本文選題：藥物過度使用性頭痛　切入點：慢性偏頭痛　出處：《山東大學》2016年博士論文　論文類型：學位論文

【摘要】：第一部分慢性偏頭痛患者藥物過度使用的危險因素分析目的：探討慢性偏頭痛患者藥物過度使用的危險因素。方法：選取2013年1月到2015年12月山東大學附屬省立醫(yī)院頭痛門診的慢性偏頭痛患者157例,其中病例組為藥物過度使用性頭痛(MOH)患者63例,對照組為不存在MOH的患者94例。調(diào)查采用統(tǒng)一的調(diào)查問卷,共45個主項內(nèi)容,對研究資料先進行單因素分析,篩選出有統(tǒng)計學意義(P0.05)的指標作為自變量,再進行多因素非條件Logistic回歸分析。結果：經(jīng)分析篩選出藥物使用頻率、ACS評分、焦慮障礙、預防治療情況4個因素為MOH的獨立危險因素。結論：慢性偏頭痛患者藥物過度使用的發(fā)生與藥物使用頻率、ACS評分、焦慮障礙、預防治療情況等危險因素密切相關。第二部分：藥物過度使用的偏頭痛患者磁共振成像研究背景：研究表明,反復發(fā)作的偏頭痛可以轉(zhuǎn)變?yōu)槁云^痛,而藥物過度使用性頭痛(medication-overuse headache, MOH)在國際上屬于繼發(fā)性慢性頭痛的一種。MOH明顯影響患者的工作及生活質(zhì)量,甚至導致嚴重的殘疾,同時也常合并癲癇、抑郁癥及情感性精神障礙等多種疾病。MOH的治療難度大,復發(fā)率高。MOH的病理生理機制目前尚未完全闡明,但是主流觀點認為與發(fā)作性偏頭痛的慢化有顯著關聯(lián)性。神經(jīng)影像學研究發(fā)現(xiàn)偏頭痛患者疼痛處理網(wǎng)絡相關區(qū)域存在功能和結構的變化,一定程度上揭示了偏頭痛的病理生理機制。磁共振檢查證實發(fā)作性偏頭痛患者的腦部結構和功能也會發(fā)生改變。彌散張量成像技術((DTI))作為一種無創(chuàng)性技術,主要用于大腦白質(zhì)纖維束的觀察和追蹤,并能清晰、直觀地反映大腦病變。目的：利用磁共振成像技術對門診MOH患者及年齡、性別相匹配的健康對照者的額頂葉、邊緣系統(tǒng)、中腦設置感興趣區(qū)進行對比觀察,以研究患者灰質(zhì)和白質(zhì)等腦結構的變化,并結合臨床特點進行相關性分析。方法：于2014年3月—2015年2月期間篩選80例山東省立醫(yī)院神經(jīng)內(nèi)科頭痛門診就診的偏頭痛患者作為MOH組,選取同期進行健康體檢者80例作為對照組。運用3T超導型MRI成像儀,自旋回波序列進行橫斷矢狀面和冠狀面的T1、T2、FLAIR掃描；采用SPM8分析磁共振影像數(shù)據(jù),結合臨床分析MRI圖像并記錄病灶數(shù)目、部位和體積；采用顱腦磁共振彌散張量成像(DTI)檢查,分別于額頂葉、邊緣系統(tǒng)、中腦設置感興趣區(qū),測取部分各向異性(FA)值、表觀彌散系數(shù)(ADC)值,統(tǒng)計結構異常的類型及病灶所在部位,比較MOH患者與健康人群腦結構的差異。結果：兩組間全腦灰質(zhì)體積(GMV)的差異無統(tǒng)計學意義(P0.05),全腦GMV與身體質(zhì)量指數(shù)及性別因素之間存在正向聯(lián)系,與年齡、頭痛慢性化時間、HAMD分數(shù)之間有顯著的負向關聯(lián)。與健康對照組比較,MOH組各腦區(qū)灰質(zhì)體積以右側顳下回、右側顳中極、左側中扣帶回、右側羅蘭迪克島蓋、雙側眶額上回減少明顯,差異有統(tǒng)計學意義(P0.05)。感興趣區(qū)域(ROI)檢查結果表明,包括顳區(qū)在內(nèi)的多個大腦區(qū)域與頭痛總病程的相關性不顯著,與頭痛病程以及頭痛頻率存在明顯的負向聯(lián)系。與健康對照組比較,MOH組右側眶額皮質(zhì)、左側額下回皮質(zhì)等區(qū)域的ADC值顯著升高,差異統(tǒng)計學有統(tǒng)計學意義(P0.05)。MOH組雙側眶額部皮質(zhì)以及右側內(nèi)囊后肢FA值與患者頭痛頻率及病程成反比,左側內(nèi)囊后肢FA值與頭痛頻率間有明顯負相關性。MOH組眶額部皮質(zhì)和扣帶回皮層區(qū)域ADC值的改變與患者的頭痛頻率及病程相關聯(lián)。結論：與健康對照組相比,MOH患者表現(xiàn)出更嚴重的情緒失調(diào)、認知障礙以及失能。MOH主要和疼痛以及心理相關的區(qū)域灰質(zhì)減少有關。MOH患者羅蘭迪克島蓋(rolandic operculum)區(qū)域灰質(zhì)減少,提示該結構可能與MOH的發(fā)病有關。MOH患者雙側額葉皮質(zhì)及扣帶回皮質(zhì)微觀結構發(fā)生改變,并且與病程和發(fā)作頻率密切相關。第三部分肉毒素A治療藥物過度使用性頭痛的療效觀察目的：觀察皮下注射肉毒素A治療藥物過度使用性頭痛的療效。方法：選取60例山東省立醫(yī)院神經(jīng)內(nèi)科頭痛門診就診的MOH(medication overuse headache)患者。隨機分為對照組和治療組。建議MOH患者停用各種止痛劑。治療組給予肉毒素A治療,根據(jù)患者病情,選取常規(guī)劑量,用lml注射器于疼痛分布區(qū)域及扳機點處行皮下多點注射,31個部位,每個部位5U,共155U。三個月后用同樣的方法和劑量重復注射1次。對照組給予口服托吡酯治療。觀察6個月。頭痛致殘程度應用偏頭痛殘疾程度評估問卷(Migraine Disability Assessment questionnaire,MIDAS)進行評估。通過簡明健康狀況調(diào)查表(SF-36)評估患者的健康狀況。比較兩組患者治療前后MIDAS和SF-36量表評分,頭痛發(fā)作次數(shù)、持續(xù)時間以及嚴重程度,分析藥物的不良反應。結果：肉毒素A對治療藥物過度使用性頭痛效果較好,患者頭痛發(fā)作次數(shù)與對照組相比明顯減少、頭痛持續(xù)時間顯著縮短,差異有統(tǒng)計學意義(P0.05)。頭痛嚴重程度以及SF-36量表結果之間也有顯著的統(tǒng)計學差異(P0.05)。兩組不良反應發(fā)生率差異無統(tǒng)計學意義(P0.05)。結論：本研究MOH患者MIDAS問卷評分提示MOH對患者的學習、生活和工作影響較大。MDQ-H評分提示受試者具有藥物依賴性特點。與單獨使用托吡酯相比,肉毒素A可有效減輕撤藥引起的戒斷性頭痛等戒斷癥狀。與口服托吡酯比較,使用A型肉毒毒素沒有增加不良反應,沒有嚴重副作用發(fā)生。
[Abstract]:The first part of the risk factors in patients with chronic migraine medication overuse analysis objective: To investigate the risk factors of drug overuse in chronic migraine patients. Methods: 157 patients with chronic migraine from January 2013 to December 2015 in Shandong University affiliated Provincial Hospital of the headache clinic cases, including cases of medication overuse headache (MOH) patients with 63 cases, the control group was 94 patients without MOH. The investigation by questionnaire, a total of 45 main items of research data were analyzed by single factor analysis, screened with statistical significance (P0.05) index as independent variables, then the multi factor non conditional Logistic regression analysis. Results: the