Guillain-Barré Syndrome

Overview

Definition

• Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy of the peripheral nervous system. This condition may occur after an infection. 
• Known causative infections: 
  • Campylobacter jejuni (most commonly identified agent)
  • Cytomegalovirus
  • Mycoplasma pneumoniae
  • Epstein-Barr virus
  • Zika virus
  • Vaccinations (e.g., flu shot)

Epidemiology

• Incidence: 1–2 cases per 100,000 person-years 
• Most common cause of acute flaccid paralysis 
• Higher prevalence among males than among females
• Incidence rises with age.

Pathophysiology

• Molecular mimicry:
  • Infection triggers normal immune response.
  • Unidentified infectious antigens create autoantibodies that attack gangliosides of the axonal myelin sheath.
  • Membrane attack complex forms on the surface of Schwann cells.
  • Macrophages target myelin.
  • Inflammatory demyelinating polyneuropathy occurs.
• Motor axonal neuropathy: 
  • Antibodies that bind to nodes in the myelinated axons are formed. 
  • Depending on the particular node, voltage-gated sodium channels or paranodal myelin may be attacked.
  • This results in failure in nerve conduction and subsequent muscle weakness.

Clinical Presentation

Clinical symptoms vary based on the subtype of GBS. Individuals may have a history of respiratory or GI symptoms 1–4 weeks prior to the appearance of GBS.

Acute inflammatory demyelinating polyneuropathy (AIDP)

• Most common form of GBS
• Symmetric weakness and paresthesia
• Ascending flaccid paralysis that typically begins in the lower extremities.
• Dysautonomia also commonly appears (in 70% of cases), causing:
  • Diarrhea/constipation 
  • Bradycardia/tachycardia 
  • Urinary retention 
  • Horner syndrome
• Decreased or absent deep tendon reflexes of the affected limbs 
• Progression is relatively rapid (within 8 weeks) and progressive (without intermittent improvement and relapses).
• Cranial nerve palsy: facial palsy

Acute motor axonal neuropathy (AMAN)

• Most commonly associated with C. jejuni infection
• Deep tendon reflexes commonly spared
• Sensory nerves not affected
• Other symptoms similar to AIDP

Acute motor and sensory axonal neuropathy (AMSAN)

• Similar to AMAN, but more severe
• Both sensory and motor fibers affected 
• Marked axonal degeneration

Miller Fisher variant

• One of the major forms of GBS
• Characteristic symptoms:
  • Ophthalmoplegia
  • Ataxia
  • Areflexia
  • Only ¼ of cases involve motor weakness of limbs

Bickerstaff encephalitis

• Brain stem encephalitis 
• Symptoms include:
  • Encephalopathy 
  • Hyperreflexia 
  • Ophthalmoplegia 
  • Ataxia

Pharyngeal-cervical-brachial weakness

• Weakness of the oropharyngeal, neck, and shoulder muscles 
• Swallowing dysfunction
• Facial weakness
• Lower-extremity strength and reflexes preserved

Paraparesis

• Mild variant
• Isolated weakness of the lower extremities 
• Rare in upper extremities 
• Reduced or absent arm reflexes 
• Electrodiagnostic studies of upper extremities abnormal in 90%

Diagnosis

General approach

• Initial diagnosis is based on clinical presentation and medical history.
• Features that are unlikely for GBS:
  • Asymmetric pattern of weakness
  • Bladder/bowel dysfunction at onset
  • Fever at onset 
  • Respiratory dysfunction without limb weakness at onset 
  • Hyperreflexia

Additional workup

• Confirmatory workup:
  • CSF analysis: often shows elevated protein with no WBCs
  • Nerve conduction studies: 
    • Serves to distinguish axonal from demyelinating form of neuropathy
    • Decreased velocity of conduction 
    • Reduced amplitude in compound muscle action potentials
  • Electromyography:
    • Serves to distinguish from pathology in neuromuscular junction 
    • Common findings on electromyography include motor conduction block and temporal dispersion.
  • Serum IgG antibodies to GQ1b: 90% sensitive for Miller Fisher syndrome
• MRI:
  • Not a routine diagnostic tool
  • Can exclude stroke, spinal cord lesions, malignancy, etc. 

