GUILLAN-BARRE SYNDROME

(GBS)
LANDRYS ASCENDING PARALYSIS, ACUTE
IDIOPATHIC POLYRADICULITIS
is an inflammatory disorder of the peripheral
nerves.
Is characterized by weakness and numbness or
tingling in the legs and arms, and possible loss of
movement and feeling in the legs, arms, upper
body, and face.

Guillain-Barre Syndrome
Synonyms
Acute inflammatory demyelinating
polyradiculoneuropathy-AIDP
Landry-Guillain-Barr syndrome,
Landry-Guillain-Barr-Strohl syndrome,
Acute idiopathic neuropathy,
Acute demyelinating neuropathy,
Infectious polyneuritis,
Acute polyradiculoneuritis,
Axonal Guillain-Barr syndrome,
Acute motor axonal neuropathy,AMAN,
acute motor-sensory axonal neuropathy-AMSAN
Miller-Fisher syndrome,
Pharyngeal-cervical-brachial GBS

Variants with rapid progressive phase:

AIDP(Acute Inflammatory Demyelinating
Polyradiculoneuropathy) = GBS
AMSAN (Acute Motor Sensory Axonal
Neuropathy
AMAN (Acute Motor Axonal Neuropathy)
MFS (Miller-Fisher Syndrome)Also known as
Miller Fish syndrome, Miller's syndrome and
Acute Disseminated Encephalomyeloradiculopathy

Variants with slow progressive phase:

CIDP (Chronic Inflammatory

Demyelinating Polyneuropathy)
MMN (Multifocal Motor Neuropathy
MMSD (Multifocal Motor Sensory
Demyelinating Neuropathy
MADSAN (Multifocal Acquired
Demyelinating Sensory Acquired
Neuropathy
PDN (Paraproteinaemic Demyelinating
Neuropathy

AIDP (Acute Inflammatory Demyelinating oAbout 80% of the patients get this form.
Polyradiculoneuropathy) = GBS
c

- AMSAN (Acute Motor Sensory Axonal

Neuropathy

c
uA serious axonal form of GBS that attacks
rmotor and sensory nerves. Fulminant
course with slow and incomplete
recovery.

m
o
r
AMAN (Acute Motor Axonal Neuropathy) eparticularly severe form, attacks the motor
nerves primarily, causing rapid progressive
weakness often with respiratory failure. Pure
faxonal cases may occur more frequently in
parts of the world outside Europe and
rother
North America. AMAN cases also may be
edifferent from cases of axonal GBS described
qin the West.
cases have been reported in rural areas
uMany
of China, especially in children and young
eadults during the summer months.
nPrognosis is often quite favorable and
recovery is rapid.

t
l

Incidence
In developed countries, Guillain-Barre
Syndrome (GBS) is the most common cause
of acute neuromuscular paralysis.
about 1 to 2 cases in every 100,000 people
per year ( 0,01%-0,02% of populations)
in the United States afflicting about 5,000
persons annually
Age:All ages, Bimodal distribution, with
peaks in age ranges of 15-35 years and 5075 years
Sex:Male-to-female ratio is 1.5:1

Incidence variant SGB(race)

Europe
demyelinating
polyneuropathy

North America
demyelinating
polyneuropathy

South America
demyelinating
polyneuropathy

Asia
Axonal degeneration

Africa
Axonal degeneration

Australia

demyelinating
polyneuropathy

Causes
autoimmune disease triggered by a preceding
bacterial or viral infection. Campylobacter jejuni,
cytomegalovirus, Epstein-Barr virus and
Mycoplasma pneumoniae Chlamydia Hepatitis
B,mononucleosis, AIDS, and herpes simplex.
Sometimes Guillain-Barre occurs following
surgery or vaccinations (such as rabies and swine
flu vaccines) or in association systemic lupus
erythematosus or Hodgkin's disease.
are commonly identified antecedent pathogens
A small number of casesto occur after a medical
procedure, such as minor surgery.

Camden, NJ. Review provided by VeriMed Healthcare Network. Update

Date: 4/25/2004

Causes
GBS is a postinfectious immune-mediated disease
cellular and humoral immune mechanisms
Most patients report an infectious illness in the weeks prior
to the onset of GBS.
Guillain-Barr syndrome may be an autoimmune disorder
in which the body produces antibodies that damage the
myelin sheath that surrounds peripheral nerves.
The myelin sheath is a fatty substance that surrounds
axons. It increases the speed at which signals travel along
the nerves.

