Overview Guillain Barre Syndrome Update,

What Should We Know

Dr. dr. Kiking Ritarwan,Sp.S (K), MKT

Department of Neurology,
Medical Faculty,
Universitas Sumatera Utara
Email: kiking@usu.ac.id
Outline
• Introduction
• Etiology
• Relationship between infection and GBS
• Nerve damage in GBS
• Pattern of symptoms
• Diagnostic criteria
• Differential Dx
• Erasmus Score
• Algorithme Treatment
• Therapy in GBS
• Prognosis
Guillain–Barré syndrome (GBS)
An inflammatory disease of the PNS and is the most
common cause of acute flaccid paralysis

Annual global incidence Incidence

increases with
of approximately 1–2 per 100,000 person- years age

Usually triggered by
More frequently in infections
MONOPHASIC ILLNESS Potentially fatal
males than in females
(before onset 6 weeks)

Leonhard SE, et al. 2019. Diagnosis and management of

Guillain–Barré syndrome in ten steps Evidence Based Guidelines. Nature review neurology.
https://doi.org/10.1038/s41582-019-0250-9
 Georges Guillain, Jean-
Alexandre Barré, and Andre
Haymaker and colleagues Feasby and colleagues
Strohl

Two soldiers with elevated

protein concentrationand a Axonal degeneration,
normal cell count in the GBS variant (AMAN,
myelin breakdown, AMSAN)
cerebrospinal fluid (CSF). and nerve edema

almost 100 years ago 1949 1986

Zika virus epidemics in French Polynesia (2013)and in Latin America

and the Caribbean in 2015–2016 were linked to an increase in
individuals being diagnosed with GBS
Mayo Clin Proc. March 2017:92(3):467-79
 A. Inflamatory infiltrates ( T Cells and complement activation) =AIDP
B. Segmental demyelination with signs of 2nd axonal degeneration = AMAN
 Etiology
The etiology and pathogenesis remain largely
enigmatic and the syndrome results in death or
severe disability in 9–17% of cases despite Molecular mimicry
immunotherapy.

Prior infections
Over two-thirds of patients with GBS refer
symptoms of respiratory or digestive infections
within 6 weeks of onset

Jasti KA, et al. 2016 Guillain-Barré syndrome: causes, immunopathogenic mechanisms and
treatment. EXPERT REVIEW OF CLINICAL IMMUNOLOGY, VOL. 12, NO. 11, 1175–1189.
 Mycoplasma pneumonia West Nile virus
Etiology Haemophilus influenza Enterovirus
Salmonella species Hantavirus
Mycobacterium bovis Measles
Brucella Parvovirus B19
1. Infectious Orientia tsutsugamushi
Legionella pneumophila
Norovirus
Parechovirus,
In 30–40% of GBS cases, Campylobacter is Bartonella henselae Coxsackieviruses
Helicobacter pylori Echovirus
the infecting agent, and it has been Francisella tularensis Mumps
estimated that 1/1058 infections results in Borrelia, cytomegalovirus Rubella
GBS Epstein–Barr virus Polio (wildtype 3)
Varicella-zoster virus Dengue
Influenza virus Chikungunya
A recent case report described the potential Human immunodeficiency virus Zika viruses
of SARS-CoV-2 infection which resulted in Parainfluenza virus type 1
the detection of reversible GBS (Zhao et al. Adenovirus
Herpes simplex virus
2020). Hepatitis (A, B, and E),
Japanese encephalitis virus

Jasti KA, et al. 2016 Guillain-Barré syndrome: causes, immunopathogenic mechanisms and
treatment. EXPERT REVIEW OF CLINICAL IMMUNOLOGY, VOL. 12, NO. 11, 1175–1189.
 Etiology

2. Noninfectious
• Ganglioside administration
• Vaccination ( eg: H1N1 influenza vaccine)
• Immunosuppression (eg: anti-TNF alpha therapy)
• Surgery

