What is the presentation, diagnosis, and management of Guillain-Barre Syndrome (GBS)?

Guillain-Barré Syndrome: Presentation, Diagnosis, and Management

Guillain-Barré syndrome is a potentially fatal immune-mediated polyradiculoneuropathy requiring immediate recognition and treatment, with mortality of 3-10% even with optimal care, primarily from respiratory failure and autonomic complications that can develop rapidly. 1, 2

Clinical Presentation

Cardinal Features

The hallmark presentation is rapidly progressive bilateral ascending weakness starting in the legs and progressing to arms and cranial muscles, accompanied by diminished or absent reflexes. 1, 3, 4

• Disease progression typically reaches maximum disability within 2 weeks of symptom onset, making early recognition critical 1, 4, 2
• Distal paresthesias or sensory loss frequently precede or accompany the weakness 1, 3
• Back and limb pain (muscular, radicular, or neuropathic) occurs in approximately two-thirds of patients and is often an early symptom 4
• Recent infection history within 6 weeks is present in about two-thirds of cases and serves as an important diagnostic clue 4

Life-Threatening Complications

Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea. 3, 4, 2

• Dysautonomia occurs commonly, including blood pressure/heart rate instability, cardiac arrhythmias, pupillary dysfunction, and bowel/bladder dysfunction 1, 3, 4
• Cranial nerve involvement occurs in 35% of patients, with facial palsy being most common (34%) due to the facial nerve's extensive myelin coverage and long intracranial course 4, 5
• Dysphagia and impaired cough increase aspiration risk 4

Clinical Variants

The classic sensorimotor form represents 70% of cases in Europe/Americas and 30-40% in Asia 4:

• Pure motor variant (5-70% of cases): weakness without sensory signs 3, 4
• Miller Fisher syndrome (5-25% of cases): ophthalmoplegia, ataxia, and areflexia 1, 3, 4
• Regional variants: bilateral facial palsy with paresthesias, pharyngeal-cervical-brachial weakness, or paraparetic variant 3

Diagnosis

Immediate Assessment Priorities

All suspected GBS cases warrant immediate assessment of respiratory function and autonomic stability, as these determine mortality risk and need for ICU-level care. 4, 2

Apply the "20/30/40 rule" for respiratory failure risk: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 4

• Single breath count ≤19 predicts need for mechanical ventilation 4
• Perform continuous cardiac monitoring and blood pressure assessment for arrhythmias and autonomic instability 3, 4
• Grade muscle strength using Medical Research Council scale in neck, arms, and legs 4
• Assess swallowing and coughing ability to identify aspiration risk 4

Diagnostic Investigations

The diagnosis is primarily clinical, supported by cerebrospinal fluid analysis showing albumino-cytological dissociation and electrophysiological studies demonstrating peripheral nerve dysfunction. 3

Cerebrospinal Fluid Analysis

• Elevated protein with normal cell count (albumino-cytological dissociation) is typical, but may be absent in the first week—do not dismiss GBS based on normal CSF protein early in disease course 3, 4
• CSF protein typically becomes elevated by the end of the first week and may persist until the third week 6
• Marked CSF pleocytosis (>50 cells/mm³) should prompt reconsideration of the diagnosis 4

Electrodiagnostic Studies

Nerve conduction studies and EMG should be performed to support diagnosis and classify the neuropathy pattern. 4

• Look for sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks 4
• "Sural sparing pattern" (normal sural sensory nerve action potential with abnormal median/ulnar responses) is typical and represents one of the most specific electrodiagnostic features 4
• Conduction block determined indirectly by absent H-reflex is noted in approximately 90% of patients 5
• Electrodiagnostic measurements might be normal when performed early (within 1 week)—repeat testing in 2-3 weeks if clinical suspicion remains high 4
• Approximately one-third of patients cannot be classified into AIDP, AMAN, or AMSAN at initial presentation 3

Additional Testing

• Initial laboratory tests: complete blood count, glucose, electrolytes, kidney function, liver enzymes, HbA1c, vitamin B12, TSH to exclude alternative diagnoses 4
• Serum creatine kinase is sensitive though nonspecific; elevation suggests muscle involvement 4
• Anti-GQ1b antibody testing should be considered when Miller Fisher syndrome is suspected 7
• MRI of spine with contrast to rule out compressive lesions and evaluate for nerve root enhancement/thickening 4

Differential Diagnosis

Ascending bilateral symmetric weakness (legs → arms → cranial nerves) strongly suggests GBS, while descending flaccid paralysis (cranial nerves → trunk → extremities) indicates botulism until proven otherwise. 3

• Areflexia or hyporeflexia in affected limbs points to GBS 3
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis 3
• Marked persistent asymmetry or bladder dysfunction at onset should prompt reconsideration of the diagnosis 4

