What is Guillain-Barré Syndrome (GBS) and how is it diagnosed?

What is Guillain-Barré Syndrome (GBS)?

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 with a potentially fatal course requiring immediate recognition and treatment. 1

Definition and Epidemiology

• GBS has an annual global incidence of approximately 1-2 per 100,000 person-years and occurs more frequently in males, with incidence increasing 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 1, 2
• Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea 1, 2

Clinical Presentation

Classic Features:

• Rapidly progressive bilateral weakness starting in the legs and ascending to arms and cranial muscles 1
• Distal paresthesias or sensory loss accompanying or preceding weakness 1
• Decreased or absent reflexes in most patients at presentation and almost all at nadir 1
• Disease progression typically reaches maximum disability within 2 weeks of onset 1

Associated Features:

• Dysautonomia (blood pressure/heart rate instability, pupillary dysfunction, bowel/bladder dysfunction) 1
• Pain (muscular, radicular, or neuropathic) is frequently reported 1
• Cardiac arrhythmias from autonomic nervous system involvement 1

Atypical Presentations:

• Weakness can be asymmetrical, predominantly proximal or distal, or start simultaneously in all limbs 1
• Young children (<6 years) may present with poorly localized pain, refusal to bear weight, irritability, meningism, or unsteady gait 1
• Some patients have normal or even exaggerated reflexes, particularly in pure motor variants with AMAN subtype 1

Clinical Variants

• Pure motor variant: Weakness without sensory signs 1
• Miller Fisher syndrome (MFS): Ophthalmoplegia, areflexia, and ataxia 1
• Regional variants: Bilateral facial palsy with paresthesias, pharyngeal-cervical-brachial weakness, or paraparetic variant 1

---

Diagnostic Investigations for GBS

The diagnosis of GBS is primarily clinical, supported by cerebrospinal fluid analysis showing albumino-cytological dissociation and electrophysiological studies demonstrating peripheral nerve dysfunction, though both tests can be normal early in the disease course. 1

Clinical Diagnostic Criteria

Key diagnostic features to establish:

• Progressive bilateral weakness of legs and/or arms in the absence of CNS involvement 1
• Time course: maximum disability reached within 4 weeks (typically within 2 weeks) 1, 3
• Monophasic illness course 1
• History of preceding infection in approximately two-thirds of patients (within 6 weeks before onset) 1

Red flags suggesting alternative diagnoses:

• Maximum disability reached within 24 hours or after 4 weeks should prompt consideration of other conditions 1
• Progression continuing after 8 weeks suggests acute-onset CIDP (A-CIDP), which occurs in approximately 5% of patients initially diagnosed with GBS 3

Cerebrospinal Fluid (CSF) Analysis

• Classic finding: Elevated protein level with normal cell count (albumino-cytological dissociation) 1
• Critical caveat: CSF can be normal early in the disease course, so normal results do not exclude GBS 1
• CSF examination is particularly valuable when the diagnosis is less certain 3

Electrophysiological Studies

Nerve conduction studies provide:

• Evidence of peripheral nervous system dysfunction 1
• Differentiation between GBS subtypes: AIDP (demyelinating), AMAN (axonal motor), and AMSAN (axonal motor-sensory) 1
• Demyelinating features in AIDP: Prolonged distal latencies, conduction block, slow conduction velocities 4

Important limitation: Normal initial studies do not exclude GBS, as electrophysiological changes may not appear until 10-14 days after symptom onset 4, 3

Serological Testing

• Anti-ganglioside antibodies: Limited clinical value in most patients with typical motor-sensory GBS 3
• Anti-GQ1b antibody testing: Should be considered when Miller Fisher syndrome is suspected 3
• Nodal-paranodal antibodies: Should be tested when autoimmune nodopathy is suspected 3

Imaging Studies

• MRI or ultrasound imaging: Should be considered in atypical cases to rule out alternative diagnoses 3
• Neuroimaging helps exclude CNS pathology when the clinical picture is unclear 5

Respiratory and Autonomic Monitoring

Critical assessments required immediately:

• Vital capacity and negative inspiratory force to assess respiratory function 4
• Continuous monitoring for cardiac arrhythmias and blood pressure instability 2, 4
• Assessment for bulbar weakness (dysphagia, dysarthria) to predict aspiration risk 4

Rationale: Respiratory failure can develop rapidly without obvious dyspnea, and autonomic dysfunction can be life-threatening 1, 2

Differential Diagnosis Considerations

Pattern of weakness progression is the most important distinguishing feature:

• Ascending bilateral symmetric weakness (legs → arms → cranial nerves) strongly suggests GBS 4
• Descending flaccid paralysis (cranial nerves → trunk → extremities) indicates botulism until proven otherwise 4
• Areflexia or hyporeflexia in affected limbs points to GBS 4
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis 4

Diagnostic Criteria Systems

• National Institute of Neurological Disorders and Stroke criteria 5
• Brighton criteria 5

These standardized criteria assist in confirming the diagnosis, particularly in research settings and when the clinical presentation is atypical.