Wakerley BR, Yuki N. 2013. Infectious and noninfectious

triggers in Guillain–Barré Syndrome. In Expert Rev. Clin. Immunol. 9(7), 627–639
 Relationship between infection and GBS
• Molecular mimicry is an important mechanism that can lead to
autoimmune responses
• Criteria need to be met before attributing disease causation to molecular
mimicry:
1. Epidemiological evidence linking the suspected infectious agent or
exogenous substance with the autoimmune disease
2. Identification of T-cell responses or specific antibodies against the target
autoantigen
3. Identification of structural homology between the infectious agent or
exogenous substance and the target autoantigen
4. Reproduction of the autoimmune disease following immunization with
the infectious agent or exogenous substance in an animal model
• The axonal subphenotype of GBS is the only autoimmune disease at
present that fulfills all four criteria for molecular mimicry
Jasti KA, et al. 2016 Guillain-Barré syndrome: causes, immunopathogenic mechanisms and
treatment. EXPERT REVIEW OF CLINICAL IMMUNOLOGY, VOL. 12, NO. 11, 1175–1189.
Campylobacter jejuni
• The first confirmed case of C. jejuni infection preceding GBS was reported in 1982
• Typically, patients present with acute gastrointestinal illness, characterized by
fever, watery or bloody diarrhea and abdominal cramps. In some patients,
diarrhea is minimal with nearly half of patients who are infected during outbreaks
remaining asymptomatic
• In the majority, symptoms resolve after 1–2 week(s) and the case-fatality rate is
low at 0.05 per 1000 infections. It has been estimated that approximately one in
every 1000 patients with C. jejuni goes on to develop GBS.
• In a large epidemiological study of 100 patients with confirmed C. jejuni-
associated GBS, the median time interval from onset of diarrhea and
development of neurological symptoms was 10 days and the shortest interval was
3 days
Wakerley BR, Yuki N. 2013. Infectious and noninfectious
triggers in Guillain–Barré Syndrome. In Expert Rev. Clin. Immunol. 9(7), 627–639
• Patients who develop C. jejuni-related AMAN often display IgG
antibodies against GM1 and GD1a, which are not present in patients
with uncomplicated C. jejuni enteritis.
• Structural homology between C. jejuni surface lipo-oligosaccharides
(LOS) isolated from patients with AMAN and the terminal
tetrasaccharide of GM1 was the first definite proof of molecular
mimicry .
• SGD1a-like LOS have also been demonstrated in the same strain of C.
jejuni
• Serum antiganglioside antibodies
represent a major player in the
induction and perpetuation of
GBS pathology.
• Gangliosides are sialic acid
containing subgroup of
glycosphingolipids with N-
acetylneuraminic acid linked to
an oligosaccharide core portion
which is expressed on cell
surface

Jasti KA, et al. 2016 Guillain-Barré syndrome: causes, immunopathogenic mechanisms and
treatment. EXPERT REVIEW OF CLINICAL IMMUNOLOGY, VOL. 12, NO. 11, 1175–1189.
The clinical course of GBS

Doorn PA,et.al. Lancet Neurolo 2008;7:939-50

Nerve damage in GBS

AIDP is characterized by segmental demyelination in

association with inflammatory cell infiltrates

AMAN is characterized by axonal motor nerve degeneration

in the absence of demyelination or inflammatory infiltrates

The pathological features of FS and BBE are less well defined

as the majority of patients make a full recovery
Features Nerve Damage in GBS
Willison, H. J., Jacobs, B. C. & van Doorn, P. A.
Guillain- Barré syndrome. Lancet 388, 717–727
Clinical subphenotypes
Pattern of symptoms in variants of Guillain–Barré syndrome.
 Diagnostic criteria for Guillain–Barré syndrome
Features required for diagnosis
• Progressive bilateral weakness of arms
and legs (initially only legs may be
involved)
• Absent or decreased tendon reflexes in
affected limbs (at some point in clinical
course
Features that strongly support diagnosis
• Progressive phase lasts from days to 4 weeks (usually <2
weeks)
• Relative symmetry of symptoms and signs
• Relatively mild sensory symptoms and signs (absent in
pure motor variant)a
• Cranial nerve involvement, especially bilateral facial palsya
• Autonomic dysfunction
• Muscular or radicular back or limb pain
• Increased protein level in cerebrospinal fluid (CSF); normal
protein levels do not rule
out the diagnosis
• Electrodiagnostic features of motor or sensorimotor
neuropathy (normal electrophysiology in the early stages
does not rule out the diagnosis
Willison, H. J., Jacobs, B. C. & van Doorn, P. A.
Guillain- Barré syndrome. Lancet 388, 717–727
 Diagnostic criteria for Guillain–Barré syndrome
Features that cast doubt on diagnosis
• Increased numbers of mononuclear or polymorphonuclear cells in CSF (>50 × 106/l)
• Marked, persistent asymmetry of weakness
• Bladder or bowel dysfunction at onset or persistent during disease course
• Severe respiratory dysfunction with limited limb weakness at onset
• Sensory signs with limited weakness at onset
• Fever at onset
• Nadir <24 h
• Sharp sensory level indicating spinal cord injury
• Hyper- reflexia or clonus
• Extensor plantar responses
• Abdominal pain
• Slow progression with limited weakness without respiratory involvement
• Continued progression for >4 weeks after start of symptoms Willison, H. J., Jacobs, B. C. & van Doorn, P. A.
Guillain- Barré syndrome. Lancet 388, 717–727
• Alteration of consciousness (except in Bickerstaff brainstem encephalitis
Wakerley BR, Uncini A, Yuki N . GBS classification group
Differential diagnosis GBS
Neuromuscular junction
Peripheral neuropathy
disorders
(Infection, Toxin, Tics Spinal cord involvement
(MG, Botulism, Lambert
paralysis, lyme disese,
eaton myasthenic
porphyria)
syndrome)

