本文關(guān)鍵詞： 局灶性皮層發(fā)育不良 臨床特征 病理分類 彌散張量成像 哺乳動物雷帕霉素靶蛋白　出處：《河北醫(yī)科大學(xué)》2014年博士論文　論文類型：學(xué)位論文

【摘要】：癲癇是常見的中樞神經(jīng)系統(tǒng)慢性疾病，我國大約有1000萬癲癇患者，每年的新發(fā)病例約40萬左右。在眾多的癲癇患者中，約有30%的患者發(fā)作得不到有效控制，最終發(fā)展成為難治性癲癇。局灶性腦皮層發(fā)育不良(Focal cortical dysplasia, FCD)是皮質(zhì)發(fā)育畸形的一種類型，是難治性癲癇的重要原因，經(jīng)手術(shù)治療的75%以上的兒童癲癇和約20%的成人癲癇存在FCD，約50%的癲癇患者是因各種不同類型的FCD所引起。自從發(fā)現(xiàn)以來，F(xiàn)CD這個(gè)定義在神經(jīng)解剖學(xué)、病理學(xué)和影像學(xué)等各個(gè)領(lǐng)域當(dāng)中被廣為應(yīng)用。 FCD包括一系列的病理現(xiàn)象，患者病理現(xiàn)象存在差異，臨床表現(xiàn)也不同，研究者一直試圖對其進(jìn)行分類，使研究更加標(biāo)準(zhǔn)化，根據(jù)不同的應(yīng)用范圍和評價(jià)方法制定了各種不同的分類方法。2004年P(guān)almini根據(jù)病理學(xué)表現(xiàn)是否包括異形細(xì)胞將FCD分為I型和II型，，這種分類方法在臨床上使用最廣泛，但也存在缺陷。2011年國際抗癲癇聯(lián)盟(InternationalLeague Against Epilepsy，ILAE)在Palmini分類基礎(chǔ)上進(jìn)行了修改，增加了結(jié)合型FCD分類，將海馬硬化、癲癇相關(guān)性腫瘤、血管畸形相鄰的FCD命名為結(jié)合型FCD。這樣FCD分為單純型FCD和結(jié)合型FCD，單純型FCD包括I型和II型，結(jié)合型FCD為III型。 對于2011年ILAE新分類下的FCD的研究很少，尤其是新的病理亞型結(jié)合型FCD。大約50%FCD發(fā)生在顳葉，本研究根據(jù)2011年ILAE分類對顳葉FCD不同病理亞型的臨床特征、手術(shù)預(yù)后、影像學(xué)表現(xiàn)、超微結(jié)構(gòu)及雷帕霉素受體表達(dá)進(jìn)行分析。第一部分人腦顳葉局灶性皮層發(fā)育不良不同亞型臨床特征分析 目的：比較2011年ILAE分類下顳葉FCD不同病理亞型的臨床特征。 方法：回顧分析2005年12月31日至2011年12月31日間在河北省人民醫(yī)院功能神經(jīng)外科進(jìn)行難治性顳葉癲癇手術(shù)患者共241例。對經(jīng)過顳葉癲癇手術(shù)患者按照2011年ILAE分類對FCD不同病理亞型進(jìn)行分類，并對不同病理亞型患者癲癇發(fā)作起始年齡、癲癇患病年限、手術(shù)年齡、發(fā)作頻率等臨床特征進(jìn)行分析，觀察不同病理亞型患者的臨床特征是否存在差異。 結(jié)果：92例患者符合FCD診斷，結(jié)合型FCD平均發(fā)作起始年齡為19.2歲，顯著高于單純型FCD，具有統(tǒng)計(jì)學(xué)意義。在結(jié)合型FCD患者中，F(xiàn)CDIIIc型平均發(fā)作起始年齡為30.7歲，顯著高于結(jié)合型FCD中的其它亞型。結(jié)合型FCD平均癲癇患病年限為7.8年，顯著短于單純型FCD。在結(jié)合型FCD的病理亞型中，F(xiàn)CD IIIb型平均癲癇患病年限為3.5年，F(xiàn)CD IIIc型平均癲癇患病年限為5.3年，顯著短于結(jié)合型FCD的其它病理亞型。FCD IIIc型平均手術(shù)年齡為35.8歲，明顯晚于結(jié)合型FCD的其它病理亞型。在結(jié)合型FCD的各個(gè)病理亞型中，18例FCD IIIa型患者有高熱驚厥病史，占44.6%，明顯多于結(jié)合型FCD的其它病理亞型。 結(jié)論：結(jié)合型FCD癲癇發(fā)作起始年齡晚，尤其是FCD IIIc型。結(jié)合型FCD手術(shù)前癲癇患病年限短，尤其是FCD IIIb型和FCD IIIc型。在結(jié)合型FCD患者中，F(xiàn)CD IIIc型平均手術(shù)年齡明顯晚于結(jié)合型FCD的其它病理亞型。FCD IIIa型患者更容易產(chǎn)生高熱驚厥。結(jié)合型FCD和單純型FCD的臨床特點(diǎn)可能存在差異。 第二部分人腦顳葉局灶性皮層發(fā)育不良不同亞型手術(shù)效果分析 目的：通過隨訪分析，比較2011年ILAE分類下顳葉FCD不同病理亞型的手術(shù)療效。 方法：對手術(shù)后92例符合FCD診斷患者進(jìn)行門診、電話、信件隨訪。對患者進(jìn)行隨訪后，根據(jù)患者癲癇發(fā)作情況按照Engel標(biāo)準(zhǔn)分級評價(jià)預(yù)后：I級，無影響功能的癲癇發(fā)作(除術(shù)后早期的癲癇發(fā)作)；II級，僅有稀少的影響功能的癲癇發(fā)作；III級，癲癇發(fā)作得到相當(dāng)?shù)母纳?發(fā)作頻率減少90%)；IV級，癲癇發(fā)作改善不明顯。(Engel I+II級)為手術(shù)效果良好，(EngelIII+IV級)為手術(shù)效果不佳。 