What is Guillain-Barré Syndrome (GBS), its causes, symptoms, treatment options, and prognosis in adults?

Guillain-Barré Syndrome: Comprehensive Overview

Definition and Epidemiology

Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory disease of the peripheral nervous system that causes rapidly progressive bilateral ascending weakness, typically starting in the legs and progressing to the arms and cranial muscles, and is the most common cause of acute flaccid paralysis worldwide. 1, 2

• GBS has an annual global incidence of approximately 1-2 per 100,000 person-years 1
• The disease occurs more frequently in males than females, with incidence increasing with age, although all age groups can be affected 1
• Mortality remains 3-10% even with optimal medical care, primarily due to respiratory failure and autonomic complications 1, 3
• Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea 1, 3

Pathophysiology

GBS is triggered by an aberrant immune response to preceding infections that results in damage to peripheral nerves through molecular mimicry, where antibodies generated against pathogen-borne antigens cross-react with gangliosides on peripheral nerve components. 1, 4

• About two-thirds of patients report a recent infection within 6 weeks prior to symptom onset 2
• Common antecedent pathogens include Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae 4
• In acute motor axonal neuropathy (AMAN), antibodies target gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a expressed on the motor axolemma, causing axonal degeneration 4
• In acute inflammatory demyelinating polyneuropathy (AIDP), immune reactions against Schwann cells or myelin result in demyelination, though exact target molecules remain unidentified 4

Clinical Presentation

Classic 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. 2, 5

• Disease progression typically reaches maximum disability within 2 weeks of symptom onset 1, 3
• Distal paresthesias or sensory loss often precede or accompany weakness 2, 5
• Diminished or absent reflexes are present in most patients at presentation and almost all at nadir 5
• Back and limb pain (muscular, radicular, or neuropathic) affects approximately two-thirds of patients and is often an early symptom 2

Cranial Nerve Involvement

Bilateral facial palsy is the most common cranial nerve manifestation in GBS due to the facial nerve's longest intracranial course, extensive myelin coverage, and vulnerability to immune-mediated demyelination. 2

• Facial weakness can occur in isolation or progress to classic ascending weakness 2
• Bilateral simultaneous facial weakness is extremely rare in Bell's palsy and should immediately raise suspicion for GBS 2
• Ophthalmoplegia can occur, particularly in Miller Fisher syndrome 2, 5
• Assess swallowing and coughing ability to identify aspiration risk 2
• Check corneal reflex in patients with facial palsy to prevent corneal ulceration 2

Autonomic Dysfunction

Dysautonomia is common and can be life-threatening, including blood pressure or heart rate instability, cardiac arrhythmias, pupillary dysfunction, and bowel or bladder dysfunction. 1, 2, 5

• Autonomic involvement contributes significantly to mortality 1
• Continuous cardiac monitoring and blood pressure surveillance are critical 2, 5

Respiratory Complications

Respiratory function should be monitored in all patients as respiratory failure can occur without symptoms of dyspnea. 1

• Measure vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures at presentation and serially 2
• 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 2
• Single breath count ≤19 predicts need for mechanical ventilation 2

Clinical Variants

GBS presents with heterogeneous clinical manifestations, and several distinct clinical variants exist beyond the classic sensorimotor form. 1

• Classic sensorimotor GBS (30-85% of cases): Rapidly progressive symmetrical weakness and sensory signs with absent or reduced tendon reflexes 2
• Pure motor variant (5-70% of cases): Motor weakness without sensory signs 2, 5
• Miller Fisher syndrome (5-25% of cases): Characterized by ophthalmoplegia, ataxia, and areflexia 2, 5
• Regional variants: Including bilateral facial palsy with paresthesias, pharyngeal-cervical-brachial weakness, or paraparetic variant 5

Electrophysiological Subtypes

Electrophysiological studies provide evidence of peripheral nervous system dysfunction and can distinguish between three main subtypes: AIDP, AMAN, and AMSAN. 1, 5

