李然,景筠
眼肌麻痹是神經(jīng)內(nèi)科、眼科及神經(jīng)眼科的常見(jiàn)癥狀和體征,與血管病相關(guān)性眼肌麻痹按照病變部位可分為核上型、核型、核間型和周圍神經(jīng)型眼肌麻痹[1-2]。本文對(duì)各種血管病相關(guān)眼肌麻痹的臨床特點(diǎn)和研究進(jìn)展進(jìn)行綜述。
核上性眼肌麻痹又稱為中樞性眼肌麻痹。大腦皮層水平同向運(yùn)動(dòng)中樞受累可導(dǎo)致側(cè)向凝視麻痹,表現(xiàn)為無(wú)復(fù)視、雙眼同時(shí)受累、癱瘓眼肌反射性運(yùn)動(dòng)保存等3個(gè)特點(diǎn),多見(jiàn)于腦出血、腦梗死和癲癇患者[3]。眼球垂直同向運(yùn)動(dòng)的皮質(zhì)下中樞損害可導(dǎo)致垂直凝視麻痹,以帕里諾綜合征(Parinaud syndrome)相對(duì)常見(jiàn)。帕里諾綜合征由中腦頂蓋前區(qū)病變引起,表現(xiàn)為上視不能、退縮性眼震、瞳孔散大、輻輳痙攣等,玩偶頭動(dòng)作可陽(yáng)性,常見(jiàn)于卒中、腦水腫、室管膜瘤、松果體囊腫或腫瘤、脫髓鞘病、腦炎及顱腦外傷等[4]。
核間性眼肌麻痹是腦橋旁正中網(wǎng)狀結(jié)構(gòu)(paramedian pontine reticular formation,PPRF)與其聯(lián)系纖維內(nèi)側(cè)縱束(medial longitudinal fasciculus,MLF)病變所致,可分為前核間性眼肌麻痹、后核間性眼肌麻痹和一個(gè)半綜合征[5]。前核間性眼肌麻痹是PPRF至動(dòng)眼神經(jīng)內(nèi)直肌核的MLF上行纖維受損,表現(xiàn)為患者眼球不能內(nèi)收,對(duì)側(cè)眼球外展時(shí)可見(jiàn)水平性眼震。后核間性眼肌麻痹是PPRF至外展神經(jīng)核的MLF下行纖維受損,表現(xiàn)為患者眼球不能外展,對(duì)側(cè)眼球可以內(nèi)收。一個(gè)半綜合征是一側(cè)腦橋被蓋部旁PPRF和對(duì)側(cè)交叉過(guò)來(lái)支配同側(cè)動(dòng)眼神經(jīng)核的MLF受損所致,表現(xiàn)為患者眼球既不能內(nèi)收,也不能外展,對(duì)側(cè)眼球不能內(nèi)收,對(duì)側(cè)眼外展時(shí)可見(jiàn)水平性眼震[6]。核間性眼肌麻痹病因包括腦血管病、脫髓鞘病、感染、外傷、腫瘤、Arnold-Chiari畸形、橄欖體腦橋小腦萎縮等[7]。
腦橋背側(cè)中央部由許多小動(dòng)脈供應(yīng),如基底動(dòng)脈旁正中支、短旋支、長(zhǎng)旋支,供應(yīng)此處的小動(dòng)脈閉塞可產(chǎn)生單側(cè)內(nèi)側(cè)縱束綜合征。一項(xiàng)關(guān)于核間性眼肌麻痹的大樣本病例研究顯示,38%的核間性眼肌麻痹由腦梗死所致,87%為單側(cè)受累,而核間性眼肌麻痹可以是腦干梗死的唯一或主要癥狀[8-9]。此外,還有關(guān)于基底動(dòng)脈尖動(dòng)脈瘤導(dǎo)致前核間性眼肌麻痹的報(bào)道,可能與動(dòng)脈瘤膨脹導(dǎo)致內(nèi)側(cè)縱束受壓有關(guān)[10]。
