DEEP BRAIN STIMULATION FOR REFRACTORY OBSESSIVE COMPULSIVE DISORDER

脑深部刺激治疗难治性强迫症

• 批准号: 6263702
• 负责人: GEORGE C CURTIS
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6263702
• 关键词: clinical research; electrostimulus; human subject; human therapy evaluation; obsessive compulsive disorder; outcomes research; psychotherapy; stereotaxic techniques

Stereotactic neurosurgical lesions in a variety of brain sites have proved helpful for many patients who remain disabled with Obsessive Compulsive Disorder (OCD) in spite of conventional therapies. Some studies suggest that lesions in the anterior limbs of the internal capsules (anterior capsulotomy) may be the most effective of these procedures. Stereotactic lesions in the nucleus ventralis intermedius (VIM) of the thalamus are beneficial in the treatment of tremors which do not respond to medical therapy. For these disorders, electrical simulation in the would-be lesion site has proved equally effective. This suggests that electrical stimulation might also be a viable substitute for surgical lesions in OCD. If so, this would be preferable for a number of reasons. Although adverse effects of neurosurgical therapy of OCD are minimal, irreversible destruction of brain tissue does occur at the site of the lesions, and, in addition we have found postoperative increase in third ventricle volume as well as reduction in volume of several cell body nuclei, including thalamus, caudate nuclei, and (in 2 of 5 subjects) hippocampi. Subtle memory difficulties have also been noted in some patients. In contrast, any changes due to electrical stimulation are completely reversible on discontinuation of the stimulation. We propose a pilot study to determine whether more extensive studies are warranted to test the safety and effectiveness of deep brain stimulation (DBS) as a substitute for anterior capsulotomy and, if so, to begin determining optimal stimulation parameters. Subjects will be five patients with OCD refractory to established therapies, who would otherwise be candidates for anterior capsulotomy. After preoperative diagnostic and baseline studies, an electrode array will be placed stereotactically in the anterior limb of each internal capsule and connected to a subcutaneous pulse generator. After surgery the DBS system will be tested in-hospital "open label" to assess for side effects and complications, to identify possible immediate therapeutic effects, and to search for optimum stimulation parameters. Subsequently, as outpatients, each patient will undergo alternating 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 prolong stimulation. Symptom severity and impairment scores will be given the choice of continued stimulation, anterior capsulotomy, or further conventional therapy. If DBS proves effective, future studies combining it with imaging and other studies may shed additional light on the mechanisms of OCD. Analogous studies of the effectiveness of DBS at other common lesion sites would also be indicated, as would assessment of the effectiveness of DBS for other psychiatric disorders for which stereotactic lesions are helpful.

立体定向神经外科病变在各种脑部位已被证明是有益的，许多患者仍然残疾的强迫症（OCD），尽管传统的治疗。 一些研究表明，内囊前肢的病变（前囊切开术）可能是这些手术中最有效的。 丘脑腹中间核（Vim）中的立体定向损伤有利于治疗对药物治疗无反应的震颤。 对于这些疾病，在可能的病变部位进行电刺激已被证明同样有效。 这表明，电刺激也可能是一个可行的替代手术损伤强迫症。如果是这样的话，这将是可取的，原因有几个。 虽然神经外科治疗强迫症的副作用很小，但在病变部位确实发生了不可逆的脑组织破坏，此外，我们还发现术后第三脑室体积增加以及几个细胞体核体积减少，包括丘脑、尾状核和（5例受试者中的2例）丘脑。 在一些患者中也注意到轻微的记忆困难。 相反，由于电刺激引起的任何变化在刺激停止时是完全可逆的。 我们提出了一项初步研究，以确定是否有必要进行更广泛的研究，以测试脑深部电刺激（DBS）作为前囊切开术的替代品的安全性和有效性，如果是，则开始确定最佳刺激参数。 受试者将是5名对既定疗法难治的强迫症患者，否则他们将是前囊切开术的候选者。 在术前诊断和基线研究后，将电极阵列立体定位地放置在每个内囊的前肢中，并连接到皮下脉冲发生器。手术后，DBS系统将在医院进行“开放标签”测试，以评估副作用和并发症，确定可能的即时治疗效果，并寻找最佳刺激参数。随后，作为门诊患者，每名患者将经历几周的交替期，其中刺激将在双盲设计中交替打开和关闭，以验证任何明显的益处并测试延长刺激的可能益处。 将根据症状严重程度和损伤评分选择继续刺激、前囊切开术或进一步常规治疗。 如果DBS被证明是有效的，未来的研究将其与成像和其他研究相结合，可能会进一步阐明强迫症的机制。 DBS在其他常见病变部位的有效性的类似研究也将被指示，如DBS对立体定向病变有帮助的其他精神疾病的有效性评估。