• Clinical science

Guillain-Barré syndrome

Abstract

Guillain-Barré syndrome (GBS) is an acute postinfectious polyneuropathy characterized by symmetric and ascending flaccid paralysis. In affected patients, cross‑reactive autoantibodies attack the host's own axonal antigens, resulting in inflammatory and demyelinating polyneuropathy. Albuminocytologic dissociation, characterized by elevated protein levels and normal cell counts in cerebrospinal fluid (CSF), is a hallmark finding of GBS. Additionally, muscle and nerve electrophysiology are used to diagnose demyelinating processes. Symptomatic and supportive treatment results in disease remission in about 70% of cases. In severe cases or patients who do not respond to treatment, intravenous immunoglobulin (IVIG) administration and/or plasmapheresis may be used. Potentially acute life-threatening complications such as respiratory insufficiency, pulmonary embolism, and/or cardiac arrest increase mortality. Although GBS is associated with a good prognosis overall, up to 20% of patients remain severely disabled and approximately 5% of cases are fatal, despite immunotherapy.

Epidemiology

  • Incidence: 1–4 cases per 100,000
  • Sex: > (1.5:1)
  • Adults are affected more frequently than children.

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3]

Pathophysiology

  • Postinfectious autoimmune reaction that generates cross-reactive antibodies (molecular mimicry)
  • Infection triggers humoral response → autoantibodies against gangliosides or other unknown antigens of peripheral Schwann cells → immune-mediated segmental demyelinationaxonal degeneration

References:[4]

Clinical features

  • Initial symptoms: back and limb pain, esp. paresthesias affecting distal extremities
  • Advanced symptoms
    • Ascending paralysis: Bilateral flaccid paralysis spreads from the lower to the upper limbs in a “stocking‑glove” distribution.
    • Reduced or absent muscle reflexes
    • Peripheral, symmetric paresthesias in the hands and feet
    • Neuropathic pain develops in about ⅔ of patients
    • Cardiovascular autonomic dysfunction (arrhythmia), voiding dysfunction, and/or intestinal dysfunction

Landry paralysis affects the muscles of respiration, possibly leading to death due to respiratory failure!

References:[5][6]

Subtypes and variants

Description Etiology Symptoms Treatment
Acute inflammatory demyelinating polyneuropathy
  • Acute variant of Guillain‑Barré syndrome.
  • Predominant sub-type affecting 60–80% of GBS patients in North America and Europe
  • Intravenous immunoglobulin G (IVIg), plasmapheresis
Chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Chronic variant of Guillain‑Barré syndrome.
  • CIDP has not been linked to any infectious agent in particular.
  • Autoantibodies against GM1 gangliosides
  • Similar to those of GBS, but lasting > 2 months
Miller-Fisher syndrome
  • A limited variant of GBS characterized by cranial nerve involvement
  • Ophthalmoplegia, ataxia, and areflexia
  • Intravenous immunoglobulin G (IVIg)
Multifocal motor neuropathy (MMN)
  • Multifocal motor conduction block (detected with electroneurography)
  • Anti‑GM1 ganglioside antibody
  • Elevated protein levels in CSF
  • Asymmetric paralysis and areflexia
  • Initially involves the distal upper limbs
Acute pandysautonomia
  • Severe impairment of the ANS (dysautonomia)
    • Dysregulation of the circulatory system, perspiration, and the secretion of saliva and tears
    • Intraocular muscle paresis
    • Voiding and/or intestinal dysfunction


References:[7][8][4][9][10][11]

Diagnostics

  • Cerebrospinal fluid
  • Slightly elevated myoglobin and total CK blood levels
  • Electroneurography: reduced nerve conduction velocity (NCV) due to demyelination : increased F‑wave latency
  • Electromyography: signs of denervation and pathologic spontaneous activity (unfavorable prognostic sign)
  • ECG: Autonomic cardiac dysregulation → impaired heart frequency variation.

References:[6][4]

Treatment

  • Supportive management
    • Monitor cardiac and respiratory function: in some cases, intensive care unit (ICU) treatment and intubation may be indicated
    • Prevent decubitus and/or thrombosis (esp. pulmonary embolism)
  • High dose of intravenous immunoglobulins
  • Plasmapheresis
    • In adults: equivalent outcome as IV immunoglobulins
    • In children: only recommended in children with rapidly progressing or severe disease

Although GBS is considered an autoimmune disease, glucocorticoids are not recommended for treatment. They have not shown to hasten recovery or affect the long-term outcome.

References:[1][6][12]

Prognosis

  • Up to 70% of patients with GBS have a good prognosis: Disease progression peaks 2–4 weeks after the onset of symptoms. Symptoms then recede in reverse order of their development, i.e., the last symptoms to appear resolve first.
  • 3–7% of patients with GBS die due to acute complications such as respiratory paralysis (apnea), pulmonary infection, pulmonary embolism, or cardiac dysfunction.

Death can occur as many as > 30 days after onset of symptoms, during the recovery phase!

References:[13]