七年制醫(yī)學(xué)課件 神經(jīng)病學(xué) 12Myopathy

MyastheniaGravis

重癥肌無力

(seeP341~346)YANYONGDep.ofNeurology,the1stHospital,ChongqingUniversityofMedicalScienceMyastheniaGravis

重癥肌無1

The

myastheniagravis(MG，重癥肌無力)isa

neuromuscular-transmissiondisorders神經(jīng)肌肉傳遞障礙,and

anacquiredimmunological獲得性免疫disorder(probablyimmunemediated),ofunknowncause,inwhichantibodiesaredirectedagainstthepostsynaptic突觸后

acetylcholine乙酰膽堿receptor(AChR).Thisresultsinweaknessandfatigabilityofskeletalmusclegroups;themostcommonlyaffectedmusclesaretheproximallimbs肢體近端

andocularandbulbar眼和延髓muscles.Themyastheniagravi2Myopathicdisorders肌病includesskeletalmusclesbygene,Inflammation,Metabolicortoxicity:Musculardystrophies肌營養(yǎng)不良:Duchenne’肌營養(yǎng)不良，Becker’sCongenitalmyopathies先天性肌病:mitochondrial肌病、肌管肌病等Myotonicdisorders

肌強直Inflammatorymyopathies炎癥性肌病AIDSMetabolicmyopathies：Hypo-hyperkalemia,osteomalacia等Endocrinemyopathies：Hyper-orhypothyroidism等AlcoholicmyopathiesDrug-inducedmyopathies：corticosteroids,certainβ-blockers,chloroquine,clofibrate,emetrine,colchicine,andsoon.Myoglobinuria肌紅蛋白尿:bymuscleinjuryorischemia,Neuromuscularjunction:MG,lambert-EatonsyndromeMyopathicdisorders肌病inclu3

A.HowdooccurtheMG?Inmotornerves,whenthestimulusreachestheendofthenerveterminalacetylcholine(Ach)isreleasedfromvesiclesviavoltage-gatedcalciumchannels.TheAchcrossesthesynapticcheftandbindsAchRsonthepostsynapticmuscleend-platemembrane.Thisresultsindepolarizationandsubsequentcontractionofmuscle.TheAchisthenbrokendownbyacetyl-cholinesterase,whichisboundtothebasallaminainthesynapticfolds.

A.HowdooccurtheMG4

A.HowdooccurtheMG?TheMGresultsfromtheAchdecreasedbyacetylcholinesteraseoverdoseorthesensitivereducedoftheAchreceptors.

A.HowdooccurtheMG?5

B.Clinicalmanifestation

1.MGcanoccuratanyage.Therearetwopeaksofincidence

forMG,splitbyageandsex:a.Youngwomen(20~40yrs),whotendtohaveanacute,severelyfluctuating,moregeneralizedcondition,withincreasedassociationwithHLA-B8andHLA-DR3.andmorecommoninfemalesthanmales.

Thereisanassociatedabnormalityofthethymus胸腺inpatientswithMG.Thymichyperplasic增生isfoundin80%ofpatientsbelowtheageof40years.B.Clinicalmanifestat6

b.Oldermen(40-75yrs),whotendtohaveamoreoculobulbarpresentationandthymoma,andmorecommoninmalesthanfemales.In10%~20%ofallpatientswithmyastheniagravis,athymictumor胸腺腫瘤(thymoma)isfound,theincidenceincreasingwithage.Inpatientswiththymoma,antibodiestostriated橫紋肌抗體musclemayalsobefound.b.Oldermen(40-75yrs),w72.ClinicalfeaturesTheclinicalfeaturesofMGischaracterizedbyfluctuatingweakness(mildatmorningandsevereatevening晨輕暮重

orwhichrelieveafterrestandworseafterexerciseoraction)andeasyfatigability易疲勞

ofvoluntarymuscles.

Theeasyfatigabilitycausefluctuatingweakness波動性無力.Themostcommonlyaffectedmusclesaretheproximallimbs肢體近端

andcranialallocatingmusclessuchasocularandbulbar.MG可累及全身骨骼肌,但最常累及的是四肢近端肌群和腦神經(jīng)支配的肌肉(如眼外肌和延髓肌肉).2.Clinicalfeatures8

Fatigabilitytest疲勞試驗

Fatigabilitycanbedemonstratedbyexercisingaffectedmuscles,e.g.letpatientslookupwardsorlookingatceilingforafewsecondstheptosis瞼下垂willbecomeapparent.Similarmaneuver手法canbecarriedoutfortheproximallimbmuscles,suchaslookingatlateral,verticalgazeorreadingfor2~3minsormovinglimbs.

