GBS : Guillian Barre syndrome (AIDP)

Pathophysiology , Diagnosis and Management

Chairperson : Prof Dr. O.P. Jatav (MD)

GUIDE : Prof Dr. Sushma Trikha (MD)
PRESENTED BY : Dr Gagan Mishra

Case -
• 44 year Female came with history of tingling and numbness of both
lower limbs since 10 days, noticed buckling of both knees 9 days,
started having di culty to get up from squatting since 1 week,
unable to lift upper limb since 5 days di culty in swallowing since 5
days

• Sensory, proximal Lower limb weakness, bulbar involvement

• Symmetrical, sensory Motor , Acute onset , Proximal history of

involvement

• Polyradiculopathy
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 Guillian barre syndrome
• Landry described it in 18th century

• Guillian barre and Andrews Strohl described other features in 19th century

• Demyelinating disease

• Involves proximal predominant peripheral nerves and symmetrical

• Polyradiculopathy / Polyradiculoneuropathy

• Large Fibre involvement (A alpha )

Rubbery legs
• Acute onset : <4 weeks (even hours to days )
Tingling and dysesthesia of lower
limbs
• M>F 1.5 times
Rapidly Progessive B/L Are exic
• Mean age of onset =40 years ( although GBS May occur at any age ) Ascending Paralysis

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• Clinical features:
• Proximal symmetrical weakness

• Ascending paralysis ( descending paralysis is seen in tetanus ,botulism and

diphtheria )

• Cranial nerve symptoms: 45-65%

• CRANIAL NERVE INVOLVEMENT

• Bifacial palsy :50% of gbs

• (CIDP:5%)

• Nerve involvement is more of upper nerves (3,7 usually) , out of which facial is more
common in GBS

• (Bulbar ,i.e, CN IX and X : more common for CIDPs)

• Motor/ sensory:
• Hypore exia , are exia

• Proximal> distal

• Ascending paralysis
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• Autonomic involvement :65% (Very common )
• Dreadful

• Like Tachycardia, Bradycardia, increased sweating, accelerated hypertension, Hypotension - HE

• Mild transient Bowel/ Bladder dysfunction ( C bres - small )

• VAGAL SPELLS, Arrhythmias

• During autonomic uctuations: risk of death is high and shift patient immediately to ICU

• Noradrenaline can be given

• Most common cause of death due to cardio respiratory failure

• Triggers : 1-4 weeks prior to onset of disease

• Mostly GI infection / respiratory tract infections.60-70%

• Most common organism : C jejuni , associated with 76% AMAN variant

• Mycoplasma , HIV( AIDP/CIDP) , CMV can also be present

• Vaccine association can also be present eg: H1N1 in uenza, Diptheria, Rabies, MCV

• Post Trauma
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GBS Variants

• AIDP : Acute In ammatory Demyelinating polyradiculopathy BEST PROGNOSIS ,

NO MUSCULAR WASTING , MOST COMMON

• AMAN : Acute Motor Axonal Neuropathy. Associated with GM1 ganglioside

Antibody neuropathy, Zika virus and C.jejuni infections - MW+

• AMSAN : Acute Motor Sensory Axonal Neuropathy. Can progress <7 days :
severe WORST PROGNOSIS -MW+
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 Other variants….
• 1. Miller Fischer syndrome : Associated with GQ1b antibodies.
• Ophthalmoplegia, ataxia and are exia
• Weakness is not a classical feature
• Corticospinal tract sign + loss of consciousness + complete weakness should be
absent

• 2.Bifacial / facial diplegia + distal parenthesis

• 3.Multiple cranial nerve variant

• 4.Pharyngo cervico brachial variant

• 5.Paraparietic variant (B/L symmetrical Lower limb weakness )

• 6.Pan dysautonomic variant ( predominant features of Autonomic dysfunction)

• 7.Pure ataxic variant ( Only Ataxia )

• 8.Pure small bre variant (Acute Painful)

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• 45-75% cranial Nerve involvement

• 50% bifacial (5% for CIDP)

• 65% - autonomic involvement

• 76% AMAN is a/w C. Jejuni

GBS : pathogenesis
• Triggering event : autoimmunity
• Activation of T helper cells (IL2 , INF gamma , and other addition molecules) and B cells
( antibodies against myelin)

