Figures 2 and 3).²

Since treatment for nonspecific back pain and spondylolysis is essentially the same, it could be argued that radiographic imaging to confirm the clinical diagnosis exposes the patient to unnecessary radiation (a particular concern in the pediatric population). But a definitive diagnosis also rules out other pathologies that would require more aggressive treatment.

If x-rays reveal abnormalities, refer the patient to an orthopedic specialist for further evaluation. Referral to orthopedics should also be prompted if spondylolysis or spondylolisthesis is suspected but x-rays are insufficient to make the diagnosis.

CT and SPECT
Standaert and Herring suggest that CT combined with SPECT is the standard for diagnosis of a pars interarticularis lesion¹; in many reported cases, CT test results may be negative even when SPECT results are abnormal, suggesting that both studies are needed. In other cases, CT can help identify the origin of an abnormality seen on SPECT.

The disadvantage to using both modalities is that the patient is exposed to additional ionizing radiation. If only one method is to be used, SPECT may be preferred; it exposes the patient to less ionizing radiation and seldom requires sedation.¹⁹

Magnetic resonance imaging
In terms of radiation exposure, MRI is preferred to CT and SPECT because it does not utilize ionizing radiation; unfortunately, it is also less effective at detection of spondylolysis and spondylolisthesis. A review of the literature indicates that MRI is not as sensitive as SPECT in identifying stress on the pars interarticularis.^16,19

In general, MRI is superior for visualizing soft tissue pathology (eg, disk disease, nerve root compression, inflammation), while CT is superior for visualization of bone. In the context of back pain, MRI may be informative when etiologies other than spondylolysis and spondylolisthesis are suspected; Feldman et al recommend MRI for patients with constant back pain, radicular pain, nighttime pain, and/or abnormal neurologic examination results.¹⁶

The advantages and disadvantages of x-rays, SPECT, CT, and MRI for the diagnosis of spondy­lolysis and spondylolisthesis are summarized in ­Table 2.^{1,15,16,18,19}

Laboratory studies
There are no laboratory tests to confirm the diagnosis of spondylolysis or spondylolisthesis. To eliminate other diagnoses, however, it is appropriate to order certain laboratory tests. In addition to radiographs, Bernstein and Cozen recommend a complete blood count, an erythrocyte sedimentation rate, and a C-reactive protein test as part of the diagnostic work-up if the history and physical are suspicious for underlying pathology, such as infection.¹³

Management and Treatment Options
Treatment for spondylolysis or spondylolisthesis ranges from basic strengthening programs to surgical intervention and is based on the severity of the patient’s condition. The goal is to alleviate symptoms and facilitate a return to normal activities. Treatment should be individualized based on the patient’s age, athletic level and demands, and severity of symptoms.¹⁰

Nonsurgical treatment
Conservative treatment options include rest, physical therapy, core strengthening, and antilordotic bracing for several months (eg, eight to 12 weeks).⁵ Most grade 1 and 2 cases can be successfully treated nonsurgically.

Studies of nonsurgical treatment of children and young adults with spondylolysis and/or mild spondylolisthesis (up to 25% slippage) were evaluated in a meta-analysis.²⁰ The authors found that approximately 84% of such patients were pain free or nearly pain free with unrestricted activities within one year of treatment. While nonsurgical treatment does not usually resolve the pars interarticularis defect, it alleviates symptoms and enables the patient’s return to unrestricted activities. Further, the authors found no significant difference in outcomes between patients who were treated with or without bracing.²⁰  

In contrast, another study demonstrated that patients who wore braces achieved higher functional outcomes than those who did not.²¹ However, the patients who were braced were restricted from physical activity longer than were those who were not braced, so it could not be definitively determined if bracing or additional rest was the reason for the improved outcomes.

A significant limitation of bracing is that it is a restrictive and sometimes uncomfortable treatment, especially for an active child or adolescent. If clinicians can treat these patients effectively without bracing, greater compliance with treatment may result.

This study also found a strong correlation between early intervention and an increased incidence of bony healing. The researchers recommend the early use of sensitive diagnostic imaging so that treatment can begin early, increasing the possibility that the fracture will heal.²⁰

Skeletally immature patients should be followed clinically at six-month to one-year intervals, including use of lateral x-rays for spinal evaluation, to ensure that progressive spondylolisthesis does not develop. Once skeletal development is complete, follow-up is no longer necessary because progressive spondylolisthesis is unlikely at or near skeletal maturity.¹⁰

Surgical treatment
When conservative treatment fails to alleviate the pediatric patient’s pain, if daily functioning is impaired, or if the spondylolisthesis is of a more severe grade or progresses, surgical correction to repair the pars interarticularis defect or laminectomy and spinal fusion may be necessary.⁵ Adolescent patients treated surgically are likely to have good long-term results but may still experience symptoms, including back pain, into adulthood.²² The procedure used in a particular case depends on the degree of severity and the patient’s specific presentation.

PRIMARY CARE IS KEY
As stated earlier, referral to an orthopedic specialist is indicated when spondylolysis or spondylolisthesis is suspected or confirmed or to a neurologic specialist when any neurologic signs are positive or deficits are noted. In these instances, the primary care clinician is key to early diagnosis and prompt treatment.

Primary health care practitioners are in a position to contribute to the management of spondylolysis or spondylolisthesis in a way that will help facilitate a full recovery. For example, the patient and parent or guardian should be counseled about the need for the child to refrain from athletic activity while awaiting an orthopedic or neurologic evaluation. Restriction of activity will prevent exacerbation of the injury and increased pain. Suggest OTC NSAIDs, taken with food to prevent gastrointestinal adverse effects, for pain relief.¹³

It can also be helpful to assess the patient’s psychosocial status to determine whether he or she might face barriers to recovery. Often a major obstacle in treating these conditions is pressure from parents, coaches, or the patients themselves to continue athletic activities despite pain and injury.

Clinicians can offer support by reinforcing the message that limiting physical activity is essential to recovery; it should not be compromised because of patient, parental, coach, or peer pressure. At the same time, it is important to recognize that a leave of absence from a competitive sport, no matter how short, can affect the patient’s mental health. If the patient feels angry or depressed about the diagnosis, mental health counseling options can be discussed.

Educating patients and parents about the numerous treatments for acute low back pain that have been proven to offer little benefit can be informative and reassuring. For example, adding spinal manipulation and chiropractic techniques to established medical treatments does not improve outcomes. Neither does the use of oral corticosteroids, acupuncture, massage, traction, or exercise programs. Bed rest should be avoided.²³

Conclusion
In the primary care setting, low back pain is a common complaint with an extensive differential diagnosis. If a thorough history and physical examination prompt suspicion for spondylolysis or spondylolisthesis, x-rays will usually confirm the diagnosis. If the patient is referred to an orthopedic specialist, the primary care clinician can supplement and reinforce the treatment plan through patient and parent education about the diagnosis and its treatment. Compliance with conservative nonsurgical treatment may enable the patient to make a speedier return to his or her usual physical activities.

The authors would like to thank Jennifer Tareco, MD, and Robert More, MD, for their revisions and support in the completion of this article.

---

CE/CME No: CR-1410

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES

•  Identify risk factors for the development of spondylolysis and spondylolisthesis
•  Discuss the differential diagnoses associated with low back pain
•  Describe physical examination findings consistent with spondylolysis and spondylolisthesis
•  List the imaging modalities that may be used to confirm these diagnoses and explain the indications for each
•  Identify when a pediatric patient with low back pain should be referred to an orthopedic or neurologic specialist for further evaluation and treatment

FACULTY

Shannon P. More is a pediatric nurse practitioner in New York City. Rita Marie John is a Professor at the Columbia University School of Nursing in New York City. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of October 2014. 

Article begins on next page >>

 

The most common causes of low back pain in adolescents, spondylolysis and spondylolisthesis can be tricky to diagnose. The primary care clinician plays a key role in optimal management so that full recovery, in most cases, is achieved.

Spondylolysis, the most common cause of low back pain in adolescents, occurs in approximately 8% to 14% of adolescent athletes.1 It is estimated that 15% to 25% of patients with spondylolysis will develop spondylolisthesis.2 This article discusses the definitions, pathophysiology, risk factors, differential diagnosis, and clinical presentation of spondylolysis and spondylolisthesis, including a review of diagnostic imaging, treatment, and the primary care clinician’s role in the optimal management of affected patients.

Spondylolysis is a congenital or acquired unilateral or bilateral defect in the portion of a vertebra—usually L5—called the pars interarticularis, the bony area between the superior and inferior articulating facets (see Figure 1a). Recurrent trauma, such as repeated flexion, hyperextension, or twisting, can weaken the pars interarticularis. During these movements, the inferior articular process of the cranial (upper) vertebra can come into contact with the pars interarticularis of the caudal (lower) vertebra. When this happens repeatedly, a stress reaction may occur in the pars interarticularis, which can result in a stress or complete nonunion fracture.

The paraspinal muscles around the lumbar spine may adjust to accommodate the weakened vertebra, resulting in postural alterations. This can predispose patients to further spinal injury because normal muscular control of that portion of the spine is impaired.³

When the break in the pars interarticularis causes slippage, or forward movement, of the upper vertebra (again, usually L5) over the vertebra (ie, S1) below it, spondylolisthesis occurs (see Figure 1b, above).^2,4  This happens more frequently with bilateral spondylolysis and is often associated with an adolescent growth spurt.⁵

Spondylolisthesis can manifest anywhere in the spine but is most common in the lumbosacral region, with most (71% to 95%) cases occurring at L5 and the remainder at L4.⁶ Some patients develop these conditions spontaneously through strenuous activity or injury; others are predisposed but remain asymptomatic until the condition is exacerbated through athletic activities.