analysis showed that the frequency of drug use. ACS score, anxiety disorder, prevention and treatment of the 4 factors were independent risk factors of MOH. Conclusion: the occurrence and drug overuse in patients with chronic migraine Use frequency, ACS score, anxiety disorder, prevention and treatment of risk factors closely related. The second part: the excessive use of drugs in patients with migraine magnetic resonance imaging study background: studies show that recurrent migraine can lead to chronic migraine, and medication overuse headache (medication-overuse headache MOH) is a kind of chronic.MOH in the international headache secondary significantly affect the work and life quality of the patients, and even lead to severe disability, but also often associated with epilepsy, depression and affective disorders and other diseases in the treatment of.MOH is difficult, pathophysiological mechanism of high recurrence rate of.MOH has not been fully elucidated, but the mainstream view is that there is significant correlation with episodic migraine slow. Neuroimaging studies found that the structure and function of patients with migraine pain treatment network related area Change to a certain extent, reveals the pathophysiology of migraine. MRI confirmed episodes of brain structure and function in patients with migraine will change. Diffusion tensor imaging ((DTI)) as a non-invasive technology, mainly used for observation and tracking brain white matter fiber, and clear. Intuitively reflect the brain lesions. Objective: to clinic MOH patients and age using magnetic resonance imaging, sex matched healthy controls in the frontal and parietal lobe, midbrain limbic system, setting a region of interest was observed, with changes of patients with gray and white matter of brain structure, and combined with clinical features were analyzed. Methods: a total of 80 patients with migraine headache clinic of Neurology Department of Shangdong Province-owned Hospital from March 2014 to February 2015 as the MOH group, select the same period 80 cases of healthy persons as control group Use the 3T superconducting MRI imager, spin echo sequence of transverse sagittal and coronal T1 scan, T2, FLAIR; SPM8 was used to analyze the magnetic resonance imaging data, combined with the clinical analysis of the MRI image and record the number of lesions, location and volume; the brain magnetic resonance diffusion tensor imaging (DTI) examination, respectively in the amount of the parietal lobe, midbrain limbic system, setting a region of interest, measuring the fractional anisotropy (FA) values, apparent diffusion coefficient (ADC) values, types and structural abnormalities of the location of lesion statistics, comparison between MOH patients and healthy people brain structure difference between the two groups. Results: the whole brain gray matter volume (GMV) no statistically significant difference (P0.05), there is a positive relationship between the whole brain GMV and body mass index and the factors of gender and age, headache chronicity time, between HAMD scores have a significant negative correlation. Compared with the healthy control group, MOH group in the areas of the brain gray matter volume Right inferior temporal gyrus, right temporal pole, left cingulate gyrus, right Rowland Dick Island cover, bilateral orbitofrontal gyrus decreased significantly, the difference was statistically significant (P0.05). The region of interest (ROI) examination showed no significant multiple brain regions including the temporal region, the