神經(jīng)肌肉接頭疾病分型與診斷

重癥肌無力

(myastheniagravis,MG)教學(xué)目的掌握重癥肌無力的臨床特點熟悉MG的臨床分型掌握MG的診斷標準熟悉MG的治療措施DiseasesofNeuromuscularJunction定義：指一組神經(jīng)-肌肉接頭處傳遞功能障礙疾病。特征表現(xiàn)是波動性無力和肌肉易疲勞。本組疾病包括：重癥肌無力：體內(nèi)產(chǎn)生AChR自身抗體使AChR受損或減少有機磷中毒：膽堿酯酶活力受抑制，使ACh作用過度延長而產(chǎn)生去極化傳遞障礙

DiseasesofNeuromuscularJunction本組疾病包括：

Lambert-Eaton綜合征和氨基甙類藥物：使ACh合成和釋放減少肉毒桿菌中毒和高鎂血癥：阻礙鈣離子進入神經(jīng)末梢美洲箭毒素與AChR結(jié)合，阻斷了AChAChR結(jié)合DiseasesofNeuromuscularJunctionMyastheniaGravis定義：乙酰膽堿受體抗體介導(dǎo)的、細胞免疫依賴的及補體參與的一種神經(jīng)-肌肉接頭處傳遞障礙的自身免疫性疾病，主要累及NMJ突觸后膜上乙酰膽堿受體臨床特征：部分或全身骨骼肌易于疲勞；癥狀的波動性Myastheniagravisischaracterizedbyfluctuatingweaknessandeasyfatigabilityofvoluntarymuscles.Etiology實驗性自身免疫性重癥肌無力(experimentalauto-immunemyastheniagravis,EAMG)動物模型的建立，在動物血清中檢測到AChR(acetylcholinereceptor)胸腺的異常，MG合并胸腺瘤(thymictumor)及胸腺肥大，發(fā)現(xiàn)肌樣細胞(myoidcell)，具有橫紋并載有AChRMG患者常合并甲亢(thyrotoxicosis)，SLE(systemiclupuserythematosus)，類風(fēng)濕性關(guān)節(jié)炎(rheumatoidarthritis)等自身免疫性疾病MG患者HLA基因型(B8,DR3,DQB1)頻率較高病理70%患者胸腺肥大10%患者有胸腺瘤，好發(fā)于年齡較大者NMJ的病理改變：突觸后膜皺褶減少，突觸間隙加寬，皺褶中有抗體和免疫復(fù)合物存在ClinicalfindingsMGcanoccuratanyage,andmorecommoninfemalesthanmales.MGisinsidiousandfollowsaslowlyprogressivecourse.Exacerbationmayoccurininfection,pregnancyorbeforemenses.Thereisapredilectionfortheexternalocularmusclesandcertainothercranialmuscles,includingthemasticatory,facial,pharyngeal,andlaryngealmuscles.Respiratoryandlimbmusclesmayalsobeaffected.Clinicalfindings

Presentation:ptosis,diplopia,difficultyinchewingorswallowing,nasalspeech,respiratorydifficulties,orweaknessofthelimbs.Clinicalfindings

Myastheniagravisischaracterizedbyfluctuatingweaknessandeasyfatigabilityofvoluntarymuscles.Thesymptomsoftenfluctuateinintensityduringtheday,andthisdiurnalvariationissuperimposedonlonger-termspontaneousrelapsesandremissionsthatmaylastforweeks.NeurologicalexaminationTheweaknessdoesnotconformtothedistributionofanysinglenerve,root,orlevelofthecentralnervoussystem.The

extraocularmusclesareofteninvolved,leadingtoasymmetricocularpalsiesandptosis.Pupillaryresponsesarenotaffected.NeurologicalexaminationSustainedactivityofaffectedmusclesleadstotemporarilyincreasedweakness.Sustainedupgazefor2minutescanleadtoincreasedptosis,withpowerintheaffectedmusclesimprovingafterabriefrest.Inadvancedcases,theremaybesomemildatrophyofaffectedmuscles.Sensationisnormal,andthereareusuallynoreflexchanges.Myastheniagraviscrisis危象：急驟發(fā)生延髓支配肌肉及呼吸肌無力，以致不能維持換氣功能classification:

