7. GBS , Gullian Barre Syndrome and Role of IVIg.pptx

gullian barre synsrome (GBS), role of IVIG

1. GBS and Role of IVIg Clinical Evidence

2. O utline GBS – overview Brief history What ? Types of GBS Etiology and pathogenesis Diagnosis and treatment IVIg What and how it works ? IVIg in GBS Current Clinical review of articles Recommendations

3. Overview GBS Source: Van den Berg, B. et al. Guillain–Barré syndrome: pathogenesis, diagnosis, treatment and prognosis; Nat. Rev. Neurol. advance online publication 15 July 2014 http://www.uptodate.com/contents/treatment-and-prognosis-of-guillain-barre-syndrome-in- adults?source = search_result&search = Guillian+barre&selectedTitle =3~150 Guillain Barre syndrome. Medscape reference 2014

4. Brushing the History In 1859, Landry published a report on 10 patients with an ascending paralysis. Subsequently, in 1916, 3 French physicians Guillain, Barré and Strohl Described 2 French soldiers With motor weakness, areflexia, cerebrospinal fluid (CSF) Albuminocytologic dissociation, and diminished deep tendon reflexes The identified syndrome was later named Guillain-Barré syndrome. Historically, GBS was a single disorder; however, current practice acknowledges several variant forms.

5. GBS – What ? Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy characterized by Progressive symmetrical muscle weakness & Hyporeflexia / Areflexia With the marked decline in the incidence of polio, Guillain-Barré syndrome is now the most common cause of acute flaccid paralysis in healthy people

6. GBS – How much common ? Rare disease Incidence of 0.81–1.89 (median 1.11) per 100,000 person–years Less frequent in children than adults Men > Women (Ratio 3:2) Incidence increases by 20% for every 10 years increase in age

7. Common clinical presentations Types of GBS

8. GBS – Common Types Heterogeneous syndrome with several variant forms The major forms are : Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) Miller Fisher syndrome (MFS) Acute motor axonal neuropathy (AMAN) Acute sensorimotor axonal neuropathy (AMSAN)

9. Various types – at glance GBS subtypes Main clinical Features NCS findings Antibodies * Acute inflammatory demyelinating polyneuropathy (AIDP) Sensorimotor GBS, often combined with cranial nerve deficits and frequent autonomic dysfunction Demyelinating polyneuropathy Various ‡ Acute motor axonal neuropathy (AMAN) Pure motor GBS; cranial nerves rarely affected Axonal polyneuropathy, sensory action potential normal GM1a, GM1b GD1a GalNAc-GD1a Acute motor sensory axonal neuropathy (AMSAN) Resembles severe AMAN, but sensory fibers are affected, leading to sensory deficits Axonal polyneuropathy, sensory action potential reduced or absent GM1, GD1a Miller Fisher syndrome Ataxia, ophthalmoplegia, areflexia Normal in most patients; discrete changes in sensory conduction or H‑reflex may be present GQ1b, GT1a Table from : Van den Berg, B. et al. Guillain–Barré syndrome: pathogenesis, diagnosis, treatment and prognosis; Nat. Rev. Neurol. advance online publication 15 July 2014

10. GBS – How it presents ? Highly variable May present with mild difficulty in walking to complete paralysis of facial, respiratory or bulbar muscles 15-30% patients require Mechanical Ventilation 20 % are having severe autonomic dysfunction Considering this, around half of the patients require ICU monitoring

11. Common etiology and proposed pathogenetic mechanism WHY & HOW ?

12. GBS – Why it occurs ? GBS is a postinfectious disorder 2/3 of patients report symptoms of a respiratory or GI tract infection before the onset of GBS Most common pathogen : C. jejuni Other Pathogens : Cytomegalovirus (CMV), Epstein– Barr virus (EBV), Mycoplasma pneumonia, Haemophilus influenzae and influenza A virus Figure from : Van den Berg, B. et al. Guillain–Barré syndrome: pathogenesis, diagnosis, treatment and prognosis; Nat. Rev. Neurol. advance online publication 15 July 2014

13. Proposed Pathogenesis Molecular mimicry of pathogen-borne antigens, leading to generation of cross-reactive antibodies that also target gangliosides Figure from : Van den Berg, B. et al. Guillain–Barré syndrome: pathogenesis, diagnosis, treatment and prognosis; Nat. Rev. Neurol. advance online publication 15 July 2014

14. DIAGNOSIS AND TREATMENT

15. How to Diagnose ? Clinical Features CSF finding: Albuminocytologic Dissociation CSF protein increases Normal CSF WBC count Electrophysiological findings – Nerve conductions studies to differentiate from demyelinating from axonal subtypes

16. Treatment Combating Respiratory failure Cardiovascular Management Bowel & Bladder care Pain control Rehabilitation Plasmapheresis/Plasma Exchange (PE) Intravenous immune globulin (IVIg) Glucocorticoids (History) Interferon beta (only few cases) Supportive Care Disease Modifying Agents

17. How it works in GBS ? IVIg ( I ntravenous I mmunoglobulin)

18. IVIg is therapeutic preparations of pooled polyspecific IgG obtained from the plasma of a large number of healthy individuals (>>1000 donors)

19. Pleotropic immunomodulatory effects Don’t know exactly which effect is responsible for its therapeutic efficacy in GBS Possible Mechanism for therapeutic effects: May inhibit Fc-mediated activation of immune cells binding of antiganglioside antibodies to their neural targets or local complement activation

20. Commonly used dose in GBS: 0.4 gm / kg / day For 5 days Side effects: Aseptic meningitis, rash, acute renal failure (mostly related to sucrose containing products), and (rarely) hyperviscosity leading to stroke. IgA deficiency can lead to anaphylaxis

21. Current Clinical Review IVIg ( I ntravenous I mmunoglobulin)

22. C ochrane R eview – 2014 Objectives : To examine the efficacy of intravenous Immunoglobulin (IVIg) in Guillain-Barré syndrome (GBS) To determine the most efficacious dose of IVIg To compare the efficacy of IVIg and plasma exchange (PE) To compare the efficacy of IVIg added to PE with PE alone

23. Selection of studies Selection Criteria: Randomized and quasi-randomized trials of IVIg (Adults & children with GBS of all degrees of severity) compared With no treatment Placebo treatment PE or other immunomodulatory treatments Also included trials in which IVIg was added to another treatment Searched : The Cochrane Neuromuscular Disease Group Specialized Register (2 December 2013) CENTRAL (2013, Issue 12 in The Cochrane Library) MEDLINE (January 1966 to November 2013) & EMBASE (January 1980 to November 2013). Total 12 trials were found eligible for this review

24. K ey F indings 536 patients (from 5 trials) comparing IVIg to PE Mean difference (MD) of change in a seven-grade disability scale after four weeks No statistical difference between 2 groups 75 children (from 3 studies): IVIg significantly hastens recovery compared with supportive care 249 patients (from 1 trial) comparing PE followed by IVIg with PE alone mean grade improvement was 0.2 (95% CI -0.14 to 0.54) more in the combined treatment group than in the PE alone group

25. A uthor’s c onclusion IVIg and PE produced a similar amount of improvement People were more likely to finish a course of IVIg compared to PE IVIg started within two weeks from onset hastens recovery as much as PE

26. R ecommendations What Guidelines say ?

27. AAN Guideline Treatment with plasma exchange (PE) or intravenous immunoglobulin (IVIg) hastens recovery from GBS PE and IVIg are equally effective in patients with advance GBS symptoms PE may carry a greater risk of side effects and is more difficult to administer Combining the two treatments is not recommended Steroid treatment is not beneficial

28. Endorses the view of AAN related to IVIg use in GBS http://www.aanem.org/Education/Patient-Resources/Disorders/Guillain-Barre-Syndrome.aspx

29. NHS – UK Two main treatments can be used to reduce the severity of Guillain-Barré syndrome They are: Intravenous immunoglobulin Plasma exchange (plasmapheresis) Both treatments are equally effective. Intravenous immunoglobulin is slightly safer and easier to give than plasma exchange. http://www.nhs.uk/Conditions/Guillain-Barre-syndrome/Pages/Treatment.aspx

30. K eep on s trengthening N erves……..