結(jié)果：成功隨訪患者68例，術(shù)后療效按Engel標(biāo)準(zhǔn)評定，Engel I級35/68(51.4%)，II級18/68(26.5%)，III級10/68(14.7%)，IV級5/68(7.3%)；效果良好(Engel I+II級)為53/68(77.9%)，效果不佳(Engel III+IV級)為19/68(22.1%)。效果良好53例，其中單純型FCD17例(70.8%)，結(jié)合型FCD36例(81.8%)，手術(shù)效果不佳15例，其中單純型FCD7例(29.2%)，結(jié)合型FCD8例(19.2%)。單純型FCD的手術(shù)效果良好率低于結(jié)合型FCD(P0.05)。 結(jié)論：手術(shù)是治療癲癇相關(guān)性顳葉FCD的重要方式，有效性較高。結(jié)合型FCD的手術(shù)效果優(yōu)于單純型FCD。 第三部分人腦顳葉局灶性皮層發(fā)育不良磁共振彌散張量成像表現(xiàn)分析 目的：對顳葉不同病理亞型的FCD的彌散張量結(jié)果進(jìn)行比較分析，以探尋彌散張量成像中的不同參數(shù)在FCD不同病理亞型中的診斷價(jià)值。 方法：對58例資料完整患者的彌散張量成像檢查結(jié)果進(jìn)行分析，在軸位T1WI圖中，取顳葉海馬顯示最完整的層面，以及上下各1層面，于對顳葉固定位置放置興趣區(qū)(region of interest,ROI)，ROI范圍避免包含空腔結(jié)構(gòu)及海馬結(jié)構(gòu)。應(yīng)用軟件內(nèi)“對稱鏡像”的方法，在對側(cè)對應(yīng)部位選取ROI，ROI圓形直徑20mm，測定兩側(cè)ROI內(nèi)的ADC值和FA值，比較不同亞型的彌散張量成像表現(xiàn)差異及彌散張量成像中不同參數(shù)的診斷價(jià)值。 結(jié)果：在單純型FCD健側(cè)的ADC值平均為9.2±3.4(×10-10mm2/s)，患側(cè)的ADC值平均為12.2±5.6(×10-10mm2/s)，兩側(cè)的ADC值差值平均為3.0±1.2(×10-10mm2/s)。在結(jié)合型FCD健側(cè)的ADC值平均為8.7±3.1(×10-10mm2/s)，患側(cè)的ADC值平均為13.1±4.3(×10-10mm2/s)，兩側(cè)的ADC值差值平均為3.4±1.9(×10-10mm2/s)。在單純型FCD健側(cè)的FA值平均為0.245±0.068，患側(cè)的FA值平均為0.186±0.048，較健側(cè)明顯降低(P0.05)；兩側(cè)的FA值差值平均為0.062±0.021。在結(jié)合型FCD健側(cè)的FA值平均為0.241±0.052，患側(cè)的FA值平均為0.156±0.052，較健側(cè)明顯降低(P0.05)；兩側(cè)的FA值差值平均為0.091±0.033，較單純型FCD差異更明顯，具有統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論：DTI可以作為顳葉FCD的重要輔助檢查手段，在DTI參數(shù)ADC值和FA值中，F(xiàn)A值的變化更明顯。在FCD的不同病理亞型中，在單純型FCD和結(jié)合型FCD的患側(cè)FA值較健側(cè)相比均減少，結(jié)合型FCD減少的相對單純型FCD更加明顯。第四部分人腦顳葉癲癇相關(guān)性局灶性皮層發(fā)育不良超微結(jié)構(gòu)觀察分析 目的：通過對不同病理亞型FCD手術(shù)標(biāo)本進(jìn)行電鏡觀察，了解FCD超微結(jié)構(gòu)改變。 方法：對單純型FCD組，結(jié)合型FCD組和對照組的手術(shù)標(biāo)本分別進(jìn)行透射電鏡觀察，分析其超微結(jié)構(gòu)的改變。 結(jié)果：1.單純型FCD：神經(jīng)元形態(tài)異常，細(xì)胞器明顯減少或消失，部分神經(jīng)元中可見脂褐質(zhì)顆粒。線粒體嵴模糊，部分縮短或缺失�；|(zhì)顆粒減少或消失。線粒體增生肥大，線粒體膜破裂。內(nèi)質(zhì)網(wǎng)擴(kuò)張。膠質(zhì)細(xì)胞腫脹，有髓神經(jīng)纖維排列混亂，髓鞘細(xì)胞膜結(jié)構(gòu)稀疏。髓鞘內(nèi)外層輕度分離。2.結(jié)合型FCD：神經(jīng)元細(xì)胞質(zhì)水腫，細(xì)胞器數(shù)量明顯減少或消失，線粒體肥大和增生。粗面內(nèi)質(zhì)網(wǎng)輕度擴(kuò)張。有髓神經(jīng)髓鞘明顯增生增厚分層，有髓神經(jīng)髓鞘增生形狀極度不規(guī)則，無序排列，髓索變小，水腫，髓內(nèi)容物減少，髓鞘細(xì)胞膜結(jié)構(gòu)稀疏。髓鞘外層與內(nèi)層分離，線粒體與微絲微管數(shù)量減少。3.對照組：未發(fā)現(xiàn)明顯腦組織異常改變，神經(jīng)元形態(tài)規(guī)則，排列緊密，核仁清楚，染色質(zhì)排列均勻一致。 結(jié)論：FCD其本身也可能具有致癇性，具有癲癇發(fā)作的結(jié)構(gòu)基礎(chǔ)，結(jié)合型FCD中有髓神經(jīng)纖維受損更加明顯。 第五部分人腦顳葉局灶性皮層發(fā)育不良哺乳動物雷帕霉素靶蛋白表達(dá)分析 目的：通過檢測不同病理亞型FCD患者術(shù)后病理組織的mTOR信號通路的表達(dá)情況，觀察mTOR信號通路在FCD發(fā)病機(jī)制中的意義。 