Guillain-Barré Syndrome (GBS) and Antecedent Campylobacter

Infection

Muhammad luthfi

Bagian Ilmu Penyakit Saraf Fakultas Kedokteran Universitas Mulawarman

Tahun 2013

Background of GBS

• Definition of GBS

– acute demyelinating disorder, primarily involving the peripheral nervous system (PNS)

– degree and location of disability depends on the myelinated nerves involved: MOTOR

H and E Stain of Nerve Tissue --Rhesus Monkey

Background of GBS• History of GBS

– 1830s - 1st clinical descriptions

– 1859 - Landry -- detailed description (Landry’s paralysis)

– 1916 - Guillain, Barré and Strohl - disease accompanied by “hyperalbuminosis”

in CSF

– 1936 - Guillain - cardinal clinical features

– 1950s - Electromyography

– 1969 - Asbury - inflammation is quintessential feature of GBS

Background of GBS

• Epidemiology of GBS

– annual incidence is fairly uniform through the world.

– 1-4 cases/100,000

– more common in males

– increases with age

– seasonal variation in incidence

Background of GBS• Clinical Features of GBS

– Motor Involvement*• “ascending paralysis”

• distal (arms/legs) to proximal

– Sensory Involvement

– Autonomic Involvement• principal cause of mortality

Background of GBS• Clinical Features of GBS

– signs and symptoms depend on the part of the nervous system involved

– usually progressive and peaks in 1-3 weeks

– most regain lost function, but time for recovery variable and depends on severity (6 weeks- 2 years)

Background of GBS

• Clinical Feature of GBS

– Atypical presentations

• Miller-Fisher Syndrome– Areflexia

– Ophthalmoplegia

– Ataxia

Background of GBS

• Diagnosis of GBS

– Patient history-- previous illness or vaccination

– Clinical presentation (Physical Exam)

– Laboratory Evaluation• Increase in protein in CSF

• Electromyography -- nerve conduction block

Background of GBS

• Treatment of GBS

– supportive care

– plasmapheresis

– corticosteroids and immunosuppressants

– artificial ventilation (if necessary)

Background of Campylobacter

• Leading cause of bacterial diarrhea in USA

• Campylobacter jejuni - principal human pathogen

• Microbiology– Gram negative, S-shaped rod

– monotrichous flagella

– many serotypes

Background of Campylobacter• Scanning electron microscope image of

Campylobacter jejuni

• Image taken from Altekruse et al. Campylobacter jejuni - an emerging foodborne pathogen. EID. 5(1):1999

Background of Campylobacter• Epidemiology of Campylobacter

– estimated 200,000-400,000 cases/yr???

• Image taken from Altekruse et al. Campylobacter jejuni - an emerging foodborne pathogen. EID. 5(1):1999

Background of Campylobacter

• Epidemiology

– mode of transmission: fecal-oral• vehicles - food, water, milk

• direct contact

– reservoirs: • poultry and cattle

• domestic pets, swine and humans

Background of Campylobacter

• Clinical features

– asymptomatic

– symptomatic • acute watery diarrhea

• usually self-limited

Pathogenesis of GBS

• Believed to have autoimmune etiology

Presence of anti-ganglioside IgG in blood

?

Loss of myelin surrounding nerves

Antecedent Events of GBS• Evidence from case control studies

suggest association with antecedent events:

– Campylobacter jejuni

– Cytomegalovirus

– Epstein-Barr virus

– Mycoplasma pneumoniae

– Rabies vaccine

– “Swine flu” vaccine

Campylobacter and GBS• Prevalence of prior C.jejuni infection varies

geographically:– 66% in China --4% in USA

• Increased incidence in GBS in China parallels seasonal increase in Campylobacter infections

• Exceptional report of 2 sisters who developed GBS at the same time following C. jejuni infection of the Penner serotype 0:19

Campylobacter and GBS

• Only 1 in a 1000 cases of symptomatic

C. jejuni enteritis is followed by GBS

• Uncommon strains of C. jejuni are often isolated from GBS patients– Penner serotype 0:19 (China, Japan)– Penner Serotype 0:41 (South Africa)

Campylobacter and GBS• Molecular mimicry hypothesis

– Host immune response to foreign antigen cross-reacts with host tissue resulting in the immune attack of nerve myelin

– Immunoglobulins, usually IgG, are elevated in GBS

– Host target antigen is unknown

(? gangliosides)

Campylobacter and GBS• Evidence for antibodies directed toward

host gangliosides in GBS patients

– gangliosides

• are complex glycospingolipids with sialic acid residues

• distinguished by # and position of sialic acid residues

• concentrated in neuronal membranes and other cells, BUT are in low concentrations in myelin

Campylobacter and GBS

• C. jejuni has GM1-like epitopes on its membranes

• Anti-ganglioside GM1 antibodies are present in 14-50% of GBS patients

• Only 50% of patients with GBS and anti-ganglioside antibodies have evidence of preceding C. jejuni infection

Campylobacter and GBS

• Fisher syndrome

– IgG1 antibodies to ganglioside GQ1b present– Highly specific for disease– Strongest evidence for autoimmune etiology,

but is not commonly preceded by C. jejuni infection

Summary • Antecedent Campylobacter infection is

common with Guillain-Barré Syndrome

• GBS patients often have auto-antibodies, but their role in pathogenesis is yet to be elucidated

• Other potential etiologic agents may precede Guillain-Barré Syndrome