GBS

INTRODUCTION

GBS is one of acute, acquired weakness and is often provoked by a preceding infection.

Autoimmune in nature
Is a polyradiculoneuropathy
Disease process that affects the nerve roots and peripheral nerves.

International Guillain Barre Syndrome Outcome Study (IGOS) :

Incidence

Average age: 50-70 years (younger in low income countries 20-40)

Male: Female 3:2 (1.5 times)
1-2/100000 person years
Seasonal variation of incidence :
Have a close association with infection,
Most common between June to October in India (diarrhoeal disease)
West: Nov-Jan (Resp infection)
PATHOGENESIS

All Myelinated Nerves (Motor, Sensory, Cranial, Sympathetic) Can Be Affected

The acute polyneuropathy of GBS is often triggered when an immune response to an

antecedent infection or other event
Antibodies cross-reacts with a shared epitope (antigen) on peripheral nerves.

Also known as molecular mimicry.

Can manifest in 2 forms

Demyelination in AIDP
==Axonal loss ==

Demyelination (Antibodies associated: GQ1B, GT1a)

 Inflammatory response develops against myelin-producing Schwann cells/Peripheral
myelin
Demyelination is thought to start at the level of nerve roots where the blood nerve barrier
is deficient leading to transudation of plasma proteins into the endoneurial space.
Blocks electrical saltatory conduction along the nerve.
Initially non-uniform leading to conduction slowing, muscle weakness and then paralysis
(unifrom)

Axonal Loss (Antibodies closely associated: Gangliosides GM1, GD1a, GD1b, GalNac-
GD1a)

Immune reactions against epitopes in the axonal (axolemma) membranes.

Subsequent axonal degeneration occurs delayed/incomplete recovery.
Direct injury to axolemma seen in acute axonal forms of GBS (AMAN and AMSAN).

Approx 2/3 patients have preceding events upto 4-6 weeks prior:
Infective Causes
Respiratory: Influenza, RSV, COVID-19
Gastrointestinal: C. jejuni, Adenovirus
Others: CMV, EBV, H. influenza, E. pneumoniae, Herpes Zoster, HIV

Drugs

TNF therapy
Tacrolimus
Isotretinoin

Vaccines

Influenza
Meningococcus
?Adenovirus vector (COVID-19)

VARIANTS
Based on:

Pattern of limb (UL/LL), sensory involvement

Bulbar, cranial nerve (CN) involvement
Spinal nerve involvement

1. Landry Paralysis

Hyperacute form of GBS

Development of weakness up to the need for mechanical ventilation within 24- 48 hours

GBS SPECTRUM

Classic (MC 60-90%): Demyelinating

Axonal (5-70%): AMAN and AMSAN
Pure Motor (20%)
Pure Sensory (<1%)
Acute Bulbar Palsy (<1%)
Pharyngeal, Cervical, Brachial GBS (<1%)
With Hyperreflexia (CIDP) (25%)
Paraplegic (5-10%)
Pan Dysautonomia: Predominant autonomic nervous system involvement

MILLER-FISHER SYNDROME (Anti-GQ1b Antibody Positive)

Classic (4-25%): Ophthalmoplegia, dysphagia, ataxia with peripheral paresis

Others: Acute ophthalmoplegia (<1%), acute ataxic neuropathy (<1%), acute ptosis (<1%),
acute mydriasis (<1%)
BICKERSTAFF BRAINSTEM ENCEPHALITIS (BBE)

GBS + Ataxia + Reduced consciousness (Encephalitis)

CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP)

Chronic form of GBS

Worse prognosis
Responsive to steroids

CLINICAL FEATURES

Clinical Motor- Motor Paraparetic Pharyngeal– Bilateral Sensory

pattern sensory cervical– facial palsy
brachial with
paraesthesias
Percentage 30–85% 5– 5–10% <5% <5% <1%
of patients 25%
Presence Yes Yes Lower limbs Proximal No No
of flaccid Upper limbs
 Clinical Motor- Motor Paraparetic Pharyngeal– Bilateral Sensory
pattern sensory cervical– facial palsy
brachial with
paraesthesias
paralysis
Altered Yes No Lower limbs No Distal Limbs Yes
sensation
Cranial Yes Yes No Bulbar Facial No
neuropathy
Central No No No No No No
nervous
system
involvement
Associated - GM1, - GT1a - GD1b
antibodies GD1a
(IgG)

Ascending (MC):
Limb weakness, though can present rarely as hyperreflexia
Absent/depressed deep tendon reflexes
Sensory symptoms: Paresthesias MC in the head and feet
Dysautonomia: Increased/decreased BP, fever, bradycardia/tachycardia, urinary retention
Cranial nerve/bulbar involvement: Facial, oropharyngeal, ophthalmoplegia (in 10-30% of
cases)

Patients typically present within a few days to a week after the onset of symptoms.

GBS symptoms typically progress over a period of 2 weeks.

