Lisa Vargish, MD, MS

ILLUSTRATIVE CASE

During a routine checkup of a 2-month-old boy, you notice that the left side of his head is slightly flatter than the right and his forehead protrudes forward more on the left than the right. His birth history and development are normal. You wonder if the asymmetry will resolve as the infant grows older or whether you should suggest immediate treatment.

The American Academy of Pediatrics recommends putting babies to sleep on their backs to reduce the risk of sudden infant death syndrome. As more parents have followed this recommendation, the incidence of positional preference and DP has increased, presumably because external pressure distorts the malleable infant cranium. Prenatal and intrapartum factors also can cause DP, but sleeping on the back likely accounts for the recent increase.^2-4

Not just a cosmetic issue
Although many clinicians consider skull deformities to be purely cosmetic,⁵ plagiocephaly is associated with auditory processing disorders, mandibular asymmetry, and visual field defects. Head deformities resulting from premature fusion of the cranial sutures (craniosynostosis) have been linked to an increased incidence of speech-language, cognitive, behavioral, and neurodevelopmental abnormalities.^6,7 Whether these associations are causal is not yet known.⁵ Many parents believe that unattractive facial features lead to adverse effects on children, such as teasing and poor self-esteem.^5,6

Conservative treatments for positional preference and DP include parental counseling, counter-positioning, simple exercises, and orthotic devices such as helmets.⁸ Scientific evidence supporting the effectiveness of these approaches is weak. The study we review in this PURL provides strong evidence of the effectiveness of 1 intervention—physical therapy (PT).

STUDY SUMMARY: Early physical therapy prevents severe DP

van Vlimmeren and colleagues conducted a prospective RCT comparing PT with usual care for preventing DP.¹ From a group of 400 infants born consecutively in the Netherlands, they identified 65 with positional preference at 7 weeks of age and randomized them to PT or a control group. Pediatric physical therapists blinded to group allocation evaluated each infant at 6 and 12 months. Babies with congenital muscular torticollis (defined as preferential posture of the head and asymmetrical cervical movements caused by a unilateral contracture of the sternocleidomastoid muscle), dysmorphisms, or congenital syndromes were excluded.

The PT and control groups were comparable at baseline. Parents of infants in the control group received a pamphlet about basic preventive measures, but no additional instructions. Infants in the intervention group received standardized pediatric PT from trained therapists who were unaware of the results of the infants’ baseline assessments.

PT consisted of 8 sessions between 7 weeks and 6 months of age. The first 4 sessions were held weekly; subsequent sessions occurred every 2 to 3 weeks. The second through fifth sessions took place at the infant’s home.

The intervention included exercises to reduce positional preference and stimulate motor development, along with parental counseling about counter-positioning, handling, nursing, and the causes of positional preference. Parents received a pamphlet describing basic measures to prevent DP. The therapists also encouraged earlier and more frequent play times in the prone position (“tummy time”). PT was discontinued when the infant no longer demonstrated positional preference while awake or asleep, parents were following advice about handling, and the baby exhibited no signs of motor developmental delay or asymmetries.

The primary outcome was severe DP, measured as an oblique diameter difference index (ODDI) score of 104% or more—a score representing asymmetry of the skull that is obviously noticeable and therefore considered clinically relevant.⁹ The secondary outcome measures were symmetry in posture and active movements, motor development, and passive range of motion of the cervical spine.

Intervention reduced DP at 6 and 12 months. By 6 months of age, the number of infants in the intervention group with severe DP had decreased significantly from 53% to 30%, compared with a decrease from 63% to 56% in the control group (relative risk [RR]=0.54; 95% confidence interval [CI], 0.30-0.98; number needed to treat [NNT]=3.85). At 12 months, the number of babies in the intervention group with severe DP had decreased further, to 24%, whereas the number in the control group remained unchanged at 56% (RR=0.43; 95% CI, 0.22-0.85; NNT=3.13).

Secondary outcomes comparable. No major differences in secondary outcomes were noted between the 2 groups. At 6 and 12 months of age, none of the infants had positional preference or differences in motor development. Passive range of motion of the cervical spine was within normal range and symmetrical in all infants at baseline and at 6 and 12 months. However, at the 6-month evaluation, parents of babies in the intervention group demonstrated greater symmetry and less left orientation in nursing, positioning, and handling of the infants.

WHAT’S NEW: Early intervention trumps conservative therapies

This is the first RCT of a pediatric PT program to treat infants with positional preference to prevent severe plagiocephaly, and the study provides strong evidence to support this practice. The study included healthy infants, much like the ones we encounter in primary care practice. If, as we suspect, many of us have been recommending conservative therapies, we have reason to consider referral for this increasingly common clinical problem.

CAVEATS: Study did not focus on serious deficits

This study excluded infants with congenital muscular torticollis, dysmorphisms, or other congenital syndromes. We need to be aware of these causes of DP, which may warrant additional referrals beyond pediatric PT. In addition, DP should be distinguished from craniosynostosis, which requires referral for surgical evaluation and treatment.

Cosmetic issues vs more serious problems. DP is the most benign of the many causes of head deformities. The outcomes of this trial mainly addressed the cosmetic issue rather than more serious deficits associated with plagiocephaly. Nevertheless, we believe that cosmetic considerations are important to parents and children. What’s more, the intervention carries no risk of adverse effects and produces notable benefit. We conclude that discussing PT referral with parents is the appropriate practice change to implement based on this study.

