Lipsman Nir, Lam Eileen, Volpini Matthew, Sutandar Kalam, Twose Richelle, Giacobbe Peter, Sodums Devin J, Smith Gwenn S, Woodside D Blake, Lozano Andres M
Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Physical Sciences Platform, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Department of Psychiatry, University Health Network, University of Toronto, Toronto, ON, Canada.
Lancet Psychiatry. 2017 Apr;4(4):285-294. doi: 10.1016/S2215-0366(17)30076-7. Epub 2017 Feb 24.
Anorexia nervosa is a life-threatening illness. Brain circuits believed to drive anorexia nervosa symptoms can be accessed with surgical techniques such as deep brain stimulation (DBS). Initial results suggest that DBS of the subcallosal cingulate is safe and associated with improvements in mood and anxiety. Here, we investigated the safety, clinical, and neuroimaging outcomes of DBS of the subcallosal cingulate in a group of patients during 12 months of active stimulation.
We did this prospective open-label trial at the Department of Surgery of the University of Toronto (Toronto, ON, Canada). Patients were eligible to participate if they were aged 20-60 years and had a diagnosis of anorexia nervosa (restricting or binge-purging subtype) and a demonstrated history of chronicity or treatment resistance. Following a period of medical stabilisation, patients underwent surgery for DBS and received open-label continuous stimulation for the entire 1 year study duration. The primary outcome was safety and acceptability of the procedure. The secondary outcomes were body-mass index (BMI), mood, anxiety, affective regulation, and anorexia nervosa-specific behaviours at 12 months after surgery, as well as changes in neural circuitry (measured with PET imaging of cerebral glucose metabolism at baseline and at 6 and 12 months after surgery). This trial was registered with ClinicalTrials.gov, number NCT01476540.
16 patients with treatment-refractory anorexia nervosa were enrolled between September, 2011, and January, 2014, and underwent DBS of the subcallosal cingulate between November, 2011, and April, 2014. Patients had a mean age of 34 years (SD 8) and average illness duration of 18 years (SD 6). Two patients requested that their devices be removed or deactivated during the study, although their reasons for doing so were poorly defined. The most common adverse event was pain related to surgical incision or positioning that required oral analgesics for longer than 3-4 days after surgery (five [31%] of 16 patients). Seven (44%) of 16 patients had serious adverse events, most of which were related to the underlying illness, including electrolyte disturbances. Average BMI at surgery was 13·83 (SD 1·49) and 14 (88%) of the 16 patients had comorbid mood disorders, anxiety disorders, or both. Mean BMI after 12 months of stimulation was 17·34 (SD 3·40; p=0·0009 vs baseline). DBS was associated with significant improvements in measures of depression (mean Hamilton Depression Rating Scale scores 19·40 [SD 6·76] at baseline vs 8·79 [7·64] at 12 months; p=0·00015), anxiety (mean Beck Anxiety Inventory score 38·00 [15·55] vs 27·14 [18·39]; p=0·035), and affective regulation (mean Dysfunction in Emotional Regulation Scale score 131·80 [22·04] vs 104·36 [31·27]; p=0·019). We detected significant changes in cerebral glucose metabolism in key anorexia nervosa-related structures at both 6 months and 12 months of ongoing brain stimulation.
In patients with chronic treatment-refractory anorexia nervosa, DBS is well tolerated and is associated with significant and sustained improvements in affective symptoms, BMI, and changes in neural circuitry at 12 months after surgery.
Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.
神经性厌食症是一种危及生命的疾病。通过深部脑刺激（DBS）等外科技术可以触及被认为驱动神经性厌食症症状的脑回路。初步结果表明，扣带回下区的DBS是安全的，并且与情绪和焦虑的改善有关。在此，我们研究了一组患者在12个月的积极刺激期间扣带回下区DBS的安全性、临床和神经影像学结果。
我们在加拿大多伦多大学外科系进行了这项前瞻性开放标签试验。年龄在20-60岁之间、被诊断为神经性厌食症（限制型或暴食-清除型）且有慢性病史或治疗抵抗史的患者有资格参与。经过一段时间的医学稳定后，患者接受DBS手术，并在整个1年的研究期间接受开放标签的持续刺激。主要结果是该手术的安全性和可接受性。次要结果是术后12个月时的体重指数（BMI）、情绪、焦虑、情感调节和神经性厌食症特异性行为，以及神经回路的变化（通过手术前、术后6个月和12个月的脑葡萄糖代谢PET成像测量）。该试验已在ClinicalTrials.gov注册，注册号为NCT01476540。
2011年9月至2014年1月期间，16例难治性神经性厌食症患者入组，并在2011年11月至2014年4月期间接受了扣带回下区DBS。患者的平均年龄为34岁（标准差8），平均病程为18年（标准差6）。两名患者在研究期间要求移除或停用他们的设备，尽管他们这样做的原因并不明确。最常见的不良事件是与手术切口或定位相关的疼痛，术后需要口服镇痛药超过3-4天（16例患者中有5例[31%]）。16例患者中有7例（44%）发生严重不良事件，其中大多数与基础疾病有关，包括电解质紊乱。手术时的平均BMI为13.83（标准差1.49），16例患者中有14例（88%）合并有情绪障碍、焦虑障碍或两者皆有。刺激12个月后的平均BMI为17.34（标准差3.40；与基线相比p=0.0009）。DBS与抑郁测量指标（汉密尔顿抑郁量表平均得分在基线时为19.40[标准差6.76]，在12个月时为8.79[7.64]；p=0.00015）、焦虑（贝克焦虑量表平均得分38.00[15.55]对27.14[18.39]；p=0.035）和情感调节（情绪调节障碍量表平均得分131.80[22.04]对104.36[31.27]；p=0.019）的显著改善有关。在持续脑刺激的6个月和12个月时，我们在关键的神经性厌食症相关结构中检测到脑葡萄糖代谢的显著变化。
在慢性难治性神经性厌食症患者中，DBS耐受性良好，并且与术后12个月时情感症状、BMI和神经回路变化的显著且持续改善有关。
克拉曼家族基金会饮食失调研究资助计划和加拿大卫生研究院。