93.PresentingsymptomsinMGSymptomspercentageofpatientsDiplopia復(fù)視41Ptosis眼瞼下垂25Dysarthria構(gòu)音困難16Lowerextremityweakness13Generalizedweakness11Dysphagia吞咽困難10Upperextremityweakness7Masticatoryweakness咀嚼無力7HerrmannCJ.WestJMed1985:142:7973.Presentingsymptoms10

C.Clinicclassification(P343)Ⅰ.Ocularmyasthenia(15%~20%)眼肌型MGⅡA.Mildgeneralizedmyastheniawithslowprogression;nocrisis;drug-responsive(30%)緩慢進展的輕度全身型,無危象ⅡB.Moderatelyseveregeneralizedmyasthenia;severeskeletalandbulbarinvolvementbutnocrisis;drugresponselessthansatisfactory(25%)中重度全身型,嚴重累及骨骼肌和延髓肌但無危象,藥物治療不滿意Ⅲ.Acutefulminatingmyasthenia;rapidprogressionofseveresymptomswithrespiratorycrisisandpoordrugresponse;highincidenceofthymoma;highmortality(15%)急性爆發(fā)性MG,快速進展伴呼吸危象,藥物效差,高胸腺瘤死亡率Ⅳ.Lateseveremyasthenia;symptomssameasⅢ,butresultingfromsteadyprogressionover2yrfromclassⅠtoⅡ(10%).晚發(fā)型重癥MG,癥狀同Ⅲ,但從Ⅰ到Ⅱ穩(wěn)緩進超2年C.Clinicc11

D.Diagnosis

Inpatientswhopresentwithchangeable(fluctuating)diplopia,typicalmyasthenicfacies,unequallydroopingeyelids,difficultyinspeaking

orswallowing,orweaknessofthelimbs----thediagnosiscanhardlybeoverlooked.Ifthosesymptomsareatfirstmildandinconstant,youcandofatigabilitytestfor

patients.Ifthediagnosisremainsindoubt,themeasurementofspecificexaminationsarenecessary.D.Diagno12

Diagnostictest1.Repeatingnerveelectricstimulation(RNES重復(fù)電刺激):Impairedneuromusculartransmissioncanbedetectedelectrophysiologicallybyadecrementalresponseofmuscletorepetitivesupramaximalstimulation(at2or3Hz)ofitsmotornerve,butnormalfindingsdonotexcludethediagnosis.2.Singlefiberelectromyography(SFEMG單纖維肌電圖)showsincreasedvariabilityintheintervalbetweentwomusclefiberactionpotentialfromthesamemotorunitinclinicallyweakmuscles.Diagnostictest133.Acetylcholinereceptorantibody:乙酰膽堿受體抗體

ThehighlyspecificAchRantibodyispresentintheserumofupto80%-90%ofpatientswithgeneralizedMG.4.Thymus胸腺imaging:ItisalwaysessentialtoimagethechestwithX-ray,CTorMRI,forthepresenceofthymichyperplasia胸腺增生orthymoma胸腺腫瘤,asremovalofahyperplasicthymusimprovestheconditioninmanypatients.3.Acetylcholinereceptoranti145.Neostigmine新斯的明

test:1.0mgofneostigminecanbegivenintramuscularly,witharesponsethatlastsforabout2hours.6.Tensilon(edrophonium騰喜龍)test:Tensilonisgiveniv.inadoseof10mg(1ml),ofwhich2mgisgiveninitiallyandtheremaining8mgabout30secondslaterifthetestdoseiswelltolerated.InMG,thereisanobviousimprovementinthestrengthofweakmusclesthatlastsforabout5minutes.Onlymildmuscarinic毒覃堿effects(pallor,nausea,vomiting,bowel,activation,sweating,salivation)5.Neostigmine新斯的明test:15

Differentialdiagnosis1.Lambert-Eatomsyndrome肌無力綜合癥Torepetitivesupramaximalstimulation(at10Hz)ofitsmotornerve,withcancerusually2.Oculardystrophies眼肌型肌營養(yǎng)不良

prognosticworse,nofluctuatingweakness,Tensilonandfatigabilitytest(-)3.Polymyositis多發(fā)性肌炎

Itisoftenassociatedwithmusclepain,nofluctuatingweakness.theserumCKisgenerallyelevated.Differentialdiagnosis16

E.