Management

Criteria for ICU admission

• Respiratory failure requiring intubation and mechanical ventilation 
• Airway compromise: 
  • Presents with diminished cough reflex or swallowing dysfunction 
  • Intubation and mechanical ventilation
• Autonomic cardiovascular dysfunction:
  • Hypotension
  • Atrioventricular blocks and asystole

Immunomodulatory therapy

• Started when individuals are unable to ambulate independently or show severe symptoms or rapid progressive weakness.
• 2 major options:
  • Intravenous immunoglobulin (IVIG)
  • Plasma exchange 
  • Both equally effective, with similar risks of complications 
  • Treatment may be repeated; however, plasma exchange must not follow IVIG, as it would wash away the immunoglobulin.

Monitoring

• Always monitor for respiratory insufficiency.
• Changes in blood pressure and new-onset arrhythmias may occur.
• To prevent pulmonary embolism for those with limited mobility
• Psychological distress must be managed early with sufficient education of the individual.
• Physical rehabilitation focusing on improving physical function, fatigue, and pain is necessary to avoid long-term residual problems of GBS.

Prognosis

• Most show significant recovery within 1 year after onset.
• Recurrence is rare; however, those who had GBS are more likely than the general population to get GBS again.
• Mortality (estimated 3%–10%) is mostly secondary to cardiovascular/respiratory complications. 

Differential Diagnosis

• Myasthenia gravis: autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. Myasthenia gravis presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs leading to difficulty in movement. Diagnosis is established on the basis of clinical presentation, detection of antibodies and electrophysiologic studies. Management is aimed at increasing the activity of acetylcholine at the neuromuscular junction and suppression of antibodies. Disease can be associated with thymomas and thymic hyperplasia, and thymectomy is sometimes indicated. The disease can progress to a life-threatening cholinergic crisis with respiratory failure, but this is preventable with appropriate management. Prognosis is generally good with treatment, and some individuals can achieve long-term remission.
• Rabies: infectious disease caused by a single-stranded, negative-sense RNA virus. This bullet-shaped virus belongs to the family Rhabdoviridae and the genus Lyssavirus. Rabies is a preventable disease most often transmitted to humans through the bite of an infected animal (e.g., bats, raccoons, skunks, and foxes). This life-threatening disease affects the CNS, resulting in severe neurologic manifestations. There are 5 stages of the disease in humans: incubation, prodrome, acute neurologic period, coma, and death. The diagnosis is made with antibody, antigen, or viral RNA detection in a tissue biopsy specimen, serum, CSF, and saliva. There is no effective treatment for symptomatic disease, so prevention with human rabies immunoglobulin and vaccination is the mainstay of management.
• Progressive multifocal leukoencephalopathy (PML): demyelinating disease of the CNS caused by polyomavirus JC virus, which causes disease only among those who are immunocompromised. Presentation is with cognitive impairments, ataxia, aphasia, or other symptoms depending on the location of the lesion. Progressive multifocal leukoencephalopathy is diagnosed with brain imaging, CT, or MRI, which show nonenhancing white matter lesions and with CSF analysis with PCR testing positive for the virus. Management is supportive and aims to reverse the cause of immunosuppression. 
• Botulism: rare neuroparalytic syndrome caused by Clostridium botulinum, which releases a fatal neurotoxin (botulinum toxin) causing varying degrees of muscle paralysis and distinct clinical syndromes. The 2 most common types are foodborne and infant botulism. Botulism presents with symmetric descending flaccid paralysis, blurred vision, and respiratory failure and is characterized by intact sensorium, normal heart rate and blood pressure, absence of fever, and absence of sensory deficits. Diagnosis is made on clinical grounds and can be confirmed by the isolation of bacteria or toxins from stool, wound specimens, or food sources. The approach to managing a case of botulism should include prompt management of respiratory failure, administration of antitoxin, and supportive care for paralysis.