4. - ACETYLECHOLINE is released normally,but its bound to postsynaptic membrene is reduced. -The concentration ACH R on the muscle end plate membrene is reduced. -antibodies and complemnt are attached to membrane. - Anti sm ,anti straited musle : the first autoantibodies discovered in MG,found in 90% of MG patient of age younger than 40. -Thymic myoid cells encode for Ach R subunits, 10 % of MG patient has thymoma in age between<30-60> & 70% has hyperplasia -it associated w other autoimmune disease such as SLE,RA,autoimmune thyrodities. - IT ALSO RAISED IN - AUTOIMMUNE LIVER DISEASE -LES -PRIMERY LUNG CA
5. - STR AB IS USUALLY ASSOCIATED W ACH –R - 25% OF MG PATIENT HAS SERONEGATIVE ANTIBODIES. _CONCENTRATION OF ANTIBODIES IS HIGHER IN SEVER DISEASE. - ANTI TITAN AB IS ONLY FOUND IN PATIENT W ACH-R W LATE ONSET DISEASE OR THYMOMA. - ANTIBODIES TO MSRTK MUSVLE SPECIFIC RECEPTOR TYROSINE KINASE IS RAISED IN MG W GENERALIZED WEAKNESS W SERONEGATIVE ACH-R. - PHASES OF MG DISEASE : Active phase most flactuant and most sever symptoms from 5-7 y of onset. Myastgenia crisis appear at this stage. Stable - remission patient become free of symptoms within one year.
6. -what is the reason for reduced action of Ach on postjunctional membrene in patient w MG? -antibodies bind to postjunctional membrene and prevent cellular action of Ach R. -antibodies bind to Ach R and reduce number of available receptor for Ach. -antibodies bind to prejunctional membrene to reduce Ach release. -which of the following statement regarding thymomas in patient w MG? -thymoma of increse frequency but not present in majority. -thymoma are present of majority of patient. -thymic hyperplasia is common, but thymoma are not common in patient w MG. MCQ
7. EPIDERMOLOGY: - Age :female in 2 ed-3 rd decade. male above 6 th decade. - 50% of the patient has intial symptoms as occular weaknese in form of ptosis and diplopia. -start as unilateral then turn to be biateral. - 1/2 of these patient develop generalized weakness within 2 years. - 15% have oropharengeal weakness as dysphagia,dysarthia, difficulty in chewing or swallowing - 5% present w proximal weakness. -intially weakness limited to single muscle group then extend to other groups.
8. -weakness is flactuant least at morning ,worse as day progress. -increase w reading,watching, driving. -decrease by dark glasses to decrease diplopia. - FACTORS WORSE MG : -emotional upset. -systemic illness as viral respiratory infection. -Hypothyrodism. -Drugs: as interferon,betablocker, ca chanel blocker, anasthia,aminoglycoside& fluroquinolone,chloroquine,AED,antipsychotic,lithium,magnisium sulphate. OCP,thyroxine and statin. DISEASE ASSOCITED W MG : -autoimmune diseas as RA,SLE,DM,Autoimmune thyrodities.
9. OCCULAR SIGNS: -more than one occular muscle weakness while pupile reflux is intact. -ptosis shift from one eye to other. -saccade reflux is superfast<occular quiver> -after down gaze,upgaze produce overshot<lid twitch>. -pseudo- INO limited adduction in one eye, lead to jerky abduction in other eye. -covering ptotic eye contraction of frontalis of contra lateral side. -passively lifting ptotic eye fall of eyelide of contral lateral side. -ice covering ptotic eye improve ptosis.
10. OROPHARENGEAL WEAKNESS: - nasal voice after prolonged talking. -palatal muscle weakness leakage of liquid from nose when swallow. -larangeal muscle weakness hoarsness & choking. -snarel smile when attemp to smile contraction of middle portion of upper lip &hoizental contraction of horizental corner of mouth. -jaw weakness cant keep jaw open against resistance,pt keep thumb under chin &middle finger above nose -can not close eye firmly.
11. LIMB WEAKNESS: -Dropped head weakness of neck flexor muscle more than extensor neck muscle. -Deltoid , tricep, extensor muscle of wrist,fingers and ankle dorsiflexion weakness than other limb. -Arm uscle weakness tend to be more than leg muscle weakness. -respiratory muscle weakness respiratory failure life threating myasthenia crisis.
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13. - seronegative immune-mediated MG are more likely to be male w milder disease w occular MG w thymic atrophy. - antibodies to muscle spacific receptor tyrosine kinase have reported in 40% of patient w generalized MG. - Many of them has sever occular and bulbar weakness w is resistance to many form of therapy. EMG RNS :-10% decremental response in amplitude after 1 st stimuli w compare w 4 th &5 th stimuli in at least one muscle. -should hold CEI 12 h before test. -it can be normal even there is high suspecion of MG.
14. SFEMG: -most sensetive test of NMJ in w show increase jitter in weak muscle. -High jitter facial muscle if patient have occular muscle weakness. -if jitter in limb muscle predicts generalized MG in ½ of purely ocular weakness. -increased jitter can be found in MND,neuropathy or myopathy. Occular cooling: -simple and fast test when putting ice on ptotic eye improve ptosis. - TFT -CXR, CT chest. - Tuberclin test.
