To the Editor: Liu et al1 are to be congratulated for describing the largest published series of bilateral anterior capsulotomy in anorexia nervosa (AN). Their work confirms that magnetic resonance imaging-guided bilateral anterior capsulotomy represents a possible treatment for refractory AN, a life-threatening condition that can be resistant to usual care. However, certain points should be clarified. These points are: (1) the definition of inclusion criteria, (2) the definition of primary endpoint, (3) the study design, (4) the target definition and the use of anterior capsulotomy, and (5) the long-term follow-up and evaluation of the included patients. The inclusion of psychiatric patients in trials assessing invasive treatment is challenging. In the specific condition of AN, the inclusion criteria pitfalls are difficult to overcome. There are no clear and strict criteria defining “refractory” AN. In addition, the minimum duration of disease before considering resistance is not clearly defined. Lastly, the definition of resistance differs between previously published studies on invasive treatment for AN.6,7 There is therefore a need for consensual operational criteria to identify treatment-refractory patients with AN.8 Another difficulty in AN studies is the absence of a clear definition of remission. Weight restoration is a crucial component of AN recovery, but is only 1 component of it, probably consisting in a first clinical step. Mood disorders and anxiety are also involved in AN relapse. This, in turn, may explain why targeted brain areas known to regulate emotion, such as the subcallosal cingulate gyrus, represent an option chosen by many authors.6 The long-term follow-up of patients included in such experimental procedure represents the gold-standard to assess the safety and efficacy in practical conditions. Complete pre- and postoperative investigations, eventually including positron emission tomography scan, could help to determine the remission of AN patients.6 The design of the present study was a case-series, a typical design for studies on this topic. It is well-known that enrollment in a study leads to different care than “regular” patients.9 A case control study, enrolling patients in the same treatment regimen except for the invasive procedure, could partly overcome this bias. Definition of the target in AN represents another challenge for the multidisciplinary team in charge of patients. Anterior capsulotomy was performed for the first time by Jean Talairach at Sainte-Anne Hospital in 1949 and had proved to be effective in obsessive compulsive disorder.10 Nevertheless, it is an irreversible procedure and the rate of complication in this study was relatively high (17.6%). More comprehensive neuropsychological tests for their patients are recommended, as well as a long-term evaluation of complications “memory loss” and “lethargy.” The cognitive evaluation consisted in Mini Mental State Examination. Mini Mental State Examination was designed for dementia and do not detect mild cognitive impairment,20 as acknowledge by the authors. Somatic complications of undernutrition and suicide make AN the psychiatric disorder with the highest mortality rate.2 Efficient treatment is still lacking as 20% of patients experience recurrent patterns of remissions and relapses, chronicity being also a problem.3 Invasive procedures for psychiatric patients should remain exceptional but have to be considered. Multicentric studies enrolling a large number of patients, with strict inclusion criteria and clear ethic rules, could help to define which patients with AN may benefit of deep brain stimulation,4,5 but such studies are still pending. Deep brain stimulation is a minimally invasive, and almost completely reversible, surgical procedure. Stimulation parameters can be adapted to each patient making deep brain stimulation an adjustable therapy.11 However, in these severely malnourished population of patients, implantation of deep brain stimulation devices is at higher risk, requiring close collaboration with intensive care specialists. Sun et al7 reported promising results of deep brain stimulation of the nucleus accumbens for treatment resistant AN. This target is promising because of the role of nucleus accumbens in the reward system.12,13 Recent neurocognitive and neuroimaging studies or animal models incriminate reward system in development and maintenance of AN.14-19 Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Liu W , Li D , Sun F et al. Long-term follow-up study of MRI-guided bilateral anterior capsulotomy in patients with refractory anorexia nervosa . Neurosurgery . 