Infant age, length of follow-up. Because this study did not evaluate the impact of the intervention on infants older than 7 to 8 weeks, it is not clear whether PT would be as effective if begun later in infancy. The relatively short follow-up (12 months) precludes conclusions about outcomes such as social functioning and school performance.

CHALLENGES TO IMPLEMENTATION: A matter of time

The incidence of positional preference has been reported to be as high as 22% at 7 weeks, making it a relatively common problem encountered by family physicians.⁷ Most children with positional preference do not develop DP and when they do, it is typically a cosmetic problem. Ruling out torticollis, craniosynostosis, and other congenital causes is critical. Ascertaining parental preference is a major consideration in the decision to refer for PT. All of this takes time.

However, parents are often concerned about their baby’s misshapen skull. We think that addressing positional preference is time well spent, especially since we now have evidence that a noninvasive approach—PT—can effectively prevent DP.

Acknowledgments

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the university of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

PURLs methodology

This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

ILLUSTRATIVE CASE

During a routine checkup of a 2-month-old boy, you notice that the left side of his head is slightly flatter than the right and his forehead protrudes forward more on the left than the right. His birth history and development are normal. You wonder if the asymmetry will resolve as the infant grows older or whether you should suggest immediate treatment.

The American Academy of Pediatrics recommends putting babies to sleep on their backs to reduce the risk of sudden infant death syndrome. As more parents have followed this recommendation, the incidence of positional preference and DP has increased, presumably because external pressure distorts the malleable infant cranium. Prenatal and intrapartum factors also can cause DP, but sleeping on the back likely accounts for the recent increase.^2-4

Not just a cosmetic issue
Although many clinicians consider skull deformities to be purely cosmetic,⁵ plagiocephaly is associated with auditory processing disorders, mandibular asymmetry, and visual field defects. Head deformities resulting from premature fusion of the cranial sutures (craniosynostosis) have been linked to an increased incidence of speech-language, cognitive, behavioral, and neurodevelopmental abnormalities.^6,7 Whether these associations are causal is not yet known.⁵ Many parents believe that unattractive facial features lead to adverse effects on children, such as teasing and poor self-esteem.^5,6

Conservative treatments for positional preference and DP include parental counseling, counter-positioning, simple exercises, and orthotic devices such as helmets.⁸ Scientific evidence supporting the effectiveness of these approaches is weak. The study we review in this PURL provides strong evidence of the effectiveness of 1 intervention—physical therapy (PT).

STUDY SUMMARY: Early physical therapy prevents severe DP

van Vlimmeren and colleagues conducted a prospective RCT comparing PT with usual care for preventing DP.¹ From a group of 400 infants born consecutively in the Netherlands, they identified 65 with positional preference at 7 weeks of age and randomized them to PT or a control group. Pediatric physical therapists blinded to group allocation evaluated each infant at 6 and 12 months. Babies with congenital muscular torticollis (defined as preferential posture of the head and asymmetrical cervical movements caused by a unilateral contracture of the sternocleidomastoid muscle), dysmorphisms, or congenital syndromes were excluded.

The PT and control groups were comparable at baseline. Parents of infants in the control group received a pamphlet about basic preventive measures, but no additional instructions. Infants in the intervention group received standardized pediatric PT from trained therapists who were unaware of the results of the infants’ baseline assessments.

PT consisted of 8 sessions between 7 weeks and 6 months of age. The first 4 sessions were held weekly; subsequent sessions occurred every 2 to 3 weeks. The second through fifth sessions took place at the infant’s home.

The intervention included exercises to reduce positional preference and stimulate motor development, along with parental counseling about counter-positioning, handling, nursing, and the causes of positional preference. Parents received a pamphlet describing basic measures to prevent DP. The therapists also encouraged earlier and more frequent play times in the prone position (“tummy time”). PT was discontinued when the infant no longer demonstrated positional preference while awake or asleep, parents were following advice about handling, and the baby exhibited no signs of motor developmental delay or asymmetries.

The primary outcome was severe DP, measured as an oblique diameter difference index (ODDI) score of 104% or more—a score representing asymmetry of the skull that is obviously noticeable and therefore considered clinically relevant.⁹ The secondary outcome measures were symmetry in posture and active movements, motor development, and passive range of motion of the cervical spine.

Intervention reduced DP at 6 and 12 months. By 6 months of age, the number of infants in the intervention group with severe DP had decreased significantly from 53% to 30%, compared with a decrease from 63% to 56% in the control group (relative risk [RR]=0.54; 95% confidence interval [CI], 0.30-0.98; number needed to treat [NNT]=3.85). At 12 months, the number of babies in the intervention group with severe DP had decreased further, to 24%, whereas the number in the control group remained unchanged at 56% (RR=0.43; 95% CI, 0.22-0.85; NNT=3.13).

Secondary outcomes comparable. No major differences in secondary outcomes were noted between the 2 groups. At 6 and 12 months of age, none of the infants had positional preference or differences in motor development. Passive range of motion of the cervical spine was within normal range and symmetrical in all infants at baseline and at 6 and 12 months. However, at the 6-month evaluation, parents of babies in the intervention group demonstrated greater symmetry and less left orientation in nursing, positioning, and handling of the infants.

WHAT’S NEW: Early intervention trumps conservative therapies

This is the first RCT of a pediatric PT program to treat infants with positional preference to prevent severe plagiocephaly, and the study provides strong evidence to support this practice. The study included healthy infants, much like the ones we encounter in primary care practice. If, as we suspect, many of us have been recommending conservative therapies, we have reason to consider referral for this increasingly common clinical problem.

