The document provides information about Guillain-Barré syndrome (GBS), including its presentation, diagnosis, treatment and prognosis. It describes a case of a 32-year-old man presenting with progressive weakness in his extremities following an upper respiratory infection, which are typical symptoms of GBS. It outlines key diagnostic features of GBS like symmetric weakness, absent reflexes and albuminocytological dissociation in cerebrospinal fluid. Treatment options discussed are intravenous immunoglobulin and plasmapheresis, with a focus on treating severely affected patients early in the disease course. Prognosis is variable but advanced age and respiratory failure indicate worse outcomes.

1. Guillain-Barre SyndromeGuillain-Barre Syndrome
and differentialsand differentials
Dr Ahmad Shahir Mawardi
Department of Neurology
Hospital Kuala Lumpur
28th
July 2015

2. 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 Syndrome
B) Myasthenia gravis
C) Poliomyelitis
D) Polymyositis

3. Guillain-Barré syndrome may be associated
with:
(a) Campylobacter jejuni infection.
(b) Use of the oral contraceptive pill.
(c) Renal transplantation.
(d) Aspirin therapy.
(e) HIV infection
Pre-test 2

4. 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

5. 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

6. In the treatment of Guillain-Barré syndrome:
(a) Non-invasive ventilation is often useful in management
of patients with early ventilatory failure.
(b) Plasmapheresis is contra-indicated in patients with IgA
deficiency.
(c) Plasmapheresis may exacerbate hypercalcaemia.
(d) Intravenous immunoglobulin therapy is the treatment of
choice in patients with uncontrolled sepsis
Pre-test 5

7. 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-Barré
syndrome: a systematic review. Brain 2007; 130:2245-57

8. 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

9. 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)

10. Epidemiology
• Annual incidence : 1·2–2·3 per 100 000
• Men: women (1.5:1)
• Incidence increases linearly with age

11. Diagnosis of typical GBS
*Adapted from Asbury and Cornblath

12. 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

13. 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

14. • 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

15. Differential diagnosis of GBS

16. 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.

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

18. 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.

19. • 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 ??

20. • 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

21. Pathogenesis
*Fewer than 1 in 1000 patients
with a C jejuni infection
will develop GBS

24. GBS Variants

25. 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

26. Natural history
• Recovery phase:
– slower
• Weakness phase:
– maximum :4 weeks
– most patients : 2
weeks
• Plateau phase:
– days/weeks/ months

27. • MFS and overlapping syndromes involving CN
dysfunction & limb weakness > common in
Japan
– Bickerstaff brainstem encephalitis (cranial/peripheral
nerve involvement, coma) --> PE
GBS Variants

28. • 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

29. Electrodiagnostic study

30. Management
General
Specific/ Immunomudulating
Pain/ Fatigue management
Rehabilitation

31. 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 dysfunction
5. Recognise and treat pain/ severe fatigue
6. Prevent and treat infections and pulmonary embolism
7. Prevent cornea ulceration due to facial weakness
8. Prevent decubitus and contractures

32. • 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

33. 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.

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

35. • 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

36. • 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

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

38. 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)

39. Atypical GBS

40. Atypical GBS

41. 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 Syndrome
B) Myasthenia gravis
C) Poliomyelitis
D) Polymyositis

42. Guillain-Barré syndrome may be associated
with:
(a) Campylobacter jejuni infection.
(b) Use of the oral contraceptive pill.
(c) Renal transplantation.
(d) Aspirin therapy.
(e) HIV infection
Pre-test 2

43. 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

44. 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

45. In the treatment of Guillain-Barré syndrome:
(a) Non-invasive ventilation is often useful in management
of patients with early ventilatory failure.
(b) Plasmapheresis is contra-indicated in patients with IgA
deficiency.
(c) Plasmapheresis may exacerbate hypercalcaemia.
(d) Intravenous immunoglobulin therapy is the treatment of
choice in patients with uncontrolled sepsis
Pre-test 5

46. Thank you