Muscular-diseases.pptx

MusculardiseasesMyastheniagravisDefinition:Myastheniagravisiscausedbyadefectofneuromusculartransmissionduetoanantibody-mediatedattackuponnicotinicacetylcholinereceptors(AChR).ClinicalCharacter:FluctuatingweaknessImprovedbyinhibitorsofcholinesteraseEtiologyandPathogenesisRelatedtodestructiveeffectsofautoantibodiestoAChREvidence:1.Experimental immunization of animalswith purified AChR from an electric fish,induces high titers of antibody to thereceptor.2.HumanserumantibodiesthatreactwithhumanAChRwerefoundinMGpatients3.Electrophysiologic features of MG wereproducedbypassivetransferofhumanIgGtomice.4.Plasmapheresisreducedplasmalevelsofanti-AChR and ameliorated myasthenicsymptomsandsigns.Howtheautoimmunedisorderstartsisnotknown.InhumanMG,hyperplasiaofthethymusabout15%ofcasesisathymoma.AChRantibodiesaresynthesizedbyBcellofhyperplasticthymusgland.WhenhumanmyasthenicthymuswastransplantedintomicetheanimalproducedantibodiestoAChRthatboundtotheirownmotorend-plates.A.Primarilyinthethymus.1.70%ofthymusglandfromadultMGpatientsarenotinvoluted.2.Thethymusweighmorethannormal.3.The thymus glands show lymphoidhyperplasia.4.Immunocytochemical:germinalcenterscontainBcells,plasmacells,andTcells.Pathology5.10%of myasthenic thymus glandscontainthymomas.B.Loss of synaptic folds and widenedcleftsC.Somenerveterminalsaresmallerthannormal.D.On residual synaptic folds show Y-shapedantibody-likestructures,IgG.Clinicalfeatures1.Incidence:0.4/100,000.Prevalence:5/100,000.Beforeage40,Male:female3:12.SymptomsThreeclinicalcharacteristics.1)Thefluctuatingnature:Theweaknessvaries in a single day;day to day;or overlongerperiods.(remissionsorexacerbations).Crisis:When an exacerbation involvesrespiratorymuscles2)Thedistributionofweakness:A.Ocularmusclesareaffectedfirstinabout40%ofthecases(Ptosisanddiplopia).B.Affected facial oropharyngeal muscles(dysarthria,dysphagia and limination offacialmovements).C.Limbandneckweakness.Crisis:occurin:oropharyngealrespiratorymuscleweakness.provokedby:respiratoryinfectionsurgicalproceduresemotionalstresssystemicillness3).Thethirdcharacteristicistheclinical response to cholinergicdrugs.Thisoccurssouniformlythatithasbecomepartofthedefinition.3.Signs:(1)The vital signs and general physicalexamination are normal limits,unless thepatientisincrisis.(2)Weakness of the facial and levatorpalpabraemusclesproducesacharacteristicexpressionlessfaceswithdroopingeyelids.(3).Completeophthalmoplegiainoneorbotheyes(diplopia).Thepupilisneverinvolved.(4).Weakness of oropharyngeal or limbmuscles,andrespiratorymuscle.(5).Sensationisnormalandthereflexesarepreserved.1.Classification:(1)Group1.About14%ofpatientshaveocularmyastheniaonly.(2)GroupIIA.Mildgeneralizedmyastheniawithocularsigns.(3)Group IIB.Moderately severe generalizedmyasthenia,with mild bulbar and ocularinvolvement.(4)Group III.Acute severe myasthenia,withbulbarandrespiratory complications.Tracheostomyisrequired.