CAVEATS: Study did not focus on serious deficits

This study excluded infants with congenital muscular torticollis, dysmorphisms, or other congenital syndromes. We need to be aware of these causes of DP, which may warrant additional referrals beyond pediatric PT. In addition, DP should be distinguished from craniosynostosis, which requires referral for surgical evaluation and treatment.

Cosmetic issues vs more serious problems. DP is the most benign of the many causes of head deformities. The outcomes of this trial mainly addressed the cosmetic issue rather than more serious deficits associated with plagiocephaly. Nevertheless, we believe that cosmetic considerations are important to parents and children. What’s more, the intervention carries no risk of adverse effects and produces notable benefit. We conclude that discussing PT referral with parents is the appropriate practice change to implement based on this study.

Infant age, length of follow-up. Because this study did not evaluate the impact of the intervention on infants older than 7 to 8 weeks, it is not clear whether PT would be as effective if begun later in infancy. The relatively short follow-up (12 months) precludes conclusions about outcomes such as social functioning and school performance.

CHALLENGES TO IMPLEMENTATION: A matter of time

The incidence of positional preference has been reported to be as high as 22% at 7 weeks, making it a relatively common problem encountered by family physicians.⁷ Most children with positional preference do not develop DP and when they do, it is typically a cosmetic problem. Ruling out torticollis, craniosynostosis, and other congenital causes is critical. Ascertaining parental preference is a major consideration in the decision to refer for PT. All of this takes time.

However, parents are often concerned about their baby’s misshapen skull. We think that addressing positional preference is time well spent, especially since we now have evidence that a noninvasive approach—PT—can effectively prevent DP.

Acknowledgments

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the university of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

PURLs methodology

This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

ILLUSTRATIVE CASE

During a routine checkup of a 2-month-old boy, you notice that the left side of his head is slightly flatter than the right and his forehead protrudes forward more on the left than the right. His birth history and development are normal. You wonder if the asymmetry will resolve as the infant grows older or whether you should suggest immediate treatment.

The American Academy of Pediatrics recommends putting babies to sleep on their backs to reduce the risk of sudden infant death syndrome. As more parents have followed this recommendation, the incidence of positional preference and DP has increased, presumably because external pressure distorts the malleable infant cranium. Prenatal and intrapartum factors also can cause DP, but sleeping on the back likely accounts for the recent increase.^2-4

Not just a cosmetic issue
Although many clinicians consider skull deformities to be purely cosmetic,⁵ plagiocephaly is associated with auditory processing disorders, mandibular asymmetry, and visual field defects. Head deformities resulting from premature fusion of the cranial sutures (craniosynostosis) have been linked to an increased incidence of speech-language, cognitive, behavioral, and neurodevelopmental abnormalities.^6,7 Whether these associations are causal is not yet known.⁵ Many parents believe that unattractive facial features lead to adverse effects on children, such as teasing and poor self-esteem.^5,6

Conservative treatments for positional preference and DP include parental counseling, counter-positioning, simple exercises, and orthotic devices such as helmets.⁸ Scientific evidence supporting the effectiveness of these approaches is weak. The study we review in this PURL provides strong evidence of the effectiveness of 1 intervention—physical therapy (PT).

STUDY SUMMARY: Early physical therapy prevents severe DP

van Vlimmeren and colleagues conducted a prospective RCT comparing PT with usual care for preventing DP.¹ From a group of 400 infants born consecutively in the Netherlands, they identified 65 with positional preference at 7 weeks of age and randomized them to PT or a control group. Pediatric physical therapists blinded to group allocation evaluated each infant at 6 and 12 months. Babies with congenital muscular torticollis (defined as preferential posture of the head and asymmetrical cervical movements caused by a unilateral contracture of the sternocleidomastoid muscle), dysmorphisms, or congenital syndromes were excluded.

The PT and control groups were comparable at baseline. Parents of infants in the control group received a pamphlet about basic preventive measures, but no additional instructions. Infants in the intervention group received standardized pediatric PT from trained therapists who were unaware of the results of the infants’ baseline assessments.

PT consisted of 8 sessions between 7 weeks and 6 months of age. The first 4 sessions were held weekly; subsequent sessions occurred every 2 to 3 weeks. The second through fifth sessions took place at the infant’s home.

The intervention included exercises to reduce positional preference and stimulate motor development, along with parental counseling about counter-positioning, handling, nursing, and the causes of positional preference. Parents received a pamphlet describing basic measures to prevent DP. The therapists also encouraged earlier and more frequent play times in the prone position (“tummy time”). PT was discontinued when the infant no longer demonstrated positional preference while awake or asleep, parents were following advice about handling, and the baby exhibited no signs of motor developmental delay or asymmetries.

The primary outcome was severe DP, measured as an oblique diameter difference index (ODDI) score of 104% or more—a score representing asymmetry of the skull that is obviously noticeable and therefore considered clinically relevant.⁹ The secondary outcome measures were symmetry in posture and active movements, motor development, and passive range of motion of the cervical spine.

Intervention reduced DP at 6 and 12 months. By 6 months of age, the number of infants in the intervention group with severe DP had decreased significantly from 53% to 30%, compared with a decrease from 63% to 56% in the control group (relative risk [RR]=0.54; 95% confidence interval [CI], 0.30-0.98; number needed to treat [NNT]=3.85). At 12 months, the number of babies in the intervention group with severe DP had decreased further, to 24%, whereas the number in the control group remained unchanged at 56% (RR=0.43; 95% CI, 0.22-0.85; NNT=3.13).

