Myasthenia gravis

HARRISON, BRADLEY AND ADAMS BASED

1. MYASTHENIA GRAVIS PRESENTER: DR JITHIN GEORGE

2. PATHOPHYSIOLOGY acetylcholine ( ACh ), releases from the motor nerve terminal in discrete packages (quanta) that cross the synaptic cleft and bind to receptors ( AChR ) on the folded muscle end-plate membrane. Muscle contraction results when ACh-AChR binding depolarizes the end-plate region and then the muscle membrane. Acetylcholinesterase attached to the postsynaptic muscle membrane hydrolyzes the released ACh , terminating its action and preventing prolonged muscle depolarization.

3. CLINICAL FEATURES

4. Factors that worsen myasthenic symptoms emotional upset, systemic illness (especially viral respiratory infections), hypothyroidism or hyperthyroidism, pregnancy, the menstrual cycle, drugs affecting NMT fever.

5. OCULAR

6. Unilateral frontalis contraction is a clue that the lid elevators are weak on that side Fatigue in these muscles may result in slight involuntary opening of the eyes as the patient tries to keep the eyes closed; this is called the peek sign

7. OROPHARYNGEAL MUSCLES

8. frequent choking or throat clearing or coughing after eating indicates difficulty in swallowing. a characteristic facial appearance. At rest, the corners of the mouth often droop downward, giving a depressed appearance. Attempts to smile often produce contraction of the medial portion of the upper lip and a horizontal contraction of the corners of the mouth without the natural upward curling, which gives the appearance of a sneer

9. LIMB MUSCLES

10. Diagnostic Procedures in Myasthenia Gravis

11. EDROPHONIUM TEST

12. Inject an initial test dose of 2 mg, and monitor the response for 60 seconds. Subsequent injections of 3 and 5 mg may then be given If clear improvement is seen within 60 seconds after any dose, the test is positive, and no further injections are necessary

13. Common side effects of edrophonium are increased salivation and sweating, nausea, stomach cramps, and fasciculations . Serious complications ( bradyarrhythmia or syncope) have been reported in only 0.16% of edrophonium tests. These symptoms generally resolve with rest in the supine position. Atropine (0.4-2 mg) should be available for intravenous (IV) injection if bradycardia is severe.

14. NEOSTIGMINE TEST

15. Autoantibodies in Myasthenia Gravis

16. ELECTRODIAGOSTIC TESTING

17. MUSCLES USED FOR RNS

18. Single fibre EMG

19. The presence of serum AChR or anti- MuSK antibodies virtually ensures the diagnosis of MG, but their absence does not exclude it. RNS confirms impaired NMT but is frequently normal in mild or purely ocular disease. Almost all patients with MG have increased jitter, and normal jitter in a weak muscle excludes MG as the cause of the weakness. Neither electrodiagnostic test is specific for MG, because increased jitter, even abnormal RNS, occurs in other motor unit disorders that impair NMT.

20. MANAGEMENT

21. TREATMENT SYMPTOMATIC Anticholinesterase : pyridostigmine quarternary 60mg neostigmine 7.5 to 15 mg. In infants and children, the initial oral dose of pyridostigmine is 1 mg/kg, and of neostigmine is 0.3 mg/kg Action begin in 45 min. Last 3-6 rs Max 960 mg

22. MANAGEMENT OF CRISES Resp failure needs artificial ventilation Crises mostly within 2 yrs Stop AChE once pt is on ventilator. Respiratory assistance is needed when the NIF( negative insp force) is less than −20 cm H2O, when tidal volume is less than 4 to 5 mL / kg body weight and maximum breathing capacity is less than three times the tidal volume, or when the forced vital capacity is less than 15 mL /kg body weight . Specific treatment is plasma exchange or IV Ig

23. Short-Term (Rapid-Onset) Immune Therapies

24. IVIg

25. Long-Term Immune Therapies

26. CORTICOSTEROIDS

27. IMMUNOSUPRESSANTS

28. THYMECTOMY

29. EVOLVING TREATMENTS

30. ASSOCIATED DISEASES Thymoma Hyperthyroidism Rheumatoid arthritis Seizures Diabetes

31. PREGNANCY AND MG

32. immune-mediated attack against the P/Q-type voltage-gated calcium channels (VGCC) on presynaptic cholinergic nerve terminals at the neuromuscular junction and in autonomic ganglia first described in patients with lung cancer( small cell ca mostly) also occurs as an organ-specific autoimmune disorder

33. gradual onset of lower-extremity weakness , sometimes with muscle tenderness. Dry mouth is a common symptom of autonomic dysfunction; other features are erectile dysfunction, postural hypotension, constipation, and dry eyes. Ocular and bulbar symptoms are generally not prominent Symptoms usually begin after age 40 , but LES can occur in children. Males and females are equally affected Tendon reflexes are almost always absent or diminished.

34. Diagnostic Procedures CMAPs with low amplitude, which increases during 20- to 50-Hz stimulation and after brief maximum voluntary muscle activation. Low-frequency repetitive nerve stimulation produces a decrementing response in a hand or foot muscle in almost all patients, and almost all have small CMAPs in some distal muscle The characteristic increase in CMAP size after activation is more prominent in distal muscles . Immunoprecipitation assays demonstrate VGCC antibodies in almost all patients with CA-LES and in more than 90% with NCA-LES

35. TREATMENT search for underlying malignancy, especially SCLC pyridostigmine , 30 to 60 mg, every 6 hours for several days. Guanidine hydrochloride . Divide the initial oral dose of 5 to 10 mg/kg daily into 3 doses, 4 to 6 hours apart, and increase as needed to a maximum of 30 mg/kg/day. Bone marrow depression is a major risk and may occur with doses as low as 500 mg/day. Other side effects include renal tubular acidosis, chronic interstitial nephritis, cardiac arrhythmia, hepatic toxicity, pancreatic dysfunction, paresthesias , ataxia, confusion, and alterations of mood. Administering 3,4-DAP facilitates release of ACh from motor nerve terminals and produces clinically significant improvement of strength and autonomic symptoms in most LES patients

36. BOTULISM

37. five forms: classic or food-borne, infantile, wound, hidden, and iatrogenic. The EMG findings in botulism include: ■ Reduced CMAP amplitude in at least two muscles. ■ At least 20% facilitation of CMAP amplitude during tetanic stimulation. ■ Persistence of facilitation for at least 2 minutes after activation. ■ No postactivation exhaustion. ■ Short-duration motor unit potentials resembling myopathic motor units in affected muscles on EMG

38. Treatment consists of administration of bivalent (type A and B) or trivalent (A, B, and E) antitoxin. Antibiotic therapy is not effective, since the cause of symptoms (in all but infantile botulism) is the ingestion of toxin rather than organisms. In infantile botulism, IV human botulism immune globulin (BIG-IV) neutralizes the toxin for several days after illness onset, shortens the length and cost of the hospital stay, and reduces the severity of illness