Georges Guillain

Guillain-Barre'

• -. Neuron

Myelin sheath

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com

Neurology Chapter of IAP

 Guillain-Barre' Syndrome
• Post-infectious polyneuropathy;
ascending polyneuropathic paralysis

• An acute, rapidly progressing and

potentially fatal form of polyneuritis

Neurology Chapter of IAP

 Guillain-Barre' Syndrome
• Affects the peripheral nervous system
• Peripheral Nervous
System

/·
Somatic Au tonom1c
.
Division Division

Parasym pathetic
Nervous System Nervous System

Lp
e Neurology Chapter of IAP
Guillain-Barre'

• T-cell sensitization occurs which causes loss

of myelin which disrupts nerve impulses
• Loss of myelin, edema and inflammation of
the affected nerves, causes a loss of
neurotransmission to the periphery.
• 85°/o of patients recover with supportive
care.

Neurology Chapter of IAP

 Pathophysiology
• Etiology unknown
• May be cell-mediated immunological
reaction directed at the peripheral
nerves
• Frequently preceded by viral infection,
trauma, surgery or other immune
system stimulation.

Neurology Chapter of IAP

Overview of Adaptive Immunity

Lymphocytes: “command & control,”

identify antigen components, respond
specifically, mobilize other elements and
direct the attack c memory for each
antigenic assault
Antibodies: specialized immunoglobulin
molecules directly neutralize and remove
antigen
T lymphocytes

CD8- recognize epitopes paired c MHC-I

CD4- activate and control the immune response
Scavenger cells break down antigen into small
peptide fragments (T cell epitopes), MHC-II
epitope complexes are expressed on the surface
& the scavenger become an APC which docks on
a CD4 c a compatible TCR. CD4 proliferates
releasing cytokines.
Antibodies

Cytokines activate other lymphocytes including B

cells that differentiate into plasma cells and
serve as immunoglobulin factories.
Abs are Ig molecules that recognize, bind,
neutralize and opsonize Ag for phagocytosis.
They activate complement(membrane attack
complex) & induce target cells to activate the
inflammatory response
Cellular & Humoral Immune
Mechanisms
Self-tolerance

The process of self recognition

T & B cells learn self tolerance
during maturation.

Autoimmunity occurs when the

mechanisms of self protection are
defective
Mechanisms of Autoimmunity

Molecular mimicry- microbe cell surface Ag

resembles self protein. Damage results from
“friendly fire” The inciting Ag is usually
unidentified & may not exist as a single
stimulus.
Excessive cytokine release due to profound
immune stimulus may awaken self tolerant T
cells or may cause expression of MHC
complexes.
Self Ags bound to drugs may lose tolerated
status
Antecedent Events: Infectious

Viral: Influenza, Coxsackie, EBV, Herpes,

HIV, Hepatitis, CMV, WNV

Bacterial: Campylobacter jejuni,

Mycoplasma, E. coli
Parasitic: Malaria, Toxoplasmosis
Antecedent Events: Systemic disease

Hodgkins
CLL
Hyperthyroidism
Sarcoidosis
Collagen Vascular d.
Renal d.
Other antecedent events

Surgery
Immunization
Pregnancy
Envenomization
Bone marrow transplantation
Drug ingestion
Subtypes of Guillain-Barre
syndrome
Several variants of GBS are recognized. These
disorders share similar patterns of evolution,
symptom overlap, and probable immune-
mediated pathogenesis.
Subtypes of Guillain-Barre syndrome

Miller-Fisher syndrome

• observed in about 5% of all GBS cases.

triad ataxia
0

0
areflexia
0
ophthal
• moplegi
a
• Ataxia tends to be out of proportion to
the(cardinal
degree of sensory loss.
feature)
• Patients may also have mild limb weakness,
ptosis, facial palsy, or bulbar palsy
• Patients have reduced or absent sensory nerve
action potentials and absent tibial H reflex.
Subtypes of Guillain-Barre syndrome

Acute inflammatory demyelinating polyneuropathy

• the most commonly identified form in the

United States.
• generally preceded by a bacterial or viral
infection
• 40% of patients are seropositive for C jejuni
• Lymphocytic infiltration and macrophage­
mediated peripheral nerve demyelination is
present
• Symptoms generally resolve with
remyelination.
Subtypes of Guillain-Barre syndrome

Acute motor axonal neuropathy

• purely motor disorder that is more prevalent in

pediatric age groups.
• generally characterized by rapidly progressive
symmetric weakness and ensuing respiratory failure.
• Nearly 70-75% of patients are seropositive for
Campylobacter.
• Patients typically have high titers of antibodies to
gangliosides
• One third of patients with AMAN may actually be
hyperreflexic.
Subtypes of Guillain-Barre syndrome