• Blood nerve barrier (BNB) is present

• These BNB attracts macrophages and other in ammatory mediators which tears this BNB

• All this activates complements forming membrane activating complements which is

followed by myelin damage

• Axons are exposed along with its ion channels

• Ion channels changes resting membrane potential and thus Saltatory conduction A ected

• Endoneurial in ammation with multifocal demyelination

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• In AIDP there’s basically demyelination and secondary Axonal
damage is rare and very late but in cases of AMAN and AMSAN the
secondary Axonal degeneration is early and severe in the course of
disease .
GBS criteria

• Clinical criteria

• Brighton criteria: Recent

• Asbury criteria: older

• Brighton’s criteria
• Level I : clinical criteria

• Level II : investigation based criteria

• Level III : exclusion based

• Clinical: bilateral , accid weakness of the limbs

• Autonomic dysfunction and Absence of Fever at onset

• Are exia , hypore exia in weak limbs (even pain may be present due to nerve root in ammation)

• Monophasic illness pattern with nadir between 12 hrs and 28 days followed by plateau

• Investigations:
• NCS : consistent with GBS ( demyelination)

• CSF: cytoalbuminogenic dissociation <50cells

• Albuminocytological dissociation
• In ammation causing increase in albumin to CSF

• <10 : classical

• <50 :acceptable

• >50 : evaluate for other conditions like HIV , Lyme’s disease .

• Exclusion :absence of identi ed alternative diagnosis ( K+ imbalance, Myopathies, Tetanus, Diptheria, Botulism, etc )
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• Level I evidence : clinical + exclusion criteria + both investigations positive (CSF/NCV)

• Level II evidence : clinical + exclusion criteria + one of the investigation positive

• Level III evidence : only clinical + exclusion positive

• Same criteria is applicable for miller Fischer syndrome with few changes

• Clinical:

• bilateral ophthalmoparesis

• Bilateral are exia or hypore exia

• Absence of limb weakness

• Monophasic illness pattern with nadir between 12 hrs and 28 days followed by plateau

• No alteration in sensorium or CST sign

• Investigations

• Exclusion

• Level of Evidence
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In AMAN / AMSAN
• trigger known + Genetics

• C.Jejuni, Zika (AMAN) , CMV, EBV, HIV, Hepatitis

• Endoneurial in ammation and Multifocal demyelination.

• Attaches to node of Ranvier and damages the Axonal ( primary ) area

• Investigations:

• EDX: normal or sensory involvement

• CSF : cytoalbuminogenic dissociation

• Exclusion : absence of identi ed alternative diagnosis

• Level I evidence : clinical + exclusion criteria + both investigations positive

• Level II evidence: clinical + exclusion criteria + one of the investigation positive

• Level III evidence: only clinical and exclusion positive

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 In AIDP there’s Primarily
damage at the Myelin
Directly.

• There’s GM1 antigen epitope on the pathogen against which B cell form Anti GM1 Antibody.
This GM1 antibody sits on the similar epitope which is present at nodes of Ranvier of Nerve
cells. This binding activates Macrophages and complement system thus causing early
damage of nerve axon leading to Motor and sensory symptoms early in the course of Disease.

Investigations
• CSF : <50 cells

• If > 50 cells : HIV , CMV , LYMES DISEASE and other infections should be ruled out

• Nerve conduction studies:

• Conduction velocity decreased

• Duration increased

• Temporal dispersion present

• Latency prolonged

• Earliest change : F wave abnormality

• Temporal dispersion
• F wave a ected : due to radiculopathy in GBS , Proximal lesion

• F can be missed in distal testing

• Sural nerve sparing : feature of GBS

• Sural snap + radial snap/ radial and ulnar snap : >1 in case of GBS (Sensory Ratio)

• All investigations can be normal in 1st week

• CSF and NCS may be normal in 1st week

• Should be repeated again after 1 week

• 2nd week : F wave abnormality , sural sparing , sensory ratio ,other classical features
of Demyelination (conduction block, dec conduction velocity, Temporal Dispersion,
prolonged Latency )
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• Normally in NCV you stimulate proximal in a nerve and record the response distally. But in GBS there
polyradiculopathy means the involvement is proximal in nerve near SC. You are gonna miss it in routine NCV testing.

