Diabetic Amyotrophy: A Rare but Striking Neuropathy

A 45-year-old man, RT, with a six-month history of poorly controlled type 2 diabetes presents for evaluation of increased weakness and pain in the left lower extremity. The symptoms developed in the past three weeks. Previously able to ambulate without assistance, he purchased a cane yesterday due to concerns about falling.

RT reports poor adherence to his diabetes medications. His fingerstick blood sugars have ranged from 200 to 380 mg/dL over the past month. His weight has been stable; his BMI is 34. Review of other systems is negative. Vital signs include a blood pressure of 125/82 mm Hg; pulse, 74 beats/min; and respiratory rate, 16 breaths/min.

Physical examination is notable for muscle atrophy and tenderness to compression in the left quadriceps. Straight leg raise does not elicit pain bilaterally. Muscle strength is 4-/5 in the left hip with pain elicited on hip flexion, 4-/5 in the left knee, and 5/5 in the left ankle. Muscle strength is 4+/5 in the right hip, 5/5 in the right knee, and 5/5 in the right ankle. Muscle strength in both upper extremities is 5/5. Patellar deep tendon reflexes (DTRs) and ankle DTRs are absent bilaterally. Biceps and triceps DTRs are each 2+ bilaterally. Gait is slow and unsteady with use of the cane. Cranial nerves I-XII are intact. Sensation to sharp and dull testing is normal in both the upper and lower extremities.

Labwork reveals an A1C of 10.8%. The patient’s thyroid function studies, creatine kinase, and vitamin B₁₂ level are all in normal range. The serum creatinine is 1.2 mg/dL, and eGFR (estimated glomerular filtration rate) is 58 mL/min/1.73 m². Liver enzymes are normal, and complete blood count and other chemistry panels are unremarkable.

RT is referred to neurology. MRI of the thoracic and lumbar spine shows no mass lesions or disc disease. Electromyography reveals findings consistent with denervation and axonal damage in the proximal muscles in both lower extremities (left > right).

RT is diagnosed with diabetic amyotrophy and begins physical therapy three days a week. He achieves aggressive improvement in blood sugar control, and after three months, his A1C has improved to 7%.  Although still using a cane, he reports improved muscle strength in the lower extremities and better gait stability.

Continued on next page >>

PREVALENCE AND TYPES OF DIABETIC PERIPHERAL NEUROPATHY

According to the CDC, 25.8 million children and adults in the United States (8.3% of the population) have diabetes. Approximately 60% to 70% of them have mild to severe neuropathy.¹

Distal symmetric neuropathy is the most common form of diabetic peripheral neuropathy, accounting for more than 50% of cases. It is characterized by distal onset, predominately sensory polyneuropathy, and slow proximal progression.²

In contrast, diabetic amyotrophy is very rare, accounting for only 1% of all cases of neuropathy in diabetes. Prevalence is higher in those with type 2 versus type 1 diabetes (1.1% and 0.3%, respectively).^3,4 The most commonly misdiagnosed of the asymmetric diabetic neuropathies, diabetic amyotrophy is characterized by acute, progressive, asymmetrical weakness and pain in the muscles of the proximal lower extremities.⁵ It is also been referred to as proximal diabetic neuropathy, ischemic mononeuropathy multiplex, diabetic femoral neuropathy, Bruns-Garland syndrome, and diabetic lumbosacral polyradiculopathy.⁵

LOCALIZATION AND PATHOGENESIS

The site of the lesion in diabetic amyotrophy remains controversial; it is theorized that diabetic amyotrophy may result from involvement of multiple sites, such as lumbosacral anterior horn cells, motor roots, plexus, or motor axons to the muscles of the proximal lower limbs.⁴

The pathogenesis remains unknown. One theory is that hyperglycemia may cause metabolic derangements in nerve conduction. Another is that there is ischemic damage followed by axonal degeneration. Immune-mediated inflammatory processes, such as microvasculitis, have also been proposed as causes.^4,6

CLINICAL FEATURES

Diabetic amyotrophy is characterized by relatively rapid, progressive asymmetrical weakness and pain in the muscles in the proximal lower extremities; it develops over weeks to months and may continue for more than one year.^2,6 It typically begins unilaterally and can progress bilaterally—normally without impairment in sensation. Patients commonly experience pain in the hip, buttock, or thigh, as well as difficulty walking, standing, or climbing stairs. Occasionally, the condition is painless and can be associated with weight loss. It causes significant acute disability, with the degree of recovery variable.^2,4