核性眼肌麻痹病因以腦干梗死、多發(fā)性硬化、腫瘤等多見(jiàn)。有報(bào)道顯示,腦干梗死以核性動(dòng)眼神經(jīng)麻痹最常見(jiàn)(56.3%)[11]。支配眼球運(yùn)動(dòng)的神經(jīng)核主要由基底動(dòng)脈的深穿支供血,任何一條供應(yīng)血管的血栓形成或栓子阻塞,都會(huì)累及相應(yīng)的神經(jīng)核,而動(dòng)眼神經(jīng)的核團(tuán)分布相對(duì)彌散,故微小栓子可以僅影響動(dòng)眼神經(jīng)的一個(gè)亞核,表現(xiàn)不全動(dòng)眼神經(jīng)麻痹[12]。腦干不同部位病變可產(chǎn)生不同綜合征,如延髓背外側(cè)綜合征(Wallenberg syndrome)、腦橋腹外側(cè)綜合征(Millard-Gubler syndrome)、腦橋被蓋下部綜合征、大腦腳綜合征(Weber syndrome)、紅核綜合征(Benedik t syndrome)等。
周圍性眼肌麻痹稱為核下性眼肌麻痹,是眼球運(yùn)動(dòng)神經(jīng)損害所致。周圍型眼肌麻痹原因眾多而復(fù)雜,血管病相關(guān)性周圍型眼肌麻痹常見(jiàn)于如下疾病。
4.1 糖尿病性眼肌麻痹 糖尿病性眼肌麻痹的發(fā)病率約為0.32%~0.5%[13-16]。其多見(jiàn)于年齡較大、糖尿病病史較長(zhǎng)的患者,也有研究認(rèn)為其與糖尿病病程及其嚴(yán)重程度無(wú)關(guān)[16-17]。糖尿病性眼肌麻痹多累及動(dòng)眼神經(jīng)[15,18],但個(gè)別研究顯示外展神經(jīng)受累最常見(jiàn)[13]。
糖尿病性眼肌麻痹的病因考慮為與糖尿病特有的微血管病變導(dǎo)致神經(jīng)缺血缺氧以致變性,從而使該神經(jīng)所支配的肌肉功能障礙所致。高血糖使正常糖酵解途徑受阻,同時(shí)干擾肌醇磷脂代謝,影響細(xì)胞和酶的功能,導(dǎo)致毛細(xì)血管周細(xì)胞變性死亡,內(nèi)皮細(xì)胞增生,基底膜增厚,毛細(xì)血管閉塞[19]。糖尿病性眼肌麻痹臨床表現(xiàn)多為急性起病,上瞼下垂及復(fù)視,可伴有眼眶周圍疼痛,局部疼痛發(fā)生率可以高達(dá)62%,其發(fā)生機(jī)制可能是由于三叉神經(jīng)眼支在動(dòng)眼神經(jīng)和外展神經(jīng)有少量分布[18]。瞳孔受累程度較輕,多數(shù)瞳孔改變?cè)?.5~1.0 mm之間,這是因?yàn)樘悄虿⌒匝奂÷楸灾饕奂皠?dòng)眼神經(jīng)的中央部分,支配瞳孔的動(dòng)眼神經(jīng)副交感纖維行走于動(dòng)眼神經(jīng)上方周邊部,故缺血對(duì)其造成的影響較輕。該病可在幾周內(nèi)恢復(fù),可反復(fù)發(fā)作[20]。