方法：應(yīng)用免疫組化、免疫熒光、Western-blot方法對不同病理亞型FCD患者的AKT、mTOR、p70S6K及p-AKT、p-mTOR、p-p70S6K進(jìn)行檢測，觀察mTOR信號通路在不同病理亞型FCD的表達(dá)。 結(jié)果：AKT、mTOR、p70S6K在正常腦組織及FCD I型組、FCD IIIa型組內(nèi)可見少量錐體神經(jīng)元胞體及星型膠質(zhì)細(xì)胞呈弱陽性表達(dá)。在FCDIIIa型中觀察到p-AKT、p-mTOR、p-p70S6K在少量錐體神經(jīng)元胞體弱陽性表達(dá)，與FCD I型及正常腦組織表達(dá)程度相似。在星型膠質(zhì)細(xì)胞p-AKT、p-mTOR、p-p70S6K呈明顯中度陽性表達(dá)，表達(dá)部位主要在胞漿，表達(dá)強(qiáng)度明顯強(qiáng)于FCD I型及正常腦組織。 結(jié)論：在FCD IIIa型中的星型膠質(zhì)細(xì)胞中p-AKT、p-mTOR、p-P70S6K的表達(dá)增加，提示PI3K-AKT-mTOR通路異常激活可能是參與FCD IIIa型的發(fā)病機(jī)制。在FCD IIIa型中的星型膠質(zhì)細(xì)胞中PI3K-AKT-mTOR通路異常激活，而FCD I型PI3K-AKT-mTOR信號通路沒有異常激活，F(xiàn)CDIIIa型和FCD I型在發(fā)病機(jī)制上可能存在差異。
[Abstract]:Epilepsy is a common chronic disease of the central nervous system, there are about 10 million patients with epilepsy in China, new cases each year is approximately 400 thousand. In many of the epilepsy patients, about 30% of the patients had no effective control, and eventually become the intractable epilepsy. Focal cortical dysplasia (Focal cortical dysplasia, FCD) is a type of malformations of cortical development, is an important cause of refractory epilepsy, by more than 75% adult epilepsy surgery in the treatment of children epilepsy and 20% in the presence of FCD, about 50% of patients with epilepsy is caused by a variety of different types of FCD. Since the discovery, the definition of FCD in neuroanatomy, pathology and imaging and other fields are widely used.
FCD includes a series of pathological phenomena, pathological phenomenon differences, clinical manifestations are different, researchers have been trying to classify it, make the research more standardized, according to the scope of application of different evaluation methods and develop a variety of different classification methods in.2004 Palmini according to whether the pathology including special cells will be divided into FCD I type and II type, this classification method widely used in clinic, but there are also shortcomings in.2011 International League Against Epilepsy (InternationalLeague Against, Epilepsy, ILAE) in Palmini on the basis of classification is modified and the increase of combination FCD classification, the hippocampal sclerosis, epilepsy associated tumors, vascular malformations of the adjacent FCD name with FCD. FCD divided into simple type FCD and type FCD with pure FCD, including I and II, with FCD as III.