 Wiltse first described spondylolisthesis in 1962 and 10 years later published a classification system based on etiology and anatomy; his research is still used today as the basis for diagnosis.^7,8 The five types of spondylolisthesis are

• Type 1, dysplastic (congenital)
• Type 2, isthmic (defect in pars interarticularis)
• Type 3, degenerative (arthritic changes in older patients)
• Type 4, traumatic (acute injury)
• Type 5, pathologic (bone disease).⁸

Types 1 and 2 occur in pediatric patients, with 85% of such cases classified as type 2.⁴

The classification is further refined according to degree of severity, defined as the percentage of slippage of the upper over the lower vertebra. Grade 1 (first degree) entails a slippage of less than 25%; grade 2 (second degree), 26% to 50%; grade 3 (third degree), 51% to 75%; and grade 4 (fourth degree), greater than 75%.⁵

Risk Factors
In general, women are at greater risk for stress fractures than men are.⁹ Yet while pars interarticularis defects are twice as common in men as in women, women are more likely to progress to spondylolisthesis.¹⁰ Similarly, in patients with bilateral spondylolysis, women are significantly more likely than men (90.9% vs 66.2%) to develop spondylolisthesis.¹¹ In general, those who repetitively hyperextend the lower back (eg, football players, rowers, dancers, gymnasts, soccer players, swimmers) are at increased risk for both spondylolysis and spondylolisthesis.

While a patient’s activities and environmental stressors play a role in the development of spondylolysis and spondylolisthesis, a genetic predisposition is believed to be a factor as well: A five-fold increase in the incidence of defects of the pars interarticularis has been noted in near relatives of patients with spondylolisthesis.⁷ In addition, patients with conditions such as spina bifida occulta, severe scoliosis, and osteogenesis imperfecta are at increased risk for these conditions.^6,12

Differential DiagnosIs
Both spondylolysis and spondylolisthesis manifest as low back pain, for which the differential diagnosis is extensive. Pathologic causes of low back pain are much less common than causes related to structural weakness or trauma; however, carefully differentiating these is important so that pathology is identified promptly and treated appropriately.¹³

The differential diagnosis for low back pain in pediatric patients, by type of pain, includes

• Pain at night or with fever or other generalized symptoms: tumor or infection
• Acute pain: herniated disk, slipped apophysis, spondylolysis, vertebral fracture, or muscle strain
• Chronic pain: Scheuermann kyphosis, inflammatory spondyloarthropathies, or psychological problems
• Pain with spinal forward flexion: herniated disk or slipped apophysis
• Pain with spinal extension: spondylolysis, spondylolisthesis, or lesion or injury in the pedicle or lamina (posterior arch)
• Pain with recent-onset scoliosis: tumor, infection, herniated disk, syrinx, or idiopathic scoliosis
• Other pain: pyelonephritis or sickle cell crisis.¹³

Clinical Presentation
A systematic approach to a patient with a chief concern of low back pain is recommended. An initial assessment of the patient’s vital signs and growth parameters should be compared to those from previous visits to determine if there have been any changes in the usual pattern.

History
Use the standard HEEADSSS (Home, Education, Eating, Activities, Drugs, Sexuality, Suicide, Safety) adolescent psychosocial assessment as part of the patient history.¹⁴ In particular, focus on details about the physical activities and sports in which the patient participates and obtain data on the amount of time spent on each. When taking the family history, pay particular attention to any predisposition to musculoskeletal disorders. In the review of systems, note any history of traumatic injury.

Next, ask the patient to point with one finger to the location at which the pain is felt; in spondylolysis and spondylolisthesis, pain localizes to the waist. Obtain a detailed history of the pain, including onset, duration, frequency, location, and all alleviating or exacerbating factors.¹⁵

Physical examination
A brief summary of key features to assess during the physical examination is presented in Table 1. When completing the physical assessment, follow the typical head-to-toe approach, with special attention to evaluation of the presenting back pain.

Visual inspection. A visual inspection of the spine for scoliosis and kyphosis is key; also be sure to examine posture, assess symmetry, and observe for any midline defects.¹³ Hemangiomas, a line of hairy patches, or other abnormal markings along the body’s vertical axis may suggest an intraspinal anomaly.

Palpation. The entire spine should be palpated to confirm the location of the pain as identified by the patient. In particular, note if tenderness is felt over bony structures of the spine or in the paraspinal musculature.

Range of motion. After the locus of the pain is confirmed, instruct the patient to flex and extend the spine to assess for worsening pain. If noted, this finding is pathognomonic for spondylolysis and spondylolisthesis.¹³

Also useful for making the diagnosis is the one-leg hyperextension test, in which the patient is asked to raise one leg off the ground and lean backward. Pain elicited during this movement is indicative of back injury, including spondylolysis or spondylolisthesis. A positive result with the one-leg hyperextension test alone, however, is not a clinical marker for spondylolysis. Not only may the test elicit pain stemming from other pathologies, but the results are dependent on the patient’s subjective reporting of pain.¹⁶

Muscular signs and symptoms. Hamstring tightness is present in 80% of symptomatic patients.⁵ Consequently, the patient may have a somewhat waddling gait due to the inability to flex the hips and extend the knee simultaneously. For this reason, physical examination for spondylolysis and spondylolisthesis includes gait assessment. Other clinical signs of spondylolisthesis include a weak and drooping abdominal wall, paravertebral muscle hypertrophy, increased lumbar lordosis, hamstring muscle spasm, and pain during lateral trunk flexion/extension and double leg raising.¹⁷

Motor and sensory function. It is important to assess motor and sensory function to differentiate neurologic from orthopedic conditions. Deep tendon reflexes and lower extremity motor strength and sensory capabilities also need careful assessment.¹³ Sensation in the region of the cauda equinus requires further evaluation due to the possibility of cauda equinus compression. Hyperreflexia indicates an upper motor lesion, whereas hyporeflexia indicates a lower motor lesion—neither of which would be expected in spondylolisthesis or spondylolysis.

A patient with any positive neurologic signs should be referred to a neurologic specialist.

Diagnostic TESTING
Unfortunately, rigorous comparative research is lacking on which to base clinical practice guidelines for diagnosis (as well as treatment) of spondylolysis and spondylolisthesis.¹⁸ Nevertheless, current standards call for a detailed physical examination as an effective diagnostic tool and recommend radiologic evaluation for a definitive diagnosis.^17,18 Lateral radiographs are also useful for identifying the degree of vertebral slippage when spondylolisthesis is diagnosed.¹⁷ The specialist may choose to utilize such diagnostic modalities as CT, single-photon-emission CT (SPECT), or MRI.

Radiologic evaluation
For complete radiologic evaluation, four x-ray views of the spine are necessary: anterior-posterior (AP), lateral, and bilateral oblique views. A fracture seen in the pars interarticularis is called the Scotty dog sign because it looks like a collar around the neck of a Scottish terrier (see Figures 2 and 3).²

Since treatment for nonspecific back pain and spondylolysis is essentially the same, it could be argued that radiographic imaging to confirm the clinical diagnosis exposes the patient to unnecessary radiation (a particular concern in the pediatric population). But a definitive diagnosis also rules out other pathologies that would require more aggressive treatment.

If x-rays reveal abnormalities, refer the patient to an orthopedic specialist for further evaluation. Referral to orthopedics should also be prompted if spondylolysis or spondylolisthesis is suspected but x-rays are insufficient to make the diagnosis.

CT and SPECT
Standaert and Herring suggest that CT combined with SPECT is the standard for diagnosis of a pars interarticularis lesion¹; in many reported cases, CT test results may be negative even when SPECT results are abnormal, suggesting that both studies are needed. In other cases, CT can help identify the origin of an abnormality seen on SPECT.

The disadvantage to using both modalities is that the patient is exposed to additional ionizing radiation. If only one method is to be used, SPECT may be preferred; it exposes the patient to less ionizing radiation and seldom requires sedation.¹⁹

Magnetic resonance imaging
In terms of radiation exposure, MRI is preferred to CT and SPECT because it does not utilize ionizing radiation; unfortunately, it is also less effective at detection of spondylolysis and spondylolisthesis. A review of the literature indicates that MRI is not as sensitive as SPECT in identifying stress on the pars interarticularis.^16,19

In general, MRI is superior for visualizing soft tissue pathology (eg, disk disease, nerve root compression, inflammation), while CT is superior for visualization of bone. In the context of back pain, MRI may be informative when etiologies other than spondylolysis and spondylolisthesis are suspected; Feldman et al recommend MRI for patients with constant back pain, radicular pain, nighttime pain, and/or abnormal neurologic examination results.¹⁶

The advantages and disadvantages of x-rays, SPECT, CT, and MRI for the diagnosis of spondy­lolysis and spondylolisthesis are summarized in ­Table 2.^{1,15,16,18,19}

Laboratory studies
There are no laboratory tests to confirm the diagnosis of spondylolysis or spondylolisthesis. To eliminate other diagnoses, however, it is appropriate to order certain laboratory tests. In addition to radiographs, Bernstein and Cozen recommend a complete blood count, an erythrocyte sedimentation rate, and a C-reactive protein test as part of the diagnostic work-up if the history and physical are suspicious for underlying pathology, such as infection.¹³

Management and Treatment Options
Treatment for spondylolysis or spondylolisthesis ranges from basic strengthening programs to surgical intervention and is based on the severity of the patient’s condition. The goal is to alleviate symptoms and facilitate a return to normal activities. Treatment should be individualized based on the patient’s age, athletic level and demands, and severity of symptoms.¹⁰

Nonsurgical treatment
Conservative treatment options include rest, physical therapy, core strengthening, and antilordotic bracing for several months (eg, eight to 12 weeks).⁵ Most grade 1 and 2 cases can be successfully treated nonsurgically.

Studies of nonsurgical treatment of children and young adults with spondylolysis and/or mild spondylolisthesis (up to 25% slippage) were evaluated in a meta-analysis.²⁰ The authors found that approximately 84% of such patients were pain free or nearly pain free with unrestricted activities within one year of treatment. While nonsurgical treatment does not usually resolve the pars interarticularis defect, it alleviates symptoms and enables the patient’s return to unrestricted activities. Further, the authors found no significant difference in outcomes between patients who were treated with or without bracing.²⁰  

In contrast, another study demonstrated that patients who wore braces achieved higher functional outcomes than those who did not.²¹ However, the patients who were braced were restricted from physical activity longer than were those who were not braced, so it could not be definitively determined if bracing or additional rest was the reason for the improved outcomes.

