Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Burnout and dropout intention in medical students: the protective role of academic engagement.

INTRODUCTION: The influence of burnout, academic engagement, and their interaction in dropout intention among medical students should be further studied. Current research shows its consequences are relevant, however, there is little understanding on burnout and academic engagement moderation in dropout intention. The current study tested a model that relates the effects of coping strategies, social support satisfaction, general distress on academic engagement, burnout, and dropout intention, on medical students. METHODS: Through an online survey a non-probabilistic sample of one Medical Faculty's 1st- and 2nd-year students was recruited. Cross-sectional data were collected using psychometric instruments (Maslach Burnout Inventory - Student Survey, Social Support Satisfaction Scale for College Students, Brief COPE Scale for College Students, University Student Engagement Inventory, and Depression, Anxiety and Stress Scale), sociodemographic and academic variables, and analyzed using structural equation modeling. RESULTS: 532 students (76% response rate) enrolled in the study. Latent variables structural model presented a satisfactory fit to the data and confirmed the expected negative path between burnout and dropout intention (ßDI<-SB=0.430; p<.001) and the latent moderation burnout x engagement (ßDI<-SB*SE=-0.218; p<.001). CONCLUSION: Academic engagement attenuates the impact of burnout on dropout intention, working as a protective factor. Social support satisfaction and adaptive coping are associated with increased levels of academic engagement, and general distress and maladaptive coping are associated with burnout. Medical Schools should develop interventions to prevent dropout intention, tackle students' stress and academic challenges, and develop their academic engagement levels.

Anterior Nucleus of Thalamus Deep Brain Stimulation: A Clinical-Based Analysis of the Ideal Target in Drug-Resistant Epilepsy.

INTRODUCTION: Deep brain stimulation of the anterior nucleus of thalamus (ANT-DBS) is an approved procedure for drug-resistant epilepsy. However, the preferred location inside ANT is not well known. In this study, we investigated the relationship between stereotactical coordinates of stimulated contacts and clinical improvement, in order to define the ideal target for ANT-DBS. METHODS: Individual contact's coordinates were obtained in the Montreal Neurological Institute (MNI) 152 space, with the utilization of advanced normalization tools and co-registration of pre- and postoperative MRI and CT images in open-source toolbox lead-DBS with the "Atlas of the Human Thalamus." Each contact's pair was either classified as a responder (≥50% seizure reduction and absence of intolerable adverse effects) or nonresponder, with a minimum follow-up of 11 continuous months of stimulation. RESULTS: A total of 19 contacts' pairs were tested in 14 patients. The responder rate was 9 out of 14 patients (64.3%). In 4 patients, a change in contacts' pairs was needed to achieve this result. A highly encouraging location inside ANT (HELIA) was delimited in MNI space, corresponding to an area in the anterior and inferior portion of the anteroventral (AV) nucleus, medially to the endpoint of the mammillothalamic tract (ANT-mtt junction) (x [3.8; 5.85], y [-2.1; -6.35] and z [6.2; 10.1] in MNI space). Statistically significant difference was observed between responders and nonresponders, in terms of the number of coordinates inside this volume. Seven responders and two nonresponders had at least 5 of 6 coordinates (2 electrodes) inside HELIA (77.8% sensitivity and 80% specificity). In 3 patients, changing to contacts that were better placed inside HELIA changed the status from nonresponder to responder. CONCLUSIONS: A relationship between stimulated contacts' coordinates and responder status was observed in drug-resistant epilepsy. The possibility to target different locations inside HELIA may help surpass anatomical variations and eventually obtain increased clinical benefit.

ESSFN Conference Proceedings, Marseille, France, September 8-11, 2021.

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Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus).

INTRODUCTION: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. METHODS: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of ≥71 % was considered as consensus. RESULTS: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. CONCLUSIONS: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS.

Anterior Limb of Internal Capsule and Bed Nucleus of Stria Terminalis Stimulation for Gilles de la Tourette Syndrome with Obsessive-Compulsive Disorder in Adolescence: A Case of Success.