(5)GroupIV.Lateseveremyasthenia,usuallydevelopingfromothergroupswithin2years.1.Routineexaminationsofblood,urine,andCSFarenormal.2.EMG:90%patients have progressivedecrementintheamplitudeofmuscleactionpotentialsevokedbyrepetitivenervestimulationat3to5Hz.Laboratorytests3.AchRAntibodiestoarefoundin90%ofpatientsofallages.Thetiterdosenotmatchtheseverityofsymptoms.4.CTscansofthemediastinumdemonstrates thymomas,especially inthoseolderthan40.Diagnosis1.Characteristichistoryandphysicalexamination.2.Jollytest3.Edrophonium(Tension)tests.4.Neostigminetest:0.04mg/kg,IM,reachesitsmaximum activity in 1-2 hours.Theeffectisgoneat3-4hours.5.EMG.6.AntibotiestoAchRtest.7.CT scans of thymus.Hyperplasia orthymoma.Differentialdiagnosis:1.Botulism:presynapticblockerofacetylcholinereleasecausedbycontaminatefoodsprogressivemuscleweaknessBeginning:extraocularpharyngealmusclesTreatment:trivalentantitoxinguanidinehydrochloride2.Lambert-Eatonsyndrome(LEMS):Myasthenia-likesyndromeoccurswithcarcinomaGeneralizedmuscleweaknessThe EMG is helpful in differentiating thesyndromefromtruemyastheniagravis.Treatment with removal of the tumor andguanidinehydrochloride.Treatment1.Anticholinesterasetherapy:Anticholinesterase drug should be given assoonasthediagnosisismade.i.Pyridostigmine60mgqidii.Neostigminebromide15mgqidiiiIfthepatientshavedifficultyeating,dosescanbetakenabout30minutesbeforeameal.2.Corticosteroidtherapy(1).High-dosecoticosteroidtherapy1).Prednisone,60-100mgdaily.Improvementbeginsatabout12days.2).Dexamethasone,20mgdailyIVfor10days.3).Prednisononmethel,480-1000mgdailyIVfor3-5days.(2).Low-dosecorticosteroidtherapy:prednisone25mg,qod,graduallyincreasingthedosageby12.5mgeveryweekuntilthetotal dosage reaches 100 mg on alternatedays.3.Immunotherapy(1).Azathioprine,50-100mg,twiceaday.(2).Cyclophophamide100mg,twiceaday.3.Thymectomy:About80%ofpatientswithoutthymomabecomeasymptomaticorgotocompleteremissionafterthymectomy.4.Plasmapheresis:Toremovetheharmfulantibody.6.Treatmentofcrisis(1).Myastheniccrisis:needassistedventilationabout10%ofmyasthenicpatientsoccur,occur in patients with dysarthria,dysphagia,respiratorymuscleweakness,respiratoryinfection,andmajorsurgerycausedbylessanticholinesterasedrugsdosage.(2).Cholinergiccrisis:overdosageofanticholineserasedrugscholinergicsideeffects,excessiveanticholinesterasetherapy.(3).Brittlecrisis:Chronic anticholinergic drugs damages thesynapse,somepatientsbecomerefractorytothemedication.Crisisisanemergency.The patients respiratory function must bemaintainedsameasrespiratoryfailuretreatmentCholinergicdrugdiscontinuedinafewdaysorweeks.The therapeutic goal is to maintain vitalfunctionsandtoavoidortreatinfection.3.DrugsofavoidedDrugsthathavemildneuromuscularblockingeffectsandsedatives,arecontraindicated.Quinine,Quinidine,Procainamide,Propranolol,Lidocaine,Aminoglycosideantibiotics,Polymyxin,Viomycin,Colistin,Morphine,Bubiurates,andothertranquilizers.8.Amongthetreatment,anticholinesterasegrugtherapyandplasmapheresisaresymptomatictreatmentsthymectomy,steroids,andotherimmunosuppressivedrugsmayalterthecourseofthedisease.Periodicparalysischaracterizedboutsoflimbweakness.someformshavebeenmappedtothegeneforthe apha subunit of the sodium channel ofmuscleregardas“channelopathies.”Thetwomaintypeswerefirstseparatedbythelevelofserumpotassium.HypokalemicperiodicParalysisThe potassium content decreases in