Acute motor-sensory axonal neuropathy

• acute severe illness differing from AMAN in that

AMSAN also affects sensory nerves and roots.
• Patients are typically adults
• often presents as rapid and severe motor and
sensory dysfunct io n.
• Marked muscle wasting is characteristic
• associated with preceding C jejuni diarrhea
• Pathologic findings show severe axonal degeneration of
motor and sensory nerve fibers with little de myeli nat
io n.
Subtypes of Guillain-Barre syndrome

Acute panautonomic neuropathy

• rarest GBS variant

• involves both the sympathetic and
parasympathetic nervous systems
• Patients have severe postural hypotension,
bowel and bladder retention, anhidrosis,
decreased salivation and lacrimation, and
pupillary abnormalities
• Cardiovascular involvement is common, and
dysrhythmias are a significant source of mortality.
Significant motor or sensory involvement is
lacking
Subtypes of Guillain-Barre syndrome

Pure sensory Gui/lain-Barre syndrome

• It is typified by a rapid onset of sensory loss

and areflexia in a symmetric and widespread
pattern
• Lumbar puncture studies show
albuminocytologic dissociation in the CSF, and
electromyography (EMG) results show
characteristic signs of a demyelinating process
in the peripheral nerves.
The typical illness evolves over weeks usually
following an infectious disease and involves:

1. Paresthesiaes usually 3. Dimunition and loss of

hearld the disease the DTRs

2. Fairly symmetric 4. Albuminocytologic

weakness in the legs, dissociation
later the arms and,
often, respiratory and 5. Recovery over weeks
facial muscles to months
 Clinical Manifestations
• Usually develop 1 to 3 weeks after URI or
GI infection
• Weakness of lower extremities
(symmetrically)
• Parathesia (numbness and tingling), followed
by paralysis
• Hypotonia and areflexia (absence of
reflexes)
• Pain in the form of muscles cramps or
hyperesthesias (worse at night).
Neurology Chapter of IAP
 Clinical manifestations
• Autonomic nervous system dysfunction results from
alterations in sympathetic and parasympathetic
nervous systems.
• Results in respiratory muscle paralysis, hypotension,
hypertension , bradycardia, heart block, asystole.
• Involvement of lower brainstem leads to facial and
eye weakness

Neurology Chapter of IAP

 Diagnostic studies
• Based on history and physical
• EMG and nerve conduction studies will
be abnormal

Neurology Chapter of IAP

 Therapeutic management
• Ventilator support!
• Plasmapheresis used within the first 2
weeks of onset. If treated within the first
2 weeks, LOS of morbidity is reduced.
After three weeks, plasmapharesis no
benefit.
• IV immunoglobin
• Nutritional support (TF, TPN, Diet)

Neurology Chapter of IAP

Psychological
Fear
Helplessness
Communication
Pain
Sleep deprivation & hallucinosis
Depression
Visits from other GBS patients
Corticosteroids

Lancet 1993 242 pts.

IV Methylprednisilone 500 mgm/day x 5.

Ineffective
May cause relapse
Plasma Exchange

Removal of the blood’s liquid soluble

components including complement,
immunoglobulin, immune complexes,
cytokines and interleukins.

A typical session removes about 60% of

the body mass of plasma proteins which is
replaced c saline, albumin & FFP
Done qod for 3-5 sessions
Plasma Exchange

Various studies since 1985

Time on ventilator reduced by ½
Full strength regained at 1 year: Exchange
71%, Untreated 52%.

Limitations: Limited availability

Avoid with autonomic instability
Intravenous Immune Globulin

Originally used for immune insufficiency

Use as an immunosuppresant “seems to defy
reason”

1981 Rx for ITP

5,000-10,000 donors/batch. Diversity of Abs

from large donor pool maximizes effect
IVIG

Mechanism of action- unknown

? Antiidiotypic antibody action
? Inhibition of cytokines
? “Sponging” of complement
? Binding to Fc receptors so macrophages
can’t bind
IVIG

Dosage: 0.4 gms/kgm/day x 5 c each dose given

over 3-4 hours preceded by IV diphenhydramine
&/or p/o ibuprofen
Caution with renal insufficiency or IgA deficiency

38 Center trial in 1997

Equal to plasma exchange
 Complications
• Most serious is respiratory failure.
• How do we manage?

Neurology Chapter of IAP

Respiratory Failure

Oropharyngeal weakness in ~25% with

impaired swallowing of secretions &
aspiration
Mechanical respiratory failure- mainly due to
diaphragmatic weakness (Phrenic nerves.)
Inspiratory c MIF (Max. Inspir. Force) a good
supplement measure to FVC
Respiratory Failure

~33% require intubation

Avg. time to intubation is 1 week & these
pts. have substantially longer recovery time
Need is unlikely if patient does well for 2
wks. post onset of paresthesiaes
Guidelines: FVC <15 mL/kgm
MIF < 25 cm water