Treatment1.Anticholinesterasedrugs抗膽堿酯酶藥物AChD:

Pyridostigminebromide吡啶斯的明—atdosesindividuallydeterminedbutusuallybetween60mg~120mg,tid~qid.Smalldosesofatropinemayattenuatesideeffectssuchasbowelhypermotilityorhypersalivation.Mysuranandneostigminebromidehasnotbeusednow.E.Treatment172.Corticosteroids:

Corticosteroids

providethemainstayofimmuno-suppressivetreatment.Theysucceedin70%ofpatients,butmustbeincreasedslowly.Methylprednisolone-1000mg,iv.qd.3~5d;Prednisolone-1~2mg/kg(60~80mg),po.qd/morning;2weeks,thengraduallyreduced,sustainedover1year.Azathioprine硫唑嘌呤:2~3mg/kg/d.CyclosporineA環(huán)孢素A:6mg.kg.dx12mons2.Corticosteroids:183.Plasmapheresis:

Itissometimesusedespeciallyduringanacuteexacerbationorwhenthereisrespiratoryinvolvement.4.Thymectomy:Itsbeneficialeffect70%forthymomaorhyperplasicthymus,maynotbeevidentimmediately.5.Medications

ThatimpairneuromusculartransmissionshouldbeavoidedsuchasQuinine,Aminoglycosides氨基糖甙類，Phenobarbital苯巴比妥,Diazepam安定,andsoon.3.Plasmapheresis:19

F.

CrisisCrisis危象—ArapiddeteriorationoftheMGitself,canbringtherespiratoryfailure呼吸衰竭

andseverequadriparesis四肢癱瘓.

1.Myastheniccrisis肌無力危象:Itisamostcommontype,anticholinesterasedrugs(AChD)arenotenough.WehavetoincreasetheAChDdoseiftheedrophonium騰喜龍testispositive.F.Crisis202.Cholinergiccrisis膽堿能危象:ItisoftenexcessoftheAChD.Overmedicationcanledtoincreasedweakness.StoppingAChDimmediately,withthemechanicalventilation機械通氣,thengraduallymodifythedosesofAChDwhenallAChDclearoutfromthebody.3.Brittlecrisis反拗性危象:TheresponsetoAChDispoor,ofunknowncause.StoppingAChDimmediately,withthemechanicalventilation,thengraduallymodifythedosesofAChDifresponsewelltoAChDincourseoftime.2.Cholinergiccrisis膽堿能危象:I21

G.Prognosis

Mostpatientscanbemanagedsuccessfullywithdrugtreatment.Thediseasemayhaveafataloutcomebecauseofrespiratorycomplicationssuchasaspirationpneumonia.G.Prognosi22

Atypicalcase

Awoman,32yrsold.Shewasadmittedinhospitalwithsymmetricallyweaknessoflimbsforamonth,theweaknessismildatmorningandsevereatevening,andthemoresevereontheproximallimbs.Shehashaddiplopiafor4dandmilddysphagia2days.It’snormalsphincter.TheexaminationofNSshowedthat:wakefulness,alitterdysarthria,milddysphagia.Themotorabnormalofbilateraleyeballanddiplopia,thepalsyofbilateralpalata.Therearelow-gradeofmuscletoneanddecreasedtendonreflexonfourlimbs.Theproximalmuscularstrengthoflimbsis4gradeand5gradeondistal.Thepathologicreflexesaredeficit.Therearenormalsensory.

對此患者，①最可能的診斷是什么？②提出應(yīng)該完成那些主要的檢查？③應(yīng)主要與哪些疾病鑒別？④治療過程中會出現(xiàn)那些危險？Atypicalcase23Keypoints

1.Classificationofsensory2.Sensorypathway(痛溫覺、觸覺和深感覺傳導(dǎo)3種通路)3.Thelocationofsensorydisorders4.Locationandlaminationofsensorypathwaysinthespinalcord5.