A significant limitation of bracing is that it is a restrictive and sometimes uncomfortable treatment, especially for an active child or adolescent. If clinicians can treat these patients effectively without bracing, greater compliance with treatment may result.

This study also found a strong correlation between early intervention and an increased incidence of bony healing. The researchers recommend the early use of sensitive diagnostic imaging so that treatment can begin early, increasing the possibility that the fracture will heal.²⁰

Skeletally immature patients should be followed clinically at six-month to one-year intervals, including use of lateral x-rays for spinal evaluation, to ensure that progressive spondylolisthesis does not develop. Once skeletal development is complete, follow-up is no longer necessary because progressive spondylolisthesis is unlikely at or near skeletal maturity.¹⁰

Surgical treatment
When conservative treatment fails to alleviate the pediatric patient’s pain, if daily functioning is impaired, or if the spondylolisthesis is of a more severe grade or progresses, surgical correction to repair the pars interarticularis defect or laminectomy and spinal fusion may be necessary.⁵ Adolescent patients treated surgically are likely to have good long-term results but may still experience symptoms, including back pain, into adulthood.²² The procedure used in a particular case depends on the degree of severity and the patient’s specific presentation.

PRIMARY CARE IS KEY
As stated earlier, referral to an orthopedic specialist is indicated when spondylolysis or spondylolisthesis is suspected or confirmed or to a neurologic specialist when any neurologic signs are positive or deficits are noted. In these instances, the primary care clinician is key to early diagnosis and prompt treatment.

Primary health care practitioners are in a position to contribute to the management of spondylolysis or spondylolisthesis in a way that will help facilitate a full recovery. For example, the patient and parent or guardian should be counseled about the need for the child to refrain from athletic activity while awaiting an orthopedic or neurologic evaluation. Restriction of activity will prevent exacerbation of the injury and increased pain. Suggest OTC NSAIDs, taken with food to prevent gastrointestinal adverse effects, for pain relief.¹³

It can also be helpful to assess the patient’s psychosocial status to determine whether he or she might face barriers to recovery. Often a major obstacle in treating these conditions is pressure from parents, coaches, or the patients themselves to continue athletic activities despite pain and injury.

Clinicians can offer support by reinforcing the message that limiting physical activity is essential to recovery; it should not be compromised because of patient, parental, coach, or peer pressure. At the same time, it is important to recognize that a leave of absence from a competitive sport, no matter how short, can affect the patient’s mental health. If the patient feels angry or depressed about the diagnosis, mental health counseling options can be discussed.

Educating patients and parents about the numerous treatments for acute low back pain that have been proven to offer little benefit can be informative and reassuring. For example, adding spinal manipulation and chiropractic techniques to established medical treatments does not improve outcomes. Neither does the use of oral corticosteroids, acupuncture, massage, traction, or exercise programs. Bed rest should be avoided.²³

Conclusion
In the primary care setting, low back pain is a common complaint with an extensive differential diagnosis. If a thorough history and physical examination prompt suspicion for spondylolysis or spondylolisthesis, x-rays will usually confirm the diagnosis. If the patient is referred to an orthopedic specialist, the primary care clinician can supplement and reinforce the treatment plan through patient and parent education about the diagnosis and its treatment. Compliance with conservative nonsurgical treatment may enable the patient to make a speedier return to his or her usual physical activities.

The authors would like to thank Jennifer Tareco, MD, and Robert More, MD, for their revisions and support in the completion of this article.

---

CE/CME No: CR-1410

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES

•  Identify risk factors for the development of spondylolysis and spondylolisthesis
•  Discuss the differential diagnoses associated with low back pain
•  Describe physical examination findings consistent with spondylolysis and spondylolisthesis
•  List the imaging modalities that may be used to confirm these diagnoses and explain the indications for each
•  Identify when a pediatric patient with low back pain should be referred to an orthopedic or neurologic specialist for further evaluation and treatment

FACULTY

Shannon P. More is a pediatric nurse practitioner in New York City. Rita Marie John is a Professor at the Columbia University School of Nursing in New York City. The authors have no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of October 2014. 

Article begins on next page >>

 

The most common causes of low back pain in adolescents, spondylolysis and spondylolisthesis can be tricky to diagnose. The primary care clinician plays a key role in optimal management so that full recovery, in most cases, is achieved.

Spondylolysis, the most common cause of low back pain in adolescents, occurs in approximately 8% to 14% of adolescent athletes.1 It is estimated that 15% to 25% of patients with spondylolysis will develop spondylolisthesis.2 This article discusses the definitions, pathophysiology, risk factors, differential diagnosis, and clinical presentation of spondylolysis and spondylolisthesis, including a review of diagnostic imaging, treatment, and the primary care clinician’s role in the optimal management of affected patients.

Spondylolysis is a congenital or acquired unilateral or bilateral defect in the portion of a vertebra—usually L5—called the pars interarticularis, the bony area between the superior and inferior articulating facets (see Figure 1a). Recurrent trauma, such as repeated flexion, hyperextension, or twisting, can weaken the pars interarticularis. During these movements, the inferior articular process of the cranial (upper) vertebra can come into contact with the pars interarticularis of the caudal (lower) vertebra. When this happens repeatedly, a stress reaction may occur in the pars interarticularis, which can result in a stress or complete nonunion fracture.

The paraspinal muscles around the lumbar spine may adjust to accommodate the weakened vertebra, resulting in postural alterations. This can predispose patients to further spinal injury because normal muscular control of that portion of the spine is impaired.³

When the break in the pars interarticularis causes slippage, or forward movement, of the upper vertebra (again, usually L5) over the vertebra (ie, S1) below it, spondylolisthesis occurs (see Figure 1b, above).^2,4  This happens more frequently with bilateral spondylolysis and is often associated with an adolescent growth spurt.⁵

Spondylolisthesis can manifest anywhere in the spine but is most common in the lumbosacral region, with most (71% to 95%) cases occurring at L5 and the remainder at L4.⁶ Some patients develop these conditions spontaneously through strenuous activity or injury; others are predisposed but remain asymptomatic until the condition is exacerbated through athletic activities.

 Wiltse first described spondylolisthesis in 1962 and 10 years later published a classification system based on etiology and anatomy; his research is still used today as the basis for diagnosis.^7,8 The five types of spondylolisthesis are

• Type 1, dysplastic (congenital)
• Type 2, isthmic (defect in pars interarticularis)
• Type 3, degenerative (arthritic changes in older patients)
• Type 4, traumatic (acute injury)
• Type 5, pathologic (bone disease).⁸

Types 1 and 2 occur in pediatric patients, with 85% of such cases classified as type 2.⁴

The classification is further refined according to degree of severity, defined as the percentage of slippage of the upper over the lower vertebra. Grade 1 (first degree) entails a slippage of less than 25%; grade 2 (second degree), 26% to 50%; grade 3 (third degree), 51% to 75%; and grade 4 (fourth degree), greater than 75%.⁵

Risk Factors
In general, women are at greater risk for stress fractures than men are.⁹ Yet while pars interarticularis defects are twice as common in men as in women, women are more likely to progress to spondylolisthesis.¹⁰ Similarly, in patients with bilateral spondylolysis, women are significantly more likely than men (90.9% vs 66.2%) to develop spondylolisthesis.¹¹ In general, those who repetitively hyperextend the lower back (eg, football players, rowers, dancers, gymnasts, soccer players, swimmers) are at increased risk for both spondylolysis and spondylolisthesis.

While a patient’s activities and environmental stressors play a role in the development of spondylolysis and spondylolisthesis, a genetic predisposition is believed to be a factor as well: A five-fold increase in the incidence of defects of the pars interarticularis has been noted in near relatives of patients with spondylolisthesis.⁷ In addition, patients with conditions such as spina bifida occulta, severe scoliosis, and osteogenesis imperfecta are at increased risk for these conditions.^6,12

Differential DiagnosIs
Both spondylolysis and spondylolisthesis manifest as low back pain, for which the differential diagnosis is extensive. Pathologic causes of low back pain are much less common than causes related to structural weakness or trauma; however, carefully differentiating these is important so that pathology is identified promptly and treated appropriately.¹³

The differential diagnosis for low back pain in pediatric patients, by type of pain, includes

• Pain at night or with fever or other generalized symptoms: tumor or infection
• Acute pain: herniated disk, slipped apophysis, spondylolysis, vertebral fracture, or muscle strain
• Chronic pain: Scheuermann kyphosis, inflammatory spondyloarthropathies, or psychological problems
• Pain with spinal forward flexion: herniated disk or slipped apophysis
• Pain with spinal extension: spondylolysis, spondylolisthesis, or lesion or injury in the pedicle or lamina (posterior arch)
• Pain with recent-onset scoliosis: tumor, infection, herniated disk, syrinx, or idiopathic scoliosis
• Other pain: pyelonephritis or sickle cell crisis.¹³

Clinical Presentation
A systematic approach to a patient with a chief concern of low back pain is recommended. An initial assessment of the patient’s vital signs and growth parameters should be compared to those from previous visits to determine if there have been any changes in the usual pattern.

History
Use the standard HEEADSSS (Home, Education, Eating, Activities, Drugs, Sexuality, Suicide, Safety) adolescent psychosocial assessment as part of the patient history.¹⁴ In particular, focus on details about the physical activities and sports in which the patient participates and obtain data on the amount of time spent on each. When taking the family history, pay particular attention to any predisposition to musculoskeletal disorders. In the review of systems, note any history of traumatic injury.

Next, ask the patient to point with one finger to the location at which the pain is felt; in spondylolysis and spondylolisthesis, pain localizes to the waist. Obtain a detailed history of the pain, including onset, duration, frequency, location, and all alleviating or exacerbating factors.¹⁵

Physical examination
A brief summary of key features to assess during the physical examination is presented in Table 1. When completing the physical assessment, follow the typical head-to-toe approach, with special attention to evaluation of the presenting back pain.

