Children's Institute, Division of Pediatric Endocrinology, University of São Paulo Medical School, São Paulo, Brazil.
Division of Functional Neurosurgery of Institute of Psychiatry, Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
JAMA Netw Open. 2018 Nov 2;1(7):e185275. doi: 10.1001/jamanetworkopen.2018.5275.
Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat.
To test the safety and study the outcome of DBS in patients with PWS.
DESIGN, SETTING, AND PARTICIPANTS: This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included.
Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months).
Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits.
Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking.
Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.
深部脑刺激 (DBS) 已被用于治疗病态肥胖症，但结果各不相同。患有普拉德-威利综合征 (PWS) 的患者会出现肥胖，这种肥胖通常很难治疗。
测试 DBS 在 PWS 患者中的安全性和研究结果。
设计、地点和参与者：本病例系列研究在巴西圣保罗大学附属医院进行。共纳入 4 名经基因证实患有 PWS 且伴有严重肥胖的患者。
双侧将 DBS 电极植入外侧下丘脑区。DBS 植入后，治疗包括以下阶段：滴定（1-2 个月）、刺激关闭（2 个月）、低频 DBS（40Hz；1 个月）、洗脱（15 天）、高频 DBS（130Hz；1 个月）和长期随访（6 个月）。
主要观察指标为刺激期间和长期 DBS 治疗期间记录的不良事件。次要结果包括治疗 6 个月后与基线相比，体重、体重指数（体重以千克为单位，身高以米为单位）、腹部和颈部周长、生物电阻抗法和热量测定的变化。在 DBS 前后进行了以下评估和测量：临床、神经、精神、神经心理学、人体测量学、热量测定、血液检查、激素水平和睡眠研究。在所有随访期间监测不良事件。
共纳入 4 例 PWS 患者（男 2 例，女 2 例；年龄 18-28 岁）。基线平均（SD）体重指数为 39.6（11.1）。2 例患者曾行减重手术，均伴有精神共病，经药物治疗得到良好控制。长期 DBS 治疗 6 个月后，患者体重平均增加 9.6%，体重指数增加 5.8%，腹部周长增加 8.4%，颈部周长增加 4.2%，体脂百分比增加 5.3%，热量测定无变化。激素水平和血液检查、睡眠研究和神经心理学评估结果也无变化。2 例患者出现刺激诱导的躁狂症状。1 例患者停止 DBS 控制了这一症状，另 1 例患者需要调整药物剂量。记录了 2 例感染，其中 1 例与皮肤搔抓有关。
外侧下丘脑刺激的安全性与接受 DBS 治疗的具有类似精神状况的患者相似。在我们研究中接受治疗的 PWS 小队列患者中，DBS 效果大多不佳。