Subacute if > 4-8 weeks progression

CIDP if >8 weeks

By 4 weeks after the onset of the disease, 90% of patients have reached plateau.

DIAGNOSTIC CRITERIA

2 scoring systems:

National Institute of Neurological Diseases and Stroke (NINDS)- 1990

Brighton Collaboration GBS working group (2011) published case definition for GBS and
Miller Fischer Syndrome
 International Consensus guideline (2016)- post ZIka outbreak
EAN-PNS (2023)

Diagnostic Evaluation for GBS

Clinically Suspected GBS:

Hyporeflexia/areflexia on examination
History of infection within the preceding 4 weeks

Any symptom atypical for GBS present:

Weakness progresses to plateau <24 hours (or) >4 weeks from symptom onset
Sensory level close below a spinal level, hyper-reflexia
Asymmetrical weakness
Bowel and bladder dysfunction at onset that becomes severe and persistent
Pulmonary dysfunction with little or no limb dysfunction

Lab screening to rule out other common causes of acute polyneuropathy:

Urine (blood, porphyrins, heavy metals)

HIV, Hepatitis A/C
Serum B12 level
Thyroid function tests
ANA, Autoantibody test (Anti-ganglioside testing)

Lumbar Puncture for CSF evaluation

CSF shows : albuminocytologic dissociation ( High proteins and low cells, usually 5 or less) -
Likely GBS but can also be seen in Basal TB Meningitis, paraproteinemia and Spinal cord
tumours/lesions

If CSF leukocyte count >50 cells?

Yes: Do tests for other etiologies including MRI brain and spine if not already done.
No: Perform additional NCS/EMG, repeat CSF after 1 week, MRI spine, antiganglioside
antibodies ( contactin 1, contactin 1–contactin-associated protein 1 complex, neurofascin
155, neurofascin 140–neurofascin 186, contactin-associated protein 1)

Nerve Conduction Velocity:

Reduced
Absent F wave
 Presence of A waves

Differential Diagnosis (in relation to rapidly progressive weakness):

Diagnosis Clinical features that distinguish Supportive tests

from Guillain–Barré syndrome
Brain
Encephalitis Drowsiness, seizures CSF: pleocytosis

MRI brain: hyperintense

lesions

EEG: slowing with or without

epileptiform discharges
Brainstem stroke Hyperacute sudden onset MRI or MRA: corresponding
infarct and vascular occlusion
Spinal cord
Transverse myelitis Sensory level, brisk reflexes MRI spine: hyperintense
lesion
Malignant infiltration Cauda equina syndrome CSF: malignant cells

MRI spine: enhancing lesions

Anterior horn cell
Polio, enterovirus 71 Fever CSF: pleocytosis
or enterovirus D58
infection NCS: normal SNAPs

Microbiology: presence of
virus
Plexus
Neuralgic Asymmetry, pain, findings limited to MRI brachial plexus: nerve
amyotrophy nerves affected enhancement

NCS: abnormalities restricted

to affected nerves
Nerve roots
CMV and HIV Subacute presentation Microbiology: HIV and CMV
radiculitis serology

CSF: pleocytosis
Diagnosis Clinical features that distinguish Supportive tests
from Guillain–Barré syndrome
NCS: abnormal H reflex and
F waves
Peripheral nerves
CIDP Subacute presentation and CSF: albumin-cytological
relapsing–remitting pattern dissociation

NCS: demyelinating
neuropathy

Neuroimaging: widespread
enlarged nerve roots
Porphyria Family history, concomitant Biochemistry: raised urinary
psychiatric symptoms and porphobilinogen
abdominal pain
NCS: axonal neuropathy
Lyme disease or History of exposure, characteristic Microbiology: Lyme disease
other tick-borne rash (erythema migrans in Lyme) and tick serology
disease
NCS: axonal neuropathy
Thiamine deficiency Precipitating factors (for example, Biochemistry: abnormal
hyperemesis gravidarum, thiamine levels and
alcoholism, nutritional deficiency), erythrocyte transketolase
other neurological features (for activity
example, Wernicke
encephalopathy) NCS: axonal neuropathy
Diphtheria Laryngeal infection Microbiology: isolation
of Corynebacterium
diphtheriae on cultures

CSF: albumin-cytological
dissociation

NCS: demyelinating
neuropathy
Critical illness Prolonged illness or ventilation NCS: axonal neuropathy with
polyneuropathy or without myopathic features
on EMG
Metabolic or Precipitating factors Biochemistry: low serum
electrolyte imbalance levels of specific electrolyte
Diagnosis Clinical features that distinguish Supportive tests
from Guillain–Barré syndrome
Neuromuscular
junction
Myasthenia gravis Fatigable weakness, relapsing– Immunology: acetylcholine
remitting receptor antibodies

