DEEP BRAIN STIMULATION FOR REFRACTORY OBSESSIVE COMPULSIVE DISORDER

在大脑内囊前肢的小区域手术破坏（病变）（前囊切开术）已被证明对许多患有强迫症（OCD）的患者有帮助，尽管有传统的治疗方法。在大脑的另一个位置，丘脑中间腹侧核的病变，已被证明对治疗无效的震颤（无法控制的颤抖）有益。对于震颤，通过在丘脑植入电极的慢性电模拟（深部脑刺激，或DBS）已被证明与损伤一样有效，因此无需破坏脑组织。这表明，通过内囊前肢的电极进行慢性刺激可以替代前囊切开术治疗强迫症。我们现在提议进行一项初步研究，以调查情况是否可能如此。如果是这样的话，出于一些原因，长期的电刺激会更可取。我们还建议使用正电子发射断层扫描（PET）与[18F]氟脱氧葡萄糖（FDG）扫描，以确定大脑的哪些区域被内胶囊的这一部分的电刺激激活。这将提供关于大脑连接和功能的基本信息，并可能为强迫症的大脑机制提供线索。研究对象为5例常规治疗难治性强迫症患者，否则他们将成为前囊切开术的候选人。在诊断和基线研究后，电极将通过精确的立体定向技术放置在每个内囊的前肢，并连接到植入皮肤下的电脉冲发生器。手术后，DBS系统将在医院进行测试，以评估副作用和并发症，确定可能的即时治疗效果，并寻找最佳的刺激环境。随后，作为门诊病人，每个病人将经历几周的时间，在这段时间里，刺激将在双盲设计中交替打开和关闭，以验证任何明显的好处，并测试长时间刺激可能带来的好处。在每个阶段将评估症状严重程度和损害评分。在研究结束时，患者将选择继续刺激、前囊切除术或进一步的常规治疗。

Small areas of surgical destruction (lesions) in the anterior limb of the internal capsule of the brain (anterior capsulotomy) have proved helpful for many patients who remain disabled with Obsessive Compulsive Disorder (OCD) in spite of conventional therapies. Lesions in a different brain location, the nucleus ventralis intermedius of the thalamus, have proved beneficial for tremors (uncontrollable shaking) which do not respond to medication. For tremors, chronic electrical simulation through electrodes implanted in the thalamus (deep brain stimulation, or DBS) has proved as effective as lesions, making it unnecessary to destroy brain tissue. This suggests that chronic stimulation through electrodes in the anterior limb of the internal capsule might substitute for anterior capsulotomy in the treatment of OCD. We now propose a pilot study to investigate whether this may be the case. If so, chronic electrical stimulation would be preferable for a number of reasons. We also propose to use scanning by positron emission tomography (PET) with [18F] fluorodeoxyglucose (FDG) to determine which areas of the brain are activated by electrical stimulation in this portion of the internal capsule. This will provide basic information on brain connections and function and may provide clues to the brain mechanisms of OCD. Subjects will be five patients with OCD refractory to conventional therapies, who would otherwise be candidates for anterior capsulotomy. After diagnostic and baseline studies, electrodes will be placed in the anterior limbs of each internal capsule by precise stereotactic technique and connected to electrical pulse generators implanted under the skin. After surgery the DBS system will be tested in-hospital to assess for side effects and complications, to identify possible immediate therapeutic effects, and to search for optimum stimulation settings. Subsequently, as outpatients, each patient will undergo periods of several weeks each, in which stimulation will alternately be turned on and off in a double blind design in order to verify any apparent benefits and to test for possible benefits of prolonged stimulation. Symptom severity and impairment scores will be assessed during each period. At the completion of the study, patients will be given the choice of continued stimulation, anterior capsulotomy, or further conventional therapy.