correlation with the total duration of headache, and headache duration and frequency of headache have obvious negative relationship. Compared with the healthy control group, MOH group, right orbitofrontal cortex, left inferior frontal cortex and other areas of the ADC level significantly increased, the difference was statistically significant statistically (P0.05) group.MOH bilateral orbitofrontal cortex and right posterior limb of the internal capsule and the value of FA in patients with headache frequency and duration inversely, the left posterior limb of the internal capsule and the value of FA is associated with headache frequency and duration of headache frequency changes and significantly negative correlation between.MOH group of orbitofrontal cortex and cingulate cortex. Conclusion: ADC value and healthy control Compared with MOH group, the patients showed more severe mood disorders, cognitive disorders and disability and psychological pain and.MOH mainly related to regional gray matter decreased in patients with.MOH (rolandic operculum Rowland Dick operculum) regional gray matter reduction, suggesting that the structure may be related to.MOH in patients with bilateral frontal cortex and cingulate cortex micro structure changes and the incidence of MOH, which is closely related with the course and seizure frequency. The third part botulinum toxin A in the treatment of medication overuse headache curative effect observation Objective: To observe the treatment of subcutaneous injection of botulinum toxin A overuse headache curative effect. Methods: 60 cases of headache clinic of Neurology Department of Shangdong Province-owned Hospital of MOH (medication overuse headache) were randomly. Divided into treatment group and control group. MOH patients discontinued various analgesics. Treatment group was treated with botulinum toxin A in the treatment of patients, according to the situation, choose Take regular doses, with LML syringe in pain distribution region and trigger point for subcutaneous injection, 31 parts, each part of 5U, a total of three months after 155U. with the same method and dosage of repeated injection of 1 times. The control group was given oral topiramate treatment for 6 months. The degree of application of migraine headache disability Disability Assessment Questionnaire (Migraine Disability Assessment questionnaire, MIDAS) were evaluated. The short form health survey (SF-36) to evaluate the health status of patients. The two groups were compared before and after treatment of MIDAS and SF-36 score, headache frequency, duration and severity of adverse reactions, drug analysis. Results: botulinum toxin A on medication overuse headache is better, patients with headache episodes significantly reduced compared with the control group, headache duration was significantly shorter, the difference was statistically significant (P0.05) headache. There are significant differences between the severity and SF-36 scale (P0.05). The adverse reactions of two groups were not statistically significant (P0.05). Conclusion: This study suggests that MOH patients with MOH MIDAS scores of patients with learning, life and work has great influence.MDQ-H score showed the subjects have the characteristics of drug dependence compared with the use of topiramate alone, botulinum toxin A can effectively relieve the withdrawal caused by withdrawal headache and other withdrawal symptoms. Compared with oral topiramate, use of botulinum toxin type A without increasing adverse reactions, no severe side effects occurred.