INFECTION

C jejuni

COMMON
INSIDEN = 13 - 72%
SEVERE MOTOR
AKSONAL NEUROPHATY
Hadden, 2001
Ab GM1

INF C jejuni PREDICT PROGNOSIS <

Hartung, 2002

ANOTHER INF CMV, EBV, MYCOP

Hadden, 2001; Mori, 2000
PNEUM H INFL
CMV= cytomegalo virus; EBV = Epstein-Barr virus

PERIPHERAL NERVE
Ranvier node
Schwann cell
nucleus
mitochondr

Cell body

axon

Salvatory conduction
Hahn, 1998

Patogenesis
The viral illnesses and triggers the onset of SGB
Reaction by the antibodies and white blood cells of
the bodys immune system
Attack on the peripheral nerves and the bodys
nervous system
Damage the myelin sheath and axon
Delaying the transmission of neurological signals

Disorders associated with antibodies to glycolipid-related saccharides

Neuropathy syndrome

Antibody target

Antibody isotype

Myelin-associated
glycoprotein (MAG)
Other: SGPG, SGLPG

IgM (monoclonal)

Chronic ataxic neuropathy

GD1b, GD2, GD3, GT1b,

GQ1b

IgM (monoclonal)

Motor neuropathy

GM1, GalNAc-GD1a

IgM (polyclonal or
monoclonal)

Chronic
Sensory-Motor
Demyelinating

GM1, GM1b, GD1a,

Acute motor axonal neuropat
GalNAc-GD1a
hy
Miller Fisher syndrome
Bickerstaffs brainstem en
cephalitis
GQ1b, GT1a
Acute ophthalmoparesis
Ataxic GBS
Pharyngealcervicalbrachia

GT1a (GQ1b)

IgG

IgG

IgG

BASIC MECHANISM OF
Pathophysiology:
GANGLIOSIDE/ GLIKOLIPID
ANTBODY
SEL T CELL & CYTOKINE
GENE TRANSCRIPTION
APOPTOSIS Th1 CELL
MOLECULAR MIMICRY

SARAF PERIFER

Antigenic comp

Hahn, 1998

Pathophysiology 1:
Many of the identified infectious agents
such as GM1 and GD1b, distributed
throughout the myelin in the peripheral
nervous system induce antibody
production against specific gangliosides and
glycolipids

Ab AGAINTS GLIKOLIPID
B Cell Antibody
SGB Abnormality B cell response
OTOAb
OTOAbPeripheral nervous system
(GLICOLIPID/PROT)
(Kusunoki, 2000).

Ag GLIKOLIPID membran cell

Vedeler, 2000

Pathophysiology 2:
SEL T CELL & CYTOKINE

Lymphocytic infiltration of spinal roots and

peripheral nervesmacrophage-mediated multifocal
stripping of myelin defects in the propagation of
electrical nerve impulses conduction block
flaccid paralysis.
severe disease-->severe inflammation 0f axonal
disruption and loss.

PATOG : SEL T, MAGR, SITOKINE

MIP-1

MCP-1

EAN
Sitokine gerak
leuk & macr & eks

MIP-1 dan MIC-1

Gold-2000, Kiesier-2000,
Fujioka-99

Cytokines
TNF
IL-1
IL-1ra
IL-6
IL-12

Macrophage

IFN-

TNF, IL-6

IL-1, IL-1ra

IL-12

Histologic Findings
Lymphocyte and macrophage infiltration of
peripheral nerves. Macrophage influx
multifocal demyelination .
in severe inflammatory changesCellular
infiltrates Wallerian degeneration
cranial nerves, nerve roots, dorsal root
ganglions, and peripheral nerves.

GENE TRANSCRIPTION
NF-B

macrofag

mRNA

protein

Immun mediator
Damage peripheral nerve
1. Ekspression NF-B correlations
with macropagh
Andorfer, 2001
Jander, 2001
2. Magr imun reactions

Pathophysiology 4:
APOPTOSIS SEL Th1
Apoptosis genetic proggramed cell death
Apop sel T cell (auto reactive) healing
(Gold et al., 1999).
Apop Schwann cell remyelinization nerve
regenerations
Th1 TNF-a Apoptosis Schwann cell

(Weishaupt et al., 2001).

APOPTOSIS
imun responseinflamation
Auto reactive
myelin-directed T cell

Gold, 1999

Remyelinisation +
Nerve regeneration
Weishaupt, 2001

Schwann cell

Pathophysiology 5:
molecular mimicry
Campylobacter jejuni antecedent illness and
GBS can be typified by infections.
The virulence presence of specific antigens in
its capsule.
Immune responses ( against the capsular
components) produce antibodiesreact with
myelin demyelination.
Ganglioside GM1cross-react with C jejuni
lipopolysaccharide antigens immunologic
damage to the peripheral nervous system.