Visual inspection. A visual inspection of the spine for scoliosis and kyphosis is key; also be sure to examine posture, assess symmetry, and observe for any midline defects.¹³ Hemangiomas, a line of hairy patches, or other abnormal markings along the body’s vertical axis may suggest an intraspinal anomaly.

Palpation. The entire spine should be palpated to confirm the location of the pain as identified by the patient. In particular, note if tenderness is felt over bony structures of the spine or in the paraspinal musculature.

Range of motion. After the locus of the pain is confirmed, instruct the patient to flex and extend the spine to assess for worsening pain. If noted, this finding is pathognomonic for spondylolysis and spondylolisthesis.¹³

Also useful for making the diagnosis is the one-leg hyperextension test, in which the patient is asked to raise one leg off the ground and lean backward. Pain elicited during this movement is indicative of back injury, including spondylolysis or spondylolisthesis. A positive result with the one-leg hyperextension test alone, however, is not a clinical marker for spondylolysis. Not only may the test elicit pain stemming from other pathologies, but the results are dependent on the patient’s subjective reporting of pain.¹⁶

Muscular signs and symptoms. Hamstring tightness is present in 80% of symptomatic patients.⁵ Consequently, the patient may have a somewhat waddling gait due to the inability to flex the hips and extend the knee simultaneously. For this reason, physical examination for spondylolysis and spondylolisthesis includes gait assessment. Other clinical signs of spondylolisthesis include a weak and drooping abdominal wall, paravertebral muscle hypertrophy, increased lumbar lordosis, hamstring muscle spasm, and pain during lateral trunk flexion/extension and double leg raising.¹⁷

Motor and sensory function. It is important to assess motor and sensory function to differentiate neurologic from orthopedic conditions. Deep tendon reflexes and lower extremity motor strength and sensory capabilities also need careful assessment.¹³ Sensation in the region of the cauda equinus requires further evaluation due to the possibility of cauda equinus compression. Hyperreflexia indicates an upper motor lesion, whereas hyporeflexia indicates a lower motor lesion—neither of which would be expected in spondylolisthesis or spondylolysis.

A patient with any positive neurologic signs should be referred to a neurologic specialist.

Diagnostic TESTING
Unfortunately, rigorous comparative research is lacking on which to base clinical practice guidelines for diagnosis (as well as treatment) of spondylolysis and spondylolisthesis.¹⁸ Nevertheless, current standards call for a detailed physical examination as an effective diagnostic tool and recommend radiologic evaluation for a definitive diagnosis.^17,18 Lateral radiographs are also useful for identifying the degree of vertebral slippage when spondylolisthesis is diagnosed.¹⁷ The specialist may choose to utilize such diagnostic modalities as CT, single-photon-emission CT (SPECT), or MRI.

Radiologic evaluation
For complete radiologic evaluation, four x-ray views of the spine are necessary: anterior-posterior (AP), lateral, and bilateral oblique views. A fracture seen in the pars interarticularis is called the Scotty dog sign because it looks like a collar around the neck of a Scottish terrier (see Figures 2 and 3).²

Since treatment for nonspecific back pain and spondylolysis is essentially the same, it could be argued that radiographic imaging to confirm the clinical diagnosis exposes the patient to unnecessary radiation (a particular concern in the pediatric population). But a definitive diagnosis also rules out other pathologies that would require more aggressive treatment.

If x-rays reveal abnormalities, refer the patient to an orthopedic specialist for further evaluation. Referral to orthopedics should also be prompted if spondylolysis or spondylolisthesis is suspected but x-rays are insufficient to make the diagnosis.

CT and SPECT
Standaert and Herring suggest that CT combined with SPECT is the standard for diagnosis of a pars interarticularis lesion¹; in many reported cases, CT test results may be negative even when SPECT results are abnormal, suggesting that both studies are needed. In other cases, CT can help identify the origin of an abnormality seen on SPECT.

The disadvantage to using both modalities is that the patient is exposed to additional ionizing radiation. If only one method is to be used, SPECT may be preferred; it exposes the patient to less ionizing radiation and seldom requires sedation.¹⁹

Magnetic resonance imaging
In terms of radiation exposure, MRI is preferred to CT and SPECT because it does not utilize ionizing radiation; unfortunately, it is also less effective at detection of spondylolysis and spondylolisthesis. A review of the literature indicates that MRI is not as sensitive as SPECT in identifying stress on the pars interarticularis.^16,19

In general, MRI is superior for visualizing soft tissue pathology (eg, disk disease, nerve root compression, inflammation), while CT is superior for visualization of bone. In the context of back pain, MRI may be informative when etiologies other than spondylolysis and spondylolisthesis are suspected; Feldman et al recommend MRI for patients with constant back pain, radicular pain, nighttime pain, and/or abnormal neurologic examination results.¹⁶

The advantages and disadvantages of x-rays, SPECT, CT, and MRI for the diagnosis of spondy­lolysis and spondylolisthesis are summarized in ­Table 2.^{1,15,16,18,19}

Laboratory studies
There are no laboratory tests to confirm the diagnosis of spondylolysis or spondylolisthesis. To eliminate other diagnoses, however, it is appropriate to order certain laboratory tests. In addition to radiographs, Bernstein and Cozen recommend a complete blood count, an erythrocyte sedimentation rate, and a C-reactive protein test as part of the diagnostic work-up if the history and physical are suspicious for underlying pathology, such as infection.¹³

Management and Treatment Options
Treatment for spondylolysis or spondylolisthesis ranges from basic strengthening programs to surgical intervention and is based on the severity of the patient’s condition. The goal is to alleviate symptoms and facilitate a return to normal activities. Treatment should be individualized based on the patient’s age, athletic level and demands, and severity of symptoms.¹⁰

Nonsurgical treatment
Conservative treatment options include rest, physical therapy, core strengthening, and antilordotic bracing for several months (eg, eight to 12 weeks).⁵ Most grade 1 and 2 cases can be successfully treated nonsurgically.

Studies of nonsurgical treatment of children and young adults with spondylolysis and/or mild spondylolisthesis (up to 25% slippage) were evaluated in a meta-analysis.²⁰ The authors found that approximately 84% of such patients were pain free or nearly pain free with unrestricted activities within one year of treatment. While nonsurgical treatment does not usually resolve the pars interarticularis defect, it alleviates symptoms and enables the patient’s return to unrestricted activities. Further, the authors found no significant difference in outcomes between patients who were treated with or without bracing.²⁰  

In contrast, another study demonstrated that patients who wore braces achieved higher functional outcomes than those who did not.²¹ However, the patients who were braced were restricted from physical activity longer than were those who were not braced, so it could not be definitively determined if bracing or additional rest was the reason for the improved outcomes.

A significant limitation of bracing is that it is a restrictive and sometimes uncomfortable treatment, especially for an active child or adolescent. If clinicians can treat these patients effectively without bracing, greater compliance with treatment may result.

This study also found a strong correlation between early intervention and an increased incidence of bony healing. The researchers recommend the early use of sensitive diagnostic imaging so that treatment can begin early, increasing the possibility that the fracture will heal.²⁰

Skeletally immature patients should be followed clinically at six-month to one-year intervals, including use of lateral x-rays for spinal evaluation, to ensure that progressive spondylolisthesis does not develop. Once skeletal development is complete, follow-up is no longer necessary because progressive spondylolisthesis is unlikely at or near skeletal maturity.¹⁰

Surgical treatment
When conservative treatment fails to alleviate the pediatric patient’s pain, if daily functioning is impaired, or if the spondylolisthesis is of a more severe grade or progresses, surgical correction to repair the pars interarticularis defect or laminectomy and spinal fusion may be necessary.⁵ Adolescent patients treated surgically are likely to have good long-term results but may still experience symptoms, including back pain, into adulthood.²² The procedure used in a particular case depends on the degree of severity and the patient’s specific presentation.

PRIMARY CARE IS KEY
As stated earlier, referral to an orthopedic specialist is indicated when spondylolysis or spondylolisthesis is suspected or confirmed or to a neurologic specialist when any neurologic signs are positive or deficits are noted. In these instances, the primary care clinician is key to early diagnosis and prompt treatment.

Primary health care practitioners are in a position to contribute to the management of spondylolysis or spondylolisthesis in a way that will help facilitate a full recovery. For example, the patient and parent or guardian should be counseled about the need for the child to refrain from athletic activity while awaiting an orthopedic or neurologic evaluation. Restriction of activity will prevent exacerbation of the injury and increased pain. Suggest OTC NSAIDs, taken with food to prevent gastrointestinal adverse effects, for pain relief.¹³

It can also be helpful to assess the patient’s psychosocial status to determine whether he or she might face barriers to recovery. Often a major obstacle in treating these conditions is pressure from parents, coaches, or the patients themselves to continue athletic activities despite pain and injury.

Clinicians can offer support by reinforcing the message that limiting physical activity is essential to recovery; it should not be compromised because of patient, parental, coach, or peer pressure. At the same time, it is important to recognize that a leave of absence from a competitive sport, no matter how short, can affect the patient’s mental health. If the patient feels angry or depressed about the diagnosis, mental health counseling options can be discussed.

Educating patients and parents about the numerous treatments for acute low back pain that have been proven to offer little benefit can be informative and reassuring. For example, adding spinal manipulation and chiropractic techniques to established medical treatments does not improve outcomes. Neither does the use of oral corticosteroids, acupuncture, massage, traction, or exercise programs. Bed rest should be avoided.²³

Conclusion
In the primary care setting, low back pain is a common complaint with an extensive differential diagnosis. If a thorough history and physical examination prompt suspicion for spondylolysis or spondylolisthesis, x-rays will usually confirm the diagnosis. If the patient is referred to an orthopedic specialist, the primary care clinician can supplement and reinforce the treatment plan through patient and parent education about the diagnosis and its treatment. Compliance with conservative nonsurgical treatment may enable the patient to make a speedier return to his or her usual physical activities.

The authors would like to thank Jennifer Tareco, MD, and Robert More, MD, for their revisions and support in the completion of this article.