aspontaneousattacktovaluesof3.0mEq/Lorlower.Attacksmaybeinduced:injectonofinsulin,orglucose,ingestionofamealhighincarbohydrates.Incidence:Male:female,3:1autosomedominantheredityThefirstattackusuallyoccursatpuberty,butitmayoccurastheageof4ordelayedtothesixthdecade.SymptomsandSigns:attackusuallybeginsafterrest.ItcommonlydevelopsduringthenightparalysisvariesfromslightweaknessofthelegtocompleteparalysisTheoropharyngealandrespiratorymusclesareusuallyspared.Theremayberetentionofurineandfecesduringasevereattack.Attackvariesfromafewhoursto24hours.Theintervalbetweenattacksmaybeoneyear,oroneormoreattacksmayoccurdaily.Weaknessisespeciallybepresentonthemorningaftertheingestionofahigh-carbohydratemealbeforeretiringonthepreviousnight.Intervalbetweenattacks,patientsarestrongandserumpotassiumnormal.In a mild attack,tendon reflexes and electricalreactionsarediminished.Insevereattacks,tendonandcutaneousreflexesare absent and muscles do not respond toelectricalstimulation.Cutaneoussensationisnotdisturbed.Fatalities are rare,but death may occur fromrespiratoryparalysis.Diagnosis:transientattacksofweakness.confirmed by finding low potassium,highsodiumcontentintheserumduringanattack,orbyinducinganattackwithIVglucose(100g)andregularinsulin(20units).Treatment1.Acute attacks,rapidly terminated byingestionof20to100mEqofpotassiumsalts.Thebasisoftherapyisoraladministrationofacetazolamide,250to1000mgdaily.Thisregimenpreventsattacksinabout90%2.spironolactonepromoteretentionpotassium.Patientswiththyrotoxicperiodicparalysisarespontaneousorinducedattacksduringtheperiodofhyperthyroidism.Glucoseandinsulinareusefulintheinterimbetweentreatmentofhyperthyroidismbydrugsorradioiodine,beforetheeuthyroidstatereturns.HyperkalemicPeriodicParalysisCharacterizedonsetbeforeage10attackstooccurinthedaytimeandtobeshorterandlesssevereMyotoniaisdemonstrablebyEMGMyotonic lid-lag is the sole clinicalevidenceofthetrait.The serum and urinary potassium contentmaybeincreasedduringanattack,thismaybeduetoleakageofpotassiumfrommuscle.The attacks tend to be precipitated byhunger,rest,andcoldandbyadministrationofpotassiumchoride.Attacksmaybeterminatedbyadministrationofcalciumgluconate,glucose,andinsulin.Acetazolamide,250 mg to 1000 mg daily,hasbeeneffectiveinreducingthenumberofattacksorinabolishingthemaltogether.ProgressiveMuscularDystrophiesDefinition:A muscular dystrophy has fiveessentialcharacteristics.1.defined by clinical,histologic,and EMGcriteria.No signs of denervation or sensory loss,unlessthereisaconcommitantandseparatedisease.2.symptoms include limb or cranial muscleweakness.(Theheartandvisceralmusclesmayalsobeinvolved.)3.Symptomsbecomeprogressivelyworse.4.Histologicchangesimplydegenerationandregeneration of muscle,but no abnormalstorageofmetabolicproductisevident.5.This disease is recognized as heritable,even if there are no other cases in theparticularfamily.Classification.Therearefourmaintypes:Duchennemusculardystrophy(DMD)Facioscapulohumeralmusculardystrophy(FSHD)limb-girdlemusculardystrophy(LGMD)myotonicmusculardystrophyEachtypediffersfromtheothersinageatonset,distributionofweakness,rateofprogression,presenceorabsenceofcalfhypertrophy,highserumlevelsofCK,andpatternofinheritance.LaboratoryDiagnosisEMGmusclebiopsyDNAanalysisSerumCKECGDuchenneMuscularDystrophyX-linkedrecessivetrait.Femalecarrythegenearecarriers.incidenceis1in3,500malebirths.nogeographic,ethnicvariation.onethirdarenewmutations;lifespanofDMDisshortened,about20-30y.prevalenceisless(1to18,000males).ClinicalFeatures1.Evident at birth if serum enzymes aremeasured.2.Thesymptomsdonotbeginuntilage3to5 years,but that may be a measure ininfants.3.Walkingdelayedandtheboysneverrunnormally;Soon toe-walking and waddinggait.4.Progresses,overt difficulty walking,climbingstairs,andrisingfromchairs.5.An exaggerated lordosis is assumed tobalance.6.Theboystendtofalleasily,andtheyhavedifficultyrisingfromtheground.