15. MCQ -Which of the following are true regarding edrophonium test in MG? -the test is positive in 90% of patient w MG. -the test maybe positive in patient w primary occular motor nerve lesion. -the test may be positive in patient w MND. - the test is perfomed by injection of 10 mg as asingle dose. - Which is true regarding antibody testing in MG? -ACH R antibodies are detected in 30%of patient w occular myasthenia. -ACH Rare identified in 80% of patient w generalized MG. -ACH R antibodies are detected in almost all patient w congenital MG. -ACH R are detected in all patient w thymoma.
16. MCQ - which of the following are true regarding single fiber EMG for evaluation of patient w suspected MG? -SFEMG is the most senstive test for NM transmission defect. -normal jitter in weak muscle excludes NM transmission defect. -blocking is not specific for MG. -increase jitter in specific for MG.
18. PLASMA EXCHANGE Indication ; -sudden worsing MG for any reason. -befor surgical operation . -use w corticosteroid at the start of MG tt. - 2-3 ml removed as 3 cycle per week. -Effecte expected after 2-3 exchange. - Adverse effect :arrythmia, nausia,vomitting,headache,blurred vision,LL edema,canula side effect as haematoma, pneumothorax,influanza like symptoms if have IgA Deficiency.
19. IVIG: -Its role in modulation of inhibitory pathway or downregulation of production of AchR antibodies. -used as alternative to PE. -improvement occure in 50%-1005 if begain within 1 st week. -Dose: 2g/kg over 2-5 days. -Adverse effect: headache, chills,aseptic menegities,retinal necrosis,alopecia ,retinal necrosis,cerebrovascular infarction or MI
20. CHOLINESTARESE INHIBITORE MESTONIN <Pyridostagmaine> -inhibite enzyme w hydrolize Ach at cholinergic synapse. -start w 40-60 mg Q8h. -can be increased to 180 mg if have sever swallowing difficulties. -available in spray & nebulizer form. -increase dose gradullly till reach optimal muscle strength. -overdose cholinergic crisis . -Adverse effect: nausia,vomitting,abdominal cramp and increase bronchial secretion.
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22. IMMUNOSUPPRENT Azathioprin:-used when no improvement on prednisolone -effect delayed to 4-8 months. -start w 5o mg/day. -increase by 50 mg/7days to total of 150-200 mg/day. -SE:flue like symptoms,rash within 2 weeks,leukopenia, leukopenia and raised liver enzyme. -CI in child bearing women.
23. -T-lymphocyte dependant immune response. -good response within 1-2 month -dose of 5-6 mg/kg bid -SE:nephrotoxicity,HTN. Cyclophosphamide -giver IV in sever generalized MG of dose of 500 mg/m2. -SE: leucopenia,hair loss, cystitis. Cyclosporine
24. Mycophenelet mofetil<cellcept> -inhibit T-lymphocyte&B l-ymphocyte proliferation and I formation of antibodies active in complement dependant lysis. -given as tablet of 2g/day. Onset of effect in 2weeks-2 months. -SE:leukopenia ,dirrohea Thymectomy: -it is recomanded to be free from medication. -to be asymptomatic -also recomanded in autoimmune MG occular MG. -best response in younger age especially women &early in caurse. - No base descion on AchR antibodies.
25. CHOLINERGIC CRISIS ; -it is occure secondry to excessive CEI w cause excessive stimulation straited muscle nicotinic junction producing flaccid paralysis. Clinically: -patient will develop bronchospasm,cynosis,diaphorosis ,miosis,SLUDGE< salivation,lacrimation,urinery incontince,diorrhea, GIT hypermotility, emesis>.
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28. CONGENITAL MYASTHENIA GRAVIS -It is genetic NMJ disease,as DOK7 gene recessive mutation. -occure mostly in male infancy ,either due to deficiency ofACHR or decrease acetylcholine estrase or decrease ACH resynthsis or packaging or abnormal interaction between ACH & ACH R -start as incomplete opthalmoparesis ,ptosis and mild facial &bulbar weakness.arthrogryposis may be present at birth. Some develop generalized fatigability w milder than occular symptoms. -no respiratory compromise. -dignosis based on RSF-EMG show decremantal response in limb muscle and limb weakness. -tt by CEI w improve muscle weakness and occular muscle
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30. DIFFERENTIAL DIAGNOSIS OF MG: - Thyroid opthalmopathy -chronic progressive external opthalmoplegia -myotonic dystrophy &occulopharangeal dystrophy -brain stem &motor cranial nerve pathology -generalized fatigability as in anemia,psychologiacl etiology. - MND as ALS. -Lambert Eaton synerome: -symptoms mostly in the morning relieved by excersice. -autonomic symptoms -RNS:incremental response in CMAP amplitud. -BOTULNISM -PENICILLAMINE INDUCED MYASTHENIA -STATIN
31. - which statement describ the position of thymectomy in mangement of MG? -thymectomy is of most benefit for elderly patients who are poorly tolerant of medical therapy. -thymectomy is only indicated for thymoma. -thymectomy is indicated mainly for patients under age of 60 w MG. -thymectomy is of no proven benefit and should not be performed. MCQ