2018 ; 83 ( 1 ): 86 - 92 . 2. Franko DL , Keshaviah A , Eddy KT et al. A longitudinal investigation of mortality in anorexia nervosa and bulimia nervosa . Am J Psychiatry . 2013 ; 170 ( 8 ): 917 - 925 . Google Scholar CrossRef Search ADS PubMed 3. Steinhausen HC . The outcome of anorexia nervosa in the 20th century . Am J Psychiatry . 2002 ; 159 ( 8 ): 1284 - 1293 . Google Scholar CrossRef Search ADS PubMed 4. Nuttin B , Wu H , Mayberg H et al. Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders . J Neurol Neurosurg Psychiatry . 2014 ; 85 ( 9 ): 1003 - 1008 . Google Scholar CrossRef Search ADS PubMed 5. Park RJ , Singh I , Pike AC , Tan JOA . Deep brain stimulation in anorexia nervosa: hope for the hopeless or exploitation of the vulnerable? The oxford neuroethics gold standard framework . Front Psychiatry . 2017 ; 8 : 1 - 10 . doi:10.3389/fpsyt.2017.00044 . Google Scholar CrossRef Search ADS PubMed 6. Lipsman N , Lam E , Volpini M et al. Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial . Lancet Psychiatry . 2017 ; 4 ( 4 ): 285 - 294 . Google Scholar CrossRef Search ADS PubMed 7. Wu H , Van Dyck-Lippens PJ , Santegoeds R et al. Deep-brain stimulation for anorexia nervosa . World Neurosurg . 2013 ; 80 ( 3-4 ): S29.e1 - S29.e10 . Google Scholar CrossRef Search ADS 8. Oudijn MS , Storosum JG , Nelis E , Denys D . Is deep brain stimulation a treatment option for anorexia nervosa? BMC Psychiatry . 2013 ; 13 ( 1 ): 1 - 9 . Google Scholar CrossRef Search ADS PubMed 9. Stiller CA . Centralised treatment, entry to trials and survival . Br J Cancer . 1994 ; 70 ( 2 ): 352 - 362 . Google Scholar CrossRef Search ADS PubMed 10. Zanello M , Pallud J , Baup N et al. History of psychosurgery at Sainte-Anne Hospital, Paris, France, through translational interactions between psychiatrists and neurosurgeons . Neurosurg Focus . 2017 ; 43 ( 3 ): 1 - 9 . Google Scholar CrossRef Search ADS 11. Nuttin B , Cosyns P , Demeulemeester H , Gybels J , Meyerson B . Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder . Lancet . 1999 ; 354 ( 9189 ): 1526 . Google Scholar CrossRef Search ADS PubMed 12. Jean A , Conductier G , Manrique C et al. Anorexia induced by activation of serotonin 5-HT4 receptors is mediated by increases in CART in the nucleus accumbens . Proc Natl Acad Sci USA . 2007 ; 104 ( 41 ): 16335 - 16340 . Google Scholar CrossRef Search ADS PubMed 13. Frank GK , Bailer UF , Henry SE et al. Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride . Biol Psychiatry . 2005 ; 58 ( 11 ): 908 - 912 . Google Scholar CrossRef Search ADS PubMed 14. Cha J , Ide JS , Bowman FD , Simpson HB , Posner J , Steinglass JE . Abnormal reward circuitry in anorexia nervosa: a longitudinal, multimodal MRI study . Hum Brain Mapp . 2016 ; 37 ( 11 ): 3835 - 3846 . Google Scholar CrossRef Search ADS PubMed 15. Clarke J , Ramoz N , Fladung AK , Gorwood P . Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism . Transl Psychiatry . 2016 ; 6 ( 6 ): e829 - e829 . Google Scholar CrossRef Search ADS PubMed 16. DeGuzman M , Shott ME , Yang TT , Riederer J , Frank GKW . Association of elevated reward prediction error response with weight gain in adolescent anorexia nervosa . Am J Psychiatry . 2017 ; 174 ( 6 ): 557 - 565 . Google Scholar CrossRef Search ADS PubMed 17. O’Hara CB , Campbell IC , Schmidt U . A reward-centred model of anorexia nervosa: a focussed narrative review of the neurological and psychophysiological literature . Neurosci Biobehav Rev . 2015 ; 52 : 131 - 152 . doi:10.1016/j.neubiorev.2015.02.012 . Google Scholar CrossRef Search ADS PubMed 18. Foldi CJ , Milton LK , Oldfield BJ . A focus on reward in anorexia nervosa through the lens of the activity-based anorexia rodent model . J Neuroendocrinol . 2017 ; 29 ( 10 ): 1 - 9 . Google Scholar CrossRef Search ADS 19. Liu TT , Hong QX , Xiang HB . The change in cerebral glucose metabolism after electroacupuncture: a possible marker to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa . Int J Clin Exp Med . 2015 ; 8 ( 10 ): 19481 - 19485 . Google Scholar PubMed 20. Folstein MF , Folstein SE , McHugh PR . “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician . J Psychiatr Res . 1975 ; 12 ( 3 ): 189 - 198 . Google Scholar CrossRef Search ADS PubMed Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
Neurosurgery – Oxford University Press
Published: Apr 18, 2018
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