Diabetic amyotrophy often presents either at diagnosis of diabetes or shortly thereafter. It most commonly affects men ages 40 to 50 and older, with higher incidence in type 2 diabetes.^2,5

Physical exam findings include proximal muscle weakness and atrophy in the quadriceps, hamstring, gluteal, hip adductors/abductors, and iliopsoas muscles.^4,5 Typically, there is no sensory impairment; however, mild sensory loss may be observed in patients with coexisting chronic distal sensorimotor polyneuropathy.^2,4 The patellar tendon reflexes are typically diminished or absent, and the ankle reflexes may be normal or diminished.⁴

Continued on next page >>

DIAGNOSTIC WORK-UP AND DIFFERENTIAL DIAGNOSIS

Although the diagnosis of diabetic amyotrophy is made primarily through detailed history taking and neurologic examination, other studies—electromyography, nerve conduction, imaging and labs, and nerve biopsy—may provide confirmation. Referral to neurology should also be considered.

The differential diagnosis is ­extensive and includes myopathies, muscular dystrophies, intervertebral disc disease, spinal stenosis, polyradiculopathies due to porphyria, amyloid, heavy metal poisoning, anterior horn cell diseases  (eg, poliomyelitis), neoplasms, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, monoclonal gammopathy, inflammatory vasculitis, hypothyroidism, vitamin B₆ or B₁₂ deficiencies, syphilis, AIDS, Lyme disease, and Charcot-Marie-Tooth disease.^2,5-7 Diabetic neuropathic cachexia should also be considered in the differential, as it presents with weight loss and lower limb pain but no weakness.⁵

Lab evaluation should begin with analysis of fasting plasma glucose, complete blood count, comprehensive metabolic profile, A1C, erythrocyte sedimentation rate (ESR), creatine kinase, vitamin B₁₂, and thyroid-stimulating hormone levels.⁷ Elevations in ESR and positive rheumatoid factor and antinuclear antibody can occur in patients with diabetic amyotrophy and are suggestive of a coexisting autoimmune disorder.⁶ Serum creatine kinase and thyroid function studies are normal.⁴ Additional lab tests, if clinically indicated, include paraneoplastic panel to evaluate for occult malignancy, antimyelin-associated glycoprotein antibodies, antiganglioside antibodies, cryoglobulins, cerebrospinal fluid analysis, porphyrin titers, and testing for heavy metals.⁷

Electrodiagnostic studies are recommended if the diagnosis of diabetic amyotrophy remains unclear following history taking, physical examination, and preliminary testing. Electromyography and nerve conduction studies typically reveal findings consistent with denervation and axonal damage in proximal muscles of the lower extremities.⁴ If demyelination is observed, a diagnosis of chronic demyelinating polyneuropathy should be considered.⁵

Nerve biopsy is considered if the diagnosis remains unclear after laboratory and electrodiagnostic testing or when confirmation of the diagnosis is needed before starting aggressive treatment. The sural and superficial peroneal nerves are preferred for biopsy. In cases of diabetic amyotrophy, sural nerve biopsy reveals significant fiber loss in an asymmetric fashion, resembling focal ischemia.⁵

MRI or CT scan of the lumbosacral spine is employed to exclude mass lesions and structural disorders such as spinal stenosis and disc disease.⁴ Cerebrospinal fluid is typically acellular, with a mildly elevated protein level of 60 to 100 mg/dL (but occasionally as high as 400 mg/dL).⁵

Continued on next page >>

PROGNOSIS AND MANAGEMENT

The course of diabetic amyo­trophy is variable. There is often gradual but incomplete restoration in muscle strength in correlation with aggressive glycemic control and physical therapy.² The majority of patients have residual muscle weakness, absent patellar and/or ankle DTRs, exercise-related pain, stiffness, and difficulty walking or climbing stairs. Full recovery of strength only occurs in 10% to 20% of patients.⁶

Treatment with IV immunoglobulin or other immuno­suppressive drugs is controversial. According to a Cochrane review of immunotherapy for diabetic amyotrophy, only one completed controlled trial using IV methylprednisolone was found. There is currently no evidence to support use of immunoglobulins to halt progression and improve symptoms.⁸

Neuropathic pain may be ­difficult to control. The severe pain associated with diabetic amyotrophy begins to diminish several months after onset, but residual pain may persist for several years. Pregabalin, duloxetine, tricyclic antidepressants, antiepileptic drugs, and narcotic analgesics can be helpful.^2,4 High doses of corticosteroids may lead to improvement of severe pain in some patients with diabetic amyotrophy.⁵

References >>

REFERENCES

1. CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.

2. Nagsayi S, Somasekhar C, James CM. Diagnosis and management of diabetic amyotrophy. Geriatric Med. 2010;40:327-329.

3. Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Diabetic neuropathy part 1: overview and symmetric phenotypes. Neurol Clin. 2013;31(2):425-445.