Gilles de la Tourette syndrome (GTS) is a neurobehavioral disorder comprising motor and vocal tics. In most cases it is associated with other disorders such as obsessive-compulsive disorder (OCD). In refractory cases deep brain stimulation (DBS) is a valid treatment option. This paper describes the case of a 15-year-old adolescent with an extremely refractory GTS with associated OCD. The patient developed catatonia associated with OCD, which partially remitted after electroconvulsive therapy. At the peak of the disease the Yale Global Tic Severity Scale (YGTSS) was 100 and the patient required sedation and intubation. All medical treatment options were unsuccessful. Bilateral DBS of the anterior limb of internal capsule (ALIC)/bed nucleus of stria terminalis (BST) region was performed, using a target below the BST and a trajectory through the ALIC, with stimulation of contacts 0 and 3. Two weeks after surgery sedatives were suspended and the patient was successfully extubated. One year after surgery the patient reached a YGTSS of 19, representing an 81% improvement. OCD completely resolved. Adverse events were a superficial infection and weight gain. In conclusion, this ALIC/BST stimulation appears to have been an effective and safe treatment for GTS with OCD in this case. Young age should not be an exclusion criterion for DBS in severe GTS and OCD. Further studies should be pursued for this target.

The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE).

BACKGROUND: The Medtronic Registry for Epilepsy (MORE; Medtronic Inc, Dublin, Ireland) is an open label observational study evaluating the long-term effectiveness, safety, and performance of deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) for the treatment of refractory epilepsy. OBJECTIVE: To compare the difference in success rate of placing contacts at ANT-target region (ANT-TR) between transventricular (TV) and extraventricular (EV) lead trajectories in 73 ANT-DBS implants in 17 European centers participating in the MORE registry. METHODS: The success rate of placing contacts at ANT-TR was evaluated using a screening method combining both individual patient imaging information and stereotactic atlas information to identify contacts at ANT-TR. RESULTS: EV lead trajectory was used in 53% of the trajectories. Approximately, 90% of the TV lead trajectories had at least 1 contact at ANT-TR, vs only 71% of the EV lead trajectories. The success rate for placing at least 1 contact at ANT-TR bilaterally was 84% for TV implants and 58% for EV implants (P < .05; Fisher's exact). No intracranial bleedings were observed, but 1 cortical infarct was reported following EV lead trajectory. CONCLUSION: The results of this registry support the use of TV lead trajectories for ANT-DBS as they have a higher probability in placing contacts at ANT-TR, without appearing to compromise procedural safety. Follow-up data collection is continuing in the MORE registry. These data will provide outcomes associated with TV and EV trajectories.

Information Sources and Decision-Making in Neurosurgery: Results of a Survey of Members of the Brazilian Neurosurgery Society

Introduction In all surgical disciplines, including neurosurgery, there are questions about the level of evidence supporting surgical practices and the mechanisms and adequacy of knowledge translation. Objectives To assess the perception of Brazilian neurosurgeons of information sources and decision-making mechanisms related to their medical practices. Methods An online questionnaire was sent to the 2,400 members of the Brazilian Neurosurgical Society. Results A total of 32% of the neurosurgeons completed the questionnaire, 53% had more than 10 years experience, 67% had worked in public hospitals, 34% had performed spine surgeries, and 30% had performed brain tumor surgeries. The therapeutic decisions were based mostly on internship learning (54%) and personal professional experience (52%). The most common information sources were scientific abstracts (53%) and the Internet (47%). A total of 89% believed that evidence-based medicine was relevant, 93% believed protocols or guidelines were necessary, and 74% subscribed to a medical journal. Nonetheless, only 43% had protocols implemented in their services, 93% highly valued a surgeon's personal experience, and 63% showed little familiarity with the interpretation of scientific concepts in the literature. Among the respondents, 83% were willing to try an innovative treatment alternative if it was shown to improve clinical outcomes and reduce severe complications. Conclusions The disparity in the responses highlights the need to implement recommendations that improve decision-making mechanisms.

Introdução Em todas as disciplinas cirúrgicas, incluindo a neurocirurgia, existem questões sobre o nível de evidência que apoia as práticas cirúrgicas e os mecanismos e adequação da translação do conhecimento. Objetivos Avaliar a percepção de fontes de informação e mecanismos de tomada de decisão dos neurocirurgiões brasileiros em relação às práticas médicas. Métodos Um questionário on-line foi enviado aos 2.400 membros da Sociedade Brasileira de Neurocirurgia. Resultados Um total de 32% dos neurocirurgiões preencheram o questionário, 53% tinham mais de 10 anos de experiência, 67% trabalharam em hospitais públicos, 34% realizaram cirurgia de coluna, e 30%, de cérebro. As decisões terapêuticas basearam-se principalmente no aprendizado de estágio (54%) e na experiência profissional pessoal (52%). As fontes de informação mais comuns foram resumos científicos (53%) e a Internet (47%). Um total de 89% acreditava que a medicina baseada em evidências era relevante, 93% acreditavam que protocolos ou diretrizes eram necessários, e 74% tinham assinaturas de uma revista médica. No entanto, apenas 43% apresentaram protocolos implementados em seus serviços, 93% valorizaram a experiência pessoal de um cirurgião, e 63% mostraram pouca familiaridade com a interpretação de conceitos científicos na literatura. Entre os respondentes, 83% estavam dispostos a tentar uma alternativa de tratamento inovador se este demonstrasse melhorar os resultados clínicos e reduzir as complicações graves. Conclusões A disparidade nas respostas destaca a necessidade de implementar recomendações que melhorem os mecanismos de tomada de decisão.

