What are the differential diagnoses for left upper‑extremity numbness and weakness and how should the work‑up be approached?

Left Upper Extremity Numbness and Weakness: Differential Diagnosis and Work-Up

Acute unilateral left upper extremity numbness and weakness is a stroke or TIA until proven otherwise and requires immediate stroke protocol activation with brain imaging within 24 hours. 1

Immediate Life-Threatening Conditions to Rule Out First

Stroke/TIA (Highest Priority)

• Transient unilateral limb weakness carries up to 36% risk of stroke within 7 days if multiple risk factors are present, even if symptoms have resolved. 1
• Hemispheric (cortical) ischemia typically presents as weakness, paralysis, numbness, or tingling affecting the same side of the body, contralateral to the culprit vascular lesion. 2
• Isolated hand weakness can result from cortical cerebral ischemia, particularly affecting the "inverted omega sign" area along the precentral gyrus. 3
• Immediate actions required:
  • Activate stroke protocol immediately 1
  • Calculate NIHSS score to quantify deficit 1
  • Check blood glucose (hypoglycemia mimics stroke) 1
  • Brain CT or MRI within 24 hours 1
  • Vascular imaging (CTA or MRA from aortic arch to vertex) within 24 hours 1

Cervical Spinal Cord Compression

• If bilateral hand involvement or any bladder/bowel dysfunction, perineal sensory changes, or saddle anesthesia are present, emergency MRI of entire spine is required. 4, 5
• Cervical myelopathy can present with hand numbness, problems with fine motor skills, and neck pain or stiffness. 6
• Patients with cervical cord injuries may show disproportionate upper extremity weakness compared to lower extremities due to corticospinal tract involvement critical for hand function. 7
• Red flags include sharp sensory level, hyperreflexia, clonus, or extensor plantar responses. 4

Secondary Differential Diagnoses

Peripheral Nerve Entrapment Syndromes

• Carpal tunnel syndrome (median nerve at wrist): Decreased pain sensation and numbness in thumb, index, and middle fingers; symptoms reproduced by wrist hyperflexion and median nerve percussion. 8
• Cubital tunnel syndrome (ulnar nerve at elbow): Decreased sensation of little finger and ulnar aspect of ring finger, along with intrinsic muscle weakness. 8
• Radial tunnel syndrome: May accompany lateral epicondylitis; radial nerve block can help differentiate. 8
• Risk factors include diabetes, smoking, alcohol consumption, rheumatoid arthritis, and hypothyroidism (though these typically produce bilateral symptoms). 8

Cervical Radiculopathy

• Compression at nerve root in neck can present with variable degrees of musculoskeletal pain, weakness, sensory changes, and reflex changes in dermatomal distribution. 6
• Differentiate from peripheral neuropathy by examining dermatomal and myotomal distributions. 6

Brachial Plexus Neuropathy

• Compression of distal branches arising from C5-T1 can cause upper extremity symptoms. 6
• Thoracic outlet syndrome may cause ulnar-sided symptoms. 8

Guillain-Barré Syndrome (GBS)

• Classic GBS presents with rapidly progressive bilateral ascending weakness with areflexia, though asymmetric patterns can occur in GBS variants. 5
• Approximately two-thirds report preceding infection within 6 weeks (Campylobacter jejuni, CMV, Hepatitis E, Mycoplasma, EBV, Zika). 5
• Red flags: areflexia/hyporeflexia, check vital capacity and negative inspiratory force, monitor for dysautonomia. 5
• If GBS suspected, urgent MRI entire spine, CSF analysis, and respiratory monitoring required as 20% develop respiratory failure. 5

Vascular Causes

• Acute limb ischemia: Check for the "6 P's" - pain, pulselessness, pallor, paresthesias, paralysis, poikilothermia. 1
• If pulses diminished or absent, obtain ankle-brachial index immediately. 1

Structured Diagnostic Algorithm

Step 1: Time Course Assessment

• Hyperacute (seconds to minutes): Stroke/TIA most likely 1
• Acute-subacute (hours to days): GBS, cord compression, acute neuropathy 5
• Chronic (weeks to months): Peripheral nerve entrapment, cervical radiculopathy 6, 8

Step 2: Localization by Physical Examination

• Check reflexes immediately: 4, 5
  • Hyperreflexia → spinal cord pathology
  • Areflexia/hyporeflexia → peripheral nerve or GBS
  • Normal reflexes → consider functional disorder or early peripheral process
• Assess sensory distribution: 6, 8
  • Dermatomal pattern → cervical radiculopathy
  • Peripheral nerve distribution → entrapment syndrome
  • Hemisensory loss → cortical lesion
• Motor examination: 1
  • Isolated hand weakness with leg sparing → consider cortical lesion or cervical cord injury 7, 3
  • Ascending weakness → GBS 5
  • Specific muscle group weakness → peripheral nerve or radiculopathy 6

Step 3: Red Flag Assessment

• Bladder/bowel dysfunction → emergency MRI spine 4
• Bilateral symptoms → cord compression or GBS 4, 5
• Respiratory symptoms → GBS requiring ICU monitoring 5
• Vascular risk factors with acute onset → stroke protocol 1

Step 4: Imaging Strategy

• If stroke/TIA suspected: Brain CT/MRI + vascular imaging within 24 hours 1
• If cord compression suspected: Emergency MRI entire spine with and without contrast 5
• If peripheral nerve suspected: Consider electromyography and nerve conduction studies after acute life-threatening causes excluded 2, 8

Critical Management Priorities

If Stroke/TIA Confirmed or Suspected:

• Admit to stroke unit with continuous neurological monitoring 1
• Initiate secondary stroke prevention: antiplatelet therapy, high-intensity statin, blood pressure management, atrial fibrillation screening 1
• Consider thrombolytic therapy if within appropriate time window 1

If GBS Confirmed or Highly Suspected:

• Admit to monitored setting with respiratory monitoring capability 5
• Initiate treatment urgently with IVIG 2 g/kg over 5 days or plasmapheresis 5
• Monitor for dysautonomia and manage neuropathic pain with gabapentin, pregabalin, or duloxetine 2, 5

If Peripheral Nerve Entrapment:

• Volar splinting and steroid injection for carpal tunnel syndrome 8
• Conservative management initially; surgical decompression if refractory 8

Critical Pitfalls to Avoid

• DO NOT reassure and discharge based on symptom resolution in acute unilateral weakness - transient symptoms are a warning of imminent stroke. 1
• DO NOT delay imaging to obtain extensive laboratory workup when stroke is suspected - time to diagnosis is critical. 1
• DO NOT assume bilateral symptoms are always peripheral - consider cord compression and GBS. 4, 5
• DO NOT overlook cortical lesions in patients with isolated hand weakness and vascular risk factors. 3