Thecompriseofmotorsystem重點是錐體系統(tǒng)6.Thefeatureoflower/upperneurondisorders7.Thelocationofmotorsystemicdisorders;8.ThedifferencediagnosisbetweenUMNandLMNparalysis.9.Reflex：kindsandclinicalsignificance,reflexarc.Keypoints2410.WherearethecommonsitsofthelesionsofMS?CNSorPNS?11.WhataretheclassicfeaturesofMS?12.WhatarethemosteffectiveinvestigationsforMS?13.HowdotreattoMS?14.AlbuminocytologicdissociationinCSF蛋白-細胞分離15.themainclinicalfeaturesofGBS(AIDP):16.WhatchangesofelectrophysiologicintheearlystageofGBS(AIDP)?17.HowdodifferentialdiagnosiswithotherLMNP?10.Wherearethecommonsits2518.WhatarethemainclinicalfeaturesofMG?

fluctuatingweakness(mildatmorningandsevereatevening晨輕暮重orwhichreliveafterrestandworseafterexerciseoraction)andeasyfatigability易疲勞ofvoluntarymuscles(fatigabilitytest).Themostcommonlyaffectedmusclesaretheproximallimbs肢體近端andcranialallocatingmusclessuchasocularandbulbar19.HowdodiagnosetheMG(clinicalfeaturesanddiagnostictest)?20.Whatisthemyastheniccrisis?21.Whatisthecholinergiccrisis?22.HowdotreattheMG?18.Whatarethemainclinical26Thankyou!!Thankyou!!27MyastheniaGravis

重癥肌無力

(seeP341~346)YANYONGDep.ofNeurology,the1stHospital,ChongqingUniversityofMedicalScienceMyastheniaGravis

重癥肌無28

The

myastheniagravis(MG，重癥肌無力)isa

neuromuscular-transmissiondisorders神經(jīng)肌肉傳遞障礙,and

anacquiredimmunological獲得性免疫disorder(probablyimmunemediated),ofunknowncause,inwhichantibodiesaredirectedagainstthepostsynaptic突觸后

acetylcholine乙酰膽堿receptor(AChR).Thisresultsinweaknessandfatigabilityofskeletalmusclegroups;themostcommonlyaffectedmusclesaretheproximallimbs肢體近端

andocularandbulbar眼和延髓muscles.Themyastheniagravi29Myopathicdisorders肌病includesskeletalmusclesbygene,Inflammation,Metabolicortoxicity:Musculardystrophies肌營養(yǎng)不良:Duchenne’肌營養(yǎng)不良，Becker’sCongenitalmyopathies先天性肌病:mitochondrial肌病、肌管肌病等Myotonicdisorders

肌強直Inflammatorymyopathies炎癥性肌病AIDSMetabolicmyopathies：Hypo-hyperkalemia,osteomalacia等Endocrinemyopathies：Hyper-orhypothyroidism等AlcoholicmyopathiesDrug-inducedmyopathies：corticosteroids,certainβ-blockers,chloroquine,clofibrate,emetrine,colchicine,andsoon.Myoglobinuria肌紅蛋白尿:bymuscleinjuryorischemia,Neuromuscularjunction:MG,lambert-EatonsyndromeMyopathicdisorders肌病inclu30

A.HowdooccurtheMG?Inmotornerves,whenthestimulusreachestheendofthenerveterminalacetylcholine(Ach)isreleasedfromvesiclesviavoltage-gatedcalciumchannels.TheAchcrossesthesynapticcheftandbindsAchRsonthepostsynapticmuscleend-platemembrane.Thisresultsindepolarizationandsubsequentcontractionofmuscle.TheAchisthenbrokendownbyacetyl-cholinesterase,whichisboundtothebasallaminainthesynapticfolds.

A.HowdooccurtheMG31

A.HowdooccurtheMG?TheMGresultsfromtheAchdecreasedbyacetylcholinesteraseoverdoseorthesensitivereducedoftheAchreceptors.

A.HowdooccurtheMG?32

B.Clinicalmanifestation

1.MGcanoccuratanyage.Therearetwopeaksofincidence

forMG,splitbyageandsex:a.Youngwomen(20~40yrs),whotendtohaveanacute,severelyfluctuating,moregeneralizedcondition,withincreasedassociationwithHLA-B8andHLA-DR3.andmorecommoninfemalesthanmales.