Secondary outcomes comparable. No major differences in secondary outcomes were noted between the 2 groups. At 6 and 12 months of age, none of the infants had positional preference or differences in motor development. Passive range of motion of the cervical spine was within normal range and symmetrical in all infants at baseline and at 6 and 12 months. However, at the 6-month evaluation, parents of babies in the intervention group demonstrated greater symmetry and less left orientation in nursing, positioning, and handling of the infants.

WHAT’S NEW: Early intervention trumps conservative therapies

This is the first RCT of a pediatric PT program to treat infants with positional preference to prevent severe plagiocephaly, and the study provides strong evidence to support this practice. The study included healthy infants, much like the ones we encounter in primary care practice. If, as we suspect, many of us have been recommending conservative therapies, we have reason to consider referral for this increasingly common clinical problem.

CAVEATS: Study did not focus on serious deficits

This study excluded infants with congenital muscular torticollis, dysmorphisms, or other congenital syndromes. We need to be aware of these causes of DP, which may warrant additional referrals beyond pediatric PT. In addition, DP should be distinguished from craniosynostosis, which requires referral for surgical evaluation and treatment.

Cosmetic issues vs more serious problems. DP is the most benign of the many causes of head deformities. The outcomes of this trial mainly addressed the cosmetic issue rather than more serious deficits associated with plagiocephaly. Nevertheless, we believe that cosmetic considerations are important to parents and children. What’s more, the intervention carries no risk of adverse effects and produces notable benefit. We conclude that discussing PT referral with parents is the appropriate practice change to implement based on this study.

Infant age, length of follow-up. Because this study did not evaluate the impact of the intervention on infants older than 7 to 8 weeks, it is not clear whether PT would be as effective if begun later in infancy. The relatively short follow-up (12 months) precludes conclusions about outcomes such as social functioning and school performance.

CHALLENGES TO IMPLEMENTATION: A matter of time

The incidence of positional preference has been reported to be as high as 22% at 7 weeks, making it a relatively common problem encountered by family physicians.⁷ Most children with positional preference do not develop DP and when they do, it is typically a cosmetic problem. Ruling out torticollis, craniosynostosis, and other congenital causes is critical. Ascertaining parental preference is a major consideration in the decision to refer for PT. All of this takes time.

However, parents are often concerned about their baby’s misshapen skull. We think that addressing positional preference is time well spent, especially since we now have evidence that a noninvasive approach—PT—can effectively prevent DP.

Acknowledgments

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the university of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

PURLs methodology

This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Illustrative case

A 45-year-old man presents to your outpatient clinic within 24 hours after onset of left-sided facial nerve weakness and inability to smile on one side of his face. He asks for a therapy to help improve his symptoms quickly, as his daughter is getting married in a few months, and he will be in the wedding pictures.

Is there a treatment that will hasten his complete recovery?

Background: Insufficient statistical power until now

Many of us treat patients with Bell’s palsy with both corticosteroids and antiviral medications, such as acyclovir or valacyclovir, largely on the basis of pathophysiologic reasoning, because we’ve had no clear guidance from outcome studies. Until now, outcome studies have had mixed findings, and have been inconclusive.² Most outcome studies have lacked the statistical power to either detect or to rule out potential benefits convincingly. The study by Sullivan and colleagues is the first to have a sufficiently large study sample from which to draw more definitive conclusions based on patient-oriented outcomes.

Steroid plus antiviral makes sense, pathophysiologically

Corticosteroids are thought to decrease inflammation of the facial nerve during an episode of facial paralysis. Some have postulated that herpes simplex virus type I may be a cause of facial nerve paralysis, hence the treatment with antivirals.³

Most of our PURL surveillance system clinician reviewers said that they prescribe both corticosteroids and antivirals.

Guidelines: “probably, possibly”

For example, a report of the Quality Standards Subcommittee of the American Academy of Neurology concluded that benefit from both steroids and antivirals has not been well established in patients with Bell’s palsy. However, the report states that evidence suggests that steroids are safe and probably effective, while antivirals are also safe and possibly effective.⁴

In contrast, UpToDate suggests treating all patients seen within a week of symptom onset with corticosteroids (prednisone 60–80 mg daily) plus valacyclovir (1 g 3 times daily) for 1 week.⁵

CLINICAL CONTEXT: Quality of life, risk of permanent harm

Bell’s palsy, defined as an acute peripheral facial weakness of unknown cause, has an annual incidence of 20 to 32 per 100,000. Most patients recover completely, with or without treatment, but 20% to 30% can have permanent facial weakness or paralysis.

The time to resolution is a quality of life issue for those in whom disease does not resolve spontaneously.⁶

We think that this study provides convincing evidence that acyclovir is not indicated for Bell’s palsy and that corticosteroids are.

STUDY SUMMARY: 10-day treatment, starting promptly

This double-blind, placebo-controlled, randomized, multifactorial trial compared recovery of facial nerve function for patients randomized to receive 10 days of treatment with prednisolone (25 mg twice daily), acyclovir (400 mg 5 times daily), both agents, or placebo (lactose).

Inclusion criteria

Patients had to be at least 16 years of age (average age=44), with unilateral facial nerve weakness of no identifiable cause (eg, a diagnosis of Bell’s palsy). They were recruited mostly through their family doctors (75%) but also through emergency rooms and dental offices, and were referred to otolaryngologists at 17 Scottish hospitals within 72 hours.

