顱內(nèi)未破裂動(dòng)脈瘤術(shù)后癲癇發(fā)作的危險(xiǎn)因素分析

夏鵬飛 王偉 鄒亮 李雙 崔朋玉 孫世昊

顱內(nèi)未破裂動(dòng)脈瘤術(shù)后癲癇發(fā)作的危險(xiǎn)因素分析

夏鵬飛 王偉 鄒亮 李雙 崔朋玉 孫世昊

目的探討顱內(nèi)未破裂動(dòng)脈瘤（UIA）患者術(shù)后癲癇發(fā)作的危險(xiǎn)因素。方法回顧性分析189例UIA患者的臨床資料，并記錄術(shù)后12個(gè)月隨訪時(shí)改良Rankin量表（mRS）評(píng)分；采用logistic回歸分析UIA術(shù)后癲癇發(fā)作的危險(xiǎn)因素。結(jié)果189例UIA患者術(shù)后發(fā)生癲癇17例，術(shù)前發(fā)作癲癇、動(dòng)脈瘤最大直徑≥15mm是術(shù)后癲癇發(fā)作的危險(xiǎn)因素（OR=2.999、3.547，均P＜0.05）。結(jié)論術(shù)前發(fā)作癲癇、動(dòng)脈瘤最大直徑≥15mm與UIA術(shù)后癲癇發(fā)作有關(guān)。

顱內(nèi)未破裂動(dòng)脈瘤癲癇危險(xiǎn)因素

顱內(nèi)動(dòng)脈瘤是引發(fā)癲癇的常見病因[1]。中國專家共識(shí)中明確提出，急性期顱內(nèi)壓升高、血性物質(zhì)刺激是顱內(nèi)破裂動(dòng)脈瘤造成癲癇的危險(xiǎn)因素[2]；而顱內(nèi)未破裂動(dòng)脈瘤（unrupture intracranial aneurysms，UIA）患者術(shù)后癲癇發(fā)作的危險(xiǎn)因素尚未提出，而流行病學(xué)調(diào)查顯示成年人UIA患病率為2%～6%[3]。本研究回顧性分析189例顯微鏡下動(dòng)脈瘤夾閉術(shù)后UIA患者的臨床資料，以探討UIA術(shù)后癲癇發(fā)作的危險(xiǎn)因素，為預(yù)防與治療UIA術(shù)后癲癇發(fā)作提供依據(jù)。

1 對(duì)象和方法

1.1 對(duì)象選擇2010年1月至2015年1月收治入院的189例UIA患者臨床資料（內(nèi)蒙古民族大學(xué)附屬醫(yī)院82例；內(nèi)蒙古民族大學(xué)第二臨床醫(yī)學(xué)院107例）。其中男90例，女99例；年齡32～71（47.6±8.2）歲。既往有過顱內(nèi)其他部位手術(shù)史63例，發(fā)生過腦卒中、顱腦損傷、顱內(nèi)腫瘤80例，發(fā)生過顱內(nèi)破裂動(dòng)脈瘤57例。189例UIA患者中，動(dòng)脈瘤最大直徑≥15mm者64例，大腦中動(dòng)脈瘤61例，多個(gè)動(dòng)脈瘤87例，術(shù)后12個(gè)月改良Rankin量表（mRS）評(píng)分＞1分147例。

1.2 方法

1.2.1 診斷標(biāo)準(zhǔn)（1）UIA：經(jīng)計(jì)算機(jī)斷層掃描血管造影或核磁共振血管造影確診，若無法確診但疑為動(dòng)脈瘤的患者經(jīng)數(shù)字減影血管造影確診。（2）癲癇：經(jīng)臨床和腦電圖證實(shí)，且符合國際抗癲癇聯(lián)盟委員會(huì)修訂的癲癇診斷標(biāo)準(zhǔn)。

1.2.2 手術(shù)方法所有患者行全麻，在神經(jīng)導(dǎo)航下定位，采用翼點(diǎn)入路，在顯微鏡輔助下分離側(cè)裂，排放腦脊液，充分暴露動(dòng)脈瘤后夾閉。

1.3 統(tǒng)計(jì)學(xué)處理應(yīng)用SPSS 19.0統(tǒng)計(jì)軟件。計(jì)數(shù)資料用率表示，組間比較采用χ2檢驗(yàn)。對(duì)差異有統(tǒng)計(jì)學(xué)意義的臨床因素進(jìn)行l(wèi)ogistic回歸分析。癲癇累積發(fā)生率用Kaplan-Meier方法分析。P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 影響UIA患者術(shù)后癲癇發(fā)作的單因素分析經(jīng)單因素分析，發(fā)現(xiàn)術(shù)前發(fā)作癲癇、動(dòng)脈瘤最大直徑≥15mm、大腦中動(dòng)脈瘤均與UIA術(shù)后癲癇發(fā)作有關(guān)（均P＜0.05）；而性別，年齡，既往顱內(nèi)其他部位手術(shù)，發(fā)生過腦卒中、顱腦損傷、顱內(nèi)腫瘤，發(fā)生過顱內(nèi)破裂動(dòng)脈瘤，多個(gè)動(dòng)脈瘤，術(shù)后12個(gè)月mRS評(píng)分＞1分均與UIA術(shù)后癲癇發(fā)作無關(guān)（均P＞0.05），見表1。

