PRESENTED BY: MAY BANJAR

SUPERVISED BY:DR.HESA ALETIBI

DEFINITION

IT IS AN AUTOIMMUNE DISEASE CHARACTERIZED BY WEAKNESS AND FATIGABILITY OF SKELETAL MUSCLE ,BULBAR,LIMBS OR RESPIRATORY MUSCLE.

PATHOPHYSIOLOGY

-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 phasemost flactuant and most sever symptoms from 5-7 y of onset. Myastgenia crisis appear at this stage.

Stable

-remissionpatient 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-3rd 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- INOlimited adduction in one eye, lead to jerky abduction in other eye.

-covering ptotic eyecontraction of frontalis of contra lateral side.

-passively lifting ptotic eyefall of eyelide of contral lateral side.

-ice covering ptotic eyeimprove ptosis.

OROPHARENGEAL WEAKNESS:

-nasal voice after prolonged talking.

-palatal muscle weakness leakage of liquid from nose when swallow.

-larangeal muscle weaknesshoarsness & choking.

-snarel smilewhen attemp to smilecontraction of middle portion of upper lip &hoizental contraction of horizental corner of mouth.

-jaw weaknesscant keep jaw open against resistance,pt keep thumb under chin &middle finger above nose

-can not close eye firmly.

LIMB WEAKNESS:

-Dropped headweakness 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 weaknessrespiratory failurelife threating myasthenia crisis.

DIAGNOSIS OF MG

Tensolin test:

-90% of patient have +ve test

-afer injectio of 10 mg of edrophonium ,start by 3mg then 5mgimprove within 60 sec.

-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.

Autoantibodies:

-Ach R present in 80% of patient of generalized MG and 55% of occular MG.

-concentration of Ach R is low at onset of disease then increase later on.

-it rised in other conditions such as SLE,RA,Gravis,ALS,Pencillamine induse MG.

-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.

EMGRNS:-10% decremental response in amplitude after 1 st stimuli w compare w 4th &5th 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 eyeimprove 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.

-overdosecholinergic crisis.

-Adverse effect:nausia,vomitting,abdominal cramp and increase bronchial secretion.

CORTICOSTEROID

-75%of patient have complete relief of them symptoms when prednisolone started in first 6-8 weeks.

-start PE befor steroid to prevent SE of steroid.

--should hospitalized patient to prevent SE of steroid

-Dose of 1.5mg-2mg/kg/day.

--increse by 10mg/day till optimal rffect

-once improve can change to alternative day,then gradual decrease of dose over months.

-can D/C prednisolone after 2 years of tt and patient do well.

-patient w thymoma show good response befor and after surgery.

-Adverse effect: mild weakness in 1st 7-10 days after start steroid can be mange by CEI, gastrities ,osteoparosis.

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.>

MYASTHENIA CRISIS

-respiratory failure from myasthenia muscle weakness.

-It is precipateded by infection ,drugs such as immunosupresent w rapid tapering or surgical operation.

-pt cant maintain inspiratory force of more than 20 cm h2o,TVmostly less than 4-5 ml,FVC<15 ml/kg.

-pt should asses his ABG,FVC,TV,intubate patient and regular suction

MG in pregnancy

-1 st trimester worsining in 1st pregnancy.

-while 3rd trimester in subsequent pregnancies

-treated by CEI and prednisolone.

-CI to use cytotoxic drug during pregnancy.

-Labor is normal unless there is obestatric indication for CS.

-Not to use Mg sulphate in eclampsia as it NMJ blockage.

-Breast feeding is not CI despite theoritical aspect of passage of AchR AB to newborn

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

Congenital myasthenia syndrome w apnea episode

<familial infantile mysthenia>

-Newborn at birth found to have generalized hypotonia and poor feeding w episode of life threating apnea.

-w progress of age patient improve.

-SNF-EMG:

Decremental response of muscle afterexhausted by RNS.

-improve on CEI.

Slow chanel congenital mysthenia

-age of onset at infancy -3rd decade.

-as ADD w +ve family history OF

-Involve limbs muscle and facial

--treatment:only get advantage from quinidine and fluxotin.

--w treatmentpt improve in strength of muscle

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