4. Sander HW, Chokroverty S. Diabetic amyotrophy: current concepts. Semin Neurol. 1996;16(2):173-177.

5. Pasnoor M, Dimachkie MM, Barohn RJ. Diabetic neuropathy part 2: proximal and asymmetric phenotypes. Neurol Clin. 2013;31(2): 447-462.

6. Idiculla J, Shirazi N, Opacka-Juffry J, Ganapathi. Diabetic amyotrophy: a brief review. Natl Med J India. 2004;17(4):
200-202.

7. Azhary H, Farooq M, Bhanushali M, Majid A. Peripheral neuropathy: differential diagnosis and management. Am Fam Physician. 2010;81(7):887-892.

8. Chan YC, Lo YL, Chan ES. Immunotherapy for diabetic amyotrophy. Cochrane Database Syst Rev. 2012;13(6):2-6.

A 45-year-old man, RT, with a six-month history of poorly controlled type 2 diabetes presents for evaluation of increased weakness and pain in the left lower extremity. The symptoms developed in the past three weeks. Previously able to ambulate without assistance, he purchased a cane yesterday due to concerns about falling.

RT reports poor adherence to his diabetes medications. His fingerstick blood sugars have ranged from 200 to 380 mg/dL over the past month. His weight has been stable; his BMI is 34. Review of other systems is negative. Vital signs include a blood pressure of 125/82 mm Hg; pulse, 74 beats/min; and respiratory rate, 16 breaths/min.

Physical examination is notable for muscle atrophy and tenderness to compression in the left quadriceps. Straight leg raise does not elicit pain bilaterally. Muscle strength is 4-/5 in the left hip with pain elicited on hip flexion, 4-/5 in the left knee, and 5/5 in the left ankle. Muscle strength is 4+/5 in the right hip, 5/5 in the right knee, and 5/5 in the right ankle. Muscle strength in both upper extremities is 5/5. Patellar deep tendon reflexes (DTRs) and ankle DTRs are absent bilaterally. Biceps and triceps DTRs are each 2+ bilaterally. Gait is slow and unsteady with use of the cane. Cranial nerves I-XII are intact. Sensation to sharp and dull testing is normal in both the upper and lower extremities.

Labwork reveals an A1C of 10.8%. The patient’s thyroid function studies, creatine kinase, and vitamin B₁₂ level are all in normal range. The serum creatinine is 1.2 mg/dL, and eGFR (estimated glomerular filtration rate) is 58 mL/min/1.73 m². Liver enzymes are normal, and complete blood count and other chemistry panels are unremarkable.

RT is referred to neurology. MRI of the thoracic and lumbar spine shows no mass lesions or disc disease. Electromyography reveals findings consistent with denervation and axonal damage in the proximal muscles in both lower extremities (left > right).

RT is diagnosed with diabetic amyotrophy and begins physical therapy three days a week. He achieves aggressive improvement in blood sugar control, and after three months, his A1C has improved to 7%.  Although still using a cane, he reports improved muscle strength in the lower extremities and better gait stability.

Continued on next page >>

PREVALENCE AND TYPES OF DIABETIC PERIPHERAL NEUROPATHY

According to the CDC, 25.8 million children and adults in the United States (8.3% of the population) have diabetes. Approximately 60% to 70% of them have mild to severe neuropathy.¹

Distal symmetric neuropathy is the most common form of diabetic peripheral neuropathy, accounting for more than 50% of cases. It is characterized by distal onset, predominately sensory polyneuropathy, and slow proximal progression.²

