66 Chapter 3 Dear editor, Anorexia nervosa (AN) is a severe and often chronic psychiatric disorder with high morbidity and mortality (1). Pilot studies and cases showed mixed but promising effects of deep brain stimulation (DBS) as a last-resort treatment option for life-threatening treatment-refractory AN (2, 3). The present study (N=4) is the first to target DBS in AN at the ventral anterior limb of the capsula interna (vALIC), part of the reward circuitry. vALIC-DBS showed strong and long-lasting effects in obsessive-compulsive disorder (OCD). We hypothesized that, due to the clinical and neurobiological similarities between AN and OCD, vALIC-DBS may exert comparable effects in treatment-refractory AN. We included a sample of patients with exceptionally severe AN. Although challenging, they reflect the prototypical patients that may be eligible for DBS as a last resort treatment option (4). Inclusion criteria included primary diagnosis of AN, a Body Mass Index (BMI) <15, a Global Assessment of Function score (GAF-score) of 45 or less for ≥2 years (5), an illness duration of ≥10 years and a lack of response to ≥2 typical modes of treatment including ≥1 inpatient treatment of hospitalization. We conducted bilateral stereotactic implantation of DBS electrodes in the vALIC. In accordance with our DBS studies (6) the study comprised four sequential phases: preoperative (T-1), surgery (T0), optimization (3-9 months; T1-T2) and maintenance phase (12 months; T2-T4) (Supplement 1, methods and statistical analysis). During the study the patients received standard medical and psychiatric care, comprised of regular visits with a nurse-practitioner and a psychiatrist. No major psychopharmacological adjustments were made. Primary outcome measures were 1) change in body mass index (BMI), 2) change in Yale-BrownCornell Eating Disorder Scale (YBC-EDS)-score (7) and 3) change in Eating Disorder Quality of Life (ED-QOL)-score (8). We established side effects and safety through frequent and intensive monitoring by a psychiatrist, including checks of vital parameters, standard laboratory assessments and ECG. All patients were assessed using (self-report) questionnaires. Four female patients were enrolled between 2016 and 2020. Patients had a mean age of 39 years (SD=10) and illness duration of 21 years (SD=3). Average baseline BMI was 12.5 (SD=1.0) kg/m2, indicating extremely severe AN. Monopolar DBS at the middle two contacts was switched on at T1 (pulse width 90 μs, frequency 130 ms) at a mean voltage of 3.0 V (2.5-3.5 V). The mean voltages at T2, T3 and T4 were respectively 3.8 V (3.0-5.0 V), 3.8 V (3.0-4.5 V) and 3.8 V (2.7-4.8 V). Adjustment of the stimulation intensity occurred in steps of 0,5 V, later fine-tuning in steps of 0,1 V. Pulse width and frequency remained unchanged during the study. BMI increased substantially and significantly at the end of follow-up (5.32 kg/m2; +42.8%; P=.017) (figure 1).
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