What are the clinical features and diagnosis of diabetic amyotrophy in a patient with a history of poorly controlled type 2 diabetes?

Diabetic Amyotrophy: Clinical Features and Diagnosis

Clinical Presentation

Diabetic amyotrophy is a distinctive form of diabetic neuropathy characterized by abrupt onset of severe proximal lower limb pain, asymmetric weakness, and muscle wasting, typically occurring in patients with type 2 diabetes who may paradoxically have good glycemic control at presentation. 1

Cardinal Features

• Proximal lower limb weakness and wasting is the predominant feature, affecting the thighs and hip flexors with significant functional impairment 1
• Severe pain in the affected limbs occurs in approximately 85% of patients, often described as burning or aching in quality and can be the presenting symptom 1
• Significant unintentional weight loss is common and may precede or accompany the neurologic symptoms 1
• Asymmetric presentation is classic but not universal—only about 40% display the textbook asymmetric pattern, while others present with unilateral or bilateral symmetric involvement 1

Atypical Presentations to Recognize

• Upper extremity involvement can occur, affecting the shoulder girdle and arms in approximately 15% of cases 1, 2
• Progression to severe quadriparesis is rare but documented, with potential for severe disability despite the generally favorable prognosis 2
• Absence of pain occurs in a minority of patients, making diagnosis more challenging 1
• Distal sensory peripheral neuropathy frequently coexists and should not exclude the diagnosis 1

Important Clinical Context

• Good glycemic control at diagnosis is paradoxically common, distinguishing this from typical diabetic peripheral neuropathy where poor control is the norm 1
• Type 2 diabetes is the typical setting, though cases in adolescents with poorly controlled type 2 diabetes have been reported 3
• Acute to subacute onset over days to weeks distinguishes this from the gradual, length-dependent progression of typical diabetic peripheral neuropathy 4, 1

Diagnostic Approach

Clinical Examination

Assessment should focus on documenting the pattern of proximal muscle weakness, degree of muscle wasting, presence and distribution of pain, and associated distal sensory findings. 1

• Proximal muscle strength testing of hip flexors, knee extensors, and thigh muscles bilaterally to document asymmetry and severity 1
• Muscle bulk assessment to identify wasting in the quadriceps and other proximal lower limb muscles 1
• Distal sensory examination using 10-g monofilament, 128-Hz tuning fork for vibration, and pinprick testing to identify coexisting distal symmetric polyneuropathy 4
• Ankle reflexes are typically reduced or absent, consistent with coexisting peripheral neuropathy 4, 1

Electrodiagnostic Testing

Bilateral electromyography and nerve conduction studies remain the most helpful diagnostic test and should be performed in all suspected cases. 1

• EMG findings show denervation changes in proximal muscles with fibrillation potentials and positive sharp waves 1, 5
• Nerve conduction studies typically reveal mild distal and moderate proximal neuropathy in lower limbs with axonal features 1, 5
• Motor nerve conduction velocities may be mildly slowed but show predominantly axonal rather than demyelinating features 5

Laboratory Evaluation

Initial blood work should focus on confirming diabetes diagnosis, assessing glycemic control, and excluding alternative causes of proximal neuropathy. 6

• HbA1c measurement to assess glycemic control, though levels may be surprisingly good at presentation 6, 1
• Vitamin B12 levels to exclude B12 deficiency neuropathy, particularly in patients on metformin 6
• Thyroid function tests (TSH) to rule out hypothyroidism as an alternative cause 6
• Renal function (creatinine, eGFR) to exclude uremic neuropathy 6
• Fasting plasma glucose or OGTT if diabetes diagnosis not yet established 7

Differential Diagnosis Considerations

Diabetic amyotrophy must be differentiated from acute inflammatory demyelinating polyneuropathy (AIDP/Guillain-Barré syndrome) and chronic inflammatory demyelinating polyneuropathy (CIDP), which can occur with increased frequency in diabetes. 8

• AIDP presents with ascending motor weakness, areflexia, and demyelinating features on electrodiagnostics (markedly prolonged distal latencies, severely slowed conduction velocities, conduction block) rather than the axonal pattern seen in diabetic amyotrophy 8
• CIDP occurs with two-fold increased risk in diabetes and requires immunotherapy, making this distinction critical 8
• Electrophysiology should be obtained urgently if presentation includes acute onset over days, motor predominance with global areflexia, or rapid progression suggesting inflammatory neuropathy 8

Diagnostic Pitfalls to Avoid

• Assuming all diabetic neuropathy is distal and symmetric—diabetic amyotrophy presents proximally and often asymmetrically 1
• Dismissing the diagnosis when glycemic control is good—paradoxically, many patients have well-controlled diabetes at presentation 1
• Failing to perform bilateral EMG/NCS—this is essential for diagnosis and cannot be replaced by clinical examination alone 1
• Missing upper extremity involvement—examine shoulder girdle and arms even when lower limbs are predominantly affected 1, 2
• Not considering inflammatory neuropathies—obtain electrophysiology if features are atypical, as CIDP requires immunotherapy 8
• Overlooking the potential for severe progression—while prognosis is generally favorable, progression to quadriparesis can occur 2

Prognosis and Natural History

• Reversibility is common, with approximately 70% of patients showing largely or totally reversible deficits over months to years 1
• No reliable prognostic factors have been identified to predict recovery 1
• Immunomodulatory therapy with intravenous immunoglobulin has shown promise in case reports with rapid clinical, functional, and electrical improvement, suggesting an immune-mediated component 9, 3