DEEP BRAIN STIMULATION FOR REFRACTORY OBSESSIVE COMPULSIVE DISORDER

立体定向神经外科病变在不同的大脑部位已被证明有助于许多患者仍然残疾与强迫症（OCD）尽管传统疗法。一些研究表明，前肢内囊的病变（前囊切开术）可能是这些手术中最有效的。丘脑中间腹侧核（VIM）的立体定向病变对治疗药物治疗无效的震颤是有益的。对于这些疾病，在潜在病变部位进行电模拟已被证明同样有效。这表明电刺激也可能是强迫症手术损伤的可行替代方法。如果是这样，出于以下几个原因，这将是更可取的。虽然神经外科治疗强迫症的不良反应很小，但在病变部位确实发生了脑组织的不可逆破坏，此外，我们发现术后第三脑室体积增加，几个细胞体核体积减少，包括丘脑、尾状核和（5名受试者中的2名）海马体。一些病人也有轻微的记忆困难。相反，电刺激引起的任何变化在停止电刺激后是完全可逆的。我们建议进行一项初步研究，以确定是否有必要进行更广泛的研究来测试深部脑刺激（DBS）作为前囊切开术替代品的安全性和有效性，如果有必要，就开始确定最佳刺激参数。研究对象将是5名对现有治疗方法难治的强迫症患者，否则他们将成为前囊切开术的候选人。在术前诊断和基线研究后，电极阵列将立体定向放置在每个内囊的前肢，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，作为门诊病人，每个病人将经历几个星期的交替期，在此期间，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，并测试延长刺激可能带来的好处。症状严重程度和损伤评分将给出继续刺激、前囊切除术或进一步常规治疗的选择。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出，以及评估DBS对其他立体定向病变有帮助的精神疾病的有效性。

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.