• So In case of GBS you stimulate at a sensory nerve the impulse goes to spinal cord relays there and comes from
Motor neuron and such you get F wave which is earliest abnormality seen in GBS.
 Treatment
• Assess progressive/ regressive/ plateau

• If plateau is reached (usually in 2 weeks) and with minimal de cits: can wait and monitor

• Treatment required or not: - it depends and di ers upon patient to patient

• Mild and not a ecting patient: can wait

• Fast progression (<7 days) , respiratory muscle involvement, Tachypnea, neck muscles
and bulbar involvement: ICU and intubation if needed

• Severe weakness

• Autonomic uctuation: should be in ICU

• Consider icu admission: rapid progression, severe limb weakness, bulbar involvement,
autonomic uctuation
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• indications of elective intubation

20-30-40 rule:

• Vital capacity <20 ml/ kg

• 30% reduction of vital capacity from baseline

• 30mm inspiratory pressure ( maximum)

• 40mm expiratory pressure ( maximum)

• Monitor : ABG , BP , PR vital capacity every 4-6 hours.

• (CO2 retention in ABG and SPO2 fall : indication of elective intubation )

Treatment options
• IVIG : 2g / kg over 5 days or 0.4 mg /kg /day for 5 days / 3 days - Fast IVIG
therapy t1/2 - 3-6 weeks

• Plasma Exchange : 250 ml / kg total volume to be ltered - can be done

at multiple settings over 14 days ( Compliaction : Hypotension, so avoid when
having autonomic instability like Low BP)

• No role of steroids

• IVIg : e ective maximum of <2 weeks , if 3rd week - plasma exchange have
some advantage

• Dual therapy not advised at same time ( may be useful if patient not
responding)

• Double therapy of IVIG

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Adverse effects of IV Ig
• Headache , chills and myalgia : pretreated with ibuprofen

• Chest discomfort within rst hour after infusion

• Aseptic meningitis: 48- 72 hr after rst dose

• Venous or arterial thromboembolic events

• Transient renal failure due to tubular damage induced by sucrose -
peaking at about 5 days after initiation of therapy

• Anaphylaxis in IgA de cient individual

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• Supportive care:
• Prevent infections

• Respiratory and vital monitoring

• DVT prophylaxis

• Physiotherapy and nutrition

Treatment related Fluctuations

• 10-20% cases

• Fall >1 score after reaching plateau or improvement initially

• <8 weeks

• Mx : repeat the Modality of Treatment

Acute CIDP

• 2-3% cases present who present as AIDP

• Progress >8 weeks

• >=2 Treatment related Fluctuations

• In follow up you see new demyelination after 8 weeks

GBS disability score ( Hughes)

• 0 : healthy

• 1 : capable of manual work/ running

• 2: incapable of manual work / running , able to walk 10m or more without support of
a stick ( cane)

• 3: Able to walk 10m with a stick (cane) , appliance or support

• 4 : con ned to bed or chair bound

• 5: requiring assisted ventilation for at least part of the day

• 6 : death
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Prognosis
• 1-5% mortality

• Around 30% respiratory failure req MV

• Around 70% improves in 1 year

• Around 80% recovery in 2 years

• Around 20% some weakness residual

• 2% Acute CIDP, 10-20% TRF

• Poor prognostic factors:

• Age> 60 years

• Severe weakness , autonomic uctuation and respiratory failures

• CMAP <20% of baseline

• Variant base : AMSAN

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 Di erentials

• In ammatory - Acute CIDP, Vasculitis, Sensory Gangliopathy

• Metabolic - Diabetes, Porphyria, Thiamine de ciency, Critical illness

neuropathy

• Pure Motor - Botulism, NMJ

• Infections - HIV, CMV
• Organophosphate and Hexa carbon
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Case 3

• 52 year old female diabetic presented with Fever followed by altered

sensorium. She had hyponatremia and then found to be COVID RAT positive.

• Her sensorium improved after Hyponatremia correction, but she has accid
Quadriparesis - proximal plus Distal. NCS done showed decreased CMAP
and SNAP with normal CV and F wave latency prolonged

• Diagnosis ?

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References

• Bradley and Daroff's Neurology in Clinical Practice 8th Edition

• Harrison's Principles of Internal Medicine 21st Edition
• Continuum Journal neurology: Lifelong learning in Neurology - Lippincott
Williams and Wilkins

• NCBI, NLM , USA - https://www.ncbi.nlm.nih.gov/books/NBK532254/