NCS: decremental response

on repetitive nerve stimulation
Botulism Rapid progression, pupillary Microbiology: presence of
abnormalities, dysautonomia, botulism toxin
descending paralysis
NCS: incremental rise on
rapid repetitive nerve
stimulation
Lambert–Eaton Proximal weakness, depressed Immunology: antibodies
syndrome tendon reflexes, autonomic changes against voltage-gated
calcium channels

NCS: post-tetanic facilitation

on repetitive nerve stimulation
Muscle
Inflammatory Proximal weakness, normal Biochemistry: raised creatine
myositis reflexes and sensation kinase

NCS: normal sensory studies

and features on EMG
Critical illness Prolonged illness or ventilation NCS and EMG: myopathic
myopathy features and normal sensory
studies unless overlap with
neuropathy
Colchicine-induced Proximal weakness, normal Biochemistry: raised
(neuro)myopathy reflexes and sensation creatinine kinase

At risk: renal insufficiency,

statins, tacrolimus

NCS: myopathic features on

EMG
 Diagnosis Clinical features that distinguish Supportive tests
from Guillain–Barré syndrome
Hypokalaemic Transient weakness, family history, Biochemistry: low potassium
periodic paralysis precipitating factors (for example, level
fasting, exercise, carbohydrate
meals) Genetic studies: mutation in
known genes

NCS: abnormal exercise test

Functional disorder Inconsistent, variable presentation Psychological evaluation

Diagnostic Criteria :

EAN-PNS 2023:

Required features
Progressive weakness of arms and legs Absent or decreased tendon reflexes in affected limbs
Progressive worsening of ≤4 weeks
Supportive features
Relative symmetry Relatively mild or absent sensory symptoms and signs Cranial nerve
involvement (especially bilateral facial palsy) Autonomic dysfunction Respiratory insufficiency
(from muscle weakness) Pain (muscular or radicular in back or limb) Recent history of infection
(<6 weeks)
Supportive laboratory tests
Cerebrospinal fluid Increased protein (normal does not exclude) and white cell count <5 × 106/l
Serology Serum anti-GQ1b antibodies in Miller Fisher syndrome
Electrodiagnostic Nerve conduction studies consistent with peripheral neuropathy (can be
normal in early disease)

(NINDS) modified to 2016

Required:

Progressive weakness of arms and legs

Areflexia/depressed DTRs

Supportive:

Symptom progression over days to 4 weeks

Relatively bilateral, symmetrical weakness ranging from minimal weakness to total
paralysis
Pain in limbs (not seen in AMAN)
 Cranial nerve symptoms/signs: Trunk, bulbar, facial
Autonomic dysfunction
No fever at symptom onset
CSF total leukocyte count <50 cells/mm3
Electrodiagnostics consistent with GBS

Management:

1. Indications for ICU level care:

Severe weakness
Autonomic instability
Impending respiratory failure
2. Supportive Management and Monitoring:
Monitoring:
Neurological: Serial neuro monitoring every 4-8 hours helps in identifying
patients at risk of respiratory failure.
Respiratory: RR, FVC, MIP (Max. Inspiratory Pressure)/NIF (Max. Expiratory
Pressure)
Autonomic dysfunction: Monitor HR, ECG, BP every 1-2 hours
Bulbar dysfunction: If the patient has asystole and the presence of maybe bulbar
>3 seconds, temporary pacemaker is mandatory.

Supportive Management:
DVT prophylaxis
Pain control: Use neuropathic pain precautions such as gabapentin, pregabalin,
and carbamazepine
Early physiotherapy and mobilization to prevent contractures and bedsores

Indications for Intubation:

Bulbar dysfunction
Use of accessory muscles while at rest
PaO2 <70 mmHg, SaO2 <92%, RR >30
FVC <20 ml/kg, NIF <-30 cm H2O, MEP <40 cmH2O

3. Immunomodulatory Therapy:
Indications:
Symptom onset <4 weeks
Unable to walk independently (GBS disability score 3-5)
 Rapidly progressing symptoms
Bickerstaff encephalitis (due to the severity of symptoms)
Selection of agent:
IVIg: 0.4g/kg x 5 days
PLEX: Preferred, easier to administer, better tolerated, 5 exchanges of 200-250
ml/kg per session, over 1-2 weeks (2 works in milder forms)
No difference in outcome between IVIg and PLEX, but better tolerability with IVIg and
less likely to stop treatment.

No steroids
Retreatment with the initial agent used is advised in case of relapse. No switch over
advised.

GBS Disability Score:

0 - Healthy

1 - Minor symptoms, can run

2 - Able to walk 10m or more, cannot run

3 - Able to walk 10m only with support

4 - Bedridden/chair bound

5 - Needs assisted ventilation

6 - Death
PROGNOSIS:

Factors for poor outcomes:

Age >60 years

Rapid onset of weakness
Severe weakness at admission
Need for ventilatory support
Preceding diarrheal illness
Severe electrodiagnostic abnormalities
ERASMUS GBS Outcome Score
Modified EGRIS in patients with milder forms of GBS