In contrast, diabetic amyotrophy is very rare, accounting for only 1% of all cases of neuropathy in diabetes. Prevalence is higher in those with type 2 versus type 1 diabetes (1.1% and 0.3%, respectively).^3,4 The most commonly misdiagnosed of the asymmetric diabetic neuropathies, diabetic amyotrophy is characterized by acute, progressive, asymmetrical weakness and pain in the muscles of the proximal lower extremities.⁵ It is also been referred to as proximal diabetic neuropathy, ischemic mononeuropathy multiplex, diabetic femoral neuropathy, Bruns-Garland syndrome, and diabetic lumbosacral polyradiculopathy.⁵

LOCALIZATION AND PATHOGENESIS

The site of the lesion in diabetic amyotrophy remains controversial; it is theorized that diabetic amyotrophy may result from involvement of multiple sites, such as lumbosacral anterior horn cells, motor roots, plexus, or motor axons to the muscles of the proximal lower limbs.⁴

The pathogenesis remains unknown. One theory is that hyperglycemia may cause metabolic derangements in nerve conduction. Another is that there is ischemic damage followed by axonal degeneration. Immune-mediated inflammatory processes, such as microvasculitis, have also been proposed as causes.^4,6

CLINICAL FEATURES

Diabetic amyotrophy is characterized by relatively rapid, progressive asymmetrical weakness and pain in the muscles in the proximal lower extremities; it develops over weeks to months and may continue for more than one year.^2,6 It typically begins unilaterally and can progress bilaterally—normally without impairment in sensation. Patients commonly experience pain in the hip, buttock, or thigh, as well as difficulty walking, standing, or climbing stairs. Occasionally, the condition is painless and can be associated with weight loss. It causes significant acute disability, with the degree of recovery variable.^2,4

Diabetic amyotrophy often presents either at diagnosis of diabetes or shortly thereafter. It most commonly affects men ages 40 to 50 and older, with higher incidence in type 2 diabetes.^2,5

Physical exam findings include proximal muscle weakness and atrophy in the quadriceps, hamstring, gluteal, hip adductors/abductors, and iliopsoas muscles.^4,5 Typically, there is no sensory impairment; however, mild sensory loss may be observed in patients with coexisting chronic distal sensorimotor polyneuropathy.^2,4 The patellar tendon reflexes are typically diminished or absent, and the ankle reflexes may be normal or diminished.⁴

Continued on next page >>

DIAGNOSTIC WORK-UP AND DIFFERENTIAL DIAGNOSIS

Although the diagnosis of diabetic amyotrophy is made primarily through detailed history taking and neurologic examination, other studies—electromyography, nerve conduction, imaging and labs, and nerve biopsy—may provide confirmation. Referral to neurology should also be considered.

The differential diagnosis is ­extensive and includes myopathies, muscular dystrophies, intervertebral disc disease, spinal stenosis, polyradiculopathies due to porphyria, amyloid, heavy metal poisoning, anterior horn cell diseases  (eg, poliomyelitis), neoplasms, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, monoclonal gammopathy, inflammatory vasculitis, hypothyroidism, vitamin B₆ or B₁₂ deficiencies, syphilis, AIDS, Lyme disease, and Charcot-Marie-Tooth disease.^2,5-7 Diabetic neuropathic cachexia should also be considered in the differential, as it presents with weight loss and lower limb pain but no weakness.⁵

Lab evaluation should begin with analysis of fasting plasma glucose, complete blood count, comprehensive metabolic profile, A1C, erythrocyte sedimentation rate (ESR), creatine kinase, vitamin B₁₂, and thyroid-stimulating hormone levels.⁷ Elevations in ESR and positive rheumatoid factor and antinuclear antibody can occur in patients with diabetic amyotrophy and are suggestive of a coexisting autoimmune disorder.⁶ Serum creatine kinase and thyroid function studies are normal.⁴ Additional lab tests, if clinically indicated, include paraneoplastic panel to evaluate for occult malignancy, antimyelin-associated glycoprotein antibodies, antiganglioside antibodies, cryoglobulins, cerebrospinal fluid analysis, porphyrin titers, and testing for heavy metals.⁷

Electrodiagnostic studies are recommended if the diagnosis of diabetic amyotrophy remains unclear following history taking, physical examination, and preliminary testing. Electromyography and nerve conduction studies typically reveal findings consistent with denervation and axonal damage in proximal muscles of the lower extremities.⁴ If demyelination is observed, a diagnosis of chronic demyelinating polyneuropathy should be considered.⁵

