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有读书笔记Deep Brain Stimulation of Nucleus Accumbens on Heroin-Seeking Behaviors: A Case Report

唐唐 添加于 2011-5-24 04:13 | 2255 次阅读 | 0 个评论

  •  作 者

    Zhou H, Xu J, Jiang J

  •  摘 要

    Drug addiction is a chronic relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors, despite severe negative consequences (1). After detoxification, the rates of craving or relapsing drug use are discouragingly high (2). Bilateral cryocingulotomy was first used to treat heroin addiction from 1999 to 2002 in Russia and demonstrated a 30% rate of immediate total remission (3). Meanwhile, Chinese doctors began to alleviate opiate drug psychological dependence by ablating the nucleus accumbens (NAc) via stereotactic surgery. After a mean follow-up of 15 months, the relapse rate was reduced to 57.5%, which suggested the effectiveness of bilateral NAc lesions for alleviating addiction (4). Subsequently, the use of stereotactic surgery or ablation of select brain areas (i.e., NAc, cingular gyri) to treat opiate drug addiction was applied in many hospitals throughout China. Hundreds of addicts were treated surgically during the 2000 to 2004 period in China. No particular complications were reported, and the relapse rate varied from 15.4% to 54.8% after a mean follow-up of more than 6 to 12 months ([5], [6] and [7]). However, the use of ablative brain surgery for drug addiction was stopped by the Ministry of Public Health of China in November 2004. Because of the lack of proper experimental models, real protocols, and long-term follow-up studies, these operations were regarded as unproven due to the related ethical controversy and possible side effects. Deep brain stimulation (DBS), as a process of neuromodulation, has been widely used in the treatment of refractory movement disorders and psychiatric disorders ([8] and [9]). Because high-frequency electrical stimulation has an inhibitory effect on the stimulated area ([10] and [11]) and produces clinical benefits similar to ablation, it seems reasonable to propose the use of DBS as a potential therapy for drug relapse. Here, the authors presented one case study of NAc DBS on the treatment of heroin addiction in a human subject. Case Report The subject was a 24-year-old man diagnosed with heroin dependence by DSM-III-R criteria. At the time of the procedure, he had been abusing heroin regularly by intravenous injection of 1.0 g to not, vert, similar1.5 g per day for over 5 years. He did not respond to multiple detoxification treatments, including compulsory detoxification, psychological and behavior interventions, and medications. He had been unemployed because of drug abuse. The NAc DBS procedure was reviewed and approved by the Ethics Committee of Renji Hospital (Shanghai, China). The subject and his family received detailed information of the procedure and gave written consent before the treatment. The procedure was performed after an anesthesia-assisted rapid opiate detoxification during a 24-hour intensive care unit admission. Quadripolar DBS leads (Model 3387, Medtronic, Minneapolis, Minnesota) were implanted stereotactically into the bilateral NAc (location of target points: 7.5 mm in front of the anterior commissural point; 6 mm below the line of anterior commissure and posterior commissure; 6.5 mm lateral to the midline). A pulse generator was internalized in the pectoral area (Figure 1). Full-size image (52K) - Opens new window Full-size image (52K) High-quality image (447K) Figure 1. Cranial magnetic resonance imaging scans and x-ray examinations after deep brain stimulation system internalization in the human subject. Pulse stimulation was initiated 7 days postoperatively with stimulation amplitude gradually increased from .8 V to 2.5 V from the second week to the fifth week, while a constant stimulation frequency of 145 Hz was maintained. The electrode contact configurations and the changes of parameter settings are shown in Figure 2. The pulse generator was switched off 2.5 years after the procedure. By request of the patient and his family, the pulse generator was removed 3 years after internalization. After intensive in-hospital monitoring, the subject was regularly followed by telephone conversation, face-to-face family interviews, and appointed outpatient services. Randomly selected examination of urine samples and naloxone challenge tests were also performed. The desired effects and adverse reactions measured by psychological and symptom scales were recorded and analyzed. Full-size image (17K) - Opens new window Full-size image (17K) High-quality image (130K) Figure 2. The electrode contact configurations and the chronological changes of parameter settings. w, week; yrs, years. Immediately following the internalization, the subject had mild confusion and urinary incontinence, and he recovered thoroughly in 12 hours. One month after the surgery, the subject gained significant weight from 60.5 kg before the procedure to 71.5 kg (height 178 cm) and maintained a stable body weight of 68.0 kg to not, vert, similar72.5 kg during the 6-year follow-up. The number of cigarettes smoked decreased from nearly 40 per day before surgery to 10 per day after surgery. The comparative results of psychological assessment (Wechsler Memory Scale, Wechsler Adult Intelligence Scale, and Minnesota Multiphasic Personality Inventory) indicated significant improvement of memory and IQ. At 3 months after surgery, the Wechsler Memory Scale Memory Quotient score was improved to a value of 100 from a baseline value before surgery of 86. His full IQ, verbal IQ, and performance IQ improved to values of 107, 102, and 112 from baseline values before surgery of 97, 94, and 101, respectively. There was no obvious change in the personality. In addition, the subject improved on multiple self-rating symptom scales (Symptom Checklist 90, Self-Rating Depression Scale, and Self-Rating Anxiety Scale). The presurgery scores of the Self-Rating Depression Scale and Self-Rating Anxiety Scale were significantly higher than those in normal subjects; the postsurgery scores decreased and returned to normal ranges on DBS stimulation. Many components of the Symptom Checklist 90 symptom scales were above normal before surgery and improved significantly on DBS stimulation. The patient stopped abusing drugs completely after the procedure, without any other ancillary treatment. There was no relapse during the 6-year follow-up. As a result, he returned to full-time work. Discussion The clinical practice of surgical ablation of the NAc in China, although controversial and currently stopped, appeared to be effective in alleviating psychological dependence on opiate drugs. The NAc represents the common pathway for drug relapse ([12], [13] and [14]), which seems to be the most promising therapeutic target in attempts to attenuate drug relapse. Compared with surgical ablation of select brain tissues (i.e., NAc, cingular gyri), DBS is a less invasive, reversible, and adjustable stereotactic neuromodulation technique. Our previous studies have revealed that high-frequency stimulation (130 Hz) of NAc can reduce the heroin-seeking behaviors elicited by conditioned cues and small dose of heroin in self-administration rats and has no effect on the locomotor activity (15). In the case report, the subject who underwent the NAc DBS procedure refrained from drug abusing during active stimulation for the first 2.5 years. He had remained drug free for 3.5 years even after the stimulation was removed with no relapse. Remarkable improvements of the subjects' memory, IQ, and psyche were observed. These findings suggest that NAc DBS could be an effective and safe therapeutic option for heroin addiction. Work was supported by the National Natural Science Foundation of China (Grant No. 30600634). All authors reported no biomedical financial interest or potential conflicts of interest.