Amygdalohippocampotomy for mesial temporal lobe sclerosis: Epilepsy outcome 5 years after surgery.

BACKGROUND: The goal of the present study is the evaluation of the long-term clinical outcome of epilepsy in patients with mesial temporal lobe sclerosis (MTLS) submitted to amygdalohippocampotomy (AHCo). AHCo consists of the lateral ablation of the amygdala and the peri-hippocampal disconnection instead of amygdalohippocampectomy (AHC), which involves the removal of both structures. We previously reported the short-term results of AHCo, so we here present the long-term results (> 5 years of follow-up) of the patients operated on with AHCo. METHOD: Since 2007, 35 patients (22 females) aged 20-61 years (mean: 42 years) were operated on with the AHCo technique, 17 patients on the left side and 18 on the right. Of these patients, 21 (14 females) have been followed up > 5 years (5 to 7.5 years, mean 6.5 years). We compare the present results with those observed shortly after surgery and with the patients operated on with AHC. FINDINGS: In all 21 cases, the diagnosis was mesial temporal lobe sclerosis (histology confirmed in 20), 11 on the left side and 10 on the right. Epilepsy results after 5 years were good/very good in 18 patients (85.7%), with Engel class IA-B in 15 (71.4%) and II in 3 (14.3%), and bad in 3 patients, with Engel Class III in 2 (9.5%) and class IV in 1 (4.8%). Concerning morbidity, one patient had hemiparesis (hypertensive capsular hemorrhage 24 h after surgery), two verbal memory worsening, two quadrantanopia and three late depression that was reversed with medication. Comparatively, the AHC long-term results were 87% Engel class I, 8% Engel class II and 5% Engel class III-IV. The morbidity was equally small. CONCLUSIONS: The good/very good results of AHCo 5 years after surgery are 86%, which is not distinct from the AHC results. So AHCo seems to be effective and potentially safer than AHC in long-term follow-up.

Advanced MR Imaging of the Human Nucleus Accumbens--Additional Guiding Tool for Deep Brain Stimulation.

OBJECTIVE: The human nucleus accumbens (Acc) has become a target for deep brain stimulation (DBS) in some neuropsychiatric disorders. Nonetheless, even with the most recent advances in neuroimaging it remains difficult to accurately delineate the Acc and closely related subcortical structures, by conventional MRI sequences. It is our purpose to perform a MRI study of the human Acc and to determine whether there are reliable anatomical landmarks that enable the precise location and identification of the nucleus and its core/shell division. METHODS: For the Acc identification and delineation, based on anatomical landmarks, T1WI, T1IR and STIR 3T-MR images were acquired in 10 healthy volunteers. Additionally, 32-direction DTI was obtained for Acc segmentation. Seed masks for the Acc were generated with FreeSurfer and probabilistic tractography was performed using FSL. The probability of connectivity between the seed voxels and distinct brain areas was determined and subjected to k-means clustering analysis, defining 2 different regions. RESULTS: With conventional T1WI, the Acc borders are better defined through its surrounding anatomical structures. The DTI color-coded vector maps and IR sequences add further detail in the Acc identification and delineation. Additionally, using probabilistic tractography it is possible to segment the Acc into a core and shell division and establish its structural connectivity with different brain areas. CONCLUSIONS: Advanced MRI techniques allow in vivo delineation and segmentation of the human Acc and represent an additional guiding tool in the precise and safe target definition for DBS.

[Deep brain stimulation: new frontier in the treatment of CNS disorders]. / Estimulação Cerebral Profunda: Nova Fronteira no Tratamento das Doenças do Sistema Nervoso Central.