Thereisanassociatedabnormalityofthethymus胸腺inpatientswithMG.Thymichyperplasic增生isfoundin80%ofpatientsbelowtheageof40years.B.Clinicalmanifestat33

b.Oldermen(40-75yrs),whotendtohaveamoreoculobulbarpresentationandthymoma,andmorecommoninmalesthanfemales.In10%~20%ofallpatientswithmyastheniagravis,athymictumor胸腺腫瘤(thymoma)isfound,theincidenceincreasingwithage.Inpatientswiththymoma,antibodiestostriated橫紋肌抗體musclemayalsobefound.b.Oldermen(40-75yrs),w342.ClinicalfeaturesTheclinicalfeaturesofMGischaracterizedbyfluctuatingweakness(mildatmorningandsevereatevening晨輕暮重

orwhichrelieveafterrestandworseafterexerciseoraction)andeasyfatigability易疲勞

ofvoluntarymuscles.

Theeasyfatigabilitycausefluctuatingweakness波動性無力.Themostcommonlyaffectedmusclesaretheproximallimbs肢體近端

andcranialallocatingmusclessuchasocularandbulbar.MG可累及全身骨骼肌,但最常累及的是四肢近端肌群和腦神經(jīng)支配的肌肉(如眼外肌和延髓肌肉).2.Clinicalfeatures35

Fatigabilitytest疲勞試驗

Fatigabilitycanbedemonstratedbyexercisingaffectedmuscles,e.g.letpatientslookupwardsorlookingatceilingforafewsecondstheptosis瞼下垂willbecomeapparent.Similarmaneuver手法canbecarriedoutfortheproximallimbmuscles,suchaslookingatlateral,verticalgazeorreadingfor2~3minsormovinglimbs.

363.PresentingsymptomsinMGSymptomspercentageofpatientsDiplopia復(fù)視41Ptosis眼瞼下垂25Dysarthria構(gòu)音困難16Lowerextremityweakness13Generalizedweakness11Dysphagia吞咽困難10Upperextremityweakness7Masticatoryweakness咀嚼無力7HerrmannCJ.WestJMed1985:142:7973.Presentingsymptoms37

C.Clinicclassification(P343)Ⅰ.Ocularmyasthenia(15%~20%)眼肌型MGⅡA.Mildgeneralizedmyastheniawithslowprogression;nocrisis;drug-responsive(30%)緩慢進展的輕度全身型,無危象ⅡB.Moderatelyseveregeneralizedmyasthenia;severeskeletalandbulbarinvolvementbutnocrisis;drugresponselessthansatisfactory(25%)中重度全身型,嚴重累及骨骼肌和延髓肌但無危象,藥物治療不滿意Ⅲ.Acutefulminatingmyasthenia;rapidprogressionofseveresymptomswithrespiratorycrisisandpoordrugresponse;highincidenceofthymoma;highmortality(15%)急性爆發(fā)性MG,快速進展伴呼吸危象,藥物效差,高胸腺瘤死亡率Ⅳ.Lateseveremyasthenia;symptomssameasⅢ,butresultingfromsteadyprogressionover2yrfromclassⅠtoⅡ(10%).晚發(fā)型重癥MG,癥狀同Ⅲ,但從Ⅰ到Ⅱ穩(wěn)緩進超2年C.Clinicc38

D.Diagnosis

Inpatientswhopresentwithchangeable(fluctuating)diplopia,typicalmyasthenicfacies,unequallydroopingeyelids,difficultyinspeaking

orswallowing,orweaknessofthelimbs----thediagnosiscanhardlybeoverlooked.Ifthosesymptomsareatfirstmildandinconstant,youcandofatigabilitytestfor

patients.Ifthediagnosisremainsindoubt,themeasurementofspecificexaminationsarenecessary.D.Diagno39

Diagnostictest1.Repeatingnerveelectricstimulation(RNES重復(fù)電刺激):Impairedneuromusculartransmissioncanbedetectedelectrophysiologicallybyadecrementalresponseofmuscletorepetitivesupramaximalstimulation(at2or3Hz)ofitsmotornerve,butnormalfindingsdonotexcludethediagnosis.2.Singlefiberelectromyography(SFEMG單纖維肌電圖)showsincreasedvariabilityintheintervalbetweentwomusclefiberactionpotentialfromthesamemotorunitinclinicallyweakmuscles.Diagnostictest403.Acetylcholinereceptorantibody:乙酰膽堿受體抗體