• AIDP (acute inflammatory demyelinating polyneuropathy): Most common form in Europe and North America, characterized by demyelinating features 5, 4
• AMAN (acute motor axonal neuropathy): More frequent in East Asia (China and Japan), characterized by motor axonal damage 5, 4
• AMSAN (acute motor and sensory axonal neuropathy): Features both motor and sensory axonal damage 5
• Approximately one-third of patients cannot be classified at initial presentation and are labeled "equivocal" or "inexcitable" 5
• The traditional demyelinating versus axonal dichotomy is increasingly challenged, and the European Academy of Neurology/Peripheral Nerve Society guidelines do not endorse this distinction 5, 6

Sural Sparing Pattern

The "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. 2

• The sural nerve remains relatively protected because median and ulnar nerves are preferentially affected due to pre-existing subclinical entrapment sites 2
• Do not dismiss GBS based on absent sural sparing in the first week—repeat testing in 2-3 weeks if clinical suspicion remains high 2

Diagnostic Approach

Clinical Assessment

Immediately assess respiratory function and autonomic stability in all patients with suspected GBS, as these determine mortality risk and need for ICU-level care. 2

• Grade muscle strength using Medical Research Council scale in neck, arms, and legs 2
• Assess functional disability using GBS disability scale 2
• Test for cranial nerve involvement, particularly bilateral facial palsy 2
• Evaluate for dysautonomia including blood pressure/heart rate instability 2

Laboratory Investigations

Cerebrospinal fluid examination should be performed to rule out alternative diagnoses and look for albumino-cytological dissociation (elevated protein with normal cell count). 2

• Do not dismiss GBS based on normal CSF protein in the first week, as this may be absent early in the disease course 2, 5
• Initial laboratory tests should include complete blood count, glucose, electrolytes, kidney function, liver enzymes to exclude metabolic or electrolyte dysfunction 2
• Serum creatine kinase (CK) is sensitive though nonspecific; elevation suggests muscle involvement 2

Electrodiagnostic Studies

Nerve conduction studies and EMG should be performed to support diagnosis and classify the neuropathy pattern, though measurements might be normal when performed early (within 1 week of symptom onset). 2, 5

• Look for sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks 2
• Repeating electrodiagnostic studies 3-8 weeks after onset may help classify initially unclassifiable cases 5

Antibody Testing

Do not wait for antibody test results before starting treatment if GBS is suspected. 2

• Testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS 7
• Anti-GQ1b antibody testing should be considered when Miller Fisher syndrome is suspected 7

Red Flags Requiring Diagnostic Reconsideration

Marked persistent asymmetry, bladder dysfunction at onset, or marked CSF pleocytosis should prompt reconsideration of the diagnosis. 2

• Descending flaccid paralysis (cranial nerves → trunk → extremities) indicates botulism until proven otherwise 5
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis 5

Treatment

Admission and Monitoring Criteria

All grades of GBS warrant workup and intervention given potential for progressive disease leading to respiratory compromise. 2

• 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) 2
• Even patients with moderate symptoms (Grade 2) require neurology consultation and close monitoring 2

First-Line Immunotherapy

Intravenous immunoglobulin (IVIg) and plasma exchange are equally effective in treating GBS; no other treatments have been proven effective. 1, 7

Initiate treatment in patients unable to walk unaided within 2-4 weeks of symptom onset. 1, 2, 7

• IVIg: 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) 2, 3, 7
• Plasma exchange: 200-250 ml/kg over 4-5 sessions within 4 weeks of symptom onset 2, 3, 7
• Treatment approach does not differ based on electrophysiological subtype—both IVIg and plasma exchange are first-line regardless of whether the patient has AIDP, AMAN, or AMSAN 6
• Early treatment (within the first 2 weeks) is associated with better outcomes 3

Treatments NOT Recommended

Corticosteroids are NOT recommended for idiopathic GBS. 2, 4, 7

• The Task Force recommends against using oral corticosteroids and weakly recommends against using IV corticosteroids 7
• PE followed immediately by IVIg is not recommended 7
• A second IVIg course in GBS patients with a poor prognosis is not recommended 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. 2, 7

