Aidp

Diabetic neuropathy

1. AIDP Update

2. AIDP Acute Onset Usually Monophasic Immune mediated disorder Peripheral Nervous System

3. Old Concept GBS = AIDP New Concept Other Variants

4. First described by Landry in 1859. Recognized as GBS since 1916, when Guillain, Barre´, and Strohl described two French soldiers who contracted the illness during World War I.

5. Incidence Rate : 1–2 / 100,000 population. The lifetime likelihood of any individual acquiring GBS is 1:1000. In Europe and North America : AIDP(90% of the cases). In China and Japan : AMAN(most common).

6. A peak incidence between June–July and Sept–October. Western countries - GBS is common in 5th decade. India - more common at a younger age. Equally common in men and women.

7. Often follows an upper or lower respiratory illness or gastroenteritis by 10 to 14 days. Approximately 70% of patients can identify a preceding illness. Infections associated with GBS - CMV, M. pneumoniae, EBV, Influenza A, H. influenzae, Enterovirus, Campylobacter jejuni and Zika virus.

8. Cytomegalovirus : most common associated virus. Campylobacter jejuni : most frequently associated bacterial infection.(overall 40%) Other less common precipitants are surgery, pregnancy, cancer, and vaccinations.

9. Evolves over days, often beginning with numbness in the lower limbs and weakness in the same distribution. Approximately 50% of patients achieve maximum weakness by 2 weeks, 80% by 3 weeks, and 90% by 4 weeks. Progression beyond 4 weeks is unusual. Neuropathic pain - 66% patients(localized to the lower back and thighs).

10. The weakness begins distally and spreads proximally. In rare cases, the weakness may be localized to the legs only (giving the appearance of paraplegia). Sensory examination : normal or show minor deficiencies in vibration and proprioception. All patients have areflexia or at least hyporeflexia at some time in the illness.

11. 50% of patients - some degree of facial weakness. Weakness attributed to cranial nerves includes ocular dysmotility, pupillary changes, and ptosis. Ophthalmoparesis : approximately 20% of patients with GBS.

12. 30% of patients develop respiratory failure from phrenic nerve disease, requiring intubation and ventilation. Autonomic involvement : tachycardia, bradycardia, hypertension and hypotension, gastric hypomotility, and urinary retention.

13. Variants of GBS

14. AMAN An axonal motor variant of GBS Reported in 1993 from Northern China So K/As Chinese paralytic illness. Can present with transient conduction block without axonal loss and this led to the term acute motor conduction block neuropathy.

15. More common in children during the summer. Pure motor without sensory symptoms and signs. NCS – decreased CMAP amplitudes, normal latencies and conduction velocities, and normal sensory studies.

16. AMSAN Sensory involvement also occurs Later age of onset Broader geographic distribution A more protracted course Slower and incomplete improvement

17. Miller Fisher syndrome Acute or subacute demyelinating polyradiculoneuropathy. Clinical presentation differs markedly from typical AIDP. Triad of ophthalmoplegia, areflexia, and ataxia. Often grouped with Bickerstaff brainstem encephalitis - similar presentation plus encephalopathy and corticospinal tract dysfunction.

18. The prognosis in both Miller Fisher syndrome and Bickerstaff brainstem encephalitis is favorable. Most patients improve within 1 to 2 months and make a complete recovery in 6 months even without specific treatment.

19. Acute Pandysautonomic Neuropathy Rare Sympathetic and parasympathetic nervous systems involved. CVS involvement, Blurry vision, anhydrosis. Recovery is often gradual and incomplete. Often combined with sensory features.

20. Pathogen e sis Molecular mimicry plays a major role. Molecular mimicry is believed to occur where the immune system recognizes the myelin epitope as ‘‘foreign’’ and targets it for destruction.

21. Di a gnostic Criteria

22. Laboratory Testing Elevated CSF protein - may not be present until 3 weeks after the onset of the illness. Pleocytosis (greater than 5 white blood cells) - not present in patients with GBS 15% of patients -10 to 50 cells per high-power field. If a pleocytosis is present, it raises suspicion for an infectious process; sarcoidosis; or carcinomatous or lymphomatous meningitis.

23. Electrod i agnos i s In first few days – NCS may be normal or only show subtle changes of demyelination, such as prolonged or absent F waves and H reflexes, and patchy changes in distal latencies in patients with AIDP. As the disease evolves - conduction block, temporal dispersion, and prolonged distal and F-wave latencies.

24. Sensory NCS - A characteristic sural nerve sparing. Sensitivity of NCS - As low as 22% in early AIDP and rise to 87% at 5 weeks. A conduction velocity of <70% of the lower limit of normal and a distal latency of >150% of the upper limit of normal was highly sensitive and had a specificity of nearly 100% for AIDP.

25. Needle EMG - Decreased recruitment initially, followed by fibrillation potentials over weeks 2 to 5 in proximal and distal muscles simultaneously.