4.2 動(dòng)脈瘤 累及動(dòng)眼神經(jīng)的動(dòng)脈瘤以中顱底動(dòng)脈瘤最多見(jiàn),好發(fā)于后交通動(dòng)脈起始部,眶內(nèi)段和管內(nèi)段眼動(dòng)脈動(dòng)脈瘤也會(huì)導(dǎo)致眼肌麻痹[21]。后交通動(dòng)脈硬化也會(huì)壓迫動(dòng)眼神經(jīng)導(dǎo)致完全性動(dòng)眼神經(jīng)麻痹[22]。動(dòng)脈瘤累及動(dòng)眼神經(jīng)多表現(xiàn)為突然起病,單側(cè)完全性動(dòng)眼神經(jīng)麻痹,可伴有同側(cè)頭痛,特別是內(nèi)眥部位疼痛。絕大多數(shù)頸內(nèi)動(dòng)脈-后交通動(dòng)脈瘤是向外,后或向下生長(zhǎng),支配瞳孔的動(dòng)眼神經(jīng)副交感纖維位于動(dòng)眼神經(jīng)背內(nèi)側(cè)淺層,易受侵犯。如果單側(cè)動(dòng)眼神經(jīng)麻痹突然發(fā)生、反復(fù)發(fā)作,伴內(nèi)眥部疼痛,且早期就出現(xiàn)瞳孔散大,應(yīng)高度懷疑顱內(nèi)動(dòng)脈瘤[23]。值得注意的是,磁共振血管成像(magnetic resonance angiography,MRA)、計(jì)算機(jī)斷層掃描血管造影(computed tomography angiography,CTA)、數(shù)字減影血管造影(digital subraction angiography,DSA)陰性者不能完全排除動(dòng)脈瘤可能,因動(dòng)脈瘤破裂、瘤體縮小、閉塞也可致MRA、DSA陰性。目前關(guān)于動(dòng)脈瘤的手術(shù)治療策略還無(wú)統(tǒng)一定論,有研究采用結(jié)扎方法治療巨大頸內(nèi)動(dòng)脈動(dòng)脈瘤取得了不錯(cuò)效果,高達(dá)87.1%患者眼肌麻痹癥狀改善[24]。
4.3 頸內(nèi)動(dòng)脈海綿竇瘺 頸內(nèi)動(dòng)脈海綿竇瘺(carotid-cavernous fistulas,CCFs)按照病因分為外傷性和自發(fā)性CCFs[25]。外傷性CCFs是最常見(jiàn)的類型,約占75%,多見(jiàn)于青年人;自發(fā)性CCFs多見(jiàn)于老年女性患者[26-27]。自發(fā)性CCFs多與破裂的動(dòng)脈瘤、動(dòng)脈粥樣硬化、糖尿病及某些遺傳性疾病有關(guān)[28]。臨床表現(xiàn)為眼肌麻痹、突眼、結(jié)膜水腫、眼壓增高,前額聽(tīng)診可聞及雜音。對(duì)疑似CCFs需首先進(jìn)行非侵入性檢查,如計(jì)算機(jī)斷層掃描(computed tomography,CT)、磁共振血管成像(magnetic resonance imaging,MRI)、CTA或MRA,但非侵入性檢查正常不能除外CCFs;對(duì)高度懷疑CCFs或影像檢查與CCFs的表現(xiàn)一致,則行DSA檢查,DSA是診斷CCFs的金標(biāo)準(zhǔn)[25]。CCFs的一線治療方案為血管內(nèi)介入治療[29]。顱神經(jīng)麻痹通常在治療后數(shù)周恢復(fù)[30-31]。
4.4 垂體卒中 垂體卒中是一種以頭痛、視力喪失伴蝶鞍內(nèi)出血或缺血改變的臨床綜合征,多發(fā)生于垂體腫瘤,以垂體腺瘤出血最常見(jiàn),而垂體梗死或壞死較少見(jiàn)[32]。眼肌麻痹在垂體腫瘤患者中的發(fā)病率為1.6%~17%,臨床表現(xiàn)為頭痛、眼肌麻痹、視力下降、惡心、嘔吐等,其中最常見(jiàn)的癥狀為頭痛[33-36]。眼肌麻痹最常累及動(dòng)眼神經(jīng),其次是外展神經(jīng),極少累及滑車神經(jīng)[37-38]。垂體出血與梗死病程不同,垂體出血癥狀持續(xù)時(shí)間短,但容易出現(xiàn)意識(shí)喪失,且視力受損嚴(yán)重[39]。垂體卒中最常用的檢查方法是顱腦MRI,敏感性可達(dá)88%~90%[40]。治療方法主要為經(jīng)蝶骨減壓手術(shù),可較快改善癥狀[41]。