---

CE/CME No: CR-1409

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Define the term concussion.
• Identify the major signs and symptoms of a concussion.
• Discuss the initial management of a pediatric patient with a suspected sports-related concussion.
• Describe the current recommendations for return to play after a pediatric concussion.
• Explain the main challenges clinicians face in the management of pediatric concussions

FACULTY
Sydney Meckler is pursuing her Doctor of Nursing Practice degree at Columbia University, New York City. The author has no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.25 hours of American Academy of Physician Assistants (AAPA) Category I CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of September 2014. 

Article begins on next page >>

 

 

This article describes the challenges of diagnosis and treatment of pediatric concussive injuries, with particular attention to the effects of concussion on the developing brain. It highlights the need for individualized, age-dependent care; standardized return-to-play and return-to-school protocols; and better-informed clinicians, parents, teachers, and coaches.

Pediatric concussions—those occurring in children younger than 18—account for almost half a million emergency department visits each year.¹ Of these, more than 25% occur during sports-related activities.² Yet it is believed that pediatric concussive injuries are significantly underreported because parents do not always seek medical attention for their concussed children and because little has been published on the management of sports-related concussions in pre–high-school-age athletes.²

The 4th International Consensus Conference on Concussion in Sport, the American Academy of Neurology, and the American Medical Society for Sports Medicine all recently updated their guidelines for concussion evaluation and management.^3-5 However, the lack of data on concussions in younger pediatric athletes presents challenges for the optimal management of these patients.⁶ In fact, in a February 2014 report, the Institute of Medicine said that more research is needed to develop evidence-based sports-related concussion management guidelines for children and adolescents.⁷

In this article, the factors that distinguish concussions in children from those in adults will be described, as will the management techniques that primary care clinicians can use to effectively address them.

WHAT IS A CONCUSSION?
Although the term concussion has been used interchangeably with head trauma and brain injury, concussion is most often described as mild traumatic brain injury (mTBI). Variations in terminology reflect both the lack of agreement on a standard definition for concussion, especially as it applies to the pediatric population, and the complexities of concussion diagnosis and management.⁸ This inherent ambiguity can lead to suboptimal recognition and awareness of concussion among clinicians, patients, families, school personnel, and sports staff, especially of its serious aftereffects in the pediatric patient.

A blow to the head can propel the brain to strike one side of the skull and then bounce off the opposite side. This can damage or tear the axons—the signal transmitters of the neurons—from their cell bodies, disrupting brain cell communications and causing neurocognitive deficits.

While a concussion is a direct injury to the brain, it is also an evolving process comprised of several pathophysiologic components that are a consequence of biomechanical forces. The brain does not directly contact the skull but is surrounded by cerebrospinal fluid and fluid-filled vessels with a greater density than the brain itself. This intracranial space provides room for the brain to move upon impact by shifting and compressing from one side of the skull to the other.⁹ The concussive injury occurs as a result of either a direct strike to the head or from an indirect force traumatic enough to be transmitted to the brain. The strike or force produces a complex disturbance to the brain that, in most cases, does not result in loss of consciousness.³

THE GREATER VULNERABILITY OF THE PEDIATRIC BRAIN
Pathophysiology
For a concussion to occur, the biomechanical threshold at which nerve cells' adaptability is impeded must be crossed.¹⁰ This sets in motion a cascade of events, developing over minutes, hours, and even days, in which homeostasis is disrupted due to an imbalance of ionic, neuronal, metabolic, and pathophysiologic processes.⁵

While many studies have sought to explain the pathophysiology of pediatric sports-related concussions, much is still unknown. One hypothesis suggests that, after the injury, neuronal depolarization occurs, releasing excitatory neurotransmitters and altering metabolism by the immediate release of potassium. Restoration of homeostasis demands response by the sodium-potassium pump, requiring energy in the form of glucose. Coupled with axonal injury and alterations in cerebral blood flow, an imbalance between energy supply and demand occurs.⁵

Maugans et al found that a single pediatric concussion does not cause a structural or metabolic injury but instead a physiologic interruption—different from what occurs in adult concussions.¹⁰ They observed a statistically significant reduction in cerebral blood flow of more than 10% in a small group of postconcussion children, ages 11 to 15, compared with a control group. This alteration persisted for two weeks in two-thirds of the children and for up to a month in the remaining third.¹⁰ The delayed return of normal cerebral blood flow is believed to be a major contributing factor to pediatric concussion-related symptoms. However, little is known about the long-term effects of concussion on the developing brain.⁹

Crucial developmental years
Because the pediatric brain is still developing, children between the ages of 5 and 12 are at greater risk for sustaining a disruption in brain function from a concussion. In addition, this group is more susceptible in general to sports injuries compared to adults, because of their stage of growth and development.¹¹

With a pediatric concussion, the individual child’s stage of brain development and the possible effects on his or her evolving neurocognitive functioning must be taken into account. Critical skills, such as language, emotion, memory, problem solving, and motor dexterity, emerge during childhood, and a disturbance during this time could have substantial consequences.¹² Motor skills and primary senses usually mature by age 5, with language maturity occurring by age 10.⁹ However, many other vital skills and processes, such as emotion, judgment, and abstract reasoning, are not fully developed until adulthood. As a result, damage to cortical areas of the brain, such as the parietal lobe and frontal areas—involved in fine motor skills and complex thinking—can hinder or delay the development of these necessary processes.⁹  

Many researchers suggest that, while a concussion to the developing brain may not significantly affect previously learned functions, it may notably delay development of new cognitive functions. As a result, recovery from a concussion during these years may be poorer.^2,9,12

On the next page: Clinical presentation and post injury evaluation >> 

 

CLINICAL PRESENTATION
Initial assessment of pediatric athletes with suspected concussive injuries can be particularly challenging because of the variability and evolving nature of associated signs and symptoms, resulting in a wide range of clinical presentations.³ These presenting signs and symptoms can, however, provide vital clues to the location of the injury within the brain because the consequences of concussion arise from injury to the brain’s cortical and subcortical systems (see Table 1).⁹

The cortical systems are located within the frontal, temporal, parietal, and occipital lobes, each of which houses control centers for specific learned skills and functions. The subcortical systems include the hypothalamus, trigeminal system, basal ganglia, and cerebellum. While a concussion most often causes diffuse harm rather than localized trauma, familiarity with the functions associated with specific brain locations aids in initial identification of the injury and allows for individualized concussion management.¹³

After a concussion occurs, it is essential to evaluate all domains of the child’s functioning through a comprehensive physical assessment, including a detailed concussion history and review of preinjury risk factors.³ In addition, there may be unobservable symptoms about which a child is unable to communicate due to his or her stage of emotional and cognitive development and restricted capacity to serve as a primary reporter.¹⁴  

Signs and symptoms
The four categories of concussion signs and symptoms include physical, cognitive, emotional, and sleep (see Table 2).¹⁵ A concussed patient may experience any variation or combination of these signs and symptoms.

It is important to recognize that, although loss of consciousness is a serious sign of a concussion, it occurs in only about 10% of concussive injuries.^5,15 In fact, current concussion guidelines no longer advocate the use of grading scales, which assessed the severity of a concussion based primarily on the presence or absence of a brief loss of consciousness. Evidence now shows that loss of consciousness does not predict clinical course or cognitive long-term impairment after a concussion.¹⁶

Duration of symptoms
The duration of concussion symptoms can vary, but in most cases symptoms last seven to 10 days, with 10% to 15% of patients reporting symptoms for more than 10 days.^3,5 While recovery duration has not been studied sufficiently in children younger than 15, younger children require longer recovery ­periods. The resolution of symptoms, however, does not necessarily correlate with absolute cognitive recovery.^5,17

Modifying and complicating factors
In addition to the patient’s presenting signs and symptoms, factors that may modify or complicate recovery from a concussion should be identified (see Table 3).³ These factors include preexisting conditions or disorders and the use of certain prescription drugs. Each factor should be assessed individually, taking into account the patient’s age.²

Some presenting symptoms may overlap with symptoms of common disorders in this group. It is important to note if symptoms of such conditions as attention-deficit/hyperactivity disorder (ADHD), sleep disorders, learning disabilities, and mood disorders were present prior to the concussion.⁵

Modifying factors provide essential information that can help predict the individual patient’s anti­cipated recovery process and must be taken into ­account throughout the process. They are particularly important when assessing the differences between a child’s preconcussion and postconcussion functioning.^3,4

POST INJURY EVALUATION OF COGNITIVE FUNCTIONING
Concussion is diagnosed clinically, based on the mechanism of the sustained injury, and is supported primarily by reported and observed signs and symptoms. The ability to systematically evaluate the patient for manifestations of concussion is essential to pediatric concussion management.^3,18

To aid in appropriately evaluating symptoms and assessing functional damage, many standardized assessment tools and neuropsychological tests have been developed. These tools have been modified for younger athletes due to differences in children’s neurocognitive development and in their ability to be symptom self-reporters.

Concussion assessment tools
The tools most commonly used to assess the effects of concussion in younger athletes are listed in Table 4. It was not until 2012, with the release of the Child Sport Concussion Assessment Tool Version 3 (Child-SCAT3), that an appropriately adapted and valid concussion assessment tool became available for children younger than 10.³

Assessment tools are useful but are not diagnostic. They do not take the place of a clinician’s thorough neurocognitive evaluation of a potentially concussed child.