26. The best electrodiagnostic indicator for a rapid or good recovery is maintained motor amplitude. Patients with an average amplitude >10% of the lower limit of normal likely have a major component of conduction block which has the potential to reverse. Amplitudes <10% during illness are seen in patients with a greater degree of axonal injury and a more prolonged recovery.

27. Imaging Studies To assess for gadolinium enhancement of nerve roots. To eliminate other causes of quadriparesis, particularly transverse myelitis, subacute compressive myelopathy, and infiltrating illnesses of the roots and the spinal cord. 95% of children with GBS show enhancement of the lumbar roots secondary to the inflammatory process.

28. Mana g ement

29. Additional predictors (1) time from GBS onset to hospital admission of less than seven days (2) inability to lift the elbows or head above the bed (3) inability to stand (4) ineffective coughing

30. Specific treatment Plasma exchange IVIg Corticosteroids(not approved)

31. Plasma exchange First treatment shown to be effective. Removes autoantibodies, immune complexes, complement, and cytokines. Boosts T-cell suppressor function. Dose - 250 mL/kg divided over 5 alternating days. Risks - central venous catheter placement, hypotension, cardiac arrhythmia, vasovagal spell, allergic reaction to albumin replacement, hypocalcemia, anemia, and thrombocytopenia.

32. 2017

33. Patients with mild GBS on admission should receive 2 PEs. Patients with moderate and severe forms should benefit from 2 further exchanges. Ann Neurol 1997

34. IV immunoglobulin (IVIg) Pooled IgG from thousands of blood donors, which results in a fivefold increase in serum IgG. Adverse events - mild infusion-related symptoms (nausea and headache), aseptic meningitis, rash, severe rare anaphylaxis, and, in fewer than 2% of cases, renal failure. IVIg may be preferred since it is easier to administer.

35. IVIg is as effective as plasma exchange. NEJM 1992

36. Lancet 1997 Combination therapy ?

37. 2016

38. Nature 2015

39. AAN Recommendations PE is recommended for nonambulant patients within 4 weeks of onset (level A, class II evidence) and for ambulant patients within 2 weeks of onset (level B, limited class II evidence). The effects of PE and IV immunoglobulin (IVIg) are equivalent. There is insufficient evidence to recommend the use of CSF filtration (level U, limited class II evidence).

40. The evidence is insufficient to recommend the use of immunoabsorption (level U recommendation, class IV evidence). IVIg is recommended for patients with GBS who require aid to walk within 2 (level A recommendation) or 4 weeks from the onset of neuropathic symptoms (level B recommendation derived from class II evidence concerning PE started within the first 4 weeks and class I evidence concerning the comparisons between PE and IVIg started within the first 2 weeks).

41. The effects of IVIg and PE are equivalent. Corticosteroids are not recommended for the treatment of patients with GBS (level A, class I evidence). PE and IVIg are treatment options for children with severe GBS (level B recommendation derived from class II evidence in adults).

42. Novel Immunomo d ulatory Approac h es Inhibition of complement using eculizumab prevents neuropathy in an animal model of Miller Fisher syndrome. Limitations - significant cost and potential complications, including a high risk of meningococcal infections. Other complement inhibitors - APT070, rEV576, nafamostat mesylate, and soluble complement receptor 1 have been evaluated in animal models.

43. One possible strategy for axon protection is sodium channel blockade. Supporting this approach are data indicating flecainide protects axons in an animal model (experimental autoimmune neuritis [EAN]). Another general approach to axon protection, or enhanced regeneration, is growth factor therapy.

44. The voltage gated potassium antagonist, 4 aminopyridine represents a potential approach for GBS patients with residual gait dysfunction.

45. Treatment-related Fluctuations Treatment-related fluctuations are defined as worsening of weakness after an initial improvement or after stabilization following treatment with IVIg or plasma exchange. Occur in approximately 10% of patients with GBS. Usually take place within the first 2 months after treatment. Treated with another course of IVIg or plasma exchange, and the treatment is often beneficial.

46. If the patient experiences more than one treatment- related fluctuation, and particularly if it occurs 2 months or more after the onset of the illness, then the diagnosis of CIDP becomes a strong consideration.

47. PROGNOSIS The prognosis for most patients with GBS is for good to excellent recovery. Approximately 87% experience full recovery or minor deficits. Most of the improvement in GBS occurs within the first year, but patients may continue to improve for up to 3 years or longer.

48. Mortality in GBS is 3% to 7% Most often attributable to respiratory failure, infection, or uncontrollable autonomic dysfunction.

49. Conc l usion New variants Diagnostic and prognostic criteria have come Newer treatment modalities under trials

50. Thank You

51. Referre n ces Guillain-Barre´ Syndrome. P D Donofrio. Continuum 2017;23(5):1295–1309. Acquired Immune Demyelinating Neuropathies. M M Dimachkie. Continuum 2014;20(5):1241–1260. Immune-Mediated Neuropathies. Y T So. Continuum Lifelong Learning Neurol 2012;18(1):85–105. Guillain-Barré Syndrome. X A Londono et al. Semin Neurol 2012;32:179–186. Inflammatory Neuropathies. J Whitesell. Semin Neurol 2010;30(4):356-364.