Acute acquired inflammatory polyneuropathy

1. Dr Chitra
Department of Critical care
BLK-MAX Super Speciality Hospital
New Delhi
Gullian Barre
Syndrome

2. Case Scenario
36 year old female, came in ER with complaints of pain and weakness in lower
limb since 3 days and weakness in upper limb since 1 day.
History
• Apparently normal till 1 week ago then she had loose motions
• Developed weakness in lower limb 3 days back
• Weakness in both upper limb for 1 day.
• Paraesthesia in fingers of upper limb & upto ankle joint in lower limb
•No bladder and bowel involvement.

4. Focused neurological examination
• Patient is conscious, oriented
• Cranial nerve involvement: Lower motor neuron type of 7
th
cranial palsy
• Sensory: altered sensation in fingers of upper limb and in
lower limb it is up to the ankle joint
• Motor: Power is 1/5 in both lower limb and 3/5 in upper limb,
with decreased/absent deep tendon reflex.

6. Differential diagnosis
CNS
Encephalitis,
Acute disseminated encephalomyelitis,
Acute transverse myelitis,
Peripheral Neuropathy
Poliomyelitis
Acute onset chronic inflammatory demyelinating neuropathy,
Guillain-Barré syndrome,
Preodic paralysis
Myasthenia gravis,
Botulism,
Motor Neuron disease
Lyme disease

7. What is your final diagnosis

9. What is Guillain–Barré syndrome ( GBS
)

10. Acute acquired inflammatory polyneuropathy mostly
characterised by
Acute Ascending Symmetrical flaccid paralysis
With or without sensory/autonomous nerve dysfunction.
Shortly after infection ( respiratory / gastroenteritis ) or
vaccination
Rapidly progressive and Monophasic course

11. EPIDEMIOLOGY
Incidence= 1-3/1,00,000 population.
M;F ratio=1.4:1
Post-infection= 60% [AGE -
Camplylobacter jejuni& RTI-EBV, CMV]
.
Post-vaccination;- SWINE FLU
influenza, rabies, Hepatitis ?? Covid-19
Antibodies against NMJ:- GM1, GD1b,
GQ1b
20-30% will require IMV due to
respiratory failure.
Mortality:-3-10%
20% will have residual weakness.
Upto 67% will develop fatigue &
muscle pain.

12. Pathophysiology

15. Classification
Acute inflammatory demyelinating polyneuropathy(AIDP)
Acute motor axonal neuropathy(AMAN),
Acute motor and sensory axonal neuropathy(AMSAN),
Miller-fisher syndrome.
AMAN AND AMSAN are common in India and SE Asia

16. Variants of GBS
Pure motor.
Pure sensory
Miller fisher
Paraparetic
Pharyngeal-cervical-brachial
B/L Facial palsy with paraesthesia
Bickerstaff brainstem encephalitis

17. Clinical Presentation

20. Clinical Course

23. Diagnostic Criteria

24. Features needed for diagnosis of Guillain-Barré syndrome in clinical
practice
Progressive weakness in legs and arms (sometimes initially only in
legs).
Areflexia (or decreased tendon reflexes) in weak limbs.
Additional symptoms
•Progressive phase lasts days to 4 weeks (often 2 weeks).
•Relative symmetry.
•Mild sensory symptoms or signs (not present in acute motor axonal
neuropathy).
•Cranial nerve involvement, especially bilateral weakness of facial
muscles.
• Autonomic dysfunction.
• Pain(common).

25. Features that should raise doubt about the diagnosis of Guillain-Barré
syndrome
• CSF: increased number of mononuclear cells or polymorphonuclear
cells (>50 cells per μL).
• Severe pulmonary dysfunction with little or no limb weakness at
onset.
• Severe sensory signs with little or no weakness at onset.
• Bladder or bowel dysfunction at onset.
• Fever at onset.
• Sharp spinal cord sensory level.
• Marked, persistent asymmetry of weakness.
• Persistent bladder or bowel dysfunction.
• Slow progression of weakness and without respiratory involvement
(consider
subacute inflammatory demyelinating polyneuropathy or acute onset
chronic inflammatory demyelinating polyneuropathy).

26. Brighton Diagnostic Criteria

27. Asbury’s Criteria

28. How to diagnosed GBS??
A.Its clinical diagnosis mostly:- based
on
1. Brighton criteria
2. Asburys criteria
B .Lumber puncture CSF analysis-
Shows Cyto-albuminological Dissociation
i:e Low TLC and high Protein
C.NCV/NCS/EMG -
Delayed distal motor latency,
Decreased nerve conduction velocity,
prolonged F-wave latency,
Increased temporal dispersion,
Conduction block

29. Nerve conduction studies
• Can be helpful in clinical practice, but are generally not required to diagnose
Guillain-Barré syndrome.
• Needed to meet all Brighton criteria for Guillain-Barré syndrome.
• Essential for classification of GBS in AIDP & AMAN.
• AIDP:- features of demyelination
(decreased motor NCV, prolonged distal motor latency,
increased F-wave latency, conduction blocks, and temporal dispersion).
• AMAN:- no features of demyelination (one demyelinating
feature in one nerve, if distal CMAP amplitude is less than 10% LLN, can be
found; distal CMAP amplitude less than 80% LLN in at least two nerves.
Transient motor nerve conduction block might be present.