表1 影響189例UIA患者顯微鏡下動(dòng)脈瘤夾閉術(shù)后癲癇發(fā)作的單因素分析結(jié)果[例（%）]

2.2 影響UIA患者術(shù)后癲癇發(fā)作的多因素分析將單因素分析結(jié)果P＜0.05的因素納入多因素logistic回歸分析，發(fā)現(xiàn)術(shù)前發(fā)作癲癇（OR=2.999，95%CI：1.003～8.968）、動(dòng)脈瘤最大直徑≥15mm（OR=3.547，95%CI：1.115～11.286）是影響UIA術(shù)后癲癇發(fā)作的危險(xiǎn)因素，見表2。

表2 影響UIA患者術(shù)后癲癇發(fā)作的多因素logistic回歸分析結(jié)果

2.3 術(shù)后隨訪情況術(shù)后隨訪12個(gè)月，術(shù)前無發(fā)作癲癇病史、動(dòng)脈瘤最大直徑＜15mm、非大腦中動(dòng)脈瘤的患者癲癇發(fā)生率為3.80%（4/105），術(shù)前發(fā)作癲癇、動(dòng)脈瘤最大直徑≥15mm、大腦中動(dòng)脈瘤的患者癲癇發(fā)生率為36.0%（9/25），兩者比較差異有統(tǒng)計(jì)學(xué)意義（χ2=23.25，P＜0.05）。Kaplan-Meier生存分析結(jié)果見圖1（插頁）。

3 討論

癲癇是顱內(nèi)動(dòng)脈瘤術(shù)后的嚴(yán)重并發(fā)癥，有文獻(xiàn)報(bào)道其發(fā)病率為0%～15.7%[4-6]。Hoh等[7]調(diào)查發(fā)現(xiàn)美國UIA住院患者術(shù)后第1次癲癇發(fā)生率為9.2%。本組189例UIA患者術(shù)后癲癇發(fā)作率為9.0%，以全身性發(fā)作為主（17例）；這與Lai等[8]研究結(jié)果相似。顱內(nèi)動(dòng)脈瘤術(shù)后癲癇發(fā)作的主要風(fēng)險(xiǎn)是術(shù)后出血[9]、醫(yī)院缺乏動(dòng)脈瘤手術(shù)經(jīng)驗(yàn)[10]；也有學(xué)者認(rèn)為UIA術(shù)后癲癇發(fā)作與動(dòng)脈瘤個(gè)數(shù)、部位及修復(fù)程度等有關(guān)[11]。O’Dnnell等[12]報(bào)道726例UIA患者中，術(shù)前發(fā)作癲癇、大腦中動(dòng)脈瘤、動(dòng)脈瘤直徑≥15mm易引發(fā)術(shù)后癲癇；這與本研究單因素分析結(jié)果一致。進(jìn)一步作多因素logistic回歸分析，發(fā)現(xiàn)術(shù)前發(fā)作癲癇、動(dòng)脈瘤最大直徑≥15mm是UIA術(shù)后癲癇發(fā)作的危險(xiǎn)因素。

UIA術(shù)后癲癇發(fā)作是否影響患者預(yù)后，目前尚存爭議[13]。Hadera等[14]認(rèn)為UIA術(shù)后急性期內(nèi)神經(jīng)膠質(zhì)細(xì)胞過多易誘發(fā)癲癇，降低患者的生活質(zhì)量。英國司法部限制行開顱手術(shù)的動(dòng)脈瘤患者術(shù)后3個(gè)月內(nèi)不能駕駛機(jī)動(dòng)車[15]。因此早期診斷和預(yù)防癲癇是提高UIA術(shù)后生活質(zhì)量的必要條件。然而，掌握UIA術(shù)后癲癇發(fā)作的危險(xiǎn)因素，有助于控制相關(guān)因素，預(yù)防癲癇發(fā)作；或提高癲癇診斷率，盡早給予治療。建議進(jìn)一步作多中心、大樣本的臨床試驗(yàn)，以驗(yàn)證UIA術(shù)后癲癇的危險(xiǎn)因素。

[1] Sethi N K.Epilepsy after aneurysmal subarachnoid hemorrhage:A population-based,long-term follow-up study[J].Neurology,2015,84(22):2229.

