What is the differential diagnosis for a 47-year-old female with paresthesia and weakness in her left foot and both hands?

Differential Diagnosis for 47-Year-Old Female with Bilateral Hand and Left Foot Paresthesias and Weakness

The most critical immediate consideration is Guillain-Barré syndrome (GBS), which requires urgent evaluation including MRI of the entire spine, CSF analysis, and respiratory monitoring, as approximately 20% of patients develop respiratory failure requiring mechanical ventilation. 1, 2

Primary Urgent Differential Diagnoses

Guillain-Barré Syndrome (Most Urgent)

• Classic presentation includes rapidly progressive bilateral weakness with paresthesias, typically ascending from legs to arms, though asymmetric patterns can occur in GBS variants. 1, 2
• The 3-4 day timeframe with progressive weakness and sensory symptoms fits the typical acute-to-subacute onset, with maximum disability usually reached within 2 weeks. 1
• Approximately two-thirds of GBS patients report preceding infection within 6 weeks (Campylobacter jejuni, CMV, Hepatitis E, Mycoplasma pneumoniae, EBV, Zika virus). 1
• Red flags requiring immediate action: Assess for areflexia/hyporeflexia, check vital capacity and negative inspiratory force (respiratory monitoring), and monitor for dysautonomia (blood pressure/heart rate instability). 1, 2

Cervical Myelopathy with Cord Compression

• Bilateral hand involvement with unilateral foot weakness suggests a cervical cord lesion at C5-C7 level affecting both upper extremities and descending motor tracts. 3
• A 37-year-old man with similar presentation (numbness and weakness in hands, burning dysesthesias in forearms) had cervical spinal cord compression with signal change from C3/4 to C6. 3
• This requires urgent MRI of the cervical spine within hours to exclude surgical emergency. 2

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Subacute presentation over days can represent the early phase of CIDP, which typically evolves over 8 weeks or longer. 4
• Presents with progressive bilateral limb weakness, numbness and tingling of feet and hands, with areflexia and length-dependent sensory loss. 4
• Distinguished from GBS by slower progression (>8 weeks to reach nadir) versus GBS (<4 weeks). 4

Cauda Equina Syndrome

• Bilateral leg weakness with sensory loss and potential bladder/bowel dysfunction requires urgent exclusion. 2
• Red flags: Ask specifically about urinary retention, bowel incontinence, saddle anesthesia, and bilateral leg symptoms. 2
• Lesion site is lumbosacral nerve roots below L1-L2 level. 2

Secondary Differential Considerations

Peripheral Polyneuropathy (Multiple Etiologies)

• Symmetric distal numbness and paresthesia with pain and weakness is characteristic, though typically more gradual onset. 5
• Key risk factors to assess: Diabetes (check glucose, HbA1c), alcohol overconsumption, vitamin B12 deficiency, thyroid dysfunction (hypothyroidism), neurotoxic medications, and cytostatic drugs. 6, 5
• Prevalence rises to 7% in elderly populations, with 20-30% remaining idiopathic despite workup. 5

Bilateral Ulnar Nerve Entrapment

• Less common cause of bilateral hand symptoms in ulnar nerve distribution. 6
• Would require nerve conduction studies to differentiate from polyneuropathy. 6

Metabolic/Toxic Causes

• Uremic neuropathy from renal insufficiency should be considered (check creatinine, eGFR, urinalysis). 6
• Fabry disease can present with episodic acroparesthesias as constant burning pain and tingling in feet and hands, though typically begins earlier in life (as early as age 2). 3

Immediate Diagnostic Algorithm

Step 1: Urgent Imaging (Within Hours)

• MRI entire spine (cervical, thoracic, lumbar) without and with contrast to exclude cord compression, transverse myelitis, or nerve root enhancement. 2
• This is the critical first test and should not be delayed. 2

Step 2: Concurrent Laboratory Evaluation

• CSF analysis: cell count, protein (elevated protein with acellular CSF supports GBS), glucose, oligoclonal bands. 1, 2
• Complete metabolic panel, creatinine, eGFR. 6
• Glucose, HbA1c, vitamin B12, TSH. 6
• Consider infectious workup if preceding illness reported. 1

Step 3: Electrodiagnostic Studies

• Nerve conduction studies and EMG to confirm polyradiculoneuropathy or polyneuropathy pattern (axonal vs. demyelinating). 6, 2
• In GBS, motor nerve conduction studies show partial conduction blocks with nonuniform slowing. 4

Step 4: Detailed Neurological Examination

• Reflexes: Areflexia or hyporeflexia strongly suggests GBS or CIDP. 1, 4
• Sensory testing: Small-fiber function (pinprick, temperature) and large-fiber function (vibration, 10-g monofilament, proprioception). 6
• Motor strength: Document proximal and distal strength in all extremities. 4
• Respiratory function: Vital capacity and negative inspiratory force if GBS suspected. 2
• Autonomic function: Blood pressure, heart rate, pupillary response, bladder/bowel function. 1, 2

Critical Management Priorities

If GBS is confirmed or highly suspected:

• Initiate treatment urgently with IVIG 2 g/kg over 5 days or plasmapheresis without waiting for all test results if clinical suspicion is high and imaging excludes structural lesion. 2
• Admit to monitored setting with respiratory monitoring capability. 2
• Monitor for dysautonomia and pain (muscular, radicular, or neuropathic). 1, 2

If spinal cord compression is identified:

• Urgent neurosurgical consultation for decompression, as delay worsens outcomes. 2

Key Clinical Pitfalls to Avoid

• Do not delay MRI spine – spinal cord compression requires urgent surgical intervention and cannot be excluded clinically. 2
• Do not wait for CSF or EMG results to initiate GBS treatment if clinical suspicion is high and imaging excludes structural lesion. 2
• Do not underestimate respiratory risk – 20% of GBS patients develop respiratory failure, requiring close monitoring of vital capacity. 1, 2
• Do not miss cauda equina syndrome – specifically ask about bladder/bowel dysfunction and saddle anesthesia. 2
• Recognize that early spinal cord injury may present with areflexia (spinal shock) before reflexes become hyperactive. 2