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Guillain-Barré Syndrome and Myasthenia Gravis

Guillain-Barré Syndrome (GBS) is an acute autoimmune inflammatory polyneuropathy affecting the peripheral nervous system. It has an incidence of 1–2 cases per 100,000 per year, with a slight male predominance.

The condition is characterized by rapidly progressive, ascending muscle weakness starting from the lower limbs, which can involve the respiratory muscles and cause flaccid paralysis.

Clinical Forms

AIDP (Acute Inflammatory Demyelinating Polyradiculoneuropathy): The most common form in Europe (85–90%).
AMAN (Acute Motor Axonal Neuropathy): Primarily affects motor axons.
AMSAN (Acute Motor-Sensory Axonal Neuropathy): Affects both motor and sensory axons.
Miller Fisher Syndrome: A variant characterized by the triad of ataxia, areflexia, and ophthalmoplegia.

Prognosis

The prognosis is generally good with appropriate treatment; however, the mortality rate remains at 3–5%.

The pathogenesis of Guillain-Barré Syndrome (GBS) is driven by an aberrant autoimmune response against peripheral nerve components, typically triggered by a preceding infection (60–70% of cases).

Pathophysiology: Molecular Mimicry

The core mechanism is molecular mimicry, where antibodies produced to fight an infection cross-react with neural antigens due to structural similarities.

Triggers: * Campylobacter jejuni: (30–40% of cases, strongly associated with the AMAN variant).
- Viruses: Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Influenza, Zika, and COVID-19.
- Bacteria: Mycoplasma pneumoniae.
- Rare Triggers: Vaccines or surgical procedures.

Target Antigens and Antibodies

The immune attack targets specific gangliosides (glycosphingolipids) on the nerve membranes:

Anti-GM1: Associated with AMAN (Acute Motor Axonal Neuropathy).
Anti-GQ1b: Specifically linked to Miller Fisher Syndrome (targeting cranial nerves).

Resulting Nerve Damage

The autoimmune assault leads to two primary pathological outcomes:

Demyelination: Destruction of the myelin sheath (characteristic of AIDP).
Axonal Degeneration: Direct damage to the nerve fiber itself (characteristic of AMAN and AMSAN).

The manifestations of Guillain-Barré Syndrome (GBS) follow a characteristic and rapidly progressive pattern:

Acute Phase (Days to Weeks)

Symmetrical Ascending Muscle Weakness: Typically begins in the lower limbs, with rapid progression over hours or days.
Flaccid Paralysis: May include facio-bulbar involvement (50% of cases).
Areflexia or Hyporeflexia: A hallmark loss of deep tendon reflexes.
Respiratory Involvement: Paralysis of the respiratory muscles (occurs in 20–30% of cases, requiring ventilation).

Sensory Symptoms

Paresthesias and Dysesthesias: Tingling and burning sensations, typically distal.
Intense Neuropathic Pain: Present in 85% of cases; often severe and debilitating.
Hypoesthesia: “Stocking-and-glove” distribution of sensory loss.
Proprioception Loss: Leading to sensory ataxia.

Autonomic Dysfunction (65% of cases)

Cardiovascular: Cardiac arrhythmias, labile hypertension (fluctuating blood pressure), and orthostatic hypotension.
Other Systems: Urinary retention, paralytic ileus, sweating alterations, and pupillary dysfunction.

Severe Complications

Respiratory Failure: 20–30% of patients require mechanical ventilation.
Fatal Arrhythmias: Potentially life-threatening cardiac irregularities.
Secondary Risks: Pulmonary embolism and nosocomial (hospital-acquired) infections.

Typical Clinical Course

Progression: Worsening symptoms for 2–4 weeks.
Plateau: Stabilization for 2–4 weeks.
Recovery: Improvement over weeks to months.

Hughes Diagnostic Criteria: Progressive symmetrical motor weakness, areflexia/hyporeflexia, rapid progression (<4 weeks), and a plateau or improvement phase following the acute stage.
Cerebrospinal Fluid (CSF): Albuminocytologic dissociation (elevated protein levels >0.45 g/L with normal cell count <10/μL); exclusion of other causes.
Blood Tests: Anti-ganglioside antibodies (GM1, GD1a, GQ1b, GT1a), infectious serology (Campylobacter, CMV, EBV, Mycoplasma), and inflammatory markers.
Definitive Electrophysiology:
AIDP Demyelination Criteria: Reduced conduction velocities (<90%), conduction blocks, and temporal dispersion.
AMAN/AMSAN Axonal Criteria: Reduction in amplitude (>50%) with relatively preserved velocities.
Differential Diagnosis: Myasthenia gravis, botulism, poliomyelitis, acute intermittent porphyria, toxic neuropathy, and spinal cord compression.
Urgent Admission Criteria: Rapid progression, bulbar involvement, autonomic dysfunction, and Vital Capacity (VC) <60% of predicted value.

Available therapies

Management and Treatment of GBS

The primary goal in treating Guillain-Barré Syndrome is to modulate the immune response and prevent life-threatening complications.

First-Line Therapies (Equivalent Efficacy)

Intravenous Immunoglobulins (IVIG):
- Dosage: 0.4 g/kg/day for 5 days (total 2 g/kg).
- Advantages: Better tolerability and more readily available in most clinical settings.
Plasmapheresis (Plasma Exchange – PE):
- Dosage: 5 sessions over 8–10 days, 50 mL/kg per session.
- Clinical Note: Often preferred in severe forms, but the combination of IVIG and PE provides no additional benefit over either treatment alone.

Therapies NOT Recommended

Corticosteroids: Not recommended as monotherapy; evidence suggests they may even worsen the prognosis.
Oral Prednisolone: Should not be used in the treatment of GBS.

Essential Supportive Care

Respiratory Support: Continuous monitoring of Vital Capacity (VC). Mechanical ventilation is required if criteria are met (Intubation criteria: VC <20 mL/kg).
Complication Management: Continuous cardiac monitoring (to detect arrhythmias), thromboembolic prophylaxis (heparin), neuropathic pain management, and infection prevention.
Acute Phase Rehabilitation: Passive mobilization to prevent contractures, management of complications related to prolonged bed rest, and respiratory physiotherapy.
Recovery Phase: Progressive active physiotherapy, occupational therapy, and psychological support.

Intensive Monitoring Requirements

Critical Parameters:

Vital Capacity (VC): Every 4–6 hours during the progressive phase.

Continuous Cardiac Monitoring: For autonomic instability/arrhythmias.

Fluid and Electrolyte Balance: Prevention of systemic complications.