[2] 張暉,劉國榮,龐江霞,等.腦卒中后癲癇發(fā)作的臨床特點(diǎn)和視頻腦電圖分析[J].中華老年心腦血管病雜志,2012,14(10):1074-1076.

[3] Kang H G,Kim B J,Lee J,et al.Risk factors associated with the presence of unruptured intracranial aneurysms[J].Stroke,2015,46(11):3093-3098.

[4] Radovanovic I,Abou-Hamden A,Bacigaluppi S,et al.A safety,length of stay,and cost anaylsis of minimally invasive microsurgery for anterior circulation aneurysms[J].Acta Neurochirurgica,2014,156(3):493-503.

[5] Lai L T,Gragnaniello C,Morgan M K,et al.Outcomes for a case series of unruptured anterior communicating artery aneurysm surgery[J].Clin Neurosci,2013,20(12):1688-1692.

[6] Ha nggiD,Winkler P A,Steiger H,et al.Primary epileptogenic unruptured intracranial aneurysms:incidence and effect of treatment on epilepsy[J].Neurosurgery,2010,66(6):1161-1165.

[7] Hoh B L,Nathoo S,ChiYY,et al.Incidence of seizures or epilepsy after clipping or coiling of ruptured and unruptured cerebral aneurysmsinthenationwideinpatientsampledatabase:2002-2007[J].Neurosurgery,2011,69(3):644-650.

[8] LaiLT,O'DonnellJ,Morgan MK,et al.The risk of seizures during the in-hospital admission for surgical or endovascular treatment of unruptured intracranial aneurysms[J].Clin Neurosci,2013,20(11):1498-1502.

[9] Hart Y,Sneade M,Birks J,et al．Epilepsy after subarachnoid hemorrhage:the frequency of seizures after clip occlusion or eoil embolization of a ruptured cerebral aneurysm:results from the Intemational Subarachnoid Aneurysm Trial[J].J Neurosurg,2011,115(6):1159-1168.

[10] Aghakhani N,Vaz G,David P,et al.Surgical management of unruptured intracranial aneurysms that are inappropriate for endovascular treatment:Experience based on two academic centers[J].Neurosurgery,2008,62(6):1227-1234.

[11] Wong J M,Ziewacz J E,Ho A L,et al.Patterns in neurosurgical adverse events:open cerebrovascular neurosurgery[J].Neurosurg Focus,2012,33(5):E15.

[12] O'Donnell J M,Morgan M K,Bervini D,et al.The risk of seizure after surgery for unruptured intracranialaneurysms:A prospective cohort study[J].Neurosurgery,2016,79(2):222-230.

[13] Riordan K C,Wingerchuk D M,Wellik K E,et al.Anticonvulsant drug therapy after aneurysmal subarachnoid hemorrhage:A critically appraised topic[J].Neurologist,2010,16(6):397-399.

[14] Hadera MG,EloqayliH,Jaradat S,et al.Astrocyte-neuronalinteractions in epileptogenesis[J].Neurosci Res,2015,93(7):1157-1164.

[15] Office of the Superintendent of Motor Vehicles.British columbria driver fitness handbook for medicalprofessionals[Z].2014.

Risk factors of epilepsy after surgery for unruptured intracranial aneurysms

XIA Pengfei,WANG Wei,ZOU Liang,etal.
Department of Neurology,the Second Clinical Medical School of Inner Mongolia University for the Nationalities,Yakeshi 022150,China

Objective To analyze the risk factors of epilepsy after surgery for unruptured intracranial aneurysms(UIA).Methods The clinical data of 189 patients with UIA treated by microsurgical clipping were analyzed retrospectively.The modified Rankin scale(mRS)was assessed at 12 months after the operation.Logistic regression analysis was used to analyze the risk factors of epilepsy after surgery for UIA.Results In 189 patients with UIA,epilepsy developed in 17 cases after surgery.Logistic regression analysis showed that the history of preoperative seizures(OR=2.999,95%∶1.003-8.968,P＜0.049)and maximum size of aneurysm≥15mm(OR=3.547,95%CI:1.115-11.286,P＜0.05)were independent risk factors of the occurrence of epilepsy.Conclusion The history of preoperative seizures and maximum size of aneurysm≥15mm are associated with epilepsy in patients with UIA after surgery.

Unruptured in tracranialaneurysms Epilepsy Risk factors

10.12056/j.issn.1006-2785.2017.39.23.2016-2123

022150呼倫貝爾，內(nèi)蒙古民族大學(xué)第二臨床醫(yī)學(xué)院（夏鵬飛、王偉、鄒亮、李雙，夏鵬飛系內(nèi)蒙古民族大學(xué)研究生）；內(nèi)蒙古民族大學(xué)附屬醫(yī)院（崔朋玉、孫世昊）

王偉，E-mail：938729899@qq.com

2016-12-17）

（本文編輯：陳丹）