Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

Cognitive deficits and clinical symptoms in patients with treatment-refractory obsessive-compulsive disorder: The role of slowness in information processing.

Patients with Obsessive-Compulsive Disorder (OCD) present neuropsychological deficits across different cognitive domains, especially in executive functioning and information processing speed. Some studies have even suggested that speed deficits may underlie poor neuropsychological performance. However, this hypothesis remains unanswered in both OCD general population and OCD refractory subgroup. In addition, it is not clear whether such deficits are secondary to the clinical symptoms or may constitute a primary deficit. The aim of this study was to explore the speed of processing hypothesis in treatment-refractory OCD patients, and to clarify to what extent slowness is related to psychopathological symptoms. Both clinical and neuropsychological examination was conducted to assess 39 OCD refractory patients candidates for neurosurgery and 39 healthy matched individuals. Principal component analysis revealed a three-component structure in the neuropsychological battery being used, including a speed of processing, working memory, and conflict monitoring components. Group comparisons revealed that OCD patients performed significantly worse than healthy individuals in speed measures, but no differences were found in executive tests not influenced by time. Correlation analyses revealed a lack of association between neuropsychological and clinical measures. The results suggest that treatment-refractory OCD patients exhibit a primary deficit in information processing speed independent of clinical symptoms.

Deep Brain Stimulation of the Nucleus Accumbens, Ventral Striatum, or Internal Capsule Targets for Medication-Resistant Obsessive-Compulsive Disorder: A Multicenter Study.

BACKGROUND: Deep brain stimulation of the nucleus accumbens, ventral striatum, or internal capsule region has shown a 45%-60% response rate in adults with severe treatment-refractory obsessive-compulsive disorder, regardless of which target is used. We sought to improve the effectiveness of deep brain stimulation by placing the electrode along a trajectory including these 3 targets, enabling a change of stimulation site depending on the patient's response. METHODS: This study used the medical records of 14 patients from 4 different Spanish institutions: 7 from the Hospital Universitario La Princesa, 3 from the Hospital Universitario Central de Asturias, 2 from Hospital Universitario Fundación Jiménez Díaz, and 2 from Hospital Universitari Son Espases. All patients were operated on under the same protocol. Qualitative and quantitative data were collected. RESULTS: Of 14 patients, 11 showed significant improvement in obsessive-compulsive disorder symptoms, as evident in a reduction ≥35% in Yale-Brown Obsessive Compulsive Scale scores following stimulation relative to preoperative scores. Seven patients responded to stimulation at the nucleus accumbens (the first area we set for stimulation), whereas 4 patients needed to have the active contact switched to the internal capsule to benefit from stimulation. CONCLUSIONS: Deep brain stimulation of the nucleus accumbens, internal capsule, and ventral striatum significantly benefited our cohort of patients with medication-resistant obsessive-compulsive disorder. Electrode insertion through the 3 main targets might confer additional therapeutic efficacy.

Network Substrates of Centromedian Nucleus Deep Brain Stimulation in Generalized Pharmacoresistant Epilepsy.

Deep brain stimulation (DBS), specifically thalamic DBS, has achieved promising results to reduce seizure severity and frequency in pharmacoresistant epilepsies, thereby establishing it for clinical use. The mechanisms of action are, however, still unknown. We evidenced the brain networks directly modulated by centromedian (CM) nucleus-DBS and responsible for clinical outcomes in a cohort of patients uniquely diagnosed with generalized pharmacoresistant epilepsy. Preoperative imaging and long-term (2-11 years) clinical data from ten generalized pharmacoresistant epilepsy patients (mean age at surgery = 30.8 ± 5.9 years, 4 female) were evaluated. Volume of tissue activated (VTA) was included as seeds to reconstruct the targeted network to thalamic DBS from diffusion and functional imaging data. CM-DBS clinical outcome improvement (> 50%) appeared in 80% of patients and was tightly related to VTAs interconnected with a reticular system network encompassing sensorimotor and supplementary motor cortices, together with cerebellum/brainstem. Despite methodological differences, both structural and functional connectomes revealed the same targeted network. Our results demonstrate that CM-DBS outcome in generalized pharmacoresistant epilepsy is highly dependent on the individual connectivity profile, involving the cerebello-thalamo-cortical circuits. The proposed framework could be implemented in future studies to refine stereotactic implantation or the parameters for individualized neuromodulation.

Prediction of Memory Impairment in Epilepsy Surgery by White Matter Diffusion.

