Improving Functions in MTBI Patients with Headache by rTMS

描述(由申请人提供)： 与爆炸伤相关的脑震荡或轻度创伤性脑损伤(MTBI)是伊拉克和阿富汗战争中最常见的战斗相关损伤形式。与创伤后应激障碍(PTSD)、认知和情绪障碍一样，头痛(HA)是MTBI退伍军人最令人虚弱的临床症状。不幸的是，传统的药物治疗MTBI相关头痛(MTBI-HA)并不有效，并且包含许多长期的不良心身和虐待性副作用。近年来，非侵入性脑刺激如重复经颅磁刺激(RTMS)在前额叶背外侧皮质(LDLPFC)的应用已经在一些慢性中枢性疼痛方面取得了良好的临床效果，包括中风后中枢性疼痛和头痛。在过去的三年中，PI的临床服务使用rTMS治疗了超过45名MTBI-HA退伍军人，并观察到在缓解和预防头痛方面取得了良好的效果。这些好处似乎对大多数每月重复治疗的患者来说是令人信服的。为了进一步验证这些观察到的有利的临床结果，研究人员提出了一个初步的随机对照项目，主要目标如下：目的1：比较LDLFC的主动rTMS和假rTMS在减少MTBI-HA的强度和持续时间方面的效果；目的2：比较LDLPFC的主动rTMS和假rTMS在改善MTBI相关的认知和抑郁症状方面的效果；此外，为了便于将来的研究评估重复rTMS治疗1个月的临床疗效及其对创伤后应激障碍的影响，并进一步建立分别与MTBI-HA和rTMS相关的疾病和治疗机制，本研究还包含三个探索性目标：探索性目标1：结合头痛和神经生理结果，本研究将利用fMRI探讨rTMS对MTBI-HA患者脊柱上静息和诱发疼痛状态的影响；探索性目标2：探讨首次治疗后1个月维持rTMS对头痛缓解的效果；探索目标3：由于头痛、MTBI和创伤后应激障碍(PTSD)是退伍军人中高度并存的疾病，本研究将探讨rTMS对MTBI-HA退伍军人中与PTSD相关的功能损害状况(与临床医生使用的PTSD量表相一致)的治疗效果。拟议的目标是密切相关的，可以在不加重老兵和调查人员负担的情况下实现。通过这些研究，研究人员的目标是进一步开发rTMS作为治疗MTBI-HA和相关神经心理障碍的非侵入性治疗工具，并增进对MTBI相关神经机制的了解。

DESCRIPTION (provided by applicant): Concussive or mild Traumatic Brain Injury (MTBI) related to blast injury is the most common form of combat-related injury in the Iraq and Afghanistan Wars. Along with post traumatic stress disorder (PTSD), cognitive and mood dysfunction, headache (HA) is the most debilitating clinical symptom in Veteran with MTBI. Unfortunately, conventional pharmacological treatments for MTBI related headache (MTBI-HA) has not shown to be effective and contain many long term untoward psychosomatic and abusive side effects. Recently, the use of non- invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex(LDLPFC) has yielded favorable clinical outcomes in a few chronic central pain conditions including post-stroke central pain and headaches. In the past three years, the PI's clinical service has treated over 45 MTBI-HA Veteran with rTMS and observed favorable outcomes in headache relief and prevention. These benefits appear to be sustaujinable for a majority of patients with monthly repeated treatment. To further validate these observed favorable clinical outcomes, the investigators propose an initial randomized controlled project with the following main objectives: Aim #1: To compare the effect of active rTMS at LDLFC with sham rTMS in reducing the intensity and the duration of MTBI-HA; Aim #2: To compare the effect of active rTMS at LDLPFC with sham rTMS in improving cognitive and depressive symptoms associated with MTBI; In addition, to facilitate future studies in assessing the effect of repeat rTMS treatment at one month as an applicable clinical protocol and its effect on PTSD, and to further establishing the disease and therapeutic mechanisms related to MTBI-HA and rTMS respectively, the proposal also contains three exploratory aims: Exploratory Aim 1: In correlation with the headache and neurophysiological outcomes, this study will explore the effect of rTMS on supraspinal resting and evoked pain states in MTBI- HA patients with fMRI; Exploratory Aim 2: To explore the effect of maintenance rTMS for headache relief at the one-month interval after the initial treatments; Exploratory Aim 3: Since Headache, MTBI and Post-traumatic Stress Disorder (PTSD) are highly co-morbid conditions in Veterans, this study will explore the treatment effect of rTMS on alleviating functionally impairing conditions associated with PTSD(as identified with Clinician Administered PTSD Scale) in MTBI-HA Veterans. The proposed aims are closely interconnected and can be achieved without over- burdening both the Veteran and the investigators . Though these studies, the investigators aim to further develop rTMS as a non-invasive treatment tool for MTBI-HA and related neuropsychological dysfunctions, and enhance the understanding in MTBI related neurological mechanisms.