Deep Brain Stimulation of the Subthalamic Nucleus in Obsessive
Total Page：16
File Type：pdf, Size：1020Kb
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-323421 on 8 October 2020. Downloaded from Neurosurgery ORIGINAL RESEARCH Deep brain stimulation of the subthalamic nucleus in obsessive–compulsives disorders: long- term follow- up of an open, prospective, observational cohort Stephan Chabardes ,1,2,3 Paul Krack,4,5 Brigitte Piallat,3 Thierry Bougerol,6 Eric Seigneuret,2 Jerome Yelnik,7 Sara Fernandez Vidal,7 Olivier David,3 Luc Mallet,7,8,9 Alim- Louis Benabid,1 Mircea Polosan3,6 ► Additional material is ABSTRACT aggressive, sexual and other that will lead to asso- published online only. To view Background Obsessive–compulsive disorder (OCD) ciated compulsions such as counting, checking, please visit the journal online (http:// dx. doi. org/ 10. 1136/ is a major cause of disability in western country and hoarding, washing, symmetry and precision. These jnnp- 2020- 323421). responsible for severe impairment of quality of life. About symptoms are supported by different neuronal 10% of patients present with severe OCD symptoms networks4 5 that may be of therapeutic interest and For numbered affiliations see and require innovative treatment such as deep brain the variability of symptoms mirror their heteroge- end of article. stimulation (DBS). Among possible targets, the non- neity in response to conventional treatment. About motor subthalamic nucleus (STN) is a key node of the 30%–40% of patients present with severe (Yale Correspondence to Pr Stephan Chabardes, basal ganglia circuitry, strongly connected to limbic and Brown Obsessive Compulsive Scale (YBOCS) neurochirurgie, Centre cortical areas known to be involved in OCD. 24–31) to very severe (YBOCS 32–40) OCD symp- Hospitalier Universitaire Method We analysed, in a prospective, observational, toms.5 6 Grenoble Alpes Hôpital monocentric, open label cohort, the effect of chronic OCD usually tends to be chronic and might Michallon, La Tronche, Rhône- non-motor STN-DBS in 19 patients with treatment- require long- term medication and cognitive- Alpes, France; schabardes@ chu- grenoble. fr resistant OCD consecutively operated in a single centre. behaviour therapy (CBT). Indeed, first- line treat- Severity of OCD was evaluated using the Yale and ments for OCD consist of CBT, including exposure Received 5 April 2020 Brown Obsessive–Compulsive Scale (YBOCS). YBOCS and ritual prevention associated or not with medi- Revised 1 July 2020 scores at 6, 12 and 24 months postoperatively were cations, particularly serotonin reuptake inhibitors. Accepted 31 August 2020 compared with baseline. Responders were defined by The above- mentioned conventional treatment >35% improvement of YBOCS scores. Global Assessment can lead to satisfactory responses but improvement Functioning (GAF) scale was used to evaluate the impact after medication and CBT is usually partial and of improvement. consequently, a 35% reduction in YBOCS severity Results At a 24-month follow-up , the mean YBOCS scores can be seen as a good response to the treat- score improved by 53.4% from 33.3±3.5 to 15.8±9.1 ment and represents a typical response criterion in (95% CI 11.2–20.4; p<0.0001). Fourteen out of 19 pharmacological trials. Despite conventional treat- patients were considered as responders, 5 out of 19 ment, approximately 10% of patients with OCD http://jnnp.bmj.com/ being improved over 75% and 10 out of 19 over remain severely disabled.7 50%. GAF scale improved by 92% from 34.1±3.9 to Multimodal functional imaging studies have 66.4±18.8 (95% CI 56.7–76.1; p=0.0003). The most led to a better definition of key brain structures frequent adverse events consisted of transient DBS- involved during the expression of OCD symp- induced hypomania and anxiety. toms.8–10 The orbital frontal region, the dorsolat- Conclusion Chronic DBS of the non-motor STN is an eral prefrontal cortex and the dorsal cingulum have effective and relatively safe procedure to treat severe been identified as key areas during the occurrence on October 3, 2021 by guest. Protected copyright. OCD resistant to conventional management. of OCD. At the subcortical level, bundles going through the anterior capsule have been identified as key neuronal streams that connect the thalamus to the orbitofrontal region. The accumbens nucleus INTRODUCTION has also been seen as a pivotal node due to its role in © Author(s) (or their Obsessive–compulsive disorder (OCD) is a major the reward system that is supposedly overactivated employer(s)) 2020. Re- use cause of disability worldwide1 and responsible in OCD. permitted under CC BY- NC. No for severe impairment of quality of life. It is The better comprehension of the neuronal commercial re- use. See rights one of the most frequent psychiatric conditions circuitry that links motor, cognitive and limbic and permissions. Published by BMJ. just after depression and affects 2%–3% of the cortex to the thalamus and the basal ganglia has population. OCD is characterised by recurrent rendered new surgical strategies possible. In 1999, To cite: Chabardes S, Krack unwanted ideas, images or impulses (obsessions), Nuttin et al11 have proposed to replace lesions of P, Piallat B, et al. J Neurol and repetitive stereotyped behaviours or mental the anterior limb of the capsule by deep brain stim- Neurosurg Psychiatry Epub ahead of print: [please acts (compulsions), often intended to neutralise the ulation (DBS), a surgical therapy developed to treat 12 include Day Month Year]. anxiety induced by the obsessions. Several obses- movement disorders. doi:10.1136/jnnp-2020- sions types can be defined2 3 like contamination, One of the key nodes of this neuronal circuitry is 323421 pathological doubt, somatic, need for symmetry, the subthalamic nucleus (STN), which receive not Chabardes S, et al. J Neurol Neurosurg Psychiatry 2020;0:1–8. doi:10.1136/jnnp-2020-323421 1 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-323421 on 8 October 2020. Downloaded from Neurosurgery only hyperdirect connections from the motor and non- motor Table 1 : Main inclusions and exclusions criteria cortex, but also indirect inhibitory connections from the stri- atum through the Globus Pallidus externus.13 14 From a clinical Inclusion criteria Exclusion criteria stand point, a posteroanterior gradient from motor, cognitive OCD defined by DSM- IV Yes Yes: bipolar disorder, and limbic territories can explain why stimulations of the poste- schizophrenic disorder; rior and dorsal part of the STN in patient with Parkinson’s current substance abuse disease (PD) can alleviate motor symptoms, whereas the more or dependence (except nicotine) anterior and ventral site of stimulation can impact non- motor Cluster A/B personality NA Yes symptoms of PD.15 disorders This was illustrated by the report of three cases of patients Recent severe depression NA Yes with PD, who also suffered from OCD as a comorbidity, and who 15 16 improved after STN- DBS. In those cases reports, the motor ► MADRS score >20 STN was the original target but the leads were a little bit more ► Risk of suicide anteriorly placed, at the junction between motor and non- motor (MADRS item-10 score STN (noM- STN). Mallet et al17 reported in 2008 the results of >2) the French multicentre, double- blind, cross- over control study Age >18 NA (STOC study) assessing the effect of noM- STN- DBS to treat YBOCS >25 NA patients with severe OCD. They mainly showed that the YBOCS GAF <45 NA was significantly improved by 31% on average as compared with CGI >4 NA Off condition. Medications Failure of three serotonin NA Following this study, we prospectively followed, in an open, reuptake inhibitors observational, prospective, monocentric cohort, 19 consecutive including clomipramine patients suffering from severe OCD refractory to conventional after a minimum of 12 weeks of adequate management in order to (1) confirm the potential effective- treatment and two ness of STN- DBS at short-term and long- term follow- ups (24 augmentation strategies months) and (2) asses the safety of STN- DBS for OCD. Psychotherapy Failure of cognitive NA behavioural therapy MATERIALS AND METHODS conducted during at least 1 year with two therapists All patients gave informed consent before their inclusion in the surgery programme. Inclusion and exclusion criteria strictly CGI, Clinical Global Impression; DSM- IV, Diagnostic And Statistical Manual OF 17 mental Disorders- 4 th edition; GAF, Global Assessment Functioning; MADRS, followed those previously used in the STOC study. One of the Montgomery- Asberg Depression Rating Scale; NA, not applicable; OCD, obsessive– senior coauthors asked the French National Ethical Committee compulsive disorder; YBOCS, Yale and Brown Obsessive–Compulsive Scale . to approve such procedure and a multidisciplinary committee selected the cases to be enrolled.18 Most of them were referred to by independent psychiatrists. the motor target position. We then marked the point located 2 mm anterior and 1 mm medial to that motor target, in the Inclusion criteria and ethics (see table 1) anteroposterior direction of the main axis of the STN.17 19 Then, a frameless, robot- assisted surgery was performed using ROSA Surgery robotic arm and Rosanna software (Zimmer Biomet, USA) that http://jnnp.bmj.com/ The surgical technique used replicated that routinely used to allowed the fusion of all imaging modalities including preopera- treat patients with PD with STN- DBS12 except that the OCD tive CT scan, T1 and T2 MRI and intraoperative, tele X-ray . All target was slightly more anterior and medial.19 In the first 11 patients had postoperative CT scan before the implantation of patients, the indirect targeting of the motor STN (M- STN) was the battery (Kinetra then Activa PC, Medtronic, Minneapolis, determined on the ventriculography schema fused with the MRI USA) that occurred 2 days after lead implantation. Surgery was and corresponded to the following coordinates: 7 of 12 of the performed in all cases except one under local anaesthesia that anterior–posterior commissural (AC- PC) length posterior to allowed intraoperative checking for side effects and for possible on October 3, 2021 by guest.