OBJECTIVE: To analyze the relationship between cognitive performance and white matter integrity in patients with temporal lobe epilepsy (TLE) to establish radiologic criteria to help with patient selection for surgery. METHODS: The study included 19 adults with temporal lobe epilepsy. A tractography analysis of fractional anisotropy and mean diffusivity (MD) of the following fascicles was performed: arcuate fascicle, cingulum, fornix, inferior fronto-occipital fascicle, inferior longitudinal fascicle, parahippocampal fibers of the cingulum, and uncinate fascicle. The Wechsler Memory Scale-Third Edition neuropsychological test was performed to evaluate short- and long-term verbal (Logical Memory I and II subtests) and nonverbal (Visual Reproduction I and II subtests) memory. Relationships between memory scores and diffusion were calculated. RESULTS: Lower Logical Memory I subtest scores were correlated with lower MD of the right inferior fronto-occipital fascicle, while lower Logical Memory II subtest scores were related to higher values of fractional anisotropy in bilateral cingulum, right uncinate, and right parahippocampal fibers of the cingulum and lower MD in left cingulum fascicle. Finally, lower values in Visual Reproduction I subtest scores were associated with lower values in MD in right cingulum and inferior fronto-occipital fascicles. CONCLUSIONS: Structural changes of some white matter tracts were associated with deterioration of both short- and long-term memory. These alterations were more associated with verbal memory than with nonverbal memory. These changes mainly consist of an increase in fractional anisotropy and a decrease in MD, which could be interpreted as reorganization phenomena. Diffusion tensor imaging could be a useful tool for cognitive assessment in surgical candidates with temporal lobe epilepsy who are not suitable for neuropsychological testing or in whom their results do not lead to definitive conclusions.

Radiofrequency Lesions through Deep Brain Stimulation Electrodes in Movement Disorders: Case Report and Review of the Literature.

BACKGROUND: Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. METHODS: We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection. The authors conduct a review of the literature regarding this method. RESULTS: Both patients had a good clinical outcome after 20 and 8 months, respectively, as assessed by a reduction in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores. The second patient underwent a second DBS system implantation surgery after his radiofrequency treatment to optimize his management, achieving optimal clinical control with lower current and drug requirements than before the radiofrequency intervention. No adverse effects were observed. CONCLUSIONS: Radiofrequency lesions through DBS electrodes allow the creation of small and localized lesions. Its effectiveness and low-risk profile, in addition to its low cost, make this procedure suitable and a possible alternative in the therapeutic repertoire for the surgical treatment of movement disorders.

[Not Available]. / Tratamiento quirúrgico de la anorexia nerviosa resistente al tratamiento médico.

Gracias a los avances técnicos en técnicas neuroquirúrgicas, y debido a que el diagnóstico y la clasificación de las enfermedades psiquiátricas han evolucionado significativamente a lo largo de las últimas décadas, se están desarrollando tratamientos a nivel experimental para aquellos pacientes resistentes al manejo conservador.La anorexia nerviosa es una enfermedad de prevalencia creciente, con la tasa de mortalidad más elevada dentro de los trastornos psiquiátricos, y con aproximadamente un 20% de pacientes que presentan una evolución tórpida. Para estos pacientes que no responden a manejo conservador, la estimulación cerebral profunda ha surgido como una alternativa terapéutica, si bien la literatura especializada al respecto es escasa.A continuación presentamos una revisión de la fisiopatología de la anorexia nerviosa, así como de los distintos tratamientos neuroquirúrgicos realizados a lo largo de la historia. Se detalla la perspectiva de tratamiento quirúrgico actual, así como los aspectos éticos que se han de considerar en relación con el surgimiento de estas nuevas terapias.

Tratamiento quirúrgico de la anorexia nerviosa resistente al tratamiento médico / Surgical treatment of medication-resistant anorexia nervosa

Gracias a los avances en técnicas neuroquirúrgicas, y debido a que el diagnóstico y la clasificación de las enfermedades psiquiátricas han evolucionado significativamente a lo largo de las últimas décadas, se están desarrollando tratamientos a nivel experimental para aquellos pacientes resistentes al manejo conservador. La anorexia nerviosa es una enfermedad de prevalencia creciente, con la tasa de mortalidad más elevada dentro de los trastornos psiquiátricos, y con aproximadamente un 20% de pacientes que presentan una evolución tórpida. Para estos pacientes que no responden a manejo conservador, la estimulación cerebral profunda ha surgido como una alternativa terapéutica, si bien la literatura especializada al respecto es escasa. A continuación presentamos una revisión de la fisiopatología de la anorexia nerviosa, así como de los distintos tratamientos neuroquirúