2. Guillain-Barre Syndrome DR. INTEKHAB AHMAD 25 JAN 2010

3. Definition It is an acute inflammatory demyelinating polyneuropathy It is an acute inflammatory demyelinating polyneuropathy leading to progressive muscle weakness & areflexia.

4. Guillain Barre Syndrome Commonest cause of rapid-onset flaccid paralysis since polio decline Commonest cause of rapid-onset flaccid paralysis since polio decline Occurs as an autoimmune response following a GI or respiratory infection Occurs as an autoimmune response following a GI or respiratory infection Potentially severely debilitating disorder affecting 1-3 per 100,000 Potentially severely debilitating disorder affecting 1-3 per 100,000 10% die from associated complications 10% die from associated complications A further 10% suffer from long term neurological sequelae and physical dependence A further 10% suffer from long term neurological sequelae and physical dependence

5. History Guillain, Barre and Strohl first described a disease affecting French soldiers ( motor weakness, areflexia and CSF abnormalities) in 1916 Guillain, Barre and Strohl first described a disease affecting French soldiers ( motor weakness, areflexia and CSF abnormalities) in 1916 Descriptions date back to 1859 when Landry described ascending paralysis Descriptions date back to 1859 when Landry described ascending paralysis

6. Aetiology All ages affected with bimodal distribution towards young adults and the elderly All ages affected with bimodal distribution towards young adults and the elderly Slight male preponderance Slight male preponderance Children less severely affected Children less severely affected Most commonly occurs within a month of GI or resp upset. Most commonly occurs within a month of GI or resp upset. Commonest organism is campylobacter Commonest organism is campylobacter Others inc EBV, CMV, HIV, herpes & mycoplasma Others inc EBV, CMV, HIV, herpes & mycoplasma

7. Have been reports of association with vaccines, surgery, epidurals, bone marrow and organ transplantation, SLE, lymphoma, sarcoidosis Have been reports of association with vaccines, surgery, epidurals, bone marrow and organ transplantation, SLE, lymphoma, sarcoidosis Pregnancy and OCP confer some protection Pregnancy and OCP confer some protection

8. Pathogenesis Immunologically mediated nerve injury Immunologically mediated nerve injury Inflammatory cell infiltrates are seen in association with the demyelination, which is regarded as the primary pathological process Inflammatory cell infiltrates are seen in association with the demyelination, which is regarded as the primary pathological process Precise mechanism of sensitisation not known Precise mechanism of sensitisation not known Antibodies formed against nonself antigens (inf agents,vacc) but misdirected to host nerve tissue (neural target- gangliosides) due to molecular mimicry leading to demyelination Antibodies formed against nonself antigens (inf agents,vacc) but misdirected to host nerve tissue (neural target- gangliosides) due to molecular mimicry leading to demyelination

9. Figure 1. Structural components of peripheral nerves. In the endoneurial compartment (En), a single Schwann cell envelops several unmyelinated axons, and another Schwann cell provides multiple wrappings of plasma membrane forming the myelin sheath of a myelinated axon. The portion of a myelinated axon myelinated by a single Schwann cell is called the internode, and internodes are separated by nodes of Ranvier. Schwann cells associated with both unmyelinated and myelinated axons are covered with a continuous basal lamina (BL). Capillaries (Cap) are present within the endoneurial compartment, and collagen fibers (Col) run primarily longitudinally between the axons. The axons, Schwann cells, collagen, and endoneurial fluid are bundled into a fascicle by the perineurium (Pe). The perineurium consists of several layers of flattened perineurial cells connected by tight junctions and covered internally and externally by a basal lamina. The layers of perineurial cells are separated by collagen fibers (Col) oriented obliquely. Several fascicles are bundled together by the epineurium (Ep) to form a nerve. The epineurium consists primarily of fibroblasts, collagen fibers (Col), and elastic fibers. The epineurium between fascicles is termed the interfascicular epineurium, and that encompassing all of the fascicles is termed the epifascicular epineurium. Arterioles (A) and veins are oriented primarily longitudinally within the epineurium. Figure 1. Structural components of peripheral nerves. In the endoneurial compartment (En), a single Schwann cell envelops several unmyelinated axons, and another Schwann cell provides multiple wrappings of plasma membrane forming the myelin sheath of a myelinated axon. The portion of a myelinated axon myelinated by a single Schwann cell is called the internode, and internodes are separated by nodes of Ranvier. Schwann cells associated with both unmyelinated and myelinated axons are covered with a continuous basal lamina (BL). Capillaries (Cap) are present within the endoneurial compartment, and collagen fibers (Col) run primarily longitudinally between the axons. The axons, Schwann cells, collagen, and endoneurial fluid are bundled into a fascicle by the perineurium (Pe). The perineurium consists of several layers of flattened perineurial cells connected by tight junctions and covered internally and externally by a basal lamina. The layers of perineurial cells are separated by collagen fibers (Col) oriented obliquely. Several fascicles are bundled together by the epineurium (Ep) to form a nerve. The epineurium consists primarily of fibroblasts, collagen fibers (Col), and elastic fibers. The epineurium between fascicles is termed the interfascicular epineurium, and that encompassing all of the fascicles is termed the epifascicular epineurium. Arterioles (A) and veins are oriented primarily longitudinally within the epineurium.

11. Distributed throughout the nerve length but focused at nerve roots, spinal nerves and major plexuses Distributed throughout the nerve length but focused at nerve roots, spinal nerves and major plexuses Macrophages actively strip myelin from bodies of schwann cells and axons Macrophages actively strip myelin from bodies of schwann cells and axons Underlying immune response is complex Underlying immune response is complex Effectiveness of plasma exchange and IgG is thought to be blocking of demyelinating antibodies Effectiveness of plasma exchange and IgG is thought to be blocking of demyelinating antibodies

12. VARIANTS Several distinct clinical pictures described Several distinct clinical pictures described Acute inflammatory demyelinating polyradiculopathy (AIDP) Acute inflammatory demyelinating polyradiculopathy (AIDP) Acute motor axonal neuropathy (AMAN) Acute motor axonal neuropathy (AMAN) Acute motor sensory axonal neuropathy (AMSAN) Acute motor sensory axonal neuropathy (AMSAN) Miller-Fisher syndrome ( ataxia, areflexia and opthalmoplegia ) which may be accompanied by limb weakness, ptosis and facial and bulbar palsy Miller-Fisher syndrome ( ataxia, areflexia and opthalmoplegia ) which may be accompanied by limb weakness, ptosis and facial and bulbar palsy

13. Clinical presentation Classical picture is that of ascending limb weakness with areflexia, although a purely sensory variant has been well documented Classical picture is that of ascending limb weakness with areflexia, although a purely sensory variant has been well documented Features of GBS include Features of GBS include Progressive motor weakness, usually ascending from the legs Progressive motor weakness, usually ascending from the legs Areflexia Areflexia Facial palsy and bulbar weakness Facial palsy and bulbar weakness Sensory symptoms—mainly subjective Sensory symptoms—mainly subjective Bladder/bowel—in severe cases Bladder/bowel—in severe cases

14. Severe pain esp girdle Severe pain esp girdle Resp muscle weakness Resp muscle weakness Autonomic dysfunction( over or underactivity of the SNS or PSNS) Autonomic dysfunction( over or underactivity of the SNS or PSNS)

15. Features required for diagnosis defined by national institute of neurological and communicative diseases and strokes Progressive muscle weakness of more than one limb Progressive muscle weakness of more than one limb Areflexia or marked hyporeflexia Areflexia or marked hyporeflexia CSF cell counts of no more than 10 CSF cell counts of no more than 10 Features highly suggestive Features highly suggestive Features required to rule out other diagnosis Features required to rule out other diagnosis

16. Doughtful diagnosis Definite sensory level Definite sensory level Marked, persistent asymmetry of motor weakness Marked, persistent asymmetry of motor weakness Severe & persistent bladder/bowel dysfunction Severe & persistent bladder/bowel dysfunction CSF cell count > 50 CSF cell count > 50

17. Monitoring Cardiac Cardiac Blood pressure Blood pressure Vital capacity measured three times a day Vital capacity measured three times a day Bulbar function monitored to prevent aspiration Bulbar function monitored to prevent aspiration

18. Investigations In over 90% patients CSF protein is raised ( >0.4g/l) within a week of onset of symptoms In over 90% patients CSF protein is raised ( >0.4g/l) within a week of onset of symptoms Level does not correlate with clinical findings Level does not correlate with clinical findings Nerve conduction studies demonstrate reduced conduction velocity Nerve conduction studies demonstrate reduced conduction velocity Liver and renal function may be impaired Liver and renal function may be impaired Antiganglioside antibody should be searched for Antiganglioside antibody should be searched for

19. SIADH may occur in association with GBS SIADH may occur in association with GBS Stool cultures for campylobacter Stool cultures for campylobacter Ecg’s for QT, T and ST abnormalities Ecg’s for QT, T and ST abnormalities Head CT to exclude raised ICP and other pathology prior to LP Head CT to exclude raised ICP and other pathology prior to LP

20. Treatment Major challenge Major challenge Outcome excellent if complications treated or avoided Outcome excellent if complications treated or avoided Prevented by meticulous attention to detail Prevented by meticulous attention to detail

21. Specific treatment-disease modifying modalities Plasma exchange Plasma exchange Immunoglobin Immunoglobin Both should be used when patient non- ambulatory or resp decompensation occurs Both should be used when patient non- ambulatory or resp decompensation occurs Both have been examined in RCT and no difference in efficacy demonstrated between them Both have been examined in RCT and no difference in efficacy demonstrated between them

22. Plasma exchange 2 RCT showed reduction in ventilation and reduced time to motor recovery 2 RCT showed reduction in ventilation and reduced time to motor recovery Mortality was not altered Mortality was not altered Most effective within 7 days of onset Most effective within 7 days of onset 3-5 exchanges of 1-2 plasma volumes each over 1-2 weeks 3-5 exchanges of 1-2 plasma volumes each over 1-2 weeks Ffp more complications than albumin Ffp more complications than albumin CI include CVS instability, sepsis and haemostatic problems CI include CVS instability, sepsis and haemostatic problems Side effects are hypotension, hypocalcaemia,coagulation abnormalities and sepsis Side effects are hypotension, hypocalcaemia,coagulation abnormalities and sepsis

23. IV Immunoglobin 0.4mg/kg daily for 5-6 days 0.4mg/kg daily for 5-6 days Easier administration Easier administration Fewer side effects Fewer side effects Commence tx within 2 weeks of onset of symptoms Commence tx within 2 weeks of onset of symptoms CI include IgA deficiency(anaphylaxis) CI include IgA deficiency(anaphylaxis) Renal function may deteriorate Renal function may deteriorate Severe congestive cardiac failure major contraindication Severe congestive cardiac failure major contraindication RCT has suggested as effective as plasma exchange RCT has suggested as effective as plasma exchange

24. Steroids No place in the treatment of GBS No place in the treatment of GBS RCT have shown no advantage RCT have shown no advantage

25. CSF filtration Few case reports Few case reports When plasmapheresis and IgG have failed When plasmapheresis and IgG have failed Logistics difficult! Logistics difficult!

26. Supportive care Respiratory, Respiratory, 25% require ventilated 25% require ventilated Physio and VC monitoring in the spont breathing. If less than 15ml/kg or rising pCO2, mechanical ventilation likely Physio and VC monitoring in the spont breathing. If less than 15ml/kg or rising pCO2, mechanical ventilation likely Monitoring of bulbar function for prevention of aspiration Monitoring of bulbar function for prevention of aspiration Non-invasive ventilation often not useful as does not eliminate the problem of not being able to clear secretions due to poor cough Non-invasive ventilation often not useful as does not eliminate the problem of not being able to clear secretions due to poor cough Early tracheostomy should be considered Early tracheostomy should be considered

27. Supportive care Cardiovascular Cardiovascular Full invasive monitoring Full invasive monitoring Care with induction of anaesthesia as leads to hypotension and arrhythmias Care with induction of anaesthesia as leads to hypotension and arrhythmias Care with suxamethonium may lead to arrhythmias Care with suxamethonium may lead to arrhythmias Instability may be worsened by other drugs Instability may be worsened by other drugs Autonomic instability common Autonomic instability common

28. Supportive care Nutrition, fluid and electrolytes Nutrition, fluid and electrolytes Paralytic ileus common Paralytic ileus common Tpn may be required Tpn may be required Energy and fluid requirements are reduced in these patients Energy and fluid requirements are reduced in these patients Physiotherapy Physiotherapy DVT prophylaxis DVT prophylaxis Sepsis survellience Sepsis survellience Psychological care Psychological care analgesia analgesia

29. Prognosis Death in up to 25% of those who require ICU has been reported often from autonomic abnormalities Death in up to 25% of those who require ICU has been reported often from autonomic abnormalities Approx 16% patients suffer permanent disability Approx 16% patients suffer permanent disability Those who require ventilation, improve after more than 3 weeks, not improved within 1 month have greater risk of poorer outcome Those who require ventilation, improve after more than 3 weeks, not improved within 1 month have greater risk of poorer outcome Gradual improvement may occur over 18months -2years Gradual improvement may occur over 18months -2years Recurrence n 2-5% cases Recurrence n 2-5% cases

30. Thank you for your attending