What are the clinical features, diagnostic work‑up, and first‑line treatment for Guillain‑Barré syndrome?

Guillain-Barré Syndrome: Clinical Features, Diagnosis, and Treatment

Clinical Features

Guillain-Barré syndrome presents as rapidly progressive bilateral ascending weakness starting in the legs and progressing to the arms and cranial muscles, accompanied by diminished or absent reflexes, typically reaching maximum disability within 2 weeks. 1

Cardinal Presenting Features

• Bilateral ascending weakness is the hallmark, beginning distally in the legs and ascending to involve arms, trunk, and cranial muscles over days to 4 weeks (usually <2 weeks) 1, 2
• Diminished or absent deep tendon reflexes occur in most patients at presentation and nearly all at nadir—this is a key diagnostic feature 1, 2
• Distal paresthesias or sensory loss frequently precede or accompany the weakness 1, 2
• Recent infection history (within 6 weeks) is present in approximately two-thirds of patients, most commonly Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, hepatitis E, Mycoplasma pneumoniae, or Zika virus 1, 2

Additional Clinical Manifestations

• Back and limb pain affects approximately two-thirds of patients and can be muscular, radicular, or neuropathic—often an early symptom 1
• Bilateral facial palsy is the most frequently affected cranial nerve finding due to the facial nerve's extensive myelin coverage and long intracranial course 1
• Dysautonomia is common and includes blood pressure/heart rate instability, pupillary dysfunction, and bowel/bladder dysfunction 1, 2
• Respiratory failure develops in approximately 20% of patients and can occur rapidly, sometimes without obvious dyspnea 1

Clinical Variants

• Classic sensorimotor GBS (30–85% of cases): Rapidly progressive symmetrical weakness with sensory signs and areflexia 1
• Pure motor variant (5–70% of cases): Motor weakness without sensory signs; may present with normal or even exaggerated reflexes in AMAN subtype 1, 3
• Miller Fisher syndrome (5–25% of cases): Ophthalmoplegia, ataxia, and areflexia 1

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Diagnostic Work-Up

Obtain neurology consultation immediately for every suspected case, as approximately 20% develop respiratory failure requiring mechanical ventilation. 1

Immediate Life-Threatening Assessment

• Assess respiratory function using vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures at presentation and serially 1
• Apply the "20/30/40 rule": Patient is at risk of respiratory failure if vital capacity <20 mL/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 1
• Single breath count ≤19 predicts need for mechanical ventilation 1
• Perform electrocardiography and continuously monitor heart rate and blood pressure for arrhythmias and autonomic instability 1

Laboratory and CSF Studies

• Cerebrospinal fluid examination should be performed to identify albumino-cytological dissociation (elevated protein with normal cell count)—do not dismiss GBS based on normal CSF protein in the first week, as this may not appear until the end of the first week or later 1, 4
• Initial laboratory tests should include complete blood count, glucose, electrolytes, kidney function, liver enzymes to exclude metabolic causes of weakness 1
• Serum creatine kinase (CK) is sensitive though nonspecific; elevation suggests muscle involvement and may indicate AMAN variant 1

Electrodiagnostic Studies

• Nerve conduction studies and EMG should be performed to support diagnosis and classify the neuropathy pattern (AIDP vs. AMAN vs. AMSAN) 1, 4
• Look for 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 represents one of its most specific electrodiagnostic features 1
• Electrodiagnostic measurements may be normal early (within 1 week)—repeat testing in 2–3 weeks if clinical suspicion remains high 1, 3

Additional Diagnostic Studies

• MRI of spine with contrast to exclude compressive lesions and assess for nerve root enhancement or thickening 1
• Serum antiganglioside antibody testing (e.g., anti-GQ1b for Miller Fisher syndrome) should be considered when specific variants are suspected 1, 4
• Screen for reversible neuropathy causes: HbA1c, vitamin B12, TSH, vitamin B6, folate 1