INFECTION _ NEUROPHATY
MOLECULAR MIMICRY
CONCEPT

MOLECULAR MIMICRY CONCEPT

C jejuni

C jejuni sialic
acid synthesaGM1,GD1, GT1 (Yuki, 2001)
Anti-GT1 IgG post infection H Infl
(Koga, 2
H. Influ
C jejunigene cst II activity(transkr
sialic acid) (Van Belkum, 2001)

Signs and Symptoms

The first symptoms: numbness or tingling
(paresthesia) in the toes and fingers ( Glove
and stocking ) progressive weakness in
the arms and legs over the next few days.
Some paresthesia only in their toes and legs
Others only experience symptoms on one
side of the body.

________________% of patient
Sensory symptoms
numbness 72
pain
37
Sensory sign
62
Reflexes
normal 5
partial loss
17
complete loss 78

__________________% 0f patient
urinary dysfunction 25
rectal disfunction 14
hypotension 14
hypertension 31
sinus tachycardia 36
Arrhythmia
16
hyponatremia (SIADH) 9

Pain
50% described the pain severe and distressing due to direct
nerve injury or the paralysis and prolonged immobilization
inflamed nerve roots.
back and leg pain as aching or throbbing, myalgic with
cramping, local muscle tenderness, visceral pain, and pain
associated with conditions of immobility (eg, pressure nerve
palsies, decubitus ulcers).
Dysesthetic symptoms 50% of patients frequently are described as
burning, tingling, or shocklike sensations more prevalent in the
lower extremities persist indefinitely in 5-10% of patients.
Intensity of pain on admission correlates poorly with neurologic
disability on admission and end outcome.

Cranial nerve involvement

Cranial nerve involvement 45-75%
Common complaints : Diplopias,
Dysarthria,Facial droop, Dysphagia
Facial and oropharyngeal weakness usually
appears after the trunk and limbs are
affected.

Weakness
Ascending and symmetrical develops acutely and
progresses over days to weeks mild weakness to
complete tetraplegia with ventilatory failure.
Peak deficits are reached by 4 weeks . Recovery
usually begins 2-4 weeks after progression ceases.
The lower limbs usually are involved before the
upper limbs. Proximal muscles may be involved
earlier and more severe than the distal onesTrunk,
bulbar, and respiratory muscles can be affected.

Diagnosis

The diagnosis of Guillain-Barr syndrome is based on

typical clinical features, electrodiagnostic examination,
and examination of the cerebrospinal fluid.
An EMG (a test of electrical activity in muscles) shows
lack of nervous stimulation.
A CSF (cerebrospinal fluid) examination may be
abnormal, showing increase in protein without increase
in white blood cell count.
Electromyogram (EMG) diagnostic tool records
muscle activity, the loss of reflexes (slowing of nerve
responses. )
Nerve conduction velocity (NCV) records the speed
at which signals travel along the nerves. An NCV (nerve
conduction velocity) shows demyelination.
Lumbar puncture : An elevated level of protein in the
fluid is characteristic of GBS.

Diagnostic Criteria for Typical Guillain-Barr

Syndrome

Features required for diagnosis

Progressive weakness in both arms and legs
Areflexia
Features strongly supporting diagnosis
Progression of symptoms over days, up to four weeks
Relative symmetry of symptoms
Mild sensory symptoms or signs
Cranial nerve involvement, especially bilateral weakness of facial
muscles
Recovery beginning two to four weeks after progression ceases
Autonomic dysfunction
Absence of fever at onset
High concentration of protein in cerebrospinal fluid, with fewer than
10 cells per cubic millimeter
Typical electrodiagnostic features

Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barr syndrome. Ann Neurol 1990;27(suppl):S21-4.

GBS EMERGENCY

SEVERE &ACUT PARALYSIS

Severe Weakness
BULBAR PARALISIS
RESP Failure
OTONOMIC Complications
MORTALITY
(Hahn, 1998). (Raphael et al, 2000).

Respiratory involvement
40% of patients have respiratory and oropharyngeal weakness.
Typical complaints may include the following:
Dyspnea on exertion
Shortness of breath
Difficulty swallowing
Slurred speech
Ventilatory failure required respiratory support in up to one
third of patients .

