药物过度使用性头痛的临床研究

发布时间：2018-03-05 22:07

本文选题：药物过度使用性头痛　切入点：慢性偏头痛　出处：《山东大学》2016年博士论文　论文类型：学位论文

【摘要】：第一部分慢性偏头痛患者药物过度使用的危险因素分析目的：探讨慢性偏头痛患者药物过度使用的危险因素。方法：选取2013年1月到2015年12月山东大学附属省立医院头痛门诊的慢性偏头痛患者157例,其中病例组为药物过度使用性头痛(MOH)患者63例,对照组为不存在MOH的患者94例。调查采用统一的调查问卷,共45个主项内容,对研究资料先进行单因素分析,筛选出有统计学意义(P0.05)的指标作为自变量,再进行多因素非条件Logistic回归分析。结果：经分析筛选出药物使用频率、ACS评分、焦虑障碍、预防治疗情况4个因素为MOH的独立危险因素。结论：慢性偏头痛患者药物过度使用的发生与药物使用频率、ACS评分、焦虑障碍、预防治疗情况等危险因素密切相关。第二部分：药物过度使用的偏头痛患者磁共振成像研究背景：研究表明,反复发作的偏头痛可以转变为慢性偏头痛,而药物过度使用性头痛(medication-overuse headache, MOH)在国际上属于继发性慢性头痛的一种。MOH明显影响患者的工作及生活质量,甚至导致严重的残疾,同时也常合并癫痫、抑郁症及情感性精神障碍等多种疾病。MOH的治疗难度大,复发率高。MOH的病理生理机制目前尚未完全阐明,但是主流观点认为与发作性偏头痛的慢化有显著关联性。神经影像学研究发现偏头痛患者疼痛处理网络相关区域存在功能和结构的变化,一定程度上揭示了偏头痛的病理生理机制。磁共振检查证实发作性偏头痛患者的脑部结构和功能也会发生改变。弥散张量成像技术((DTI))作为一种无创性技术,主要用于大脑白质纤维束的观察和追踪,并能清晰、直观地反映大脑病变。目的：利用磁共振成像技术对门诊MOH患者及年龄、性别相匹配的健康对照者的额顶叶、边缘系统、中脑设置感兴趣区进行对比观察,以研究患者灰质和白质等脑结构的变化,并结合临床特点进行相关性分析。方法：于2014年3月—2015年2月期间筛选80例山东省立医院神经内科头痛门诊就诊的偏头痛患者作为MOH组,选取同期进行健康体检者80例作为对照组。运用3T超导型MRI成像仪,自旋回波序列进行横断矢状面和冠状面的T1、T2、FLAIR扫描；采用SPM8分析磁共振影像数据,结合临床分析MRI图像并记录病灶数目、部位和体积；采用颅脑磁共振弥散张量成像(DTI)检查,分别于额顶叶、边缘系统、中脑设置感兴趣区,测取部分各向异性(FA)值、表观弥散系数(ADC)值,统计结构异常的类型及病灶所在部位,比较MOH患者与健康人群脑结构的差异。结果：两组间全脑灰质体积(GMV)的差异无统计学意义(P0.05),全脑GMV与身体质量指数及性别因素之间存在正向联系,与年龄、头痛慢性化时间、HAMD分数之间有显著的负向关联。与健康对照组比较,MOH组各脑区灰质体积以右侧颞下回、右侧颞中极、左侧中扣带回、右侧罗兰迪克岛盖、双侧眶额上回减少明显,差异有统计学意义(P0.05)。感兴趣区域(ROI)检查结果表明,包括颞区在内的多个大脑区域与头痛总病程的相关性不显著,与头痛病程以及头痛频率存在明显的负向联系。与健康对照组比较,MOH组右侧眶额皮质、左侧额下回皮质等区域的ADC值显著升高,差异统计学有统计学意义(P0.05)。MOH组双侧眶额部皮质以及右侧内囊后肢FA值与患者头痛频率及病程成反比,左侧内囊后肢FA值与头痛频率间有明显负相关性。MOH组眶额部皮质和扣带回皮层区域ADC值的改变与患者的头痛频率及病程相关联。结论：与健康对照组相比,MOH患者表现出更严重的情绪失调、认知障碍以及失能。MOH主要和疼痛以及心理相关的区域灰质减少有关。MOH患者罗兰迪克岛盖(rolandic operculum)区域灰质减少,提示该结构可能与MOH的发病有关。MOH患者双侧额叶皮质及扣带回皮质微观结构发生改变,并且与病程和发作频率密切相关。第三部分肉毒素A治疗药物过度使用性头痛的疗效观察目的：观察皮下注射肉毒素A治疗药物过度使用性头痛的疗效。方法：选取60例山东省立医院神经内科头痛门诊就诊的MOH(medication overuse headache)患者。随机分为对照组和治疗组。建议MOH患者停用各种止痛剂。治疗组给予肉毒素A治疗,根据患者病情,选取常规剂量,用lml注射器于疼痛分布区域及扳机点处行皮下多点注射,31个部位,每个部位5U,共155U。三个月后用同样的方法和剂量重复注射1次。对照组给予口服托吡酯治疗。观察6个月。头痛致残程度应用偏头痛残疾程度评估问卷(Migraine Disability Assessment questionnaire,MIDAS)进行评估。通过简明健康状况调查表(SF-36)评估患者的健康状况。比较两组患者治疗前后MIDAS和SF-36量表评分,头痛发作次数、持续时间以及严重程度,分析药物的不良反应。结果：肉毒素A对治疗药物过度使用性头痛效果较好,患者头痛发作次数与对照组相比明显减少、头痛持续时间显著缩短,差异有统计学意义(P0.05)。头痛严重程度以及SF-36量表结果之间也有显著的统计学差异(P0.05)。两组不良反应发生率差异无统计学意义(P0.05)。结论：本研究MOH患者MIDAS问卷评分提示MOH对患者的学习、生活和工作影响较大。MDQ-H评分提示受试者具有药物依赖性特点。与单独使用托吡酯相比,肉毒素A可有效减轻撤药引起的戒断性头痛等戒断症状。与口服托吡酯比较,使用A型肉毒毒素没有增加不良反应,没有严重副作用发生。
[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.

【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R741

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