Management

Admission and Monitoring Criteria

Admit to inpatient unit with capability for rapid transfer to ICU-level monitoring for Grade 3-4 disease (severe weakness limiting self-care, any dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms). 4

• Even patients with moderate symptoms (Grade 2) require neurology consultation and close monitoring 4
• All grades of GBS warrant workup and intervention given potential for progressive disease leading to respiratory compromise 4
• Frequent pulmonary function assessment with serial vital capacity and NIF measurements 4
• Daily neurologic evaluation 4

First-Line Immunotherapy

Initiate treatment in patients unable to walk unaided within 2-4 weeks of symptom onset with either IVIg or plasma exchange—both are equally effective first-line treatments regardless of electrophysiological subtype. 3, 4, 7

Treatment Options

• IVIg 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) 4, 2, 7
• Plasma exchange 200-250 ml/kg over 4-5 sessions within 4 weeks of symptom onset 4, 2, 7
• Do not use plasma exchange followed immediately by IVIg—this combination is not recommended 7
• Corticosteroids are NOT recommended for idiopathic GBS 4, 7

Treatment Response and Complications

Approximately 40% of patients do not improve in the first 4 weeks following treatment—this does not necessarily mean treatment failed, as progression might have been worse without therapy. 4, 2

• Treatment-related fluctuations (TRFs) occur in 6-10% of patients within 2 months following initial treatment-induced improvement 4, 2, 7
• Consider changing diagnosis to acute-onset CIDP if progression continues after 8 weeks from onset or if patient has three or more TRFs—this occurs in approximately 5% of patients initially diagnosed with GBS 4, 7
• Do not recommend a second IVIg course in GBS patients with a poor prognosis based on current evidence 7

Supportive Care

Comprehensive supportive care is critical and includes pain management, prevention of complications, and psychological support. 1

Pain Management

• Use gabapentinoids (gabapentin, pregabalin), tricyclic antidepressants, or carbamazepine for neuropathic pain 4, 7
• Gabapentin can be initiated alongside IVIg without contraindication or interaction, as they work through different mechanisms 4
• Encourage mobilization for muscle pain and arthralgia 1

Complication Prevention

• Standard preventive measures for pressure ulcers, hospital-acquired infections, and deep vein thrombosis 4
• Treatment of constipation/ileus 4
• Check corneal reflex in patients with facial palsy to prevent corneal ulceration 4
• Avoid medications that can worsen neuromuscular transmission: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 4

Psychological Support

Rapid loss of physical function can be severely traumatic and may cause anxiety and/or depression—early recognition and management of psychological distress is important as mental status can influence physical recovery. 1

• Screen for anxiety, depression, and hallucinations, which are frequent complications 4
• Recognize that patients with GBS, even those with complete paralysis, usually have intact consciousness, vision, and hearing—be mindful of what is said at bedside 4
• Provide accurate information that full recovery is expected in approximately 90% of cases, with recurrence risk of only 2-5% 1, 4

Rehabilitation and Long-Term Management

Arrange a rehabilitation programme with a rehabilitation specialist, physiotherapist, and occupational therapist as a crucial step towards recovery. 1

Physical Recovery

• Exercise programmes including range-of-motion exercises, stationary cycling, walking and strength training improve physical fitness, walking ability and independence in activities of daily living 1
• The intensity of exercise must be closely monitored as overwork can cause fatigue 1

Long-Term Sequelae

• Fatigue, unrelated to residual motor deficits, is found in 60-80% of patients and is often one of the most disabling complaints 1
• Severe pain is reported in at least one-third of patients 1 year after disease onset and can persist for >10 years 1
• Graded, supervised exercise programmes have been shown to be useful in reducing fatigue 1

Prognosis

80% of patients regain independent walking ability at 6 months, with mortality of 3-10% primarily from cardiovascular and respiratory complications. 4, 2

• Recovery can continue for more than 3 years, with improvement possible even more than 5 years after onset 4, 2
• Advanced age and severe disease at onset are risk factors for poor outcome 4, 2
• Use the modified Erasmus GBS outcome score (mEGOS) to predict probability of regaining walking ability 4, 7
• Use the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation 7

Common Pitfalls

• Do not delay treatment waiting for antibody test results if GBS is suspected 4
• Do not dismiss GBS based on normal CSF protein in the first week or absent sural sparing pattern early in disease 4
• Bilateral simultaneous facial weakness is extremely rare in Bell's palsy and should immediately raise suspicion for GBS 4
• Do not delay gabapentin initiation waiting for IVIg to "work first"—pain control should begin immediately as part of comprehensive supportive care 4