What are the etiologies and recommended work‑up for bilateral upper‑extremity weakness?

Bilateral Upper Extremity Weakness: Etiologies and Diagnostic Approach

Immediate Life-Threatening Evaluation

The most critical first step is to immediately assess for Guillain-Barré Syndrome (GBS), as approximately 20% of patients develop life-threatening respiratory failure requiring urgent intervention. 1, 2

Urgent GBS Assessment

• Check for rapidly progressive bilateral ascending weakness with paresthesias and areflexia or hyporeflexia, which are key diagnostic features of GBS, though asymmetric patterns can occur in variants 1, 2
• Measure vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures immediately using the "20/30/40 rule" to assess respiratory failure risk 1, 2
• Assess for preceding infection within 6 weeks, such as Campylobacter jejuni, CMV, Hepatitis E, Mycoplasma, EBV, or Zika, as approximately two-thirds of GBS patients report this history 1, 2
• Monitor for dysautonomia including blood pressure and heart rate instability, as this can be life-threatening 1, 2

Critical Imaging Priority

Order MRI of the entire spine with and without contrast as the critical first test to exclude cord compression, transverse myelitis, or nerve root enhancement characteristic of GBS 1, 2

• Bilateral hand involvement with fine motor dysfunction suggests a cervical cord lesion at C5-C7 level affecting both upper extremities, which may require urgent surgical decompression if confirmed 1, 3
• Hyperreflexia, clonus, or extensor plantar responses indicate spinal cord pathology requiring emergency MRI 4

Primary Etiologies by Anatomic Localization

Central Nervous System Causes

Cervical myelopathy presents with progressive bilateral upper extremity weakness, often with multilevel degenerative changes, compressive myelopathy, significant spinal canal stenosis, and severe spondylosis on imaging 3

• Check for bladder/bowel dysfunction and sensory level on examination, as these distinguish cord compression from peripheral causes 1, 4
• Presence of hyperreflexia distinguishes central from peripheral etiologies 4

Peripheral Nerve/Root Causes

GBS remains the most urgent peripheral cause, characterized by sensorimotor polyradiculoneuropathy with reduced conduction velocities, temporal dispersion, or conduction blocks on electrodiagnostic studies 1, 2

• CSF analysis should demonstrate albumino-cytological dissociation (elevated protein with normal cell count), though protein may be normal in the first week 1, 2
• Look for "sural sparing pattern" where sural sensory nerve action potential is normal while median and ulnar sensory nerve action potentials are abnormal—typical for GBS 2

Bilateral brachial plexopathy can occur from trauma, radiation, or inflammatory causes 5

Bilateral peripheral neuropathies typically affect feet before hands and progress more gradually, but metabolic causes should be evaluated 1, 2

Vascular Causes

Bilateral subclavian stenosis can cause upper extremity weakness and paresthesias 6

• Measure blood pressure in both arms and note inter-arm difference, as this can indicate subclavian stenosis 2
• Palpate bilateral radial, ulnar, and brachial pulses and auscultate supraclavicular fossae for bruits 2

Rare Causes

Bilateral musculocutaneous neuropathy can occur after vigorous stretching of both upper extremities, presenting with bilateral forearm tingling and upper extremity weakness 7

Diagnostic Workup Algorithm

First-Line Studies (Immediate)

1. MRI entire spine with and without contrast to exclude structural lesions 1, 2
2. Nerve conduction studies and EMG to identify sensorimotor polyradiculoneuropathy patterns 1, 2
3. CSF analysis for albumino-cytological dissociation if demyelinating pattern suspected 1, 2
4. Vital capacity and respiratory function monitoring if GBS suspected 1, 2

Second-Line Metabolic Workup

• Fasting glucose and HbA1c to diagnose diabetes, the most common cause of symmetric polyneuropathy 2
• Vitamin B12 level with methylmalonic acid to identify B12 deficiency neuropathy 2
• Thyroid function tests, complete blood count, and comprehensive metabolic panel 2
• Anti-ganglioside antibodies for demyelinating patterns 2

Vascular Assessment

• Bilateral arm blood pressures with inter-arm difference measurement 2
• Pulse examination and auscultation for bruits 2

Immediate Management Based on Etiology

If GBS Suspected

Initiate IVIG 2 g/kg over 5 days or plasmapheresis urgently if clinical suspicion is high and imaging excludes structural lesion 1, 2

• Admit to monitored setting with respiratory monitoring capability 1, 2
• Do not wait for CSF or EMG results to initiate treatment if clinical suspicion is high and imaging excludes structural lesion 1

If Cervical Cord Compression Confirmed

Urgent neurosurgical consultation for potential decompression 1, 3

Critical Pitfalls to Avoid

• Never dismiss GBS based on normal CSF protein in the first week, as protein elevation may be delayed 1, 2
• Never delay MRI spine, as this can result in permanent paralysis from missed cord compression 1, 2
• Never assume vascular disease without objective testing including blood pressure measurements and pulse examination 2, 4
• Recognize that mild pleocytosis (10-50 cells/μL) in CSF, though compatible with GBS, should prompt consideration of infectious polyradiculitis 2
• Always check reflexes immediately to distinguish between GBS (areflexia/hyporeflexia) and spinal cord pathology (hyperreflexia) 4
• Functional neurological disorder should only be considered after excluding life-threatening structural and inflammatory causes, characterized by inconsistency on examination and improvement with distraction techniques 1