Guillain-Barre SyndromeGuillain-Barre Syndromeand differentialsand differentials

Dr Ahmad Shahir MawardiDepartment of NeurologyHospital Kuala Lumpur

28th July 2015

Pre-test 1

A 32 year old man has a 4 day history of progressive weakness in his extremities. He has been healthy except for an upper respiratory tract infection 10 days ago. His temperature is 37.8C. BP is 130/80 mmHg, Pulse 94bpm, and respiration rate is 42 and shallow. He has symmetric weakness of both sides of his face as well as proximal and distal extremity muscles. Sensation is intact. No tendon reflexes can be elicited and the plantar responses are flexor.

Which of the following is the most likely diagnosis?

A) Guillain-Barré SyndromeB) Myasthenia gravisC) PoliomyelitisD) Polymyositis

Guillain-Barré syndrome may be associatedwith:

(a) Campylobacter jejuni infection.(b) Use of the oral contraceptive pill.(c) Renal transplantation.(d) Aspirin therapy.(e) HIV infection

Pre-test 2

In Guillain-Barré syndrome:

(a) Weakness typically occurs more in proximal than distal

muscles.

(b) Pathological changes tend to affect the motor end

plates.

(c) Hypoxaemia is an early indicator of disease progression.

(d) Ventricular arrhythmias may be an early feature.

(e) Sensory symptoms occur in up to 80% patients

Pre-test 3

Recognised findings on investigation of Guillain- Barré syndrome include:

(a) Hyponatraemia.(b) Elevated transaminases.(c) Low protein concentrations in the CSF.(d) Antiganglioside antibody.(e) ST segment depression on the ECG.

Pre-test 4

In the treatment of Guillain-Barré syndrome:

(a) Non-invasive ventilation is often useful in managementof patients with early ventilatory failure.(b) Plasmapheresis is contra-indicated in patients with IgAdeficiency.(c) Plasmapheresis may exacerbate hypercalcaemia.(d) Intravenous immunoglobulin therapy is the treatment ofchoice in patients with uncontrolled sepsis

Pre-test 5

Overview

• Charaterized by acute areflexic paralysis with albuminocytologic dissociation

• 20% disabled, ~5% died

• No specific diagnostic tests. (Hallmark) clinical diagnosis: – rapidly progressive symmetrical weakness in the arms

and legs – + sensory disturbances– hypoflexia/ areflexia

• the absence of a CSF cellular reaction

Hughes RAC, Swan AV, Raphaël JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for Guillain-Barrésyndrome: a systematic review. Brain 2007; 130:2245-57

Overview

• Post-infectious disorder

• Not typically associated with autoimmune or other systemic disorder

• First symptoms:– pain, numbness, paraesthesia, or limbs

weakness• rapidly progressive, bilateral, symmetrical • + respiratory muscles or CN-innervated muscles

Historical aspect

1859 : Landry first described an acute ascending paralysis

1916- ‐Guillain, Barré and Strohl – 2 soldiers who developed acute paralysis with

areflexia, spontaneously recovered.

– CSF : albuminocytological dissociation

Landry and Strohl….neglected?

Syndrome called Guillain Barré syndrome (GBS)

Epidemiology

• Annual incidence : 1·2–2·3 per 100 000

• Men: women (1.5:1)

• Incidence increases linearly with age

Diagnosis of typical GBS

*Adapted from Asbury and Cornblath

CSF in GBS

• CSF protein (0 cell count):– normal in the first week– increased at the end of the second week (90%)– Recent studies: increased haptoglobin, α1-antitrypsin,

apolipoprotein, and neurofilaments*

• Increased CSF cell count– leptomeningeal malignancy,– Lyme disease, West Nile virus infection, HIV-related

GBS

*Yang YR, Liu SL, Qin ZY et al. Comparative proteomics analysis of cerebrospinal fl uid of patients with Guillain-Barré syndrome. Cell Mol Neurobiol 2008; 28: 737–44