Nerve biopsy is considered if the diagnosis remains unclear after laboratory and electrodiagnostic testing or when confirmation of the diagnosis is needed before starting aggressive treatment. The sural and superficial peroneal nerves are preferred for biopsy. In cases of diabetic amyotrophy, sural nerve biopsy reveals significant fiber loss in an asymmetric fashion, resembling focal ischemia.⁵

MRI or CT scan of the lumbosacral spine is employed to exclude mass lesions and structural disorders such as spinal stenosis and disc disease.⁴ Cerebrospinal fluid is typically acellular, with a mildly elevated protein level of 60 to 100 mg/dL (but occasionally as high as 400 mg/dL).⁵

Continued on next page >>

PROGNOSIS AND MANAGEMENT

The course of diabetic amyo­trophy is variable. There is often gradual but incomplete restoration in muscle strength in correlation with aggressive glycemic control and physical therapy.² The majority of patients have residual muscle weakness, absent patellar and/or ankle DTRs, exercise-related pain, stiffness, and difficulty walking or climbing stairs. Full recovery of strength only occurs in 10% to 20% of patients.⁶

Treatment with IV immunoglobulin or other immuno­suppressive drugs is controversial. According to a Cochrane review of immunotherapy for diabetic amyotrophy, only one completed controlled trial using IV methylprednisolone was found. There is currently no evidence to support use of immunoglobulins to halt progression and improve symptoms.⁸

Neuropathic pain may be ­difficult to control. The severe pain associated with diabetic amyotrophy begins to diminish several months after onset, but residual pain may persist for several years. Pregabalin, duloxetine, tricyclic antidepressants, antiepileptic drugs, and narcotic analgesics can be helpful.^2,4 High doses of corticosteroids may lead to improvement of severe pain in some patients with diabetic amyotrophy.⁵

References >>

REFERENCES

1. CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.

2. Nagsayi S, Somasekhar C, James CM. Diagnosis and management of diabetic amyotrophy. Geriatric Med. 2010;40:327-329.

3. Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Diabetic neuropathy part 1: overview and symmetric phenotypes. Neurol Clin. 2013;31(2):425-445.

4. Sander HW, Chokroverty S. Diabetic amyotrophy: current concepts. Semin Neurol. 1996;16(2):173-177.

5. Pasnoor M, Dimachkie MM, Barohn RJ. Diabetic neuropathy part 2: proximal and asymmetric phenotypes. Neurol Clin. 2013;31(2): 447-462.

6. Idiculla J, Shirazi N, Opacka-Juffry J, Ganapathi. Diabetic amyotrophy: a brief review. Natl Med J India. 2004;17(4):
200-202.

7. Azhary H, Farooq M, Bhanushali M, Majid A. Peripheral neuropathy: differential diagnosis and management. Am Fam Physician. 2010;81(7):887-892.

8. Chan YC, Lo YL, Chan ES. Immunotherapy for diabetic amyotrophy. Cochrane Database Syst Rev. 2012;13(6):2-6.

A 45-year-old man, RT, with a six-month history of poorly controlled type 2 diabetes presents for evaluation of increased weakness and pain in the left lower extremity. The symptoms developed in the past three weeks. Previously able to ambulate without assistance, he purchased a cane yesterday due to concerns about falling.

RT reports poor adherence to his diabetes medications. His fingerstick blood sugars have ranged from 200 to 380 mg/dL over the past month. His weight has been stable; his BMI is 34. Review of other systems is negative. Vital signs include a blood pressure of 125/82 mm Hg; pulse, 74 beats/min; and respiratory rate, 16 breaths/min.

Physical examination is notable for muscle atrophy and tenderness to compression in the left quadriceps. Straight leg raise does not elicit pain bilaterally. Muscle strength is 4-/5 in the left hip with pain elicited on hip flexion, 4-/5 in the left knee, and 5/5 in the left ankle. Muscle strength is 4+/5 in the right hip, 5/5 in the right knee, and 5/5 in the right ankle. Muscle strength in both upper extremities is 5/5. Patellar deep tendon reflexes (DTRs) and ankle DTRs are absent bilaterally. Biceps and triceps DTRs are each 2+ bilaterally. Gait is slow and unsteady with use of the cane. Cranial nerves I-XII are intact. Sensation to sharp and dull testing is normal in both the upper and lower extremities.