Neuropsychologic testing
In order to properly manage pediatric concussions, postconcussion status must be assessed relative to preconcussion status in order to ensure optimal resolution of symptoms and cognitive recovery.¹⁹

The American Medical Society for Sports Medicine supports baseline testing for high-risk athletes, defined as those with a prior history of concussions or “confounding” conditions (learning disability, mood and attention disorders, migraine headaches).⁵ The International Consensus Statement on Concussion in Sport states that there is insufficient evidence to recommend routine baseline testing, but its early use after pediatric concussion may provide helpful information for determining when the child may return to school. The American Academy of Neurology suggests that clinicians “… might utilize baseline scores on concussion assessment tools, especially in younger athletes, those with prior concussions, or those with preexisting learning disabilities/ADHD, as doing so fosters better interpretation of postinjury scores.”⁴

Assessment tools can provide essential insight into the cognitive functional state of a concussed child athlete, even after symptom resolution.^3,5,20 They are not stand-alone measures of recovery but can be useful components of the pediatric concussion evaluation and management process and an aid to clinical decision making.^3,13    

Paper-and-pencil or computerized neuropsychologic tests provide objective measures of brain-behavior relationships and are more sensitive in detecting subtle cognitive impairments than a clinical examination.⁵ Although neuropsychologic testing has not been validated as a diagnostic tool, it may be useful for both baseline (preinjury) testing of athletes and for monitoring recovery from a concussive event.^5,20 (For more information on motor control assessment, see Dirks RP, McLeod TCV. Sport-related mild traumatic brain injury. Clinician Reviews. 2008;18[9]:22. http://bit.ly/1mjizIa.)

On the next page: Postconcussion management >>

 

POSTCONCUSSION MANAGEMENT
All concussion management guidelines concur that immediate removal from play of a pediatric athlete with a suspected concussion is the most important initial action. Regardless of how short the duration or mild the symptoms may be, same-day return to play should never occur.^3-5 This is particularly true because acute concussion is an evolving injury and manifestation of symptoms, including cognitive deficits, is often delayed.³

The foundation of postconcussion recovery is rest, both physical and cognitive. Acute symptoms must diminish before a gradual resumption of activities.^3,5

Cognitive rest
Cognitive rest is the cornerstone of concussion management.⁵ The latest guidelines stress the importance, particularly in the pediatric age-group, of decreasing any activities of daily living that may aggravate symptoms.³ This includes such common childhood pastimes as playing video games, watching television, and using a computer.¹⁵ More important, cognitive rest means academic rest, which is essential to postconcussion recovery and preparing the child for a “return to school” or “return to learn.”^{21, 22}

Return to play
In pediatric concussion management, a conservative approach to the determination of when a concussed child may return to play (RTP) is key. RTP decisions are guided by the resolution of the child’s symptoms and are based on clinical judgment.^3-5

Current guidelines outline a gradual, stepwise approach to RTP after full recovery, which must be individualized and age-appropriate.^3,5 These include

• Light aerobic exercise: Increase heart rate to 70% maximum predicted by walking, swimming, or using stationary bike. No resistance training.

• Sport-specific exercise: Add movement with skating or running drills. No head impact activities.

• Noncontact training drills: Add exercise, coordination, and cognitive load with progression to more complex training drills (eg, passing drills in football and ice hockey). May introduce progressive resistance training.

• Full contact practice: To restore confidence and allow coaching staff to assess functional skills, permit participation in normal training activities after obtaining medical clearance.

At any step, if symptoms develop with activity, the process is stopped and, after a 24-hour period of rest, is restarted at the previous symptom-free step.^3,5

The goal of this approach is to ensure that the pediatric brain recovers fully and can resume normal developmental acquisition of cognitive skills and functions. Further, as previously noted, children and adolescents require more time to recover from the effects of a concussion than adults do.^2,3 If a child returns too quickly to activity postconcussion, clinical evidence suggests that worsening of cognitive deficits is likely.⁹ Therefore, cautious postconcussion management that allows sufficient recovery time before clearance is given for a return to sports participation is highly recommended.^2,4,5 No child should RTP unless cleared by a health care provider trained in the evaluation and management of pediatric concussive injuries.^4,5,15

Return to school
Inadequate knowledge of concussion on the part of parents, teachers, and school officials can be a barrier to appropriate return-to-school decisions after pediatric concussive injuries.²² Since pre–high-school-age children spend the majority of their time in school, it is essential that a child’s school attendance and workload demands be decreased during recovery from a concussion.

Evidence indicates that an increase in cognitive or physical activity before complete recovery—ie, before normal brain cellular function is restored—may prolong cognitive dysfunction.⁵ Arbogast et al found that, in many pediatric concussion patients, unresolved symptoms impeded learning and school-based functioning: 10% to 18% of the children studied experienced fatigue, difficulty concentrating, feeling foggy, and/or vision problems.²¹ Within the first two weeks postinjury, 80% reported an increase in symptom severity while at school.

Academic demands should be increased gradually, with adjustments made for the individual student as needed, in order to avoid the exacerbation of such school-setting symptoms as headache, dizziness, light and/or noise sensitivity, and difficulty concentrating or remembering.²²

While RTP guidelines are widely understood and implemented by clinicians, one survey found that return-to-school guidance is provided less often.²¹ Clinicians should be mindful of the importance of both physical rest and cognitive rest during recovery from pediatric concussion and should provide parents with clear guidance for both.²¹

On the next page: Role of the primary care clinician >>

 

THE ROLE OF THE PRIMARY CARE CLINICIAN
Primary care clinicians are central to pediatric concussion management because they facilitate and oversee a child’s recovery. They may administer neuropsychologic testing, monitor symptom resolution, and supervise the concussed child’s gradual return to physical and academic activities through the individualized phases of RTP and return-to-school ­protocols.^4,20,23

The NP or PA functions as the main point of contact within the heath care team, organizing the plan of care and coordinating with parents, teachers, and coaches throughout the recovery process. Close follow-up care, including detailed documentation, should take place at well-child examinations to help ensure that the child’s development continues to progress as expected.

Referrals
Although referrals to a specialist are not typically necessary, persistent symptoms—those lasting longer than 10 days and not usually specific to concussion—warrant immediate and appropriate referral.^3,22 Approximately 30% of mTBI patients experience long-term, often significant aftereffects, underscoring that mTBI is not a single entity and that each patient is unique.²⁴

Risk factors for protracted symptoms
Factors that may be associated with prolonged or persistent duration of symptoms include early posttraumatic headache, previous concussion, early amnesia, alteration in mental status, disorientation, fatigue/fogginess, developmental disorders (eg, learning disabilities, ADHD), and psychiatric disorders (eg, anxiety, depression).^4,13 Studies have examined this association, and there is conflicting evidence as to whether prolonged symptoms are attributed to, or are a combination of, preconcussion modifying factors, concussive episode severity, and/or coexistent pathologies.^3,4

Concussion complications
Postconcussion syndrome can occur in pediatric athletes after a single concussion.^3,23 The syndrome is not clearly understood but is characterized by the persistence of multiple cognitive, physical, and/or emotional symptoms of a concussion for weeks or even months, making it difficult to both diagnose and manage.^5,15

Second impact syndrome, only documented in pediatric athletes, occurs when a child sustains a concussion before fully recovering from a prior concussion. This can lead to cerebral vascular congestion, cerebral swelling, and in some cases, death.¹⁵ Immediate removal of a concussed child from play until completely asymptomatic is obviously essential to the prevention of this rare catastrophe.

Any child with persistent symptoms should be referred to a multidisciplinary team of providers experienced in concussion management. This team may include, but is not limited to, neurologists, developmental pediatricians, concussion specialists, and psychologic, cognitive, and/or physical therapists.^3,5

CONCUSSION EDUCATION
Family
Family-centered education is another essential component of pediatric concussion management. Parents and guardians are extremely influential and important to a child’s overall recovery, especially a younger child’s. While older pre–high-school-age children are much more capable of self-reporting symptoms, the younger child may not yet be developmentally able to do so, making the parent or guardian’s assistance and input essential.¹⁴

Unfortunately, studies have shown that a significant number of parents lack a good understanding of what constitutes a concussion as well as of the appropriate steps to ensure their child’s safe return to sport and school.^22,25 Many parents view concussion as meaning a less severe head injury than if mild TBI or minor TBI is used.²⁶ It is imperative that clinicians ensure that parents understand the seriousness of their child’s concussive injury and how to judge when their child may safely return to school.

GAAME is an acronym for a simple concussion action plan for parents of young sports participants. The name is based on the first word of each step in the plan:

Get out, Assess, Ask, Medical attention, and Emergency situation.

The GAAME handout (see "Parent Guide") briefly explains the steps to take if a child experiences a blow to the head during a sports activity. It can be given to parents of all pre–high-schoolers, whether their children participate in organized sports or not.

GAAME utilizes a five-step approach that immediately pulls the child out of the game and highlights the important information a clinician will need when the child receives medical attention.³ Parents, guardians, and other involved parties serve as a child’s best advocate by being informed and alert to the early signs and symptoms of a concussion and by helping the child to identify his or her own symptoms.

School personnel
Teachers and other school officials must recognize both the necessity of cognitive rest during concussion recovery and their role in enabling a child’s gradual return to the cognitive demands of school. A child may require such adjustments as a shorter school day or week, a reduced workload, and extra time for tests to avoid exacerbation of concussion symptoms.^5,22 In light of state concussion laws (see below), schools commonly ensure that personnel are well-informed about concussion and its aftereffects in the classroom.

Sports officials
Heightened awareness of the need for more effective concussion education and management in youth sports has led to enactment of laws on youth sports-related concussions in all 50 states and the District of Columbia.²⁷ Most of these laws include

1. Inform and educate coaches, athletes, and their parents and guardians about concussion through training and/or a concussion information sheet.

2. An athlete who is believed to have a concussion is to be removed from play right away.

3. An athlete can only return to play or practice after at least 24 hours and with permission from a health care professional.

Clinicians should also be familiar with the laws in their states as they may affect clinical decisions (eg, timing of RTP protocol).

On the next page: Conclusion >>

 

CONCLUSION
Optimal management of pediatric concussions is a multifaceted challenge that is best addressed by age-appropriate, individualized patient care. Educational initiatives based on the latest concussion guidelines will increase awareness of appropriate concussion management by all involved in overseeing the recovery of the pre-high-school-age child.

A greater understanding of concussion, coupled with management based on current, standardized RTP and return-to-school protocols, will enhance coordination among the multidisciplinary team overseeing the child’s recovery and facilitate the return to full preconcussion functioning. More research about the effects of concussion on the developing brain is needed in order to create evidence-based guidelines specific to this pediatric population.