(Gowerssign)7.Asthediseaseprogresses:thearmsandhandsareaffectedswallowing,ocularmovementsaresparedIliotibialcontractureslimithipflexionheelcordcontracturescausetoe-walking8.Atage9-12,theboynolongerwalksandenters a wheelchair;scoliosis may becomeserious;contributetodisability.9.Byaboutage20,respirationiscompromised and mechanical ventilation isneeded.10.heartissparedclinically,butECGisabnormal:increasedR-Samplitude,anddeep,narrowQwaves.congestivefailuremaysuperveneinafewcases.gastrointestinalsystemissparedbutacutegastricdilatationinafewcases.MentalretardationaffectaboutonethirdofboyswithDMD.BeckerMuscularDystrophy(BMD)resemblesDMDinessentialcharacteristics:X-linked,calf hypertrophy,weakness isgreatestproximally,andserumCKlevelsarehigh.EMGandmusclehistologyaresame.Thetwodifferenceareageatonset(usuallyafterage12)andrateofprogression(stillwalkingafterage20,oftenlater).Diagnosis1.The clinical diagnosis of DMD is evident fromclinicalfeatures.In sporadic,atypical cases,spinal muscularatrophy might be mistake for DMD fasciculationand EMG denervation,identify the neurogenicdisorder.2.SerumCKlevelofDMDandBMDareusuallyatleast20timesnormal3.Dystrophingeneandproteinanalysiscanmakethecorrectdiagnosis.TreatmentThere is no specific drug therapy for DMDandBMD.Prednisonetherapywasbetterthanplaceboincontrolledtrials.Bracingmaypreventscoliosisinwheelchair-boundpatients.Surgical correction of spinal and limbdeformitiestomaintainambulationaslongaspossible.Facioscapulohumeral(FSH)MuscularDystrophyautosomaldominantfashion.characteristicdistributionofweakness:thefaceisalwaysaffected.Progressionisslow;evenbeasymptomatic.Onsetinadolesence,occasionallydetectedinchildren.Serumenzymelevelsarenormal.FSHDgenemapsto4q35-qter.ClinicalManifestations1.Facialweakness,Patientshaveneverbeenabletowhistleorblowupaballoon.2.Scapularwingingisprominent.3.The shoulder girdle has a characteristicappearance.cannotraisethearmslaterallytoshoulderlevel.4.Weaknessinthelegsmayaffectproximalmuscles.Laboratorystudies:EMG and muscle biopsy show amyopathicpattern.Thehistologicchangesaremild.Serumenzymevaluesareusuallynormalortriviallyelevated.ECGisnormal.Diagnosis:Accordingtotheclinicalfeatures,autosomaldominantfashion,serumCKlevel,andEMG.Management:Treatmentissymptomatic.Limb-GirdleMuscularDystrophy(LGMD)LGMDisamyopathicsyndromesofproximallimbweaknessthatareusuallyslowlyprogressive.Clinicalmanifestations1.Onsetinadolescenceoradult,andinheritance:autosomaldominantorrecessive.2.The legs are usually affected first,withdifficultyclimbingstairsandrisingfromchairs.3.Awaddinggait.risingthearmsdifficult,andwingingofthescapula4.Kneejerkstendtolostbeforetheanklejerks.Cranial muscles are usually spared.Progressionisslow.5.EMGandmusclebiopsyshowmyopathicchanges.SerumCKmaybeelevatedbutlesssothaninDMD.Diagnosis:According to the clinical features andexclusiontoincludesyndromesthatdidnotmeetcriteriaforDMD,FSHD,ormyotoniccategorise.Management:Treatmentissymptomatic.