Few studies on the new classification of 2011 under ILAE FCD, especially the pathological subtype of type FCD. with about 50%FCD in the temporal lobe, according to clinical features, the 2011 ILAE classification of temporal lobe FCD in different subtypes of surgical outcomes, imaging features, expression of hormone receptor and ultrastructure of ray Palmer mold. The first part is the analysis of human temporal lobe of focal cortical dysplasia in different subtypes of clinical features
Objective: To compare the clinical features of different pathological subtypes of FCD in the temporal lobes of the temporal lobes in the 2011 ILAE classification.
Methods: a retrospective analysis from December 31, 2005 to December 2011 31 during the day for patients with intractable temporal lobe epilepsy surgery 241 cases in Hebei People's Hospital Department of neurosurgery. The function of patients with temporal lobe epilepsy surgery according to the classification of ILAE in 2011 to FCD in different subtypes are classified, and the onset age of different subtypes of patients with epilepsy, epilepsy duration, surgical age the clinical features, seizure frequency were analyzed, to observe the clinical characteristics of patients with different pathological subtypes of whether there is a difference.
Results: 92 patients with the diagnosis of FCD, the average age at onset was 19.2 years with FCD, was significantly higher than that of pure FCD, with statistical significance. In combination with FCD, FCDIIIc average onset age was 30.7, significantly higher than with other subtypes of type FCD. According to FCD the average prevalence of epilepsy for 7.8 years, was significantly shorter than the pure FCD. in combination with FCD pathological subtype, FCD III B average prevalence of epilepsy for 3.5 years, FCD IIIc average prevalence of epilepsy for 5.3 years, significantly shorter than other pathological subtypes of.FCD type IIIc type FCD with the average operative age was 35.8 years. Combined type FCD was significantly later than other pathological subtypes. In combination with the FCD type of various pathological subtypes, 18 cases of FCD type IIIa patients with a history of febrile seizures, accounted for 44.6%, significantly more than the combined FCD of other pathological subtypes.