The degree of initial facial paralysis was moderate to severe, based on the House-Brackmann scale, a widely used system for grading recovery from facial nerve paralysis. After the onset of symptoms, most patients (53.8%) initiated treatment within 24 hours, 32.1% within 48 hours, and 14.1% within 72 hours. Patients were assessed at baseline, 3 months, and 9 months.

Exclusion criteria

Exclusion criteria included pregnancy, breastfeeding, uncontrolled diabetes (Hb A_1c >8.0%), peptic ulcer disease, suppurative otitis media, herpes zoster, multiple sclerosis, systemic infection, sarcoid or other rare disorder, and inability to give informed consent.

FIGURE
Facial weakness or paralysis may be permanent

Primary outcome: Complete recovery

The study was designed to test the effectiveness of prednisolone and acyclovir’s effects on facial nerve recovery. The House-Brackmann scale was used to score recovery. The scale divides patients into 1 of 6 categories depending on the severity of facial nerve dysfunction, with grade 1 describing normal function and grade 6 indicating total paralysis.

The scale was applied to photographs of patients taken while smiling, raising eyebrows, at rest, and closing eyes. The photographs were assessed and graded independently by 3 experts: an otolaryngologist, a neurologist, and a plastic surgeon. They were unaware of the study group assignment or stage of assessment.

Of 496 patients who completed the study, 357 recovered fully at 3 months, with no further treatment needed. Of the remaining patients, 80 had fully recovered at 9 months and 59 still had some facial-nerve deficit. At 3 months, there was a significant difference in recovery rates in prednisolone comparison groups: 83% with prednisolone vs 63.6% without prednisolone, a difference of 19.4 percentage points (95% confidence interval [CI], 11.7 to 27.1; P<.001, number needed to treat [NNT]=5). There was no significant difference in recovery rates in acyclovir comparison groups: 71.2% with acyclovir vs 75% not treated with acyclovir, a difference of 4.5 % percentage points (95% CI, –12.4 to 3.3; unadjusted P=.30; adjusted P=.50). At 9 months, the rates of complete recovery were 94.4% in prednisolone treated groups vs 81.6% in no prednisolone treatment groups (NNT=8) (TABLE).

TABLE
Complete recovery was significantly higher in the group that received prednisolone without an antiviral

Adverse events

Adverse events included an expected range of minor symptoms associated with use of prednisolone and acyclovir, such as dizziness and vomiting. During the study, 3 patients died under circumstances unrelated to treatment: 2 were receiving double placebo and 1 received only acyclovir.¹

WHAT’S NEW: A treatment based on patient-oriented evidence

Neither corticosteroids nor antivirals are new treatments for Bell’s palsy. What is new is that we know what works (corticosteroids) and what does not work (antivirals). This randomized controlled trial finally gives us the evidence on patient-oriented outcomes that we need to make confident recommendations, primarily because it enrolled twice as many patients as all trials compiled for the Cochrane systematic reviews on this topic.^7,8

As an interesting side note, this is a good case study of how pathophysiologic reasoning sometimes leads us to good medical practice (corticosteroids in this case) and sometimes does not (antivirals in this case).

Isn’t it good to know that we can actually help patients with Bell’s palsy with corticosteroids and that antivirals are not necessary?

CAVEATS: Valacyclovir

Hato et al,⁹ in a Japanese study, showed that valacyclovir reaches a level of bioavailability that is 3 to 5 times more than acyclovir and may add some benefit to recovery when used in conjunction with prednisolone, particularly in more severe cases of Bell’s palsy.

The Hato study was a prospective, multicenter, randomized, placebo-controlled study that investigated the effects of valacyclovir (1000 mg/d for 5 days) and prednisolone in comparison with the effects of placebo and prednisolone for the treatment of Bell’s palsy.

The study outcomes included complete recovery from palsy; patients were followed until recovery occurred or more than 6 months in cases with severe prognosis. The patients in the Hato study had an average Yanagihara score of 15 when rating their facial palsy (which falls between House–Brackmann grades 4 and 5).

The overall rate of recovery of those treated with valacyclovir and prednisolone (96.5%) was significantly better (P<.05) than the rate among those treated with placebo and prednisolone (89.7%). In cases of complete or severe palsy, the rates of patients treated with both agents vs prednisolone alone who recovered were 95.7% (n=92) and 86.6% (n=82) (P<.05; NNT=11).

One big difference between the Sullivan and Hato studies is that the patients recruited for the Hato study had much more severe facial palsy (rated between 4 and 5) than in the Sullivan study (average=3.6), which suggests that there may be a use for valacyclovir in treating patients with complete facial palsy.⁶ Patients were all recruited from tertiary care centers as opposed to mainly from primary care settings as in the Sullivan study, consistent with the greater severity of cases in the Hato study.

Outcome assessors were not blinded to treatment assignments or stage of assessment in the Hato study, raising major concerns about the validity of the findings given the nature of facial paralysis as an outcome measure. We find the Sullivan study a more rigorous and convincing study. Nonetheless, future research may verify their findings and support the use of valacyclovir in the most severe cases of Bell’s palsy. For now, we are not convinced.

CHALLENGES TO IMPLEMENTATION: Easy to put into practice

Thankfully, some changes in practice are easy to implement. This is one of them. For those who prefer to prescribe prednisone, the dose of prednisolone used in the study, 25 mg bid, is equivalent to 60 mg of prednisone.

PURL surveillance system methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) surveillance system methodology.

Illustrative case

A 45-year-old man presents to your outpatient clinic within 24 hours after onset of left-sided facial nerve weakness and inability to smile on one side of his face. He asks for a therapy to help improve his symptoms quickly, as his daughter is getting married in a few months, and he will be in the wedding pictures.

