What are the key considerations for differential diagnosis and treatment of Guillain-Barré Syndrome (GBS) in a patient with potential recent infections, vaccinations, or exposures to toxins?

Differential Diagnosis of Guillain-Barré Syndrome

When evaluating suspected GBS, systematically exclude acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP), metabolic/toxic neuropathies, infectious polyradiculoneuropathies, neuromuscular junction disorders, and spinal cord pathology before confirming the diagnosis. 1

Key Distinguishing Features to Assess

Temporal Pattern (Critical for Differentiation)

• GBS reaches maximum disability within 2-4 weeks of symptom onset, with most patients progressing to nadir within 2 weeks 1, 2
• A-CIDP presents with progression continuing beyond 8 weeks or three or more treatment-related fluctuations, occurring in approximately 5% of patients initially diagnosed with GBS 3, 4
• Progression beyond 4 weeks should prompt reconsideration of the diagnosis 4

Clinical Red Flags That Suggest Alternative Diagnoses

• Marked persistent asymmetry of weakness argues against GBS and suggests alternative pathology such as vasculitic neuropathy or focal lesions 1
• Bladder dysfunction at onset is atypical for GBS and should raise suspicion for spinal cord pathology (transverse myelitis, cord compression) 1
• Marked CSF pleocytosis (>50 cells/μL) suggests infectious causes including Lyme disease, HIV-associated polyradiculopathy, or cytomegalovirus polyradiculitis rather than GBS 1, 4

Essential Diagnostic Workup

Laboratory Testing to Exclude Mimics

• Complete blood count, glucose, electrolytes, kidney and liver function to exclude metabolic causes of weakness (uremia, hypokalemia, hypophosphatemia) 1
• Serum creatine kinase (CK) elevation suggests primary muscle disease (polymyositis, rhabdomyolysis) rather than GBS 1
• CSF examination looking for albumino-cytological dissociation (elevated protein with normal cell count <10 cells/μL), though normal CSF protein in the first week does not exclude GBS 1, 4

Electrodiagnostic Studies for Pattern Recognition

• Nerve conduction studies and EMG should demonstrate sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks 1
• "Sural sparing pattern" (normal sural sensory nerve action potential with abnormal median/ulnar responses) is typical for GBS and helps distinguish from length-dependent toxic/metabolic neuropathies 1
• Electrodiagnostic findings may be normal in the first week, so clinical suspicion should guide treatment decisions 4

Specific Differential Diagnoses to Consider

Neuromuscular Junction Disorders

• Myasthenia gravis: Look for fluctuating weakness, ocular involvement without sensory symptoms, normal reflexes, and absence of preceding infection 1
• Botulism: Descending paralysis (cranial nerves first), dilated pupils, absence of sensory symptoms, and potential food/wound exposure history 1

Spinal Cord Pathology

• Transverse myelitis or cord compression: Presence of sensory level, early bladder dysfunction, hyperreflexia below the lesion (versus areflexia in GBS), and MRI showing cord signal abnormality 1, 4

Infectious Polyradiculoneuropathies

• Lyme disease: CSF pleocytosis, positive Lyme serology, endemic area exposure 4
• HIV polyradiculopathy: Known HIV status, CSF pleocytosis, rapid progression 4
• Cytomegalovirus polyradiculitis: Immunocompromised state, CSF pleocytosis, positive CMV PCR in CSF 4

Metabolic and Toxic Causes

• Critical illness polyneuropathy: ICU setting, sepsis, multi-organ failure, prolonged immobilization 1
• Porphyria: Abdominal pain, psychiatric symptoms, dark urine, elevated porphyrins 1
• Toxic neuropathies: Heavy metal exposure, medication history (vincristine, platinum agents), occupational exposures 1

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

• A-CIDP mimics GBS initially but shows progression beyond 8 weeks or multiple relapses (≥3 treatment-related fluctuations) 3, 4
• Approximately 5% of patients initially diagnosed with GBS ultimately have A-CIDP 3, 4

Clinical Variants of GBS (Not Differential Diagnoses)

Recognized GBS Subtypes

• Classic sensorimotor GBS (AIDP): 30-85% of cases, most common in Western countries, with both motor and sensory involvement 1
• Pure motor variant (AMAN): 5-70% of cases, more common in Asia, motor weakness without sensory signs 1, 5
• Miller Fisher syndrome: 5-25% of cases, characterized by ophthalmoplegia, ataxia, and areflexia; consider anti-GQ1b antibody testing 1, 4
• Facial nerve variant: Bilateral facial palsy with or without limb weakness; bilateral simultaneous facial weakness is extremely rare in Bell's palsy and should raise immediate suspicion for GBS 1

Common Diagnostic Pitfalls to Avoid

• Do not dismiss GBS based on normal CSF protein in the first week, as albumino-cytological dissociation may not develop until later 1
• Do not wait for antibody test results before starting treatment if clinical suspicion is high, as treatment within 2 weeks improves outcomes 1, 2
• Do not overlook bilateral facial palsy as a presenting feature before limb weakness develops 1
• Recognize that back and limb pain affects two-thirds of patients and may precede weakness, potentially causing diagnostic confusion 1, 5
• In children, nonspecific features including irritability and refusal to bear weight may precede obvious weakness, leading to delayed diagnosis 1