【學位授予單位】：山東大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R741

【相似文獻】

相關期刊論文 前10條

1 連亞軍,滕軍放,王春燕,方樹友;偏頭痛患者血清和腦脊液腫瘤壞死因子α水平變化[J];中華神經(jīng)科雜志;2001年03期

2 李廣安,李金芳,劉洪玲,程立新;偏頭痛患者綜合干預的對照研究[J];中國心理衛(wèi)生雜志;2001年04期

3 陳志強,洪加林,孫晟,朱敏;偏頭痛患者血漿內(nèi)皮素與降鈣素基因相關肽水平檢測的臨床意義[J];臨床醫(yī)學;2005年06期

4 Hershey A.D.,Powers S.W ,陳云春;偏頭痛及慢性偏頭痛患者的基因組異常:血液基因表達的初步研究提示血小板出現(xiàn)異常[J];世界核心醫(yī)學期刊文摘(神經(jīng)病學分冊);2005年04期

5 Anagnostou E.,Mitsikostas D.D. ,郭俊;偏頭痛患者的時間知覺:一項實驗性配對研究[J];世界核心醫(yī)學期刊文摘(神經(jīng)病學分冊);2005年06期

6 Hamelsky S.W.,Lipton R.B. ,Stewart W.F. ,夏峰;采用支付意愿模式評估偏頭痛患者的負擔[J];世界核心醫(yī)學期刊文摘(神經(jīng)病學分冊);2005年06期

7 程偉進 ,胡紅玲 ,藍利民;偏頭痛患者的情緒[J];上海針灸雜志;2005年10期

8 Oelkers-Ax R.;Parzer P.;ReschF.;Weisbrod M. ;夏峰;;圖像反轉(zhuǎn)習慣范例調(diào)查偏頭痛患者早期視覺處理的成熟度發(fā)生改變[J];世界核心醫(yī)學期刊文摘(神經(jīng)病學分冊);2005年09期

9 Foley K.A.;Cady R.;Martin V.;江山;;早期和輕度治療:確診偏頭痛患者服用藥物的時機[J];世界核心醫(yī)學期刊文摘(神經(jīng)病學分冊);2005年10期

10 Aurora S.K.;Barrodale P.;Chronicle E.P.;Mulleners W.M.;江山;;慢性和發(fā)作性偏頭痛患者的皮質(zhì)抑制減少和所表示的疾病譜[J];世界核心醫(yī)學期刊文摘(神經(jīng)病學分冊);2005年10期

相關會議論文 前10條

1 許賢平;易飛;;偏頭痛患者焦慮抑郁狀態(tài)的調(diào)查[A];江西省第六次中西醫(yī)結合神經(jīng)科學術交流會論文集[C];2013年

2 李鳳鵬;于生元;董釗;姜磊;邱恩超;劉若卓;;偏頭痛患者磁共振彌散張量成像的初步研究[A];中華醫(yī)學會疼痛學分會第八屆年會暨CASP成立二十周年論文集[C];2009年

3 許賢平;易飛;;偏頭痛患者焦慮抑郁狀態(tài)的調(diào)查[A];江西省第五次中西醫(yī)結合神經(jīng)科學術交流會論文集[C];2011年

4 秦近近;陳春富;;肥胖指標對偏頭痛患者的影響[A];山東省2013年神經(jīng)內(nèi)科學學術會議暨中國神經(jīng)免疫大會2013論文匯編[C];2013年

5 袁鳴芳;何世民;蔣健;;靈通膠囊治療頭痛的臨床研究[A];中華醫(yī)學會疼痛學分會第七屆年會論文摘要集[C];2007年

6 薛慎伍;;老年偏頭痛患者血細胞鈣含量與腦血流量變化的關系[A];第七屆全國老年醫(yī)學進展學術會議論文集[C];2007年

7 余海;朱海兵;鐘善全;劉錚;賴燕蔚;;偏頭痛患者的皮膚異常性疼痛[A];江西省第五次中西醫(yī)結合神經(jīng)科學術交流會論文集[C];2011年

8 王運鋒;周冀英;譚戈;李雪蓮;冉麗;陳力學;;神經(jīng)內(nèi)科門診偏頭痛患者頭痛頻率相關性臨床特征分析[A];中華醫(yī)學會第十三次全國神經(jīng)病學學術會議論文匯編[C];2010年