Is there a treatment that will hasten his complete recovery?

Background: Insufficient statistical power until now

Many of us treat patients with Bell’s palsy with both corticosteroids and antiviral medications, such as acyclovir or valacyclovir, largely on the basis of pathophysiologic reasoning, because we’ve had no clear guidance from outcome studies. Until now, outcome studies have had mixed findings, and have been inconclusive.² Most outcome studies have lacked the statistical power to either detect or to rule out potential benefits convincingly. The study by Sullivan and colleagues is the first to have a sufficiently large study sample from which to draw more definitive conclusions based on patient-oriented outcomes.

Steroid plus antiviral makes sense, pathophysiologically

Corticosteroids are thought to decrease inflammation of the facial nerve during an episode of facial paralysis. Some have postulated that herpes simplex virus type I may be a cause of facial nerve paralysis, hence the treatment with antivirals.³

Most of our PURL surveillance system clinician reviewers said that they prescribe both corticosteroids and antivirals.

Guidelines: “probably, possibly”

For example, a report of the Quality Standards Subcommittee of the American Academy of Neurology concluded that benefit from both steroids and antivirals has not been well established in patients with Bell’s palsy. However, the report states that evidence suggests that steroids are safe and probably effective, while antivirals are also safe and possibly effective.⁴

In contrast, UpToDate suggests treating all patients seen within a week of symptom onset with corticosteroids (prednisone 60–80 mg daily) plus valacyclovir (1 g 3 times daily) for 1 week.⁵

CLINICAL CONTEXT: Quality of life, risk of permanent harm

Bell’s palsy, defined as an acute peripheral facial weakness of unknown cause, has an annual incidence of 20 to 32 per 100,000. Most patients recover completely, with or without treatment, but 20% to 30% can have permanent facial weakness or paralysis.

The time to resolution is a quality of life issue for those in whom disease does not resolve spontaneously.⁶

We think that this study provides convincing evidence that acyclovir is not indicated for Bell’s palsy and that corticosteroids are.

STUDY SUMMARY: 10-day treatment, starting promptly

This double-blind, placebo-controlled, randomized, multifactorial trial compared recovery of facial nerve function for patients randomized to receive 10 days of treatment with prednisolone (25 mg twice daily), acyclovir (400 mg 5 times daily), both agents, or placebo (lactose).

Inclusion criteria

Patients had to be at least 16 years of age (average age=44), with unilateral facial nerve weakness of no identifiable cause (eg, a diagnosis of Bell’s palsy). They were recruited mostly through their family doctors (75%) but also through emergency rooms and dental offices, and were referred to otolaryngologists at 17 Scottish hospitals within 72 hours.

The degree of initial facial paralysis was moderate to severe, based on the House-Brackmann scale, a widely used system for grading recovery from facial nerve paralysis. After the onset of symptoms, most patients (53.8%) initiated treatment within 24 hours, 32.1% within 48 hours, and 14.1% within 72 hours. Patients were assessed at baseline, 3 months, and 9 months.

Exclusion criteria

Exclusion criteria included pregnancy, breastfeeding, uncontrolled diabetes (Hb A_1c >8.0%), peptic ulcer disease, suppurative otitis media, herpes zoster, multiple sclerosis, systemic infection, sarcoid or other rare disorder, and inability to give informed consent.

FIGURE
Facial weakness or paralysis may be permanent

Primary outcome: Complete recovery

The study was designed to test the effectiveness of prednisolone and acyclovir’s effects on facial nerve recovery. The House-Brackmann scale was used to score recovery. The scale divides patients into 1 of 6 categories depending on the severity of facial nerve dysfunction, with grade 1 describing normal function and grade 6 indicating total paralysis.

The scale was applied to photographs of patients taken while smiling, raising eyebrows, at rest, and closing eyes. The photographs were assessed and graded independently by 3 experts: an otolaryngologist, a neurologist, and a plastic surgeon. They were unaware of the study group assignment or stage of assessment.

Of 496 patients who completed the study, 357 recovered fully at 3 months, with no further treatment needed. Of the remaining patients, 80 had fully recovered at 9 months and 59 still had some facial-nerve deficit. At 3 months, there was a significant difference in recovery rates in prednisolone comparison groups: 83% with prednisolone vs 63.6% without prednisolone, a difference of 19.4 percentage points (95% confidence interval [CI], 11.7 to 27.1; P<.001, number needed to treat [NNT]=5). There was no significant difference in recovery rates in acyclovir comparison groups: 71.2% with acyclovir vs 75% not treated with acyclovir, a difference of 4.5 % percentage points (95% CI, –12.4 to 3.3; unadjusted P=.30; adjusted P=.50). At 9 months, the rates of complete recovery were 94.4% in prednisolone treated groups vs 81.6% in no prednisolone treatment groups (NNT=8) (TABLE).

TABLE
Complete recovery was significantly higher in the group that received prednisolone without an antiviral

Adverse events

Adverse events included an expected range of minor symptoms associated with use of prednisolone and acyclovir, such as dizziness and vomiting. During the study, 3 patients died under circumstances unrelated to treatment: 2 were receiving double placebo and 1 received only acyclovir.¹

WHAT’S NEW: A treatment based on patient-oriented evidence

Neither corticosteroids nor antivirals are new treatments for Bell’s palsy. What is new is that we know what works (corticosteroids) and what does not work (antivirals). This randomized controlled trial finally gives us the evidence on patient-oriented outcomes that we need to make confident recommendations, primarily because it enrolled twice as many patients as all trials compiled for the Cochrane systematic reviews on this topic.^7,8

As an interesting side note, this is a good case study of how pathophysiologic reasoning sometimes leads us to good medical practice (corticosteroids in this case) and sometimes does not (antivirals in this case).