31. Clinical prediction models:
1. Erasmus GBS Respiratory Insufficiency Score (EGRIS) score (mechanical
ventilation)
2. Neck weakness, single breath count, and bulbar palsy score (mechanical
ventilation)
3. Sharshar model (mechanical ventilation)
4. Ning Score (mechanical ventilation nomogram [MVN])
5. Erasmus GBS Outcome Score (EGOS) (independent ambulation)
6. Modified EGOS (mEGOS) (independent ambulation)

32. Erasmus Guillain–Barré Syndrome Respiratory Insufficiency
Score

33. Guillain–Barré syndrome disability scale

34. Erasmus Guillain–Barré Syndrome Outcome
Score

35. Modified Erasmus Guillain–Barré Syndrome Out- come Score
(mEGOS)

36. Management of GBS

37. Evaluation -
History & Clinical examination ,
Investigations
Supportive care -
1. Respiratory support ,
2. Pain control ,
3. Prophylactic Antibiotics ,
4. Nutrition ,
5. DVT prophylaxis
6. Stress Ulcer management
Specific Treatment -
A. IVIG
B. PE /
C. Immunomodulators
Rehabilitation -
• Physiotherapy ,
• Psychological Support
Management of GBS

38. ICU admission
Indication : (Leonhard et al., 2019)
(a) Requiring mechanical ventilation
(b) Evolving respiratory distress;
(c) Autonomic dysfunction
(d) Erasmus GBS respiratory insufficiency score (EGRIS) > 4.
( e ) Rapidly progressive disease

39. ICU monitoring
Purpose - monitor progression as well as prevention of fatal
complications
Blood pressure and heart rate /rhtythm
Respiratory function
Muscles strength & tone & volume
Swallowing function
Gastrointestinal function
Bowel / bladder control
Blood gas & biochemistry
Routine blood & Urine biochemistry
CK , LDH and isoenzyme

40. MECHANICAL VENTILATION

41. Indications
A. ‘‘20/30/40 rule’’
VC falls below 20 mL/kg,
MIP ( Maximum inspiratory pressure ) above 30 cm H2O,
MEP below 40 cm H20.
B. Bulbar Symptoms
C. Quadriparesis
D. Inadequate Cough
E. Onset of symptoms to hospital admission < 7 days

42. Specific treatment of GBS

43. Specific treatment of GBS
Corticosteroids ( controversial )
IVIG
Plasma Exchange
Immunomodulators

44. Corticosteroids
oral steroids and intravenous methylprednisolone are not beneficial in the disorder.
((Hughes et al., 2016)
The combination of IVIg and methylprednisolone is not more effective than IVIg
alone
Combination of plasma exchange followed by IVIg is not significantly better than
plasma exchange or IVIg alone.
No evidence exists that shows a second course of IVIg is effective in patients with
Guillain-Barré syndrome who continue to deteriorate. (SID-GBS RCT trial)

45. IVIG
To be started as soon as possible, before irreversible nerve damage has taken place.
Contraindicated in patients who are :-
Hypersensitive to the active substance in the product
Previous history of severe systemic or anaphylactic responses to IVIg
Anti-IgA antibodies
Selective IgA deficiencies.
Adverse events
Stroke,
Hemolytic anemia,
Transfusion-related acute lung injury (TRALI),
Aseptic meningitis,
Venous embolism
The most common IVIg dose is 2 g/kg split evenly over 5 days, but the optimal
dose and dosing regimen remains unknown.

46. Plasma exchange (PE)
Nonselectively removes immunoglobulins, complement, and cytokines, all of which may play a role in the pathogenesis of
For severe GBS, the relative risk of improving one or more functional grades by 4 weeks after PE treatments was 1.64 (95
Treatment also significantly
reduced the number of patients requiring mechanical ventilation,
shortened the time to extubation,
increased the number of patients achieving full strength at 1 year,
reduced the number of patients experiencing severe sequelae at 1 year.
Prothrombin time, PTT, CBC, and calcium levels are typically followed daily to detect coagulopathy, thrombocytopenia,
The optimal dose of PE has not been firmly established.
French Cooperative Group study has provided several guidelines:-
Mild GBS (patients able to walk, but not run)- 2 exchanges are better than none.
Moderate GBS (unable to walk, but not mechanically ventilated), 4 exchanges are better than 2