• Treatment-related fluctuations (TRFs) occur in 6-10% of patients within 2 months after initial improvement 2, 3, 7
• Repeating a full course of IVIg or plasma exchange is common practice for TRFs, although evidence is lacking 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 2, 7

Pain Management

Use gabapentinoids (gabapentin, pregabalin) or duloxetine for neuropathic pain—these are weakly recommended. 2, 7

• Gabapentin can be used alongside IVIg to manage paresthesias and neuropathic pain, as these treatments address different aspects of the disease and do not interfere with each other 2
• Do not delay gabapentin initiation waiting for IVIg to "work first"—pain control should begin immediately as part of comprehensive supportive care 2
• Tricyclic antidepressants or carbamazepine are alternative options for neuropathic pain 2, 7
• Encourage mobilization for muscle pain and arthralgia 2

Medications to Avoid

Avoid medications that can worsen neuromuscular transmission: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides. 2

Supportive Care

Comprehensive supportive care is critical for patient outcomes and includes respiratory monitoring, autonomic surveillance, pain management, prevention of complications, and psychological support. 2

• Frequent pulmonary function assessment with serial vital capacity and NIF measurements 2
• Daily neurologic evaluation 2
• Treatment of constipation/ileus 2
• Standard preventive measures for pressure ulcers, hospital-acquired infections, and deep vein thrombosis 2
• Screen for anxiety, depression, and hallucinations, which are frequent complications 2
• Recognize that patients with GBS, even those with complete paralysis, usually have intact consciousness, vision, and hearing 2
• Be mindful of what is said at bedside and explain procedures to reduce anxiety 2

Rehabilitation

Arrange a rehabilitation programme with a rehabilitation specialist, physiotherapist, and occupational therapist as a crucial step towards recovery. 2

• Exercise programmes, including range-of-motion exercises, stationary cycling, walking, and strength training, can improve physical fitness, walking ability, and independence in activities of daily living 2
• Clinical improvement is usually most extensive in the first year after disease onset and can continue for >5 years 1

Prognosis

80% of patients regain independent walking ability at 6 months, though recovery can continue for more than 3 years, with improvement possible even more than 5 years after onset. 2, 3, 7

• 60-80% of patients are able to walk independently 6 months after disease onset, with or without treatment 1
• Despite the severe acute presentation, full recovery can be expected in approximately 90% of cases 2
• However, recovery may take up to 2 years in some patients 2
• Advanced age and severe disease at onset are risk factors for poor outcome 2, 7
• Use the modified Erasmus GBS outcome score (mEGOS) to predict probability of regaining walking ability 2, 7
• Use the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation 7

Disease Course

GBS is a monophasic illness with a characteristic triphasic course: progressive phase, plateau phase, and recovery phase. 1

• Most patients reach their maximum disability within 2 weeks 1, 3
• After the initial progressive phase, patients reach a plateau phase that can last from days to weeks or months 1
• Recurrence is rare (2-5% of patients) but higher than the general population lifetime risk (0.1%) 2, 7
• Prior GBS is not a strict contraindication for vaccination 2

Common Pitfalls

• Do not dismiss GBS based on normal CSF protein or absent sural sparing in the first week—both can be normal early in the disease course 2
• Do not wait for electrodiagnostic confirmation before initiating treatment—clinical diagnosis is sufficient to start immunotherapy 2
• Do not underestimate respiratory risk—approximately 20% require mechanical ventilation, often without obvious dyspnea 1, 3
• Do not overlook autonomic dysfunction—cardiac arrhythmias and blood pressure instability contribute significantly to mortality 1
• Do not delay pain management—neuropathic pain is common and should be treated immediately alongside immunotherapy 2
• Bilateral simultaneous facial weakness is extremely rare in Bell's palsy—this presentation should immediately raise suspicion for GBS 2