What is Guillain-Barré Syndrome (GBS)?

Guillain-Barré Syndrome: A Clinical Overview

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 moving to the arms, and represents 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 mortality rate remains 3-10% even with optimal medical care, primarily due to respiratory failure and autonomic complications 2, 1, 3
• Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea 2, 1, 3

Clinical Presentation

The classic presentation is rapidly progressive bilateral weakness starting in the legs and ascending to arms and cranial muscles, accompanied by decreased or absent reflexes. 1

Core Clinical Features:

• Motor symptoms: Ascending bilateral weakness beginning in lower extremities, progressing over hours to days 1
• Sensory symptoms: Distal paresthesias or sensory loss that may accompany or precede weakness 1
• Reflex changes: Decreased or absent reflexes in most patients at presentation and almost all at nadir 1
• Rapid progression: Most patients reach maximum disability within 2 weeks of symptom onset 2, 1, 3

Autonomic Dysfunction:

• Blood pressure and heart rate instability ranging from severe hypertension to hypotension 1, 3
• Cardiac arrhythmias that can be fatal 2, 1, 3
• Pupillary dysfunction and bowel/bladder dysfunction 1

Additional Features:

• Pain (muscular, radicular, or neuropathic) is frequently reported 1
• Cranial nerve involvement may occur 1

Clinical Variants

GBS presents with several distinct clinical variants beyond the classic form 1:

• Pure motor variant: Weakness without sensory signs 1
• Miller Fisher syndrome: Characterized by the triad of ophthalmoplegia, areflexia, and ataxia 1
• Regional variants: Including bilateral facial palsy with paresthesias, pharyngeal-cervical-brachial weakness, or paraparetic variant 1

Diagnostic Approach

The diagnosis of GBS is primarily clinical, supported by cerebrospinal fluid analysis and electrophysiological studies. 1

Cerebrospinal Fluid Analysis:

• Typically shows elevated protein level with normal cell count (albumino-cytological dissociation) 1
• However, normal CSF findings do not exclude GBS, especially early in the disease course 2

Electrophysiological Studies:

• Provide evidence of peripheral nervous system dysfunction 1
• Can distinguish between three main subtypes: AIDP (acute inflammatory demyelinating polyneuropathy), AMAN (acute motor axonal neuropathy), and AMSAN (acute motor and sensory axonal neuropathy) 2, 1
• Approximately one-third of patients cannot be classified at initial presentation and are labeled "equivocal" or "inexcitable" 1
• The traditional demyelinating versus axonal dichotomy is increasingly challenged, and treatment does not differ based on electrophysiological subtype 1

Respiratory Monitoring:

• Vital capacity and negative inspiratory force should be assessed to evaluate respiratory function 1
• Patients are at imminent risk when vital capacity falls below 20 ml/kg, maximum inspiratory pressure is less than 30 cmH₂O, or maximum expiratory pressure is less than 40 cmH₂O 3
• A single breath count of ≤19 predicts the need for mechanical ventilation 3

Cardiac Monitoring:

• Continuous monitoring for cardiac arrhythmias and blood pressure instability is critical 1, 3

Differential Diagnosis: Key Distinguishing Features

Ascending bilateral symmetric weakness (legs → arms → cranial nerves) strongly suggests GBS, while descending flaccid paralysis (cranial nerves → trunk → extremities) indicates botulism until proven otherwise. 1

• Areflexia or hyporeflexia in affected limbs points to GBS 1
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis 1

Disease Course and Prognosis

Natural History:

• After the initial progressive phase, patients reach a plateau phase lasting from days to weeks or months 2
• Recovery then begins, with 60-80% of patients able to walk independently 6 months after disease onset 2, 4
• Clinical improvement is usually most extensive in the first year after disease onset and can continue for >5 years 2

Treatment-Related Fluctuations:

• Occur in 6-10% of patients within 2 months of initial improvement, representing disease reactivation 3, 4
• Some patients can deteriorate after first stabilizing or improving on therapy 2

Relapses:

• GBS is typically a monophasic illness, but relapses can occur in 2-5% of patients 2

Pathophysiology

GBS is thought to be caused by an aberrant immune response to infections that results in damage to peripheral nerves through molecular mimicry. 2

• In a subgroup of patients, serum antibodies are found against gangliosides, which reside at high densities in the axolemma and other components of peripheral nerves 2
• Complement activation, infiltration of macrophages, and edema are typical characteristics of affected peripheral nerves and nerve roots 2
• The incidence of GBS can increase during outbreaks of infectious illnesses, most recently demonstrated during Zika virus epidemics in French Polynesia (2013) and Latin America/Caribbean (2015-2016) 2

Critical Management Pitfalls to Avoid

• Delayed diagnosis due to variable clinical presentations and regional variants 3
• Failure to monitor respiratory function closely, as respiratory failure can occur without obvious dyspnea 2, 1
• Use of medications that worsen neuromuscular function: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides should be avoided 3
• Underestimating autonomic instability: Cardiovascular complications can occur unpredictably and require continuous cardiac monitoring 3
• Missing the narrow treatment window: Early treatment with immunotherapy within the first 2 weeks is associated with better outcomes 4