肌無力危象(myastheniccrisis)，膽堿能危象(cholinergiccrisis)，反拗性危象(brittlecrisis)ClassificationofMGOssermanclassificationⅠ型：眼肌型ⅡA型：輕度全身型

ⅡB型：中度全身型Ⅲ型：重癥激進型，胸腺瘤高發(fā)Ⅳ型：遲發(fā)重癥型，由ⅡA及ⅡB

轉(zhuǎn)化來Ⅴ型：伴肌萎縮型ClassificationofMG其他分型青少年型和成人型新生兒MG：母親為MG患者，生后48小時內(nèi)出現(xiàn)癥狀先天性MG：常隱遺傳，屬于離子通道病。AChR基因突變，嬰兒期出現(xiàn)癥狀藥源性MG：青霉胺實驗室檢查(laboratoryexamination)X-raysandCTscansofthechest:thymomaelectrophysiology:decrementalresponseofmusclestorepetitivestimulation(at2or3Hz)ofmotornerve,butnormalfindingsdonotexcludethediagnosis.Serumacetylcholinereceptorantibodylevelsareincreasedin80~90%ofpatientswithgeneralizedMG.Diagnosis病變主要侵犯骨骼肌，癥狀的波動性疲勞試驗(Jollytest)高滴度的AChR-Ab重復(fù)頻率刺激檢查抗膽堿酯酶藥物實驗：新斯的明實驗(neostigminetest)，騰喜龍實驗(Tensilontest)Differentialdiagnosis伴有口咽、肢體肌無力的疾病，如進行性肌營養(yǎng)不良(progressivemusculardystrophy,PMD)，肌萎縮性側(cè)索硬化(amyotrophiclateralsclerosis,ALS)，神經(jīng)癥(neurosis)等引起的肌無力Lambert-EatonSyndrome肉毒桿菌中毒(Botulism)、有機磷農(nóng)藥中毒(organophosphorousinsecticidestoxicosis)、蛇咬傷(venomoussnakebite)等引起的肌無力Treatment抗膽堿酯酶藥物(anticholinesterasedrugs)：吡啶斯的明(pyridostigmine)病因治療腎上腺皮質(zhì)類固醇類(corticosteroids)：適應(yīng)癥：抗膽堿酯酶藥不足以控制癥狀的輕癥者所有年齡的中至重度MG病人胸腺切除術(shù)的術(shù)前處理胸腺切除術(shù)后的過度期胸腺切除無效者療法有三種，大劑量遞減隔日療法，小劑量遞增隔日療法，大劑量沖擊療法

Treatment病因治療免疫抑制劑(immunodepressive)：激素治療半年內(nèi)無效。環(huán)孢霉素A：100~300mg/次，2~3次/周。血漿置換(plasmapheresis)：用于胸腺切除的術(shù)前處理，或MG危象。免疫球蛋白(intravenousimmunoglobulins)：用于MG危象。0.4g/(kg·d)靜脈滴注，連用5天。胸腺切除(thymectomy)：適用于全身型MG。危象的處理立即氣管切開，人工呼吸器輔助呼吸鑒別危象的類型，采取相應(yīng)的措施甲基強的松龍沖擊療法。也可應(yīng)用環(huán)磷酰胺或血漿置換防止肺部并發(fā)癥保證營養(yǎng)，防止水電解質(zhì)和酸堿平衡紊亂危象的處理肌無力危象：抗膽堿酯酶藥量不足引起，注射騰喜龍后癥狀減輕。常見于有肺部感染和胸腺切除術(shù)后的患者停用抗膽堿酯酶藥，使運動終板得到休息，增加AChR對ACh的敏感性維持呼吸功能，預(yù)防及