What are the differential diagnoses and initial evaluation steps for upper extremity weakness?

Upper Extremity Weakness: Differential Diagnoses and Initial Evaluation

Immediate Life-Threatening Conditions to Rule Out First

Guillain-Barré syndrome (GBS) must be excluded immediately in any patient with bilateral upper extremity weakness, as approximately 20% develop respiratory failure requiring mechanical ventilation. 1, 2

Critical GBS Features

• Rapidly progressive bilateral ascending weakness with paresthesias, typically reaching maximum disability within 2 weeks 3, 2
• Areflexia or hyporeflexia is the hallmark finding, though the AMAN variant can paradoxically present with preserved or even brisk reflexes despite ascending paralysis 3, 2
• Preceding infection in two-thirds of cases within 6 weeks (Campylobacter jejuni, CMV, Hepatitis E, Mycoplasma, EBV, Zika) 3, 1, 2
• Dysautonomia (blood pressure/heart rate instability) can be life-threatening 3, 1, 2

Immediate GBS Workup

• 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
• MRI of entire spine with and without contrast to exclude cord compression and identify nerve root enhancement characteristic of GBS 1
• CSF analysis for albuminocytologic dissociation (elevated protein with normal cell count), though protein may be normal in first week 3, 1, 2
• Nerve conduction studies showing sensorimotor polyradiculoneuropathy with reduced conduction velocities, temporal dispersion, or conduction blocks 3, 1, 2
• Initiate IVIG 2 g/kg over 5 days or plasmapheresis urgently if clinical suspicion is high and imaging excludes structural lesion 1

Cervical Spinal Cord Lesions

Bilateral hand involvement with fine motor dysfunction (e.g., inability to button shirt) localizes to cervical cord at C5-C7 level and requires urgent MRI to exclude surgical emergencies. 1, 4

Key Features

• Cervical spondylotic myelopathy presents with fine motor skill impairment, hand numbness, neck pain/stiffness, and gait difficulty 4
• Bilateral upper extremity involvement distinguishes cord lesions from unilateral cortical or peripheral nerve pathology 1, 4
• Look for upper motor neuron signs: hyperreflexia, spasticity, Babinski sign 5, 6

Urgent Imaging

• MRI spine without and with contrast is the critical first test to identify cord compression, transverse myelitis, or central cord syndrome 1
• Delaying MRI can result in permanent paralysis if surgical decompression is needed 1

Central Nervous System Lesions

Stroke/Cerebral Lesions

• Unilateral upper extremity weakness suggests contralateral cortical or subcortical lesion 7, 8
• "Hand knob" area lesions in precentral gyrus cause isolated hand weakness mimicking peripheral nerve damage (pseudoperipheral palsy) 8
• Acute onset with vascular risk factors points to stroke; subacute progression may indicate tumor or abscess 8

Multiple Sclerosis

• Asymmetric weakness at onset, not ascending and symmetric like GBS 7
• Unilateral limb weakness or paraparesis from focal demyelinating lesions 7
• MRI showing periventricular, juxtacortical, infratentorial, or spinal cord lesions in characteristic distributions 7
• Dissemination in space and time (multiple lesions at different CNS locations occurring at different time points) 7

Peripheral Nerve and Nerve Root Pathology

Cervical Radiculopathy

• Dermatomal sensory loss and myotomal weakness corresponding to specific nerve root level 4
• C5: deltoid/biceps weakness, lateral arm numbness 4
• C6: wrist extensors/biceps weakness, thumb/index finger numbness 4
• C7: triceps/wrist flexors weakness, middle finger numbness 4
• C8: finger flexors/intrinsic hand weakness, ring/little finger numbness 4

Brachial Plexus Neuropathy

• Compression of distal branches from C5-T1 causing variable musculoskeletal pain, weakness, sensory changes, and reflex changes 4
• Pattern of involvement helps localize to upper trunk (C5-C6), middle trunk (C7), or lower trunk (C8-T1) 4

Peripheral Nerve Entrapment

• Radial nerve: wrist drop, finger extension weakness, dorsal first web space numbness 4
• Median nerve: thenar weakness, thumb opposition loss, thumb/index/middle finger numbness 4
• Ulnar nerve: intrinsic hand weakness, claw hand deformity, ring/little finger numbness 4
• Nerve conduction studies differentiate peripheral nerve pathology from central causes 8, 6

Neuromuscular Junction and Muscle Disorders

Myasthenia Gravis

• Fatigable weakness worsening with repetitive use, improving with rest 3
• Ptosis, diplopia, bulbar symptoms often accompany limb weakness 3
• Paraneoplastic autoantibody testing and EMG with repetitive nerve stimulation 3

Inflammatory Myopathy

• Symmetric proximal weakness, not distal fine motor dysfunction 3, 7
• Elevated CK (often >1000), AST, ALT, LDH, aldolase 3
• Muscle pain more prominent than in neurogenic causes 3
• EMG, MRI of proximal limbs, and muscle biopsy if diagnosis uncertain 3

Muscular Dystrophy

• Progressive symmetric proximal weakness, not acute bilateral ascending pattern 7
• Family history, elevated CK, genetic testing 3

Algorithmic Approach to Upper Extremity Weakness

Step 1: Assess Acuity and Bilaterality

• Acute bilateral ascending weakness → Rule out GBS immediately with respiratory monitoring, MRI spine, CSF, NCS 1, 2
• Acute unilateral weakness → Brain imaging (CT/MRI) to exclude stroke, tumor, abscess 8
• Subacute/chronic bilateral weakness → Consider MS, ALS, myopathy, or systemic causes 7

Step 2: Localize Anatomically

• Upper motor neuron signs (hyperreflexia, spasticity, Babinski) → MRI brain and spine for stroke, MS, cord compression 7, 5
• Lower motor neuron signs (hyporeflexia, atrophy, fasciculations) → NCS/EMG for radiculopathy, plexopathy, peripheral neuropathy 4, 6
• Mixed UMN/LMN signs → Consider ALS, cervical myelopathy with radiculopathy 4, 6

Step 3: Pattern Recognition

• Dermatomal/myotomal distribution → Cervical radiculopathy; order MRI cervical spine 4
• Peripheral nerve distribution → Entrapment neuropathy; order NCS/EMG 4, 8
• Proximal > distal → Myopathy; check CK, consider EMG/muscle biopsy 3
• Distal > proximal → Peripheral neuropathy; check metabolic labs, NCS/EMG 9

Step 4: Critical Pitfalls to Avoid

• Never delay MRI spine in bilateral upper extremity weakness – missing cord compression causes permanent paralysis 1
• Never dismiss GBS based on normal CSF protein in first week – protein elevation lags clinical presentation 1, 2
• Never assume peripheral nerve pathology without NCS/EMG confirmation – central lesions can mimic peripheral patterns 8
• Never wait for diagnostic confirmation to initiate GBS treatment if clinical suspicion is high and imaging excludes structural lesion 1
• Always assess respiratory function in suspected GBS – 20% develop respiratory failure 1, 2