- 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
- 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.
-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
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.
-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.
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.
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.
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.
<ul><li>DIAGNOSIS OF MG </li></ul><ul><li>Tensolin test : </li></ul><ul><li>- 90% of patient have +ve test </li></ul><ul><li>-afer injectio of 10 mg of edrophonium ,start by 3 mg then 5 mg improve within 60 sec. </li></ul><ul><li>-some patient who not response to edrophonium,will response to neostagmine w has long duration of action & helpful in dignosis of MG in neonate or infant. </li></ul><ul><li>Autoantibodies: </li></ul><ul><li>Ach R present in 80% of patient of generalized MG and 55% of occular MG. </li></ul><ul><li>-concentration of Ach R is low at onset of disease then increase later on. </li></ul><ul><li>-it rised in other conditions such as SLE,RA,Gravis,ALS,Pencillamine induse MG. </li></ul>
- 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.
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.
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.
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.
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.
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
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.
<ul><li>CORTICOSTEROID </li></ul><ul><li>-75%of patient have complete relief of them symptoms when prednisolone started in first 6-8 weeks. </li></ul><ul><li>start PE befor steroid to prevent SE of steroid. </li></ul><ul><li>-should hospitalized patient to prevent SE of steroid </li></ul><ul><li>Dose of 1.5mg-2mg/ kg/day. </li></ul><ul><li>-increse by 10 mg/day till optimal rffect </li></ul><ul><li>-once improve can change to alternative day,then gradual decrease of dose over months. </li></ul><ul><li>-can D/C prednisolone after 2 years of tt and patient do well. </li></ul><ul><li>-patient w thymoma show good response befor and after surgery. </li></ul><ul><li>-Adverse effect: mild weakness in 1 st 7-10 days after start steroid can be mange by CEI, gastrities ,osteoparosis. </li></ul>
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.
-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
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.
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>.
<ul><li>MYASTHENIA CRISIS </li></ul><ul><li>-respiratory failure from myasthenia muscle weakness. </li></ul><ul><li>It is precipateded by infection ,drugs such as immunosupresent w rapid tapering or surgical operation. </li></ul><ul><li>-pt cant maintain inspiratory force of more than 20 cm h2o,TVmostly less than 4-5 ml,FVC<15 ml/kg. </li></ul><ul><li>-pt should asses his ABG,FVC,TV,intubate patient and regular suction </li></ul>
<ul><li>MG in pregnancy </li></ul><ul><li>-1 st trimester worsining in 1 st pregnancy. </li></ul><ul><li>-while 3 rd trimester in subsequent pregnancies </li></ul><ul><li>-treated by CEI and prednisolone. </li></ul><ul><li>-CI to use cytotoxic drug during pregnancy. </li></ul><ul><li>Labor is normal unless there is obestatric indication for CS. </li></ul><ul><li>-Not to use Mg sulphate in eclampsia as it NMJ blockage. </li></ul><ul><li>- Breast feeding is not CI despite theoritical aspect of passage of AchR AB to newborn </li></ul>
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
<ul><li>Congenital myasthenia syndrome w apnea episode </li></ul><ul><li><familial infantile mysthenia> </li></ul><ul><li>-Newborn at birth found to have generalized hypotonia and poor feeding w episode of life threating apnea. </li></ul><ul><li>-w progress of age patient improve. </li></ul><ul><li>-SNF-EMG: </li></ul><ul><li>Decremental response of muscle afterexhausted by RNS. </li></ul><ul><li>-improve on CEI. </li></ul><ul><li>Slow chanel congenital mysthenia </li></ul><ul><li>- age of onset at infancy -3 rd decade. </li></ul><ul><li>-as ADD w +ve family history OF </li></ul><ul><li>Involve limbs muscle and facial </li></ul><ul><li>-treatment:only get advantage from quinidine and fluxotin. </li></ul><ul><li>-w treatment pt improve in strength of muscle </li></ul>
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
- 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
REFERANCE Uptodate.com Emedicine.com Neurology of clinical practic