Deep Brain Stimulation for Severe Anorexia Nervosa

Main objective:

To selectively target for neuromodulation the key structures known to be involved in the motivational aspect of food intake, i.e. the nucleus accumbens, while evaluating safety and tolerance in the specific setting of AN patients (monitoring of serious adverse events [SAE])

Secondary objectives:

• Evaluation of patient's acceptance,
• Effect of DBS on weight stabilization (maintenance of patients' BMI above 14kg/m2),
• Effect of DBS on pupillometry in patients with severe and resistant AN,
• Effect of DBS on intermediate clinical variables such as loss of cognitive flexibility, overestimation of delayed rewards, and central coherence defect,
• Effect of DBS on psychiatric comorbidities of patients suffering from severe and resistant AN.

Prospective multicenter study: interventional cohort

Practical conduct:

A. If all the inclusion criteria are met, proposal to participate in the study allowing a time window of 2 weeks of reflection before giving consent, B. Joint neurosurgeon/psychiatrist information consultation with delivery of a consent form, C. Preoperative assessment carried out after a delay of at least 2 weeks (anaesthesia consultation, brain MRI and neurocognitive assessment), D. Admisison in neurosurgery for one week to perform the DBS procedure. Post-operative CT Scan. The stimulation is turned on for all patients upon discharge from the hospital , E. Joint follow-up visit with the referring physician (once a month) and the neurosurgeon (once every 2 months) for 12 months F. Two neurocognitive assessments during follow-up visit : one early and one late postoperative (respectively at 5 and 11 months)

Inclusion period: 24 months Duration of preoperative assessment and reflection phase: 3 months Duration of participation (treatment + follow-up): 12 months Total duration: 40 months

Statistical analyses:

Descriptive results are presented as means ± standard deviations for continuous data and as percentages for categorical data.

The unpaired and paired t-test because of repeated measures in the same subjects, the Fisher's exact test will be use. A p<0.05 will be considered as statistically significant. A binomial sequence test is performed after each patient inclusion to check that the rate of SAE remains inferior to 25%.

Inclusion criteria

• Diagnosis of Anorexia nervosa according to DSM V criteria.
• Age 18 to 65 years.
• Chronic, treatment-resistant anorexia nervosa, defined as:

• Anorexia nervosa evolving for at least 7 years.
• Inability to maintain a BMI ≥ 17kg/m² for 2 months following hospitalization in a center specialized for the management of patients suffering from eating disorders according to the criteria of the French Federation of Anorexia and Bulimia nervosa and the Directorate General of Care Provision (Direction Générale de l'Offre de Soins - DGOS, in French). Failure of at least 2 hospitalizations in a specialized center during the history of the disease.
• Inability to maintain a BMI ≥ 17kg/m² for more than 3 consecutive months during an outpatient treatment conducted by a team specialized for the care of patients suffering from eating disorders according to the criteria of the French Federation of Anorexia and Bulimia and the Directorate General of Care Provision (Direction Générale de l'Offre de Soins - DGOS, in French) in the year preceding the inclusion. Failure of at least 2 outpatient treatments conducted by a specialized team during the AN care.
• Impaired psychological, social and occupational functioning defined by a score ≤ 45 on the Global Assessment of Functioning Scale.
• Anorexia nervosa is judged to be the primary disorder if there are psychiatric comorbidities such as depression, anxiety disorder, obsessive-compulsive disorder, or personality disorder by at least two independent experts.
• The patient is able to comply with the operational and administrative requirements of the study and is able to complete the protocol forms.
• Patient provides written informed consent.
• Patient is drug-free or on a medication that has been stable for at least 6 weeks at the time of study entry.
• If female subject and of childbearing age: use of an effective method of contraception.
• Membership in a health insurance plan or beneficiary.

Exclusion criteria

• Presence of an Axis I disorder that is primary to anorexia nervosa.
• Presence of a personality disorder that could compromise compliance with post-surgical follow-up assessed by 2 independent experts
• Presence of severe neurological pathology or significant MRI abnormalities (excluding anorexia-related atrophy).
• Cognitive and intellectual ability to understand the risks and constraints of the technique or to give informed consent.
• Albumin levels <30g/L.
• Presence of medical contraindications to undergo implantation of a DBS system or to realize an MRI (pacemaker).
• Pregnant or breastfeeding woman.
• Previous DBS.
• Trusted person and/or family object to patient's participation.
• Contraindication to general anesthesia.