What is the appropriate diagnostic workup and treatment for a female patient with progressive lower then upper limb weakness, normal reflexes in the lower limbs, and reduced reflexes in the upper limbs?

Progressive Ascending Weakness with Mixed Reflex Pattern: Diagnostic Approach

This clinical presentation—progressive lower limb weakness ascending to upper limbs with normal lower limb reflexes but reduced upper limb reflexes—strongly suggests Guillain-Barré syndrome (GBS), and requires urgent neurologic evaluation with MRI spine, lumbar puncture, and electrodiagnostic studies to confirm diagnosis and exclude alternative diagnoses such as transverse myelitis or spinal cord pathology.

Clinical Recognition and Differential Diagnosis

Key Diagnostic Features of GBS

The presentation described fits the classic pattern of GBS with some atypical features 1:

• Progressive bilateral weakness starting in legs and ascending to arms is characteristic of classic sensorimotor GBS 1
• Reflexes are typically decreased or absent in most patients at presentation and almost all at nadir 1
• However, the normal reflexes in lower limbs represents an atypical feature that warrants careful consideration 1
• In a minority of GBS patients, particularly those with pure motor variant and AMAN subtype, normal or even exaggerated reflexes might be observed throughout the disease course 1
• The reduced upper limb reflexes combined with weakness supports a peripheral nerve process 1

Critical Red Flags Requiring Immediate Attention

This pattern of ascending weakness with mixed reflexes necessitates urgent evaluation to exclude 1:

• Transverse myelitis: Acute/subacute weakness with sensory changes, often bilateral with increased deep tendon reflexes 1
• Spinal cord compression: Progressive neurologic deficits require urgent imaging 1
• Cauda equina syndrome: Though typically presents with decreased reflexes and bowel/bladder dysfunction 1

Immediate Diagnostic Workup

First-Line Imaging

MRI spine without contrast is the critical initial imaging study 1:

• MRI of entire spine (cervical, thoracic, lumbar) with thin axial cuts through regions of suspected abnormality 1
• MRI brain should also be obtained to evaluate for demyelinating lesions or other CNS pathology 1
• MRI can reveal T2/FLAIR changes in spinal cord (transverse myelitis) or nerve root enhancement (GBS) 1
• Urgent MRI is indicated when progressive neurologic deficits are present 1

Lumbar Puncture

CSF analysis is essential for diagnosis 1:

• Cell count, protein, glucose: Classic GBS shows elevated protein with normal cell count (albuminocytologic dissociation) 1
• Mild pleocytosis (10-50 cells/μl) is compatible with GBS but should prompt consideration of infectious polyradiculitis 1
• Oligoclonal bands, viral PCRs (especially HSV), cytology, and onconeural antibodies to exclude alternative diagnoses 1
• Gram stain and culture to exclude infectious causes 1

Electrodiagnostic Studies

Nerve conduction studies and EMG should be performed 1:

• Will reveal sensorimotor polyradiculoneuropathy or polyneuropathy in GBS 1
• Findings include reduced conduction velocities, reduced amplitudes, temporal dispersion, and/or partial motor conduction blocks 1
• "Sural sparing pattern" is typical: normal sural sensory nerve action potential while median/ulnar are abnormal 1
• Early studies may be normal (within 1 week of onset) or in patients with proximal weakness—repeat in 2-3 weeks if initial study normal 1

Additional Laboratory Testing

Blood work to evaluate for systemic causes 1:

• CBC, ESR, CRP: Evaluate for inflammatory/infectious processes 1
• B12, HIV, RPR, ANA, Ro/La, TSH: Exclude other causes of neuropathy 1
• Aquaporin-4 IgG: If transverse myelitis suspected 1
• Metabolic panel: Evaluate for concurrent conditions 1

Diagnostic Criteria Application

GBS Diagnostic Features Present 1

• Progressive bilateral weakness of legs then arms ✓
• Progression over days to weeks (typically <2 weeks) - needs confirmation
• Decreased reflexes in affected limbs (upper limbs) ✓

Atypical Features Requiring Explanation 1

• Normal lower limb reflexes: While atypical, this can occur in pure motor variant with AMAN subtype 1
• Asymmetry of reflex changes suggests need for careful evaluation of alternative diagnoses 1

Features That Would Cast Doubt on GBS Diagnosis 1

• Marked persistent asymmetry of weakness
• Bladder/bowel dysfunction at onset
• Sharp sensory level (suggests spinal cord pathology)
• Hyper-reflexia or clonus
• Extensor plantar responses
• Continued progression >4 weeks

Urgent Neurologic Consultation

Immediate neurology consultation is mandatory 1:

• GBS can progress rapidly to respiratory failure requiring ICU monitoring 1
• Disease typically reaches maximum disability within 2 weeks 1
• Early treatment with IVIG or plasmapheresis improves outcomes when initiated promptly 1
• Evaluation for urinary retention and constipation is essential 1

Management Considerations

If GBS Confirmed

Treatment should be initiated urgently once diagnosis established 1:

• IVIG 2 g/kg over 5 days or plasmapheresis are first-line treatments 1
• Respiratory monitoring: Vital capacity, negative inspiratory force 1
• Dysautonomia monitoring: Blood pressure, heart rate instability common 1
• Pain management: Muscular, radicular, or neuropathic pain frequently reported 1

If Transverse Myelitis Suspected

Permanently discontinue any immune checkpoint inhibitors if applicable 1:

• Methylprednisolone 2 mg/kg for moderate symptoms 1
• Consider higher doses 1 g/day for 3-5 days for severe symptoms 1
• Strongly consider IVIG in moderate to severe cases 1

Common Pitfalls to Avoid

• Do not delay imaging waiting for "classic" reflex pattern—atypical presentations are common 1
• Do not assume normal early electrodiagnostic studies exclude GBS—repeat testing in 2-3 weeks if clinical suspicion remains high 1
• Do not miss the window for treatment—GBS patients benefit most from early intervention 1
• Do not overlook respiratory compromise—patients can deteriorate rapidly requiring mechanical ventilation 1
• Do not dismiss alternative diagnoses based solely on reflex pattern—spinal cord pathology must be excluded with imaging 1