Guillain-Barre Syndrome

(GBS)

Iman binti Jeffrey

0611750
Outline

Definition
Epidemiology
Etiology
Pathogenesis & Pathology
Clinical features
Investigations
Diagnosis
Differential diagnosis
Treatment
Prognosis
Definition
 Postinfectious polyneuropathy involving
mainly motor but sometimes also sensory and
autonomic nerves
 Affects people of all ages and is not
hereditary
 Most patients have a demyelinating
neuropathy, but primarily axonal degeneration
is documented in some cases.
 also known as: Acute inflammatory demyelinating
polyneuropathy (AIDP)
Epidemiology

 usually in children over 4-9 years

 overall frequency is 1.9 cases per 100,000
population
 follows infection or immunization by 10
days
 follows respiratory tract infection or
gastrointestinal infection
Etiology

GIT infection
Campylobacter jejuni (26-41%)
Cytomegalovirus (10-22%)
Respiratory tract infection
Mycoplasma pneumoniae
Ebstein-Barr virus (10%)
Vaccines
 Rabies
 Avian-flu influenza
Pathogenesis

Molecular mimicry
Cross-reactive immune attack by host Ab & T cell
with are directed against the pathogen & nerve
components.
Eg: Campylobacter jejuni
Immune response directed against capsular LPS
producing Ab cross-reacting with myelin to cause
demyelination (mimics the gangliosides)
Pathogenesis

Presentation of Ag to naïve T cell → activation

↓
Activated T cells attach to venular endothelium of
peripheral nerves
↓
Migrate through endothelial lining to perivascular
location
↓
Sensitized → contact myelin → segmental
demyelination
Pathology

Inflammatory lesions scattered throughout the

peripheral nervous system
Circumscribed areas of myelin loss associated
with presence of lymphocytes and macrophages
Initial lesion: nodes of Ranvier
Myelin damage: penetration of macrophages into
basement membrane around nerve fibers & strip
myelin away
Severe cases: interruption of axon & wallerian
degeneration
Clinical Features

Weakness
o Onset is gradual and progresses over weeks
o Lower extremities (unable/refusal to walk)  trunks  upper limbs 
bulbar muscles  flaccid tetraplegia = Landry Ascending Paralysis
o Proximal and distal muscles are involved relatively symmetrically, but
asymmetry is found in 9% of patient

Muscle tenderness – At the onset

Paraesthesias – in some cases

Areflexia (83%)
Clinical Features
Bulbar involvement (50%)
o Dysphagia and facial weakness – signs of impending respiratory failure
o Interfere with eating. Increase risk of aspiration

Cranial nerve involvement (50%)

o Facial nerve
o Oculomotor nerve

Autonomic involvement
o Lability of blood pressure
o Postural hypotension
o Profound bradycardia
o Occasional asystole
o Urinary
o retention or incontinence (20% of cases, usually transient)
Clinical Features
Symptoms of viral meningitis / meningoencephalitis
o In young children

CNS involvement
o ataxia
o papilledema

Miller-Fisher syndrome
o External ophtalmoplegia
o ataxia
o areflexia
 Table 1:Clinical features in 49
children with GBS*
Features Prevalence
Age 7.1years (mean)
Male/female ratio 1.2:1
Weakness 73%
Pain 55%
Ataxia 44%
Paraesthesias 18%
Shortness of 4%
breath
* Data from unpublished observation of John Sladky. Two patients had consistent
findings of Fisher syndrome
Course
Initial phase
 Gradually increasing involvement lasts 10-30 days (less
than 4 weeks)

Plateau phase
 Short phase (within 2 weeks)

 Long plateau phase → poor prognosis

Recovery phase
 Within months

 Usually complete

 Motor sequelae (5-25%)

 Relapse & late recurrences (3%)

Investigations
Lumbar puncture – cerebrospinal fluid (CSF)
o Elevation of CSF protein (more than twice upper limit of
normal)
o Cell content of CSF is normal (<10 cells/mm³)
o Glucose level normal
o Bacterial and viral culture is negative