9 王正銀;楊新榮;;健康教育對偏頭痛患者干預作用的對照研究[A];中華醫(yī)學會疼痛學分會第六屆年會論文摘要[C];2005年

10 薛慎伍;;老年頸動脈病變偏頭痛患者血細胞中鈣含量與腦血流量變化的關系[A];首屆泰山微量元素高級論壇論文匯編[C];2007年

相關重要報紙文章 前10條

1 上海楊浦 吳永國;偏頭痛患者要注意些什么?[N];上海中醫(yī)藥報;2013年

2 北京市西苑醫(yī)院神經(jīng)二科 吳妍彥 張寶利;偏頭痛患者吃東西要當心[N];健康報;2009年

3 袁浩龍;偏頭痛患者的冬季保健[N];江蘇經(jīng)濟報;2001年

4 阿勝 編譯;“頭痛”令人真頭痛[N];醫(yī)藥經(jīng)濟報;2003年

5 ;特異性癥狀治療藥物應受重視[N];醫(yī)藥經(jīng)濟報;2004年

6 金良;女性為何多頭痛[N];云南科技報;2002年

7 益生;麻醉劑往往對非偏頭痛患者的頭痛癥狀無效[N];中國高新技術產(chǎn)業(yè)導報;2001年

8 ;慢性每天頭痛的治療[N];農(nóng)村醫(yī)藥報（漢）;2006年

9 丁香;鮮為人知的疼痛事實[N];醫(yī)藥經(jīng)濟報;2008年

10 王功立;辨明頭痛類型 薦藥不再“頭痛”[N];中國醫(yī)藥報;2005年

相關博士學位論文 前6條

1 張娜;預防性治療對偏頭痛患者中樞敏化影響的研究[D];山東大學;2015年

2 張立功;藥物過度使用性頭痛的臨床研究[D];山東大學;2016年

3 喻大華;無先兆偏頭痛患者大腦結構與功能異常的磁共振影像學研究[D];西安電子科技大學;2013年

4 薛婷;基于磁共振成像的無先兆偏頭痛患者大腦靜息狀態(tài)異常模式研究[D];西安電子科技大學;2013年

5 張勇;針刺治療對無先兆偏頭痛患者默認模式網(wǎng)絡影響的功能磁共振研究[D];北京中醫(yī)藥大學;2014年

6 任毅;針刺足臨泣對無先兆偏頭痛患者默認模式網(wǎng)絡影響的功能磁共振研究[D];北京中醫(yī)藥大學;2014年

相關碩士學位論文 前10條

1 朱海生;偏頭痛患者腦白質(zhì)磁共振成像異常與臨床相關因素研究[D];河北醫(yī)科大學;2015年

2 周華祥;偏頭痛患者頭暈的調(diào)查及預防性藥物的影響[D];山東大學;2015年

3 許飛;基于磁共振影像的無先兆偏頭痛患者的功能改變研究[D];電子科技大學;2015年

4 杜菡萏;偏頭痛患者的腦功能和結構影像研究[D];電子科技大學;2015年

5 沈玫彤;偏頭痛患者血清中親環(huán)素A水平的變化[D];大連醫(yī)科大學;2015年

6 李曉霞;高原地區(qū)偏頭痛患者診治情況及誘發(fā)因素分析[D];青海大學;2016年

7 蔡濤鍵;平衡針灸針刺無先兆偏頭痛患者頭痛穴的臨床觀察[D];廣州中醫(yī)藥大學;2016年

8 刁曉君;偏頭痛患者下丘腦—垂體—性腺軸及下丘腦—垂體—腎上腺軸的研究[D];山東大學;2016年

9 鄧光輝;中國云南地區(qū)漢族偏頭痛患者的BDNF基因單核苷酸多態(tài)性研究[D];昆明理工大學;2016年

10 吳迪;偏頭痛患者靜息態(tài)神經(jīng)網(wǎng)絡的腦磁圖研究[D];南京醫(yī)科大學;2016年

，

本文編號：1572085