Diagnostic Red Flags Suggesting Alternative Diagnosis

• Marked persistent asymmetry, bladder dysfunction at onset, or marked CSF pleocytosis (>50 cells/μL) should prompt reconsideration of the diagnosis 1
• Progression continuing after 8 weeks from onset or three or more treatment-related fluctuations suggest acute-onset CIDP rather than GBS—this occurs in approximately 5% of patients initially diagnosed with GBS 1, 4

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First-Line Treatment

Administer intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) in patients unable to walk unaided within 2–4 weeks of symptom onset. 1, 4

Immunotherapy Options

• IVIg 0.4 g/kg/day for 5 days (total 2 g/kg) is first-line treatment for patients unable to walk unaided 1, 4
• Plasma exchange (200–250 mL/kg total over 4–5 sessions) is equally effective as IVIg; for patients requiring mechanical ventilation, 4 sessions are sufficient 1, 4
• Do not use corticosteroids alone for idiopathic GBS—they are ineffective 1, 4, 5
• Do not use sequential plasma exchange followed by IVIg (or vice versa)—this has not shown benefit 1, 4

Treatment Timing and Response

• Do not wait for antibody test results before starting treatment if GBS is suspected 1
• Approximately 40% of patients do not improve in the first 4 weeks after treatment—this does not necessarily mean treatment failed, as progression might have been worse without therapy 1
• Treatment-related fluctuations (TRFs) occur in 6–10% of patients within 2 months after initial improvement; repeating a full course of IVIg or plasma exchange is common practice, though high-quality evidence is lacking 1, 4

Admission and Monitoring Criteria

• Grade 2 (moderate) disease—patients with some limitation of daily activities require neurology consultation and close monitoring 1
• Grade 3–4 (severe) disease—admit to inpatient unit capable of rapid ICU transfer for patients with severe weakness limiting self-care, dysphagia, facial or respiratory muscle weakness, or rapidly progressive symptoms 1
• Perform daily neurologic examinations to track disease progression 1
• Frequent pulmonary function testing with serial vital capacity and NIF measurements 1

Supportive Care

• Pain management: Gabapentinoids (gabapentin or pregabalin) or duloxetine are preferred for neuropathic pain—gabapentin can be started concurrently with IVIg without drug interaction 1, 4
• Avoid medications that worsen neuromuscular transmission: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 1
• Standard preventive measures for pressure ulcers, hospital-acquired infections, and deep vein thrombosis 1
• Psychological support: Recognize that patients with complete paralysis usually have intact consciousness, vision, and hearing; screen for anxiety, depression, and hallucinations 1

Special Consideration: Immune Checkpoint Inhibitor-Associated GBS

• Permanently discontinue the immune checkpoint inhibitor when GBS is diagnosed 1
• Consider adding concurrent corticosteroids (methylprednisolone 2–4 mg/kg/day) to IVIg or plasma exchange in these patients 1
• For Grade 3–4 severity, pulse corticosteroid therapy (methylprednisolone 1 g/day for 5 days) may be employed as adjunct 1

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Prognosis and Rehabilitation

• 80% of patients regain independent walking ability at 6 months, though recovery may continue for more than 3 years and improvements are possible beyond 5 years 1, 4
• Mortality is 3–10%, primarily from cardiovascular and respiratory complications 1, 4
• Advanced age and severe disease at onset are risk factors for poor outcome 1, 4
• Arrange a structured rehabilitation program with physiotherapists, occupational therapists, and rehabilitation specialists—exercise programs (range-of-motion, stationary cycling, walking, strength training) improve physical fitness, walking ability, and independence 1
• Fatigue affects 60–80% of survivors and is a major disabling symptom 1
• Severe pain affects at least one-third of patients at 1 year and may persist for more than a decade 1
• Recurrence is uncommon (2–5%) but higher than background lifetime risk (0.1%); prior GBS is not an absolute contraindication to vaccination, though vaccination within one year should be discussed with specialists 1