ThehighlyspecificAchRantibodyispresentintheserumofupto80%-90%ofpatientswithgeneralizedMG.4.Thymus胸腺imaging:ItisalwaysessentialtoimagethechestwithX-ray,CTorMRI,forthepresenceofthymichyperplasia胸腺增生orthymoma胸腺腫瘤,asremovalofahyperplasicthymusimprovestheconditioninmanypatients.3.Acetylcholinereceptoranti415.Neostigmine新斯的明

test:1.0mgofneostigminecanbegivenintramuscularly,witharesponsethatlastsforabout2hours.6.Tensilon(edrophonium騰喜龍)test:Tensilonisgiveniv.inadoseof10mg(1ml),ofwhich2mgisgiveninitiallyandtheremaining8mgabout30secondslaterifthetestdoseiswelltolerated.InMG,thereisanobviousimprovementinthestrengthofweakmusclesthatlastsforabout5minutes.Onlymildmuscarinic毒覃堿effects(pallor,nausea,vomiting,bowel,activation,sweating,salivation)5.Neostigmine新斯的明test:42

Differentialdiagnosis1.Lambert-Eatomsyndrome肌無力綜合癥Torepetitivesupramaximalstimulation(at10Hz)ofitsmotornerve,withcancerusually2.Oculardystrophies眼肌型肌營養(yǎng)不良

prognosticworse,nofluctuatingweakness,Tensilonandfatigabilitytest(-)3.Polymyositis多發(fā)性肌炎

Itisoftenassociatedwithmusclepain,nofluctuatingweakness.theserumCKisgenerallyelevated.Differentialdiagnosis43

E.

Treatment1.Anticholinesterasedrugs抗膽堿酯酶藥物AChD:

Pyridostigminebromide吡啶斯的明—atdosesindividuallydeterminedbutusuallybetween60mg~120mg,tid~qid.Smalldosesofatropinemayattenuatesideeffectssuchasbowelhypermotilityorhypersalivation.Mysuranandneostigminebromidehasnotbeusednow.E.Treatment442.Corticosteroids:

Corticosteroids

providethemainstayofimmuno-suppressivetreatment.Theysucceedin70%ofpatients,butmustbeincreasedslowly.Methylprednisolone-1000mg,iv.qd.3~5d;Prednisolone-1~2mg/kg(60~80mg),po.qd/morning;2weeks,thengraduallyreduced,sustainedover1year.Azathioprine硫唑嘌呤:2~3mg/kg/d.CyclosporineA環(huán)孢素A:6mg.kg.dx12mons2.Corticosteroids:453.Plasmapheresis:

Itissometimesusedespeciallyduringanacuteexacerbationorwhenthereisrespiratoryinvolvement.4.Thymectomy:Itsbeneficialeffect70%forthymomaorhyperplasicthymus,maynotbeevidentimmediately.5.Medications

ThatimpairneuromusculartransmissionshouldbeavoidedsuchasQuinine,Aminoglycosides氨基糖甙類，Phenobarbital苯巴比妥,Diazepam安定,andsoon.3.Plasmapheresis:46

F.

CrisisCrisis危象—ArapiddeteriorationoftheMGitself,canbringtherespiratoryfailure呼吸衰竭

andseverequadriparesis四肢癱瘓.

1.Myastheniccrisis肌無力危象:Itisamostcommontype,anticholinesterasedrugs(AChD)arenotenough.WehavetoincreasetheAChDdoseiftheedrophonium騰喜龍testispositive.F.Crisis472.Cholinergiccrisis膽堿能危象:ItisoftenexcessoftheAChD.Overmedicationcanledtoincreasedweakness.StoppingAChDimmediately,withthemechanicalventilation機械通氣,thengraduallymodifythedosesofAChDwhenallAChDclearoutfromthebody.3.Brittlecrisis反拗性危象:TheresponsetoAChDispoor,ofunknowncause.StoppingAChDimmediately,withthemechanicalventilation,thengraduallymodifythedosesofAChDifresponsewelltoAChDincourseoftime.2.Cholinergiccrisis膽堿能危象:I48

G.Prognosis

Mostpatientscanbemanagedsuccessfullywithdrugtre