Isn’t it good to know that we can actually help patients with Bell’s palsy with corticosteroids and that antivirals are not necessary?

CAVEATS: Valacyclovir

Hato et al,⁹ in a Japanese study, showed that valacyclovir reaches a level of bioavailability that is 3 to 5 times more than acyclovir and may add some benefit to recovery when used in conjunction with prednisolone, particularly in more severe cases of Bell’s palsy.

The Hato study was a prospective, multicenter, randomized, placebo-controlled study that investigated the effects of valacyclovir (1000 mg/d for 5 days) and prednisolone in comparison with the effects of placebo and prednisolone for the treatment of Bell’s palsy.

The study outcomes included complete recovery from palsy; patients were followed until recovery occurred or more than 6 months in cases with severe prognosis. The patients in the Hato study had an average Yanagihara score of 15 when rating their facial palsy (which falls between House–Brackmann grades 4 and 5).

The overall rate of recovery of those treated with valacyclovir and prednisolone (96.5%) was significantly better (P<.05) than the rate among those treated with placebo and prednisolone (89.7%). In cases of complete or severe palsy, the rates of patients treated with both agents vs prednisolone alone who recovered were 95.7% (n=92) and 86.6% (n=82) (P<.05; NNT=11).

One big difference between the Sullivan and Hato studies is that the patients recruited for the Hato study had much more severe facial palsy (rated between 4 and 5) than in the Sullivan study (average=3.6), which suggests that there may be a use for valacyclovir in treating patients with complete facial palsy.⁶ Patients were all recruited from tertiary care centers as opposed to mainly from primary care settings as in the Sullivan study, consistent with the greater severity of cases in the Hato study.

Outcome assessors were not blinded to treatment assignments or stage of assessment in the Hato study, raising major concerns about the validity of the findings given the nature of facial paralysis as an outcome measure. We find the Sullivan study a more rigorous and convincing study. Nonetheless, future research may verify their findings and support the use of valacyclovir in the most severe cases of Bell’s palsy. For now, we are not convinced.

CHALLENGES TO IMPLEMENTATION: Easy to put into practice

Thankfully, some changes in practice are easy to implement. This is one of them. For those who prefer to prescribe prednisone, the dose of prednisolone used in the study, 25 mg bid, is equivalent to 60 mg of prednisone.

PURL surveillance system methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) surveillance system methodology.

Illustrative case

A 45-year-old man presents to your outpatient clinic within 24 hours after onset of left-sided facial nerve weakness and inability to smile on one side of his face. He asks for a therapy to help improve his symptoms quickly, as his daughter is getting married in a few months, and he will be in the wedding pictures.

Is there a treatment that will hasten his complete recovery?

Background: Insufficient statistical power until now

Many of us treat patients with Bell’s palsy with both corticosteroids and antiviral medications, such as acyclovir or valacyclovir, largely on the basis of pathophysiologic reasoning, because we’ve had no clear guidance from outcome studies. Until now, outcome studies have had mixed findings, and have been inconclusive.² Most outcome studies have lacked the statistical power to either detect or to rule out potential benefits convincingly. The study by Sullivan and colleagues is the first to have a sufficiently large study sample from which to draw more definitive conclusions based on patient-oriented outcomes.

Steroid plus antiviral makes sense, pathophysiologically

Corticosteroids are thought to decrease inflammation of the facial nerve during an episode of facial paralysis. Some have postulated that herpes simplex virus type I may be a cause of facial nerve paralysis, hence the treatment with antivirals.³

Most of our PURL surveillance system clinician reviewers said that they prescribe both corticosteroids and antivirals.

Guidelines: “probably, possibly”

For example, a report of the Quality Standards Subcommittee of the American Academy of Neurology concluded that benefit from both steroids and antivirals has not been well established in patients with Bell’s palsy. However, the report states that evidence suggests that steroids are safe and probably effective, while antivirals are also safe and possibly effective.⁴

In contrast, UpToDate suggests treating all patients seen within a week of symptom onset with corticosteroids (prednisone 60–80 mg daily) plus valacyclovir (1 g 3 times daily) for 1 week.⁵

CLINICAL CONTEXT: Quality of life, risk of permanent harm

Bell’s palsy, defined as an acute peripheral facial weakness of unknown cause, has an annual incidence of 20 to 32 per 100,000. Most patients recover completely, with or without treatment, but 20% to 30% can have permanent facial weakness or paralysis.

The time to resolution is a quality of life issue for those in whom disease does not resolve spontaneously.⁶

We think that this study provides convincing evidence that acyclovir is not indicated for Bell’s palsy and that corticosteroids are.

STUDY SUMMARY: 10-day treatment, starting promptly

This double-blind, placebo-controlled, randomized, multifactorial trial compared recovery of facial nerve function for patients randomized to receive 10 days of treatment with prednisolone (25 mg twice daily), acyclovir (400 mg 5 times daily), both agents, or placebo (lactose).

Inclusion criteria

Patients had to be at least 16 years of age (average age=44), with unilateral facial nerve weakness of no identifiable cause (eg, a diagnosis of Bell’s palsy). They were recruited mostly through their family doctors (75%) but also through emergency rooms and dental offices, and were referred to otolaryngologists at 17 Scottish hospitals within 72 hours.