Anterior horn cell Muscle disorders

Brain stem stroke
involvement (Acute myositis, periodic
Brain stem encephalitis
(poliomyelitis) paralysis)

Wernicke
encephalopathy

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Ten- step approach to the diagnosis and management of
Guillain–Barré syndrome
 Erasmus GBS Respiratory Insufficiency Score (EGRIS)

Predicts development of
respiratory insufficiency within
1 week in patients with GBS,
using clinical characteristics
available at admission

Walgaard C, Lingsma HF, Ruts L, et al. Prediction of respiratory

insuffi ciency in Guillain-Barré syndrome. Ann Neurol 2010;
67: 781–87.
Leonhard SE, et al. 2019. Diagnosis and management of
Guillain–Barré syndrome in ten steps Evidence Based Guidelines. Nature review neurology.
https://doi.org/10.1038/s41582-019-0250-9
Modified Erasmus
GBS outcome Score
(mEGOS)

Preceding diarrhea in GBS is

frequently caused by
infections with C. jejuni, and
associated with a severe, pure
motor, and axonal variant

31
Syafri AY, Fitri A, Hadnani H, Gunadhrama S, Mahama CN. 2018. Sindroma Guillain
Barre. Dalam: Pedoman Tatalaksana BGS, CIDP, MG, Imunoterapi. Jakarta: Perdossi 32
 Treatment
Algorithm

Treatment Related
Fluctuation: Perbaikan skala
disabilitas GBS sedikitnya 1
poin setelah pemberian
imunoterapi diikuti
perburukan skala disabilitas
GBS sedikitnya 1 poin
dalam 2 bulan pertama
setelah imunoterapi.

Syafri AY, Fitri A, Hadnani H, Gunadhrama S, Mahama CN.

2018. Sindroma Guillain Barre. Dalam: Pedoman
33
Tatalaksana BGS, CIDP, MG, Imunoterapi. Jakarta: Perdossi
 Therapy GBS

IVIG Dosis : 4 – 6 kali exchange selang satu hari antar prosedur

Dosis anak : 1 -2 g/KgBB IV, selama 2 – 5 hari
Dosis dewasa: 400 mg/kgBBIV, selama 5 hari
berturut-turut dalam14 hari sejak onset GBS

Syafri AY, Fitri A, Hadnani H, Gunadhrama S, Mahama CN. 2018. Sindroma Guillain
Barre. Dalam: Pedoman Tatalaksana BGS, CIDP, MG, Imunoterapi. Jakarta: Perdossi 34
American Academic Neurology
 Prognosis
• After the initial progressive phase,
patients with GBS reach a plateau phase
that can last from days to weeks or
months, after which they start to
recover, and 60–80% of patients with
GBS are able to walk independently 6
months after disease onset, with or
without treatment.
• GBS is a monophasic illness, although
some patients can deteriorate after first
stabilizing or improving on therapy — a
phenomenon that is referred to as a
treatment- related fluctuation (TRF).
Willison, H. J., Jacobs, B. C. & van Doorn, P. A.
Guillain- Barré syndrome. Lancet 388, 717–727
Prognosis
• Disease progression can be rapid, and most patients with GBS reach
their maximum disability within 2 weeks. About 20% of patients with
GBS develop respiratory failure and require mechanical ventilation.
• Cardiac arrhythmias and blood pressure instability can occur owing to
involvement of the autonomic nervous system. This involvement of
the autonomic nervous system contributes to mortality, which is
estimated at 3–10% for patients with GBS even with the best medical
care available.

37
 Take home message
• Guillain Barre Syndrome (GBS) is an inflamatory disorders 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
• ACUTE INFLAMATORY DEMYELINATING POLYNEUROPATHY
• Incidence increase with age
• Immune theories: molecular mimicry
• Treatment of GBS with intensive care and ventilatory support and specific
immunomodulating treatment that shorten the progressive course of GBS
Thank You

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