Electromyography
o Motor nerve conduction velocities are greatly reduced, and
sensory nerve conduction time is often slow
o evidence of acute denervation of muscle

Serum Creatine Kinase

o Elevated or normal
 Muscle biopsy
o appear normal in early stages
o show evidence of denervation atrophy in chronic stages
 Sural nerve biopsy
o segmental demyelination, focal inflammation, and wallerian
degeneration
o Serologic testing for Campylobacter infection
This is a high-power image of an nerve stained with the standard H&E. The
GBS is fairly acute, and the nerve contains significant inflammation. The
majority of the small round nuclei are those of lymphocytes infiltrating
the nerve.
Some residual myelinated axons can be seen. The denser pink lines (black
arrow) are the axons and the bubbly-appearing pink areas surrounding
them are myelin sheaths
This is a mid-power image of a nerve which has been stained with a
different myelin stain, which stains the myelin blue. There is patchy myelin
loss within the nerve. You an also see some small round lymphocyte nuclei.
Subdivision of GBS
Subdivision Clinical manifestation
Sporadic GBS (AIDP) As mentioned

Acute motor-sensory Relatively infrequent

axonal neuropathy Severe degeneration of motor and sensory axons
(AMSAN) Little demyelination
Fulminant, extensive and severe weakness with
delayed and incomplete recovery
Acute motor-axonal Severe pure motor axonal neuropathy
neuropathy Clinical course and recovery is similar to AIDP
(AMAN)
Miller-Fisher Triad: ophthalmoplegia, ataxia, & areflexia
syndrome
Chronic IDP Neurologic symptoms are slower (>4 weeks)
(CIDP)
Diagnosis
Required Progressive motor weakness involving >1 extremities
for Areflexia or marked hyporeflexia
diagnosis No more than 50 monocytes or 2 granulocytes per µL CSF

Supportive Initial absence of fever

Progression over days to few weeks
Onset of recovery 2-4 weeks after cessation of progress
Relatively symmetric weakness
Mild sensory signs & symptoms
Cranial nerve signs
Elevation of CSF protein after 1 week of symptom
Slowed nerve conduction velocity
Autonomic dysfunction

From National Institute of Neurologic and Communicative Disorders and Stroke

Differential Diagnosis

 Spinal cord compression

 Transverse myelitis
 Tick paralysis
 Poliomyelitis
 Botulism
 Diphtheria
Treatment
Patients with early stages of this acute disease
Should be admitted to the hospital for observation because the ascending
paralysis may rapidly involve respiratory muscles during the next 24 hour.

 Patients with slow progression:

may simply be observed for stabilization and spontaneous remission without
treatment.

 Patients with rapidly progressive ascending paralysis:

o Intravenous immunoglobulin (IVIG), administered for 2, 3, or 5 days
o Plasmapheresis, steroids, and/or immunosuppressive drugs are alternatives,
if IVIG is ineffective
o Combined administration of immunoglobulin and interferon is effective in
some patients.

Supportive care, such as respiratory support, prevention of decubiti in children

with flaccid tetraplegia, and treatment of secondary bacterial infections, is
important
Prognosis
Spontaneous recovery begins within 2–3 weeks.
Most regain normal muscular function
Tendon reflexes are usually the last function to recover
Improvement usually follows a gradient inverse to the direction
of involvement.
Bulbar and respiratory muscle involvement may lead to death if
the syndrome is not recognized and treated
3 clinical features predictive to poor outcome:
 Cranial nerve involvement

 Intubation

 Maximum disability at the time of presentation

References

 Menkes & Sarnat: Child Neurology, 6th ed.

USA, Lippincott Williams & Wilkins, 2000
 Aicardi, Jean: Clinics in Developmental
Medicine: Diseases of The Nervous System
in Childhood, 2nd ed. London, Mac Keith
Press, 1998
 Behrman, Kliegman, Jenson: Nelson
Textbook of Pediatrics, 17th ed. China,
Elsevier Saunders, 2004