Guillain-Barré syndrome

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.

• About ⅔ of GBS patients experience symptoms of an upper respiratory or gastrointestinal tract infection 1–4 weeks prior to onset of GBS.
• Pathogens associated with GBS: Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, HIV, influenza, and Mycoplasma pneumoniae
  • Campylobacter enteritis is the most common disease associated with GBS.
  • Cytomegalovirus is the most common virus associated with GBS

References:^[3]

• 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 demyelination → axonal degeneration

References:^[4]

• 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.
    • Cranial nerve involvement: frequently bilateral facial nerve involvement (facial diplegia)
      • Glossopharyngeal nerve (XI) and vagal nerve (X)
    • Landry paralysis: involvement of the respiratory muscles
  • 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

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

References:^[5][6]

	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	Associated with Campylobacter enteritis and CMV Autoantibodies against various antigens	Ascending paralysis, autonomic neuropathy, CN defects and pain, clinical nadir ∼4 weeks	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	Glucocorticoids, azathioprine, cyclophosphamide, plasmapheresis, or intravenous immunoglobulin therapy (IVIg)
Miller-Fisher syndrome	A limited variant of GBS characterized by cranial nerve involvement	Autoantibodies directed against ganglioside GQ1b, GT1a	Ophthalmoplegia, ataxia, and areflexia	Intravenous immunoglobulin G (IVIg)
Multifocal motor neuropathy (MMN)	A variant of GBS solely affecting the motor neurons. Differential diagnosis for amyotrophic lateral sclerosis (ALS) .	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	Immunosuppression
Acute pandysautonomia	A variant of GBS that is characterized by exclusive involvement of the autonomic nervous system (ANS)		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]}

• Cerebrospinal fluid
  • Albuminocytologic dissociation: elevated protein levels and normal cell counts in cerebrospinal fluid (CSF); CSF cell counts higher than 50 cells per μl CSF indicate that GBS is unlikely!
• Serological screening
  • To identify potential pathogens (e.g., Campylobacter jejuni)
  • Detection of antibodies directed against gangliosides (e.g., anti‑GM1 antibodies)
• 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]

• 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]

• 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, as Schwann cells remyelinate peripheral nerve axons.
• 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]