Features that should raise doubt about the diagnosis*

*Adapted from Asbury and Cornblath

• Severe pulmonary dysfunction with limited limb weakness at onset

• Severe sensory signs with limited weakness at onset• Bladder or bowel dysfunction at onset• Fever at onset• Sharp sensory level• Slow progression with limited weakness without respiratory

involvement (consider subacute inflammatory demyelinating• polyneuropathy or CIDP)• Marked persistent asymmetry of weakness• Persistent bladder or bowel dysfunction• Increased number of mononuclear cells in CSF (>50×106/L)• Polymorphonuclear cells in CSF

• Acute spinal cord disease• Carcinomatous or lymphomatous meningitis• Myasthenia gravis• Critical illness neuropathy• Thiamine deficiency• Periodic paralysis• Corticosteroid-induced myopathy• Toxins (such as neurotoxic shellfish poisoning)• Acute hypophosphataemia• Prolonged use of neuromuscular junction blocking drugs• Tick paralysis• West Nile poliomyelitis• Acute intermittent porphyria• Functional paralysis

Differential diagnosis of GBS

Differential diagnosis of GBS

Preceding events

• 2/3 have sx of an infection in the 3 weeks before the onset of weakness.

• Antecedent symptoms (URTI/GI Sx)*– fever (52%)– cough (48%)– sore throat (39%)– nasal discharge (30%)– diarrhoea (27%)

• Infection related to GBS– CMV, EBV, M. pneumoniae & H. influenzae

Koga M, Yuki N, Hirata K. Antecedent symptoms in Guillain-Barré syndrome: an important indicator for clinical and serological subgroups. Acta Neurol Scand 2001; 103: 278–87.

Relation between infections, antiganglioside antibodies, and clinical course of GBS

Preceding events (II)

• Vaccinations, operations or stressful events-debatable– slight increase in incidence after swine influenza vaccines

(USA,1976)– Other influenza vaccines: NR

• A case–control survey involving about 200 patients with GBS from the UK did not show any significant association between GBS and previous immunisation*

• hepatitis vaccinations?tetanus?• Post GBS vaccination issue?

*Hughes R, Rees J, Smeeton N, Winer J. Vaccines and Guillain-Barré syndrome. BMJ 1996; 312: 1475–76.

• 1/2 pts have serum antibodies to various gangliosides– specific tissue distribution in peripheral nerves – play a part in the maintenance of the cell membrane

structure– antibodies are specific to subgroups

Antigangliosides antibody

pathological significance ??

• C jejuni isolates from patients express lipo-oligosaccharides (LOS) that mimic the carbohydrates of gangliosides/ganglioside-like LOS--> cross-reactive --> local complement activation at the nerve damage --> clinical sx

Pathogenesis

*Fewer than 1 in 1000 patients with a C jejuni infectionwill develop GBS

GBS Variants

GBS Variants

• Subtype– Demyelinating: (AIDP) -common in Europe and North America– Axonal: AMAN/AMSAN (<5%)– Other variants: pure sensory, pure dysautonomic, pharyngeal-

brachial-cervical, and paraparetic variants

• MFS: ophthalmoplegia, ataxia, and areflexia

• CN palsies– Facial nerve palsy (70%). – Bulbar and oculomotor nerves less affected

Natural history

• Recovery phase:– slower

• Weakness phase: – maximum :4 weeks– most patients : 2

weeks

• Plateau phase: – days/weeks/ months

• MFS and overlapping syndromes involving CN dysfunction & limb weakness > common in Japan– Bickerstaff brainstem encephalitis (cranial/peripheral

nerve involvement, coma) --> PE

GBS Variants

• NCV slowing /conduction block (80%)• Patchy reduction in NCV < 60% of normal• Prolonged DML (3x)• Prolonged F wave• Normal (15-20%)

• Normal NSC for several weeks

Electrodiagnostic study

Electrodiagnostic study

Management

GeneralSpecific/ ImmunomudulatingPain/ Fatigue management

Rehabilitation

General care

Monitor progression and prevent fatal cpx:

1. Regularly monitor pulmonary function, (vital capacity, RR)

2. Regularly check for autonomic dysfunction (BP, HR, pupils, ileus)

3. Continuous monitor heart rate (ECG), BP, PR initial stage

4. Check for swallowing dysfunction5. Recognise and treat pain/ severe fatigue6. Prevent and treat infections and pulmonary embolism7. Prevent cornea ulceration due to facial weakness8. Prevent decubitus and contractures

• Aim of treatment : – lessen nerve damage, – reduce progression– shorten hospitalization

• IVIG vs PE– similar effectiveness

• PE + IVIG– not significantly better than

either alone.

