Nir Lipsman1, D Blake Woodside2, Peter Giacobbe2, Clement Hamani1, Jacqueline C Carter2, Sarah Jane Norwood3, Kalam Sutandar2, Randy Staab4, Gavin Elias1, Christopher H Lyman5, Gwenn S Smith5, Andres M Lozano6. 1. Division of Neurosurgery, Toronto Western Hospital, Department of Surgery, University of Toronto, Toronto, ON, Canada. 2. Department of Psychiatry, University of Toronto, Toronto General Hospital, ON, Canada. 3. Department of Psychology, York University, Toronto, ON, Canada. 4. Division of Psychiatry, Credit Valley Hospital, Mississauga, ON, Canada. 5. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 6. Division of Neurosurgery, Toronto Western Hospital, Department of Surgery, University of Toronto, Toronto, ON, Canada. Electronic address: lozano@uhnresearch.ca.
Abstract
BACKGROUND: Anorexia nervosa is characterised by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinson's disease and major depression, with promising results. We aimed to assess the safety of DBS to modulate the activity of limbic circuits and to examine how this might affect the clinical features of anorexia nervosa. METHODS: We did a phase 1, prospective trial of subcallosal cingulate DBS in six patients with chronic, severe, and treatment-refractory anorexia nervosa. Eligible patients were aged 20-60 years, had been diagnosed with restricting or binge-purging anorexia nervosa, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimisation preoperatively and had baseline body-mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also done at various intervals. This trial is registered with ClinicalTrials.gov, number NCT01476540. FINDINGS: DBS was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events were panic attack during surgery, nausea, air embolus, and pain. After 9 months, three of the six patients had achieved and maintained a BMI greater than their historical baselines. DBS was associated with improvements in mood, anxiety, affective regulation, and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite PET scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder. INTERPRETATION: Subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory anorexia nervosa. FUNDING: Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.
BACKGROUND:Anorexia nervosa is characterised by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinson's disease and major depression, with promising results. We aimed to assess the safety of DBS to modulate the activity of limbic circuits and to examine how this might affect the clinical features of anorexia nervosa. METHODS: We did a phase 1, prospective trial of subcallosal cingulate DBS in six patients with chronic, severe, and treatment-refractory anorexia nervosa. Eligible patients were aged 20-60 years, had been diagnosed with restricting or binge-purging anorexia nervosa, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimisation preoperatively and had baseline body-mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also done at various intervals. This trial is registered with ClinicalTrials.gov, number NCT01476540. FINDINGS: DBS was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events were panic attack during surgery, nausea, air embolus, and pain. After 9 months, three of the six patients had achieved and maintained a BMI greater than their historical baselines. DBS was associated with improvements in mood, anxiety, affective regulation, and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite PET scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder. INTERPRETATION: Subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory anorexia nervosa. FUNDING: Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.
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Authors: Ausaf A Bari; Charles B Mikell; Aviva Abosch; Sharona Ben-Haim; Robert J Buchanan; Allen W Burton; Stephen Carcieri; G Rees Cosgrove; Pierre-Francois D'Haese; Zafiris Jeffrey Daskalakis; Emad N Eskandar; Jason L Gerrard; Wayne K Goodman; Benjamin David Greenberg; Robert E Gross; Clement Hamani; Zelma H T Kiss; Peter Konrad; Brian H Kopell; Lothar Krinke; Jean-Philippe Langevin; Andres M Lozano; Donald Malone; Helen S Mayberg; Jonathan P Miller; Parag G Patil; DeLea Peichel; Erika A Petersen; Ali R Rezai; R Mark Richardson; Patricio Riva-Posse; Tejas Sankar; Jason M Schwalb; Helen Blair Simpson; Konstantin Slavin; Paul H Stypulkowski; Tor Tosteson; Peter Warnke; Jon T Willie; Kareem A Zaghloul; Joseph S Neimat; Nader Pouratian; Sameer A Sheth Journal: J Neurol Neurosurg Psychiatry Date: 2018-01-25 Impact factor: 10.154