  •  详细资料

    • 文献种类: Journal Article
    • 期刊名称: Biological Psychiatry
    • 期刊缩写: Biological Psychiatry
    • 期卷页: 2011年  第69卷 第11期 e41-e42页
    • ISBN: 0006-3223

  • 学科领域 生物医药 » 药学

  •  所属群组

    生物综合   医学综合   药学综合  

  • 相关链接 DOI URL 

  •  唐唐 的文献笔记  订阅

    脑深部电刺激治疗戒断药物成瘾
    来自上海交通大学附属仁济医院神经外科的研究人员发表了利用脑深部电刺激（DBS）治疗阿片成瘾患者的长期随访结果的论文，这是目前文献报告的首例DBS戒断药物成瘾的成功案例，这一研究成果公布在《生物精神病学》（BIOL PSYCHIATRY）杂志上（近五年影响因子9.48）。
     
    这项研究由仁济医院神经外科，“百人计划”入选者周洪语副教授等人共同完成，其所在的仁济 医院功能神经外科组在外科戒毒领域临床和科研方面开展了深入的研究，先后承担国家自然基金课题《DBS戒除阿片药物心理依赖的实验研究》以及上海市科委项 目等多项课题，进行了大量动物实验研究，发表专业论文十余篇，在该领域居领先水平。
     
    药物成瘾，又称吸毒，是当今危害人类生存的最严重的医学和社会问题之一。以往的各种方法虽 然能够使吸毒者生理上脱毒，但却很难戒除吸毒者对毒品的精神依赖而复吸，半年内复吸率高达95%以上。所以，“心瘾”是导致复吸的首要因素，如何戒除“心 瘾”，防复吸成为治疗的重点和难点，这也是世界性难题。
     
    这项研究中的患者为24岁男性，吸毒5年，吸食海洛因、杜冷丁、摇头丸等多种毒品，反复多 次常规戒毒无效，均在戒毒完成当日或第二日复吸，患者及家属强烈要求手术。患者在DBS植入术后即停止吸毒，通过6年的临床随访观察，至今无复吸现象，患 者已恢复工作。经心理学量表评估，未发现有人格、情感、智力等方面影响。
     
    DBS是近年来在国际迅速发展的神经调制新技术。据周洪语介绍，中脑-边缘多巴胺系统是成 瘾药物产生奖赏效应的结构基础，其中伏隔核在调节药物强化作用方面居核心地位。外科手术戒毒通过立体定向技术定位伏隔核，予以射频毁损，使短期复吸率降低 到30~35%以下，为戒毒开辟了新的途径。然而神经核团毁损手术在戒断毒瘾的同时，可能会损伤其它的正常生理功能，导致诸如情感、智力、食欲和性欲等方 面的远期影响，以及某些脑结构功能的不确定性，受到了专家的质疑，2004年11月被卫生部通知叫停，同时也引发了社会各界的广泛关注及业内的较大争论。 而DBS治疗不毁损脑组织，具有微创、可调节性和可逆性等优点。它主要通过在脑深部置入微小的针状电极，利用与之相连的脉冲发生器，发出电流对伏隔核进行 功能刺激，达到神经调制的目的。附属仁济医院功能神经外科组2004年进行了首例DBS戒毒手术，患者随访至今无复吸。（来源：生物通）
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