4.5 海綿竇血栓形成 海綿竇血栓形成是一種少見(jiàn)的致死性疾病,病因包括感染性因素和非感染性因素,以感染性因素最常見(jiàn)。感染性海綿竇血栓形成常由面部、眼眶、鼻竇、耳部、牙齒、皮膚等部位感染導(dǎo)致,其中鼻竇炎是感染性海綿竇血栓形成最常見(jiàn)的原因[42-44]。研究顯示,感染性海綿竇血栓形成最常見(jiàn)的致病菌為金黃色葡萄球菌,可占到70%左右,此外,鏈球菌、梅毒、獲得性免疫缺陷綜合征、真菌也是致病原因[42-45]。該病急性起病,臨床表現(xiàn)主要為發(fā)熱、頭痛、眼肌麻痹、突眼、結(jié)膜水腫、視盤水腫,一般發(fā)病初期病變?cè)谝粋?cè),但數(shù)日后可擴(kuò)展到對(duì)側(cè)[44]。海綿竇血栓形成治療主要是抗感染治療,同時(shí)手術(shù)去除感染灶。
4.6 眼肌麻痹性偏頭痛 國(guó)際頭痛協(xié)會(huì)將眼肌麻痹性偏頭痛定義為發(fā)作性偏頭痛樣頭痛,伴一條或多條眼球運(yùn)動(dòng)神經(jīng)麻痹,除了受累神經(jīng)MRI異常改變外,顱內(nèi)未見(jiàn)明顯病灶,往往兒童期或嬰兒期起病,也可在成年期首次發(fā)病[46]。通常認(rèn)為,動(dòng)眼神經(jīng)受累最常見(jiàn),約占55%,外展神經(jīng)受累不常見(jiàn),滑車神經(jīng)受累罕見(jiàn),但也有研究顯示,56.5%的患者以外展神經(jīng)受累起病[47-50]。眼肌麻痹性偏頭痛早期瞳孔多不受累,后期瞳孔對(duì)光反射及調(diào)節(jié)反射可受累[46]。關(guān)于眼肌麻痹性偏頭痛的發(fā)病機(jī)制目前還不清楚,病毒感染、眼球運(yùn)動(dòng)神經(jīng)脫髓鞘都曾被認(rèn)為是導(dǎo)致偏頭痛的發(fā)病機(jī)制[51-52]。還有研究認(rèn)為,頸動(dòng)脈及基底動(dòng)脈管壁腫脹,壓迫供應(yīng)顱神經(jīng)的小血管,導(dǎo)致缺血進(jìn)而引起發(fā)病[53]。另外,炎性過(guò)程影響混雜于支配眼球運(yùn)動(dòng)神經(jīng)中的三叉神經(jīng)感覺(jué)纖維,也被認(rèn)為可能觸發(fā)偏頭痛發(fā)作[54]。但有觀點(diǎn)認(rèn)為,偏頭痛發(fā)作時(shí)血管痙攣導(dǎo)致可逆性血-神經(jīng)屏障功能障礙是其發(fā)病的機(jī)制[55]。眼肌麻痹性偏頭痛是一種自限性疾病,可自發(fā)緩解,但也可采用糖皮質(zhì)激素治療,能較快緩解癥狀[56]。
綜上所述,對(duì)于擬診為血管病相關(guān)性眼肌麻痹的患者,應(yīng)仔細(xì)詢問(wèn)病史,認(rèn)真查體,恰當(dāng)應(yīng)用影像學(xué)檢查,以免誤診、延誤治療。
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