Labwork reveals an A1C of 10.8%. The patient’s thyroid function studies, creatine kinase, and vitamin B₁₂ level are all in normal range. The serum creatinine is 1.2 mg/dL, and eGFR (estimated glomerular filtration rate) is 58 mL/min/1.73 m². Liver enzymes are normal, and complete blood count and other chemistry panels are unremarkable.

RT is referred to neurology. MRI of the thoracic and lumbar spine shows no mass lesions or disc disease. Electromyography reveals findings consistent with denervation and axonal damage in the proximal muscles in both lower extremities (left > right).

RT is diagnosed with diabetic amyotrophy and begins physical therapy three days a week. He achieves aggressive improvement in blood sugar control, and after three months, his A1C has improved to 7%.  Although still using a cane, he reports improved muscle strength in the lower extremities and better gait stability.

Continued on next page >>

PREVALENCE AND TYPES OF DIABETIC PERIPHERAL NEUROPATHY

According to the CDC, 25.8 million children and adults in the United States (8.3% of the population) have diabetes. Approximately 60% to 70% of them have mild to severe neuropathy.¹

Distal symmetric neuropathy is the most common form of diabetic peripheral neuropathy, accounting for more than 50% of cases. It is characterized by distal onset, predominately sensory polyneuropathy, and slow proximal progression.²

In contrast, diabetic amyotrophy is very rare, accounting for only 1% of all cases of neuropathy in diabetes. Prevalence is higher in those with type 2 versus type 1 diabetes (1.1% and 0.3%, respectively).^3,4 The most commonly misdiagnosed of the asymmetric diabetic neuropathies, diabetic amyotrophy is characterized by acute, progressive, asymmetrical weakness and pain in the muscles of the proximal lower extremities.⁵ It is also been referred to as proximal diabetic neuropathy, ischemic mononeuropathy multiplex, diabetic femoral neuropathy, Bruns-Garland syndrome, and diabetic lumbosacral polyradiculopathy.⁵

LOCALIZATION AND PATHOGENESIS

The site of the lesion in diabetic amyotrophy remains controversial; it is theorized that diabetic amyotrophy may result from involvement of multiple sites, such as lumbosacral anterior horn cells, motor roots, plexus, or motor axons to the muscles of the proximal lower limbs.⁴

The pathogenesis remains unknown. One theory is that hyperglycemia may cause metabolic derangements in nerve conduction. Another is that there is ischemic damage followed by axonal degeneration. Immune-mediated inflammatory processes, such as microvasculitis, have also been proposed as causes.^4,6

CLINICAL FEATURES

Diabetic amyotrophy is characterized by relatively rapid, progressive asymmetrical weakness and pain in the muscles in the proximal lower extremities; it develops over weeks to months and may continue for more than one year.^2,6 It typically begins unilaterally and can progress bilaterally—normally without impairment in sensation. Patients commonly experience pain in the hip, buttock, or thigh, as well as difficulty walking, standing, or climbing stairs. Occasionally, the condition is painless and can be associated with weight loss. It causes significant acute disability, with the degree of recovery variable.^2,4

Diabetic amyotrophy often presents either at diagnosis of diabetes or shortly thereafter. It most commonly affects men ages 40 to 50 and older, with higher incidence in type 2 diabetes.^2,5

Physical exam findings include proximal muscle weakness and atrophy in the quadriceps, hamstring, gluteal, hip adductors/abductors, and iliopsoas muscles.^4,5 Typically, there is no sensory impairment; however, mild sensory loss may be observed in patients with coexisting chronic distal sensorimotor polyneuropathy.^2,4 The patellar tendon reflexes are typically diminished or absent, and the ankle reflexes may be normal or diminished.⁴

Continued on next page >>

DIAGNOSTIC WORK-UP AND DIFFERENTIAL DIAGNOSIS

Although the diagnosis of diabetic amyotrophy is made primarily through detailed history taking and neurologic examination, other studies—electromyography, nerve conduction, imaging and labs, and nerve biopsy—may provide confirmation. Referral to neurology should also be considered.