47. Table adapted from :- Shang P, Feng J, Wu W and Zhang H-L (2021) Intensive Care and Treatment of Severe Guillain–Barré Syndrome. Front. Pharmacol. 12:608130. d

48. Eculizumab
Humanised monoclonal antibody with high affinity to the complement factor
C5 and prevents its cleavage to C5a and the proinflammatory, cytolytic
C5b-9 complex.
As the pathophysiology of GBS has been elucidated, complement
activation draws attention as a key treatment point.
Tested in in two randomised, double-blind, placebo-controlled phase 2
trials (JET-GBS) .
Neither showed benefit versus immunoglobulins alone on disability level at
4 weeks, although one study importantly suggested possible, clinically
highly relevant, late effects on normalising function.
A phase 3 trial is in progress. (ClinicalTrials.gov Identifier: NCT04752566)

49. Thromboembolism
prophylaxis

50. Deep-vein thrombosis and subsequent pulmonary embolism are
recognised complications of immobility from GBS.
Unfractionated heparin (5000 units twice daily)
Low–molecular-weight heparin (40 mg daily)
Compression stockings or
Sequential compression devices.

51. Physiotherapy & Rehabilitation

52. Physiotherapy - earlier , the better
Rehabilitation - as soon as improvement starts
Physical training programme - for severe fatigue

53. Controversies & dilema in
Gullian Barre syndrome

54. Controversies & dilema in
GBS
1. Start of (standard) treatment
A. Therapeutic time window
B. Mild form of GBS
C. Clinical variants and electrophysiological subtypes
of GBS
D. Children
2. Change or repeat of treatment
A. Insufficient clinical response
B. Add on treatment
C. Other treatments than PE or IVIg
D. Treatment-related fluctuations (TRFs)

55. The Lacunae
Outcome in many patients is still poor
A. 2-10 % mortality
B. Unable to walk after 6 months
C. Residual symptoms , including pain and severe fatigue

56. Therapeutic Time window
What is exactly the time to hit the hammer on the nail ?
It should be started as soon as possible to prevent further nerve damage

57. Treatment of mildly affected patients
What exactly constitute “ mildly affected patient “ ?
No consensus
?? When patient is still able walk without assistance ( I:e GBS
disability score 1or 2 )

58. Clinical Variants and Sub types of GBS
Should all the clinical variants and
sub types of GBS be treated ??

59. IVIG v/s PE
Which one is better ??

60. Insufficient Clinical Response
40-50 % of the patient do not show any improvement in GBS disability
score at 4 weeks
• Should we start over again ?
• Should we think out of the box ??
There is no clear cut consensus or evidence that the patient will benefit
from either
- Second course of same treatment
- Change in the treatment

61. Second dose of IVIG
Is repeating the second course of IVIG beneficial in improving the outcome ?
SID-GBS trial showed no significant clinical benefit of a second intravenous immunoglobulin
course administered shortly after the first standard intravenous immunoglobulin dose in patients
with Guillain-Barré syndrome with poor prognosis.
Additionally, the group given a second series of intravenous immunoglobulin had more serious
adverse events than those given placebo.

62. SID-GBS Trial

63. Role of steroids in GBS
Evidences have shown that corticosteroids alone dose not improve
recovery in GBS.
Some studies have shown that steroids delay the recovery .
Hughes RAC, Brassington R, Gunn AA, van Doorn PA.
Corticosteroids for Guillain-Barré syndrome.
Cochrane Database of Systematic Reviews 2016, Issue 10. Art. No.: CD001446. DOI: 10.1002/14651858.CD001446

64. Role of steroids in GBS

65. Switch to another Therapy
Rationale of therapy switching
Different treatment modality has got different mechanism of
action , so switching therapy might help .
One randomised trial compared the efficacy of PE, IVIg, and PE followed immediately
by IVIg in 379 severely affected patients, but did not find significant differences
between the three treatment modalities in any of the outcome measures. (Plasma
Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Lancet 1997;349:225–30. )
On the contrary, the patients who received both treatments had a worse GBS
disability grade at discharge and were longer hospitalised. (Oczko-Walker M, Manousakis G, Wang
S, et al. Plasma exchange after initial intravenous immunoglobulin treatment : J Clin Neuromuscul Dis 2010;12:55–61.)
PE after IVIG should be avoided

66. Summary of Treatment dilemmas in GBS
Oczko-Walker M, Manousakis G, Wang S, et al. Plasma exchange after initial intravenous immunoglobulin treatment
in Guillain-Barré syndrome: critical reassessment of effectiveness and cost-efficiency. J Clin Neuromuscul Dis
2010;12:55–61.

67. Conclusion
The evidence regarding various treatment effect is limited .
Standard guidelines for the GBS and its various subtype is not established.

68. Thank you