48 Chapter 3 INTRODUCTION Anorexia nervosa (AN) has a lifetime prevalence of 4.2% (1) and a crude mortality rate of 5.6% per decade, due to suicide and other medical complications (2, 3). Even with the best available treatments, 21% of AN-patients will become chronic and treatment-refractory (4). In search of novel treatments for these patients, pioneering studies have investigated deep brain stimulation (DBS) (5-14). DBS is a treatment involving implantation of electrodes, which send electrical impulses to alter activity in specific neurocircuits. Past research has investigated the subgenual cingulate cortex (SCC), ventral striatum (VS), nucleus accumbens (NAc), medial fore brain (MFB)/post hypothalamic area (PHA), and the bed nucleus of the stria terminalis (BNST) as stereotactic target in AN-patients, although AN was not always the primary disease for which DBS was implanted. Cumulatively, the literature described 56 AN patients treated with DBS worldwide. Studies were usually small, consisting of cases/case series, with varying in- and exclusion criteria and outcome measures. Results are mixed, with some studies showing promise, while others showed limited effectiveness. As a result of this small number of heterogeneous studies, the evidence of the efficacy, feasibility and safety of DBS for chronic, treatment-refractory AN, remains unclear. Our 15 year experience with DBS in OCD-patients showed strong and long-lasting effects of targeting the ventral anterior limb of internal capsule (vALIC), part of the reward-circuitry (15). Interestingly, AN and OCD show several clinical similarities, including anorectic obsessions and compulsive food-related behavior. Therefore, we hypothesized that targeting the vALIC may exert comparable beneficial effects in treatment-refractory AN. Moreover, our DBS methodology has distinctive characteristics, including an extensive optimization period during which DBS-settings are optimized with thorough phenotyping. This may provide new insight in the psychological, somatic and functional effects of (vALIC) DBS in AN. In the present study, we targeted DBS in AN for the first time to vALIC. We included a highly selective sample of patients with exceptionally severe and enduring AN, with an a priori low expected response to treatment. Although challenging, they reflect the prototypical patients that may be eligible for DBS as a last resort treatment option in AN (16).
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