INTRODUCTION: The author reviews the present indications of deep brain stimulation, its progress and outcomes, its targets and techniques, the main neurosurgeons and medical centers involved. MATERIAL AND METHODS: This review is based on the experience of the Functional Neurosurgery group of the Hospital Santa Maria (Centro Hospitalar de Lisboa Norte) since 1995 and on the bibliography published since 1980 indexed on PubMed. RESULTS AND DISCUSSION: The deep brain stimulation applications in the different functional neurosciences fields are presented and discussed: Movement disorders, including Parkinson's disease, dystonia and tremor, Gilles de la Tourette, chronic pain, epilepsy and psychosurgery with its different aims: Obsessive-compulsive disorder, severe resistant depression, resistant aggressiveness with disruptive behavior, eating behavior disorders (anorexia nervosa, morbid obesity) and drug addiction (alcohol, opioids, cocaine). CONCLUSIONS: In most of these clinical situations, deep brain stimulation is a safe and useful therapeutic resource that must be considered whenever the usual therapies are useless or not enough; in the other cases a greater experience is needed to make it a regular indication.

Introdução: O autor faz uma revisão das indicações atuais da estimulação cerebral profunda, dos seus desenvolvimentos e resultados, dos alvos e técnicas utilizados, dos principais neurocirurgiões e centros médicos envolvidos.Material e Métodos: Esta revisão é baseada na experiência do grupo de Neurocirurgia Funcional do Hospital de Santa Maria (Centro Hospitalar Lisboa Norte) desde 1995 e na revisão bibliográfica dos artigos publicados sobre esta matéria desde 1980 indexados na PubMed.Resultados e Discussão: São apresentadas e discutidas as aplicações da estimulação cerebral profunda nos diferentes domínios das neurociências funcionais: Doenças do Movimento, incluindo doença de Parkinson, distonias e tremores, síndrome de Gilles de la Tourette, dor crónica, epilepsia e psicocirurgia nas múltiplas áreas que esta compreende: perturbação obsessiva-compulsiva, depressão grave refratária, comportamento disruptivo com agressividade intratável, deterioração da memória e demência, perturbações do comportamento alimentar (anorexia nervosa, obesidade mórbida) e toxicodependências refratárias (álcool, opioides, cocaína).Conclusões: Na maioria das situações clínicas referidas a estimulação cerebral profunda constitui um recurso terapêutico seguro e eficaz a ter em consideração quando as terapias habituais se mostram insuficientes; nos restantes casos há que reunir maior experiência até adotar o seu uso regular.

The nucleus accumbens beyond the anterior commissure: implications for psychosurgery.

INTRODUCTION: The nucleus accumbens (Acc) is a basal forebrain structure integrated in the dopaminergic cerebral rewarding circuits and implicated in some neuropsychiatric disorders. It has become a target for deep brain stimulation for some of these disorders when refractory to medical treatment. However, it is controversial as to which target is the best and similar results have been achieved with the stimulation of neighboring structures such as the bed nucleus of the stria terminalis (BNST). Previous studies have established the stereotactic anatomy of the human Acc, but some difficulties remain concerning its precise posterior limit, which is assumed to be at the level of the anterior commissure (AC). It is our purpose to clarify the anatomy of this zone, given the importance of its exact identification in psychosurgery. METHODS: A total of 16 Acc were collected by autopsy, fixed, dissected, embedded and cut in coronal 5-µm slices. The slices were stained with hematoxylin and eosin, marked with anti-D1 and anti-D2 antibodies and analyzed under a microscope. RESULTS: The human Acc has the same cellular structure as the dorsal striatum, except in its posterior subcommissural part where voluminous neurons prevail, similar to and contiguous with the BNST. CONCLUSIONS: The Acc is longer than previously described, with a sub- and postcommissural extension behind the AC, continuous with the BNST.

Cavernous sinus lesions biopsy with neuronavigation and tip-cut needle.

BACKGROUND: Transoval biopsy of cavernous sinus (CS) lesions is the last non-invasive diagnostic option in those 15% of patients in whom etiology remains unclear in spite of extensive neuroradiological imaging, clinical assessment, and laboratory evaluation. However, there are no guidelines defining indications and the most appropriate technique for this procedure. CASE DESCRIPTION: We present four patients in whom we performed X-ray and neuronavigation-assisted transoval CS biopsies using tip-cut needles. CONCLUSION: The technique described allows the operator to determine the optimal angle for entering the CS, avoiding the complications due to distorted anatomy, and facilitating orientation once inside the CS. It reduces both radiation exposure as well as general anesthesia duration.