The differential diagnosis is ­extensive and includes myopathies, muscular dystrophies, intervertebral disc disease, spinal stenosis, polyradiculopathies due to porphyria, amyloid, heavy metal poisoning, anterior horn cell diseases  (eg, poliomyelitis), neoplasms, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, monoclonal gammopathy, inflammatory vasculitis, hypothyroidism, vitamin B₆ or B₁₂ deficiencies, syphilis, AIDS, Lyme disease, and Charcot-Marie-Tooth disease.^2,5-7 Diabetic neuropathic cachexia should also be considered in the differential, as it presents with weight loss and lower limb pain but no weakness.⁵

Lab evaluation should begin with analysis of fasting plasma glucose, complete blood count, comprehensive metabolic profile, A1C, erythrocyte sedimentation rate (ESR), creatine kinase, vitamin B₁₂, and thyroid-stimulating hormone levels.⁷ Elevations in ESR and positive rheumatoid factor and antinuclear antibody can occur in patients with diabetic amyotrophy and are suggestive of a coexisting autoimmune disorder.⁶ Serum creatine kinase and thyroid function studies are normal.⁴ Additional lab tests, if clinically indicated, include paraneoplastic panel to evaluate for occult malignancy, antimyelin-associated glycoprotein antibodies, antiganglioside antibodies, cryoglobulins, cerebrospinal fluid analysis, porphyrin titers, and testing for heavy metals.⁷

Electrodiagnostic studies are recommended if the diagnosis of diabetic amyotrophy remains unclear following history taking, physical examination, and preliminary testing. Electromyography and nerve conduction studies typically reveal findings consistent with denervation and axonal damage in proximal muscles of the lower extremities.⁴ If demyelination is observed, a diagnosis of chronic demyelinating polyneuropathy should be considered.⁵

Nerve biopsy is considered if the diagnosis remains unclear after laboratory and electrodiagnostic testing or when confirmation of the diagnosis is needed before starting aggressive treatment. The sural and superficial peroneal nerves are preferred for biopsy. In cases of diabetic amyotrophy, sural nerve biopsy reveals significant fiber loss in an asymmetric fashion, resembling focal ischemia.⁵

MRI or CT scan of the lumbosacral spine is employed to exclude mass lesions and structural disorders such as spinal stenosis and disc disease.⁴ Cerebrospinal fluid is typically acellular, with a mildly elevated protein level of 60 to 100 mg/dL (but occasionally as high as 400 mg/dL).⁵

Continued on next page >>

PROGNOSIS AND MANAGEMENT

The course of diabetic amyo­trophy is variable. There is often gradual but incomplete restoration in muscle strength in correlation with aggressive glycemic control and physical therapy.² The majority of patients have residual muscle weakness, absent patellar and/or ankle DTRs, exercise-related pain, stiffness, and difficulty walking or climbing stairs. Full recovery of strength only occurs in 10% to 20% of patients.⁶

Treatment with IV immunoglobulin or other immuno­suppressive drugs is controversial. According to a Cochrane review of immunotherapy for diabetic amyotrophy, only one completed controlled trial using IV methylprednisolone was found. There is currently no evidence to support use of immunoglobulins to halt progression and improve symptoms.⁸

Neuropathic pain may be ­difficult to control. The severe pain associated with diabetic amyotrophy begins to diminish several months after onset, but residual pain may persist for several years. Pregabalin, duloxetine, tricyclic antidepressants, antiepileptic drugs, and narcotic analgesics can be helpful.^2,4 High doses of corticosteroids may lead to improvement of severe pain in some patients with diabetic amyotrophy.⁵

References >>

REFERENCES

1. CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.

2. Nagsayi S, Somasekhar C, James CM. Diagnosis and management of diabetic amyotrophy. Geriatric Med. 2010;40:327-329.

3. Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Diabetic neuropathy part 1: overview and symmetric phenotypes. Neurol Clin. 2013;31(2):425-445.

4. Sander HW, Chokroverty S. Diabetic amyotrophy: current concepts. Semin Neurol. 1996;16(2):173-177.

5. Pasnoor M, Dimachkie MM, Barohn RJ. Diabetic neuropathy part 2: proximal and asymmetric phenotypes. Neurol Clin. 2013;31(2): 447-462.

6. Idiculla J, Shirazi N, Opacka-Juffry J, Ganapathi. Diabetic amyotrophy: a brief review. Natl Med J India. 2004;17(4):
200-202.

7. Azhary H, Farooq M, Bhanushali M, Majid A. Peripheral neuropathy: differential diagnosis and management. Am Fam Physician. 2010;81(7):887-892.

8. Chan YC, Lo YL, Chan ES. Immunotherapy for diabetic amyotrophy. Cochrane Database Syst Rev. 2012;13(6):2-6.