---

CE/CME No: CR-1409

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Define the term concussion.
• Identify the major signs and symptoms of a concussion.
• Discuss the initial management of a pediatric patient with a suspected sports-related concussion.
• Describe the current recommendations for return to play after a pediatric concussion.
• Explain the main challenges clinicians face in the management of pediatric concussions

FACULTY
Sydney Meckler is pursuing her Doctor of Nursing Practice degree at Columbia University, New York City. The author has no significant financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.25 hours of American Academy of Physician Assistants (AAPA) Category I CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of September 2014. 

Article begins on next page >>

 

 

This article describes the challenges of diagnosis and treatment of pediatric concussive injuries, with particular attention to the effects of concussion on the developing brain. It highlights the need for individualized, age-dependent care; standardized return-to-play and return-to-school protocols; and better-informed clinicians, parents, teachers, and coaches.

Pediatric concussions—those occurring in children younger than 18—account for almost half a million emergency department visits each year.¹ Of these, more than 25% occur during sports-related activities.² Yet it is believed that pediatric concussive injuries are significantly underreported because parents do not always seek medical attention for their concussed children and because little has been published on the management of sports-related concussions in pre–high-school-age athletes.²

The 4th International Consensus Conference on Concussion in Sport, the American Academy of Neurology, and the American Medical Society for Sports Medicine all recently updated their guidelines for concussion evaluation and management.^3-5 However, the lack of data on concussions in younger pediatric athletes presents challenges for the optimal management of these patients.⁶ In fact, in a February 2014 report, the Institute of Medicine said that more research is needed to develop evidence-based sports-related concussion management guidelines for children and adolescents.⁷

In this article, the factors that distinguish concussions in children from those in adults will be described, as will the management techniques that primary care clinicians can use to effectively address them.

WHAT IS A CONCUSSION?
Although the term concussion has been used interchangeably with head trauma and brain injury, concussion is most often described as mild traumatic brain injury (mTBI). Variations in terminology reflect both the lack of agreement on a standard definition for concussion, especially as it applies to the pediatric population, and the complexities of concussion diagnosis and management.⁸ This inherent ambiguity can lead to suboptimal recognition and awareness of concussion among clinicians, patients, families, school personnel, and sports staff, especially of its serious aftereffects in the pediatric patient.

A blow to the head can propel the brain to strike one side of the skull and then bounce off the opposite side. This can damage or tear the axons—the signal transmitters of the neurons—from their cell bodies, disrupting brain cell communications and causing neurocognitive deficits.

While a concussion is a direct injury to the brain, it is also an evolving process comprised of several pathophysiologic components that are a consequence of biomechanical forces. The brain does not directly contact the skull but is surrounded by cerebrospinal fluid and fluid-filled vessels with a greater density than the brain itself. This intracranial space provides room for the brain to move upon impact by shifting and compressing from one side of the skull to the other.⁹ The concussive injury occurs as a result of either a direct strike to the head or from an indirect force traumatic enough to be transmitted to the brain. The strike or force produces a complex disturbance to the brain that, in most cases, does not result in loss of consciousness.³

THE GREATER VULNERABILITY OF THE PEDIATRIC BRAIN
Pathophysiology
For a concussion to occur, the biomechanical threshold at which nerve cells' adaptability is impeded must be crossed.¹⁰ This sets in motion a cascade of events, developing over minutes, hours, and even days, in which homeostasis is disrupted due to an imbalance of ionic, neuronal, metabolic, and pathophysiologic processes.⁵

While many studies have sought to explain the pathophysiology of pediatric sports-related concussions, much is still unknown. One hypothesis suggests that, after the injury, neuronal depolarization occurs, releasing excitatory neurotransmitters and altering metabolism by the immediate release of potassium. Restoration of homeostasis demands response by the sodium-potassium pump, requiring energy in the form of glucose. Coupled with axonal injury and alterations in cerebral blood flow, an imbalance between energy supply and demand occurs.⁵

Maugans et al found that a single pediatric concussion does not cause a structural or metabolic injury but instead a physiologic interruption—different from what occurs in adult concussions.¹⁰ They observed a statistically significant reduction in cerebral blood flow of more than 10% in a small group of postconcussion children, ages 11 to 15, compared with a control group. This alteration persisted for two weeks in two-thirds of the children and for up to a month in the remaining third.¹⁰ The delayed return of normal cerebral blood flow is believed to be a major contributing factor to pediatric concussion-related symptoms. However, little is known about the long-term effects of concussion on the developing brain.⁹

Crucial developmental years
Because the pediatric brain is still developing, children between the ages of 5 and 12 are at greater risk for sustaining a disruption in brain function from a concussion. In addition, this group is more susceptible in general to sports injuries compared to adults, because of their stage of growth and development.¹¹

With a pediatric concussion, the individual child’s stage of brain development and the possible effects on his or her evolving neurocognitive functioning must be taken into account. Critical skills, such as language, emotion, memory, problem solving, and motor dexterity, emerge during childhood, and a disturbance during this time could have substantial consequences.¹² Motor skills and primary senses usually mature by age 5, with language maturity occurring by age 10.⁹ However, many other vital skills and processes, such as emotion, judgment, and abstract reasoning, are not fully developed until adulthood. As a result, damage to cortical areas of the brain, such as the parietal lobe and frontal areas—involved in fine motor skills and complex thinking—can hinder or delay the development of these necessary processes.⁹  

Many researchers suggest that, while a concussion to the developing brain may not significantly affect previously learned functions, it may notably delay development of new cognitive functions. As a result, recovery from a concussion during these years may be poorer.^2,9,12

On the next page: Clinical presentation and post injury evaluation >> 

 

CLINICAL PRESENTATION
Initial assessment of pediatric athletes with suspected concussive injuries can be particularly challenging because of the variability and evolving nature of associated signs and symptoms, resulting in a wide range of clinical presentations.³ These presenting signs and symptoms can, however, provide vital clues to the location of the injury within the brain because the consequences of concussion arise from injury to the brain’s cortical and subcortical systems (see Table 1).⁹

The cortical systems are located within the frontal, temporal, parietal, and occipital lobes, each of which houses control centers for specific learned skills and functions. The subcortical systems include the hypothalamus, trigeminal system, basal ganglia, and cerebellum. While a concussion most often causes diffuse harm rather than localized trauma, familiarity with the functions associated with specific brain locations aids in initial identification of the injury and allows for individualized concussion management.¹³

After a concussion occurs, it is essential to evaluate all domains of the child’s functioning through a comprehensive physical assessment, including a detailed concussion history and review of preinjury risk factors.³ In addition, there may be unobservable symptoms about which a child is unable to communicate due to his or her stage of emotional and cognitive development and restricted capacity to serve as a primary reporter.¹⁴  

Signs and symptoms
The four categories of concussion signs and symptoms include physical, cognitive, emotional, and sleep (see Table 2).¹⁵ A concussed patient may experience any variation or combination of these signs and symptoms.

It is important to recognize that, although loss of consciousness is a serious sign of a concussion, it occurs in only about 10% of concussive injuries.^5,15 In fact, current concussion guidelines no longer advocate the use of grading scales, which assessed the severity of a concussion based primarily on the presence or absence of a brief loss of consciousness. Evidence now shows that loss of consciousness does not predict clinical course or cognitive long-term impairment after a concussion.¹⁶

Duration of symptoms
The duration of concussion symptoms can vary, but in most cases symptoms last seven to 10 days, with 10% to 15% of patients reporting symptoms for more than 10 days.^3,5 While recovery duration has not been studied sufficiently in children younger than 15, younger children require longer recovery ­periods. The resolution of symptoms, however, does not necessarily correlate with absolute cognitive recovery.^5,17

Modifying and complicating factors
In addition to the patient’s presenting signs and symptoms, factors that may modify or complicate recovery from a concussion should be identified (see Table 3).³ These factors include preexisting conditions or disorders and the use of certain prescription drugs. Each factor should be assessed individually, taking into account the patient’s age.²

Some presenting symptoms may overlap with symptoms of common disorders in this group. It is important to note if symptoms of such conditions as attention-deficit/hyperactivity disorder (ADHD), sleep disorders, learning disabilities, and mood disorders were present prior to the concussion.⁵

Modifying factors provide essential information that can help predict the individual patient’s anti­cipated recovery process and must be taken into ­account throughout the process. They are particularly important when assessing the differences between a child’s preconcussion and postconcussion functioning.^3,4

POST INJURY EVALUATION OF COGNITIVE FUNCTIONING
Concussion is diagnosed clinically, based on the mechanism of the sustained injury, and is supported primarily by reported and observed signs and symptoms. The ability to systematically evaluate the patient for manifestations of concussion is essential to pediatric concussion management.^3,18

To aid in appropriately evaluating symptoms and assessing functional damage, many standardized assessment tools and neuropsychological tests have been developed. These tools have been modified for younger athletes due to differences in children’s neurocognitive development and in their ability to be symptom self-reporters.

Concussion assessment tools
The tools most commonly used to assess the effects of concussion in younger athletes are listed in Table 4. It was not until 2012, with the release of the Child Sport Concussion Assessment Tool Version 3 (Child-SCAT3), that an appropriately adapted and valid concussion assessment tool became available for children younger than 10.³

Assessment tools are useful but are not diagnostic. They do not take the place of a clinician’s thorough neurocognitive evaluation of a potentially concussed child.