Guillain Barre Disability Score

(Greenwood, Osterman, GBSG studies)

1=minor symptoms
2=able to walk 5 meters without assistance
3=able to walk 5 meters with assistance
4=confined to bed or chair5=requiring
assisted ventilation for at least part of the
day or night

MANAGEMENT
Early intensive care
R) spesifik against otoantibody &
reaktivitas el imunokomp IVIg (dosis
& plasmaph(PE)
(Hartung et al., 2002).
R) General supportif & Complications

GENERAL
1. Respiratoy failure : Intubation; volume control
ventilation;
antibiotics; glycopyrrolate (for
controlling secretion & diarrhea).
2. Nutrition
3. Prophylaxis against deep vein thrombosis and
pulmonary embolism
4. Stress ulcer prophylaxis
5. Prevention of decubitus ulcers
6. Keeping patients head 30-45% above the bed
7. Others (treat hypokalemia; hypophosphatemia;
HCt < 30%)

SPECIFIC
1. Plasmaferesis
immunoglobulin (IvIg)
3. AChE inhibitors
5. Imunosupressive agents

2. Intravenous
4. Corticosteroid
6. Tensilon

VENTILATOR
Predikt ventilasi onset < 7 days, tdk mampu
difficult to cough,stand,hold arrms, VC < 60%
Intubation & ventilator :
Clinical status tachikardi, diaphoresis
disorientation, hiperpnea,
paradoxical abdominal
breathing
Vetilator inspiratory pressure< 5 cm H2O,

VC < 15 ml/kg &RR > 30-40/menit.

Tracheostomi bulbar palsy (aspiration)

(Sharshar et al, 2003).

ASSESSMENT OF SYMPTOMS FOR

INTUBATION AND MECHANICAL
VENTILATION (Leshner 1984)
SYMPTOM
RESULT
_____________________________________________________________
Vital capacity
3 times predicted tidal volume
Poor cough
2 times predicted tidal volume
Intubation indicated
Maximum respiratory forces
PE max 40 cm H2O
Inability to clear secretions
PI max 20 cm H2O
Marked weakness inspiratory muscles
Dysphagia with bulbar paralysis
Danger of aspiration
Arterial blood gases:
Hypoxia with normal PCO2
Probable severe ventilatory
impairment
____________________________________________________________
PE = max. pressure on expiration; PI = max. pressure on
inspiration

 Postponing intubation may lead to so-called "crash"

intubation in the middle of the night which may have
additional complications.
Time on the ventilator varies but most modern intensive
care series report a median of 30 days.
A tracheostomy is soon considered. In the vast majority of
patients, this is usually postponed until
the third week after intubation,
bulbar symptoms or in thosesevere damage to the axons
tracheostomy considered earlier

IVIg
Indication : severe paralysis, resp failure, bulbar
Dose = 0.4 g /kgBW/day (5 days) 2g
Efektive 2 first week
R) gagal = 25%
trial Ig &prednisolon
Side effect (10%) headache (respon NSAID),
myialgia,

aseptic meningitis(5%), Self limiting 24-48 hours

Profilak100mg Solu-Cortef IV
anafilaksis (def IgA) rare (Raphael et al, 2000).

 High dose prednisone and imuran again put

me in remission, this time for two years. In
May 1995, I was started on IV-IG (80g) and
imuran (175mg). The imuran did nothing
and was stopped after a year. In 1997, I was
put on low dose

PLASMAPHERESIS = PE

CHANGE humoral immunity

ventil time , motoris , squele
Efektive < 7 days
Indication:paralisis prog, bulbar/resp
Dose = 200-250 ml/bw (5 X/10-14days)
albumin low Na 5%
Compl phlebitis & hypotension
(Raphael et al, 2000).

Complications:
Breathing difficulty (respiratory failure)
aspiration of food/fluids into the lungs
pneumonia
increased risk of infections
deep vein thrombosis
permanent loss of movement of an area
contractures of joints or other deformity

Complications
Monitor heart rate, blood pressure, and cardiac
arrhythmias allows early detection of lifethreatening situations.
Antihypertensives and vasoactive drugs patients
with autonomic instability.
Enteric or parental feedings for patients on
mechanical ventilation and severe dysphagia
to ensure that adequate caloric needs are met when
the metabolic demand is high.

Complications
Bowel and bladder dysfunction Initial
managementsafe evacuation and
prevention of overdistension.
Monitoring for secondary infections, such
as a urinary tract infection.

Mortality/Morbidity:
In epidemiologic surveys, the overall death
rates range from 2-12% of patients.
GBS-associated mortality rates increase
markedly with age. Though the death rate
increases with age
Males have a death rate 1.3 times greater
than females after the age of 40 years.