Conclusion: the combination of FCD type of seizure onset age of late, especially FCD IIIc. Combined FCD preoperative epilepsy in a short time, especially FCD III and FCD IIIc. B in combination with FCD, the average age of surgery for FCD type IIIc was significantly later than that in combination with other.FCD subtypes in patients with type IIIa type FCD more prone to convulsion. Combined with clinical features of FCD type and simple type FCD may differ.
Analysis of the effect of different subtypes of subtypes of focal temporal cortical dysplasia in the second parts of the human brain
Objective: To compare the curative effect of different pathological subtypes of FCD in the temporal lobes of the temporal lobe in 2011 through the follow-up analysis.
Methods: 92 cases after surgery with the diagnosis of FCD patients were outpatient, telephone, mail follow-up. The patients were followed up, according to the patient's seizures in accordance with the Engel standard to evaluate the prognosis grading: grade I, without affecting the function of the seizures (except for early postoperative seizure); grade II, influence function only rare seizures; epilepsy III level, improve considerably (90% reduction in seizure frequency); grade IV, seizures did not improve obviously. (Engel I+II) for the good operation effect, (EngelIII+IV) surgery was ineffective.
Results: 68 cases were successfully followed up patients, the postoperative curative effect according to Engel standard, Engel I 35/68 (51.4%), II 18/68 (26.5%), III 10/68 (14.7%), IV 5/68 (7.3%); good effect (Engel I+II) 53/68 (77.9%), poor effect (Engel III+IV 19/68) (22.1%). The effect is good in 53 cases, FCD17 cases of simple type (70.8%), FCD36 (81.8%) cases with surgery, 15 cases were ineffective, which FCD7 cases of simple type (29.2%), FCD8 (19.2%) cases with surgery. Effect of simple type FCD good rate is lower than the combination of type FCD (P0.05).
Conclusion: operation is an important way to treat temporal lobe FCD in epilepsy, and its effectiveness is higher. The effect of combined type FCD is better than that of simple FCD..
Analysis of magnetic resonance diffusion tensor imaging in the third part of the temporal lobe focal cortical dysplasia of the human brain
Objective: To compare and analyze the diffusion tensor results of FCD in different pathological subtypes of temporal lobe, so as to explore the diagnostic value of diffusion-tensor imaging in different pathological subtypes of FCD.
Methods: diffusion tensor imaging findings of 58 patients with complete data were analyzed in the axial T1WI diagram, the temporal hippocampus showed the most complete level, and the 1 level, in Duinie leaf fixed position of region of interest (region of, interest, ROI, ROI) to avoid including the cavity structure and scope the application software in the hippocampus. "Mirror symmetry" method, on the side of the site selection of ROI, ROI circular diameter 20mm, determination of ROI on both sides within the ADC and FA values, the diagnostic value of different parameters of the performance difference of diffusion tensor imaging and diffusion tensor imaging in different subtypes.
緇撴灉錛氬湪鍗曠函鍨婩CD鍋ヤ晶鐨凙DC鍊煎鉤鍧囦負(fù)9.2鹵3.4(脳10-10mm2/s),鎮(zhèn)ｄ晶鐨凙DC鍊煎鉤鍧囦負(fù)12.2鹵5.6(脳10-10mm2/s),涓や晶鐨凙DC鍊煎樊鍊煎鉤鍧囦負(fù)3.0鹵1.2(脳10-10mm2/s).鍦ㄧ粨鍚堝瀷FCD鍋ヤ晶鐨凙DC鍊煎鉤鍧囦負(fù)8.7鹵3.1(脳10-10mm2/s),鎮(zhèn)ｄ晶鐨凙DC鍊煎鉤鍧囦負(fù)13.1鹵4.3(脳10-10mm2/s),涓や晶鐨凙DC鍊煎樊鍊煎鉤鍧囦負(fù)3.4鹵1.9(脳10-10mm2/s).鍦ㄥ崟綰瀷FCD鍋ヤ晶鐨凢A鍊煎鉤鍧囦負(fù)0.245鹵0.068,鎮(zhèn)ｄ晶鐨凢A鍊煎鉤鍧囦負(fù)0.186鹵0.048,杈冨仴渚ф槑鏄鵑檷浣

本文編號：1507523