Neuropsychologic testing
In order to properly manage pediatric concussions, postconcussion status must be assessed relative to preconcussion status in order to ensure optimal resolution of symptoms and cognitive recovery.¹⁹

The American Medical Society for Sports Medicine supports baseline testing for high-risk athletes, defined as those with a prior history of concussions or “confounding” conditions (learning disability, mood and attention disorders, migraine headaches).⁵ The International Consensus Statement on Concussion in Sport states that there is insufficient evidence to recommend routine baseline testing, but its early use after pediatric concussion may provide helpful information for determining when the child may return to school. The American Academy of Neurology suggests that clinicians “… might utilize baseline scores on concussion assessment tools, especially in younger athletes, those with prior concussions, or those with preexisting learning disabilities/ADHD, as doing so fosters better interpretation of postinjury scores.”⁴

Assessment tools can provide essential insight into the cognitive functional state of a concussed child athlete, even after symptom resolution.^3,5,20 They are not stand-alone measures of recovery but can be useful components of the pediatric concussion evaluation and management process and an aid to clinical decision making.^3,13    

Paper-and-pencil or computerized neuropsychologic tests provide objective measures of brain-behavior relationships and are more sensitive in detecting subtle cognitive impairments than a clinical examination.⁵ Although neuropsychologic testing has not been validated as a diagnostic tool, it may be useful for both baseline (preinjury) testing of athletes and for monitoring recovery from a concussive event.^5,20 (For more information on motor control assessment, see Dirks RP, McLeod TCV. Sport-related mild traumatic brain injury. Clinician Reviews. 2008;18[9]:22. http://bit.ly/1mjizIa.)

On the next page: Postconcussion management >>

 

POSTCONCUSSION MANAGEMENT
All concussion management guidelines concur that immediate removal from play of a pediatric athlete with a suspected concussion is the most important initial action. Regardless of how short the duration or mild the symptoms may be, same-day return to play should never occur.^3-5 This is particularly true because acute concussion is an evolving injury and manifestation of symptoms, including cognitive deficits, is often delayed.³

The foundation of postconcussion recovery is rest, both physical and cognitive. Acute symptoms must diminish before a gradual resumption of activities.^3,5

Cognitive rest
Cognitive rest is the cornerstone of concussion management.⁵ The latest guidelines stress the importance, particularly in the pediatric age-group, of decreasing any activities of daily living that may aggravate symptoms.³ This includes such common childhood pastimes as playing video games, watching television, and using a computer.¹⁵ More important, cognitive rest means academic rest, which is essential to postconcussion recovery and preparing the child for a “return to school” or “return to learn.”^{21, 22}

Return to play
In pediatric concussion management, a conservative approach to the determination of when a concussed child may return to play (RTP) is key. RTP decisions are guided by the resolution of the child’s symptoms and are based on clinical judgment.^3-5

Current guidelines outline a gradual, stepwise approach to RTP after full recovery, which must be individualized and age-appropriate.^3,5 These include

• Light aerobic exercise: Increase heart rate to 70% maximum predicted by walking, swimming, or using stationary bike. No resistance training.

• Sport-specific exercise: Add movement with skating or running drills. No head impact activities.

• Noncontact training drills: Add exercise, coordination, and cognitive load with progression to more complex training drills (eg, passing drills in football and ice hockey). May introduce progressive resistance training.

• Full contact practice: To restore confidence and allow coaching staff to assess functional skills, permit participation in normal training activities after obtaining medical clearance.

At any step, if symptoms develop with activity, the process is stopped and, after a 24-hour period of rest, is restarted at the previous symptom-free step.^3,5

The goal of this approach is to ensure that the pediatric brain recovers fully and can resume normal developmental acquisition of cognitive skills and functions. Further, as previously noted, children and adolescents require more time to recover from the effects of a concussion than adults do.^2,3 If a child returns too quickly to activity postconcussion, clinical evidence suggests that worsening of cognitive deficits is likely.⁹ Therefore, cautious postconcussion management that allows sufficient recovery time before clearance is given for a return to sports participation is highly recommended.^2,4,5 No child should RTP unless cleared by a health care provider trained in the evaluation and management of pediatric concussive injuries.^4,5,15

Return to school
Inadequate knowledge of concussion on the part of parents, teachers, and school officials can be a barrier to appropriate return-to-school decisions after pediatric concussive injuries.²² Since pre–high-school-age children spend the majority of their time in school, it is essential that a child’s school attendance and workload demands be decreased during recovery from a concussion.

Evidence indicates that an increase in cognitive or physical activity before complete recovery—ie, before normal brain cellular function is restored—may prolong cognitive dysfunction.⁵ Arbogast et al found that, in many pediatric concussion patients, unresolved symptoms impeded learning and school-based functioning: 10% to 18% of the children studied experienced fatigue, difficulty concentrating, feeling foggy, and/or vision problems.²¹ Within the first two weeks postinjury, 80% reported an increase in symptom severity while at school.

Academic demands should be increased gradually, with adjustments made for the individual student as needed, in order to avoid the exacerbation of such school-setting symptoms as headache, dizziness, light and/or noise sensitivity, and difficulty concentrating or remembering.²²

While RTP guidelines are widely understood and implemented by clinicians, one survey found that return-to-school guidance is provided less often.²¹ Clinicians should be mindful of the importance of both physical rest and cognitive rest during recovery from pediatric concussion and should provide parents with clear guidance for both.²¹

On the next page: Role of the primary care clinician >>

 

THE ROLE OF THE PRIMARY CARE CLINICIAN
Primary care clinicians are central to pediatric concussion management because they facilitate and oversee a child’s recovery. They may administer neuropsychologic testing, monitor symptom resolution, and supervise the concussed child’s gradual return to physical and academic activities through the individualized phases of RTP and return-to-school ­protocols.^4,20,23

The NP or PA functions as the main point of contact within the heath care team, organizing the plan of care and coordinating with parents, teachers, and coaches throughout the recovery process. Close follow-up care, including detailed documentation, should take place at well-child examinations to help ensure that the child’s development continues to progress as expected.

Referrals
Although referrals to a specialist are not typically necessary, persistent symptoms—those lasting longer than 10 days and not usually specific to concussion—warrant immediate and appropriate referral.^3,22 Approximately 30% of mTBI patients experience long-term, often significant aftereffects, underscoring that mTBI is not a single entity and that each patient is unique.²⁴

Risk factors for protracted symptoms
Factors that may be associated with prolonged or persistent duration of symptoms include early posttraumatic headache, previous concussion, early amnesia, alteration in mental status, disorientation, fatigue/fogginess, developmental disorders (eg, learning disabilities, ADHD), and psychiatric disorders (eg, anxiety, depression).^4,13 Studies have examined this association, and there is conflicting evidence as to whether prolonged symptoms are attributed to, or are a combination of, preconcussion modifying factors, concussive episode severity, and/or coexistent pathologies.^3,4

Concussion complications
Postconcussion syndrome can occur in pediatric athletes after a single concussion.^3,23 The syndrome is not clearly understood but is characterized by the persistence of multiple cognitive, physical, and/or emotional symptoms of a concussion for weeks or even months, making it difficult to both diagnose and manage.^5,15

Second impact syndrome, only documented in pediatric athletes, occurs when a child sustains a concussion before fully recovering from a prior concussion. This can lead to cerebral vascular congestion, cerebral swelling, and in some cases, death.¹⁵ Immediate removal of a concussed child from play until completely asymptomatic is obviously essential to the prevention of this rare catastrophe.

Any child with persistent symptoms should be referred to a multidisciplinary team of providers experienced in concussion management. This team may include, but is not limited to, neurologists, developmental pediatricians, concussion specialists, and psychologic, cognitive, and/or physical therapists.^3,5

CONCUSSION EDUCATION
Family
Family-centered education is another essential component of pediatric concussion management. Parents and guardians are extremely influential and important to a child’s overall recovery, especially a younger child’s. While older pre–high-school-age children are much more capable of self-reporting symptoms, the younger child may not yet be developmentally able to do so, making the parent or guardian’s assistance and input essential.¹⁴

Unfortunately, studies have shown that a significant number of parents lack a good understanding of what constitutes a concussion as well as of the appropriate steps to ensure their child’s safe return to sport and school.^22,25 Many parents view concussion as meaning a less severe head injury than if mild TBI or minor TBI is used.²⁶ It is imperative that clinicians ensure that parents understand the seriousness of their child’s concussive injury and how to judge when their child may safely return to school.

GAAME is an acronym for a simple concussion action plan for parents of young sports participants. The name is based on the first word of each step in the plan:

Get out, Assess, Ask, Medical attention, and Emergency situation.

The GAAME handout (see "Parent Guide") briefly explains the steps to take if a child experiences a blow to the head during a sports activity. It can be given to parents of all pre–high-schoolers, whether their children participate in organized sports or not.

GAAME utilizes a five-step approach that immediately pulls the child out of the game and highlights the important information a clinician will need when the child receives medical attention.³ Parents, guardians, and other involved parties serve as a child’s best advocate by being informed and alert to the early signs and symptoms of a concussion and by helping the child to identify his or her own symptoms.

School personnel
Teachers and other school officials must recognize both the necessity of cognitive rest during concussion recovery and their role in enabling a child’s gradual return to the cognitive demands of school. A child may require such adjustments as a shorter school day or week, a reduced workload, and extra time for tests to avoid exacerbation of concussion symptoms.^5,22 In light of state concussion laws (see below), schools commonly ensure that personnel are well-informed about concussion and its aftereffects in the classroom.

Sports officials
Heightened awareness of the need for more effective concussion education and management in youth sports has led to enactment of laws on youth sports-related concussions in all 50 states and the District of Columbia.²⁷ Most of these laws include

1. Inform and educate coaches, athletes, and their parents and guardians about concussion through training and/or a concussion information sheet.

2. An athlete who is believed to have a concussion is to be removed from play right away.

3. An athlete can only return to play or practice after at least 24 hours and with permission from a health care professional.

Clinicians should also be familiar with the laws in their states as they may affect clinical decisions (eg, timing of RTP protocol).

On the next page: Conclusion >>

 

CONCLUSION
Optimal management of pediatric concussions is a multifaceted challenge that is best addressed by age-appropriate, individualized patient care. Educational initiatives based on the latest concussion guidelines will increase awareness of appropriate concussion management by all involved in overseeing the recovery of the pre-high-school-age child.

A greater understanding of concussion, coupled with management based on current, standardized RTP and return-to-school protocols, will enhance coordination among the multidisciplinary team overseeing the child’s recovery and facilitate the return to full preconcussion functioning. More research about the effects of concussion on the developing brain is needed in order to create evidence-based guidelines specific to this pediatric population.