• Steroids??

• When to treat?– first 4/52– best time (2/52)

Specific treatment

Specific treatment

• Severely affected patients– inability to walk unaided– GBS disability scale ≥3)1,2

– rapidly progressive limbs weakness/ resp compromise/severe autonomic dysf(x)/swallowing problem

• IVIg – preferably within first 2 weeks from onset – 0·4 g/kg for 5 days – 1·0 g/kg for 2 days ?? 6 days??

• Or 5× PE with total exchange volume of five plasma volumes in 2 weeks

1.Hughes RA, Swan AV, Raphael JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for Guillain-Barré syndrome: a systematic review. Brain 2007; 130: 2245–57.2. Hughes RA, Newsom-Davis JM, Perkin GD, Pierce JM. Controlled trial prednisolone in acute polyneuropathy. Lancet 1978; 2: 750–53.

Hughes RA, Newsom-Davis JM, Perkin GD, Pierce JM. Controlled trial prednisolone in acute polyneuropathy. Lancet 1978;2:750-753.

• Indication ICU admission – Rapid progressive severe weakness often with

impaired respiration (vital capacity <20 mL/kg)– ventilation– Insufficient swallowing with high chance of pulmonary

infection– Severe autonomic dysfunction

• Rehabilitation and fatigue– Start physiotherapy early during course of ds– Start rehabilitation as soon as improvement starts– Consider a physical training programme for severe

fatigue

Specific treatment

• Mildly affected patients (GBS disability scale ≤2) or MFS patients– Unknown whether IVIg is effective

• Indications for re-treatment with IVIg:– Secondary deterioration after initial improvement

or stabilisation– Dose: 0·4 g/kg for 5 days

• No proven effect of re-treatment with IVIg in patients who continue to worsen

Specific treatment

GBS, treatment-related fluctuations (TRF), and acute-onset CIDP (A-CIDP)

Prognosis

• Difficult to predict because of the substantial variation in outcome

• Worse prognosis: advanced age

• Respiratory failure – reduction in vital capacity of more than 20% – and signs of demyelination ( reduced AP in peronel

nerve)

Atypical GBS

Atypical GBS

Post-test 1

A 32 year old man has a 4 day history of progressive weakness in his extremities. He has been healthy except for an upper respiratory tract infection 10 days ago. His temperature is 37.8C. BP is 130/80 mmHg, Pulse 94bpm, and respiration rate is 42 and shallow. He has symmetric weakness of both sides of his face as well as proximal and distal extremity muscles. Sensation is intact. No tendon reflexes can be elicited and the plantar responses are flexor.

Which of the following is the most likely diagnosis?

A) Guillain-Barré SyndromeB) Myasthenia gravisC) PoliomyelitisD) Polymyositis

Guillain-Barré syndrome may be associatedwith:

(a) Campylobacter jejuni infection.(b) Use of the oral contraceptive pill.(c) Renal transplantation.(d) Aspirin therapy.(e) HIV infection

Pre-test 2

In Guillain-Barré syndrome:

(a) Weakness typically occurs more in proximal than distal

muscles.

(b) Pathological changes tend to affect the motor end

plates.

(c) Hypoxaemia is an early indicator of disease progression.

(d) Ventricular arrhythmias may be an early feature.

(e) Sensory symptoms occur in up to 80% patients

Pre-test 3

Recognised findings on investigation of Guillain- Barré syndrome include:

(a) Hyponatraemia.(b) Elevated transaminases.(c) Low protein concentrations in the CSF.(d) Antiganglioside antibody.(e) ST segment depression on the ECG.

Pre-test 4

In the treatment of Guillain-Barré syndrome:

(a) Non-invasive ventilation is often useful in managementof patients with early ventilatory failure.(b) Plasmapheresis is contra-indicated in patients with IgAdeficiency.(c) Plasmapheresis may exacerbate hypercalcaemia.(d) Intravenous immunoglobulin therapy is the treatment ofchoice in patients with uncontrolled sepsis

Pre-test 5

Thank you