The degree of initial facial paralysis was moderate to severe, based on the House-Brackmann scale, a widely used system for grading recovery from facial nerve paralysis. After the onset of symptoms, most patients (53.8%) initiated treatment within 24 hours, 32.1% within 48 hours, and 14.1% within 72 hours. Patients were assessed at baseline, 3 months, and 9 months.

Exclusion criteria

Exclusion criteria included pregnancy, breastfeeding, uncontrolled diabetes (Hb A_1c >8.0%), peptic ulcer disease, suppurative otitis media, herpes zoster, multiple sclerosis, systemic infection, sarcoid or other rare disorder, and inability to give informed consent.

FIGURE
Facial weakness or paralysis may be permanent

Primary outcome: Complete recovery

The study was designed to test the effectiveness of prednisolone and acyclovir’s effects on facial nerve recovery. The House-Brackmann scale was used to score recovery. The scale divides patients into 1 of 6 categories depending on the severity of facial nerve dysfunction, with grade 1 describing normal function and grade 6 indicating total paralysis.

The scale was applied to photographs of patients taken while smiling, raising eyebrows, at rest, and closing eyes. The photographs were assessed and graded independently by 3 experts: an otolaryngologist, a neurologist, and a plastic surgeon. They were unaware of the study group assignment or stage of assessment.

Of 496 patients who completed the study, 357 recovered fully at 3 months, with no further treatment needed. Of the remaining patients, 80 had fully recovered at 9 months and 59 still had some facial-nerve deficit. At 3 months, there was a significant difference in recovery rates in prednisolone comparison groups: 83% with prednisolone vs 63.6% without prednisolone, a difference of 19.4 percentage points (95% confidence interval [CI], 11.7 to 27.1; P<.001, number needed to treat [NNT]=5). There was no significant difference in recovery rates in acyclovir comparison groups: 71.2% with acyclovir vs 75% not treated with acyclovir, a difference of 4.5 % percentage points (95% CI, –12.4 to 3.3; unadjusted P=.30; adjusted P=.50). At 9 months, the rates of complete recovery were 94.4% in prednisolone treated groups vs 81.6% in no prednisolone treatment groups (NNT=8) (TABLE).

TABLE
Complete recovery was significantly higher in the group that received prednisolone without an antiviral

Adverse events

Adverse events included an expected range of minor symptoms associated with use of prednisolone and acyclovir, such as dizziness and vomiting. During the study, 3 patients died under circumstances unrelated to treatment: 2 were receiving double placebo and 1 received only acyclovir.¹

WHAT’S NEW: A treatment based on patient-oriented evidence

Neither corticosteroids nor antivirals are new treatments for Bell’s palsy. What is new is that we know what works (corticosteroids) and what does not work (antivirals). This randomized controlled trial finally gives us the evidence on patient-oriented outcomes that we need to make confident recommendations, primarily because it enrolled twice as many patients as all trials compiled for the Cochrane systematic reviews on this topic.^7,8

As an interesting side note, this is a good case study of how pathophysiologic reasoning sometimes leads us to good medical practice (corticosteroids in this case) and sometimes does not (antivirals in this case).

Isn’t it good to know that we can actually help patients with Bell’s palsy with corticosteroids and that antivirals are not necessary?

CAVEATS: Valacyclovir

Hato et al,⁹ in a Japanese study, showed that valacyclovir reaches a level of bioavailability that is 3 to 5 times more than acyclovir and may add some benefit to recovery when used in conjunction with prednisolone, particularly in more severe cases of Bell’s palsy.

The Hato study was a prospective, multicenter, randomized, placebo-controlled study that investigated the effects of valacyclovir (1000 mg/d for 5 days) and prednisolone in comparison with the effects of placebo and prednisolone for the treatment of Bell’s palsy.

The study outcomes included complete recovery from palsy; patients were followed until recovery occurred or more than 6 months in cases with severe prognosis. The patients in the Hato study had an average Yanagihara score of 15 when rating their facial palsy (which falls between House–Brackmann grades 4 and 5).

The overall rate of recovery of those treated with valacyclovir and prednisolone (96.5%) was significantly better (P<.05) than the rate among those treated with placebo and prednisolone (89.7%). In cases of complete or severe palsy, the rates of patients treated with both agents vs prednisolone alone who recovered were 95.7% (n=92) and 86.6% (n=82) (P<.05; NNT=11).

One big difference between the Sullivan and Hato studies is that the patients recruited for the Hato study had much more severe facial palsy (rated between 4 and 5) than in the Sullivan study (average=3.6), which suggests that there may be a use for valacyclovir in treating patients with complete facial palsy.⁶ Patients were all recruited from tertiary care centers as opposed to mainly from primary care settings as in the Sullivan study, consistent with the greater severity of cases in the Hato study.

Outcome assessors were not blinded to treatment assignments or stage of assessment in the Hato study, raising major concerns about the validity of the findings given the nature of facial paralysis as an outcome measure. We find the Sullivan study a more rigorous and convincing study. Nonetheless, future research may verify their findings and support the use of valacyclovir in the most severe cases of Bell’s palsy. For now, we are not convinced.

CHALLENGES TO IMPLEMENTATION: Easy to put into practice

Thankfully, some changes in practice are easy to implement. This is one of them. For those who prefer to prescribe prednisone, the dose of prednisolone used in the study, 25 mg bid, is equivalent to 60 mg of prednisone.

PURL surveillance system methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) surveillance system methodology.