What is Guillain-Barre Syndrome?

Guillain-Barré Syndrome: Definition and Clinical Overview

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

Epidemiology and Mortality Risk

• GBS has an annual global incidence of approximately 1-2 per 100,000 person-years, occurring more frequently in males and with increasing incidence with age 1
• The disease carries a mortality rate of 3-10% even with optimal medical care, primarily due to respiratory failure and autonomic complications 2, 1
• Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea 3, 1

Characteristic Clinical Presentation

Hallmark Features

• Rapidly progressive bilateral ascending weakness starting in the legs and progressing to the arms and cranial muscles over days to weeks is the defining clinical feature 3, 2
• Decreased or absent reflexes occur in most patients at presentation and almost all patients at nadir 2, 1
• Distal paresthesias or sensory loss frequently precede or accompany the weakness 2, 1
• Maximum disability is typically reached within 2 weeks of symptom onset 2, 1

Associated Symptoms

• Pain (muscular, radicular, or neuropathic) is frequently reported and can be an early symptom 2
• Dysautonomia including blood pressure/heart rate instability, pupillary dysfunction, and bowel/bladder dysfunction can occur 2, 1
• Cardiac arrhythmias from autonomic nervous system involvement may develop 1
• Cranial nerve involvement occurs in approximately 35% of patients, with facial palsy being the most common manifestation 2, 4

Etiology and Pathophysiology

• About two-thirds of patients report symptoms of infection in the 6 weeks preceding disease onset 2
• Six pathogens have been temporally associated with GBS in case-control studies: Campylobacter jejuni, Cytomegalovirus, Hepatitis E virus, Mycoplasma pneumoniae, Epstein-Barr virus, and Zika virus 2
• The pathophysiology involves molecular mimicry where pathogen-borne antigens lead to generation of crossreactive antibodies that target gangliosides in peripheral nerves 5
• Complement activation, macrophage infiltration, and edema characterize affected peripheral nerves 2

Clinical Variants

• Acute inflammatory demyelinating polyneuropathy (AIDP) is the most common form in Europe and North America 6
• Acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) are axonal variants, with AMAN occurring more frequently in East Asia 1, 6
• Miller Fisher syndrome presents with the triad of ophthalmoplegia, areflexia, and ataxia 1
• Regional variants include bilateral facial palsy with paresthesias, pharyngeal-cervical-brachial weakness, or paraparetic variant 1

Diagnostic Approach

Clinical Diagnosis

• The diagnosis is primarily clinical, supported by cerebrospinal fluid analysis and electrophysiological studies 1
• Ascending bilateral symmetric weakness (legs → arms → cranial nerves) strongly suggests GBS 1
• Areflexia or hyporeflexia in affected limbs is a key diagnostic feature 1

Laboratory Findings

• Cerebrospinal fluid analysis typically shows elevated protein level with normal cell count (albumino-cytological dissociation) 1
• Mean CSF protein levels are approximately 113.8 ± 11.8 mg/dl 4
• Electrophysiological studies demonstrate peripheral nerve dysfunction and help differentiate between GBS subtypes 1
• Conduction block determined indirectly by absent H-reflex is noted in approximately 90% of patients 4

Important Diagnostic Caveats

• Approximately one-third of patients cannot be classified into AIDP, AMAN, or AMSAN at initial presentation and are labeled "equivocal" or "inexcitable" 1
• 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

Disease Course and Prognosis

• The disease course is typically monophasic with maximum disability reached within 2 weeks 2
• Recovery can continue for more than 3 years after onset 2
• 60-80% of patients can walk independently 6 months after disease onset 2
• Treatment-related fluctuations occur in 2-5% of patients, defined as disease progression within 2 months following initial treatment-induced improvement 3, 2
• Approximately 5% of patients initially diagnosed with GBS may actually have acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) if progression continues after 8 weeks from onset 7

Critical Monitoring Requirements

• Vital capacity and negative inspiratory force should be assessed to evaluate respiratory function 1
• Continuous monitoring for cardiac arrhythmias and blood pressure instability is critical 1
• Perform frequent neurochecks and pulmonary function monitoring 3
• Watch for dysphagia, facial weakness, or respiratory muscle weakness—these warrant immediate escalation of care 3
• Peak flow testing may be a predictor of assessing requirement of mechanical ventilation and prognosis 4

Treatment Principles

• Intravenous immunoglobulin (IVIg) 0.4 g/kg daily for 5 days or plasma exchange (12-15 L in four to five exchanges over 1-2 weeks) should be initiated within 2-4 weeks of symptom onset in patients unable to walk unaided 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 1
• IVIg treatment is more expensive but is associated with less duration of hospital stay compared to plasma exchange 4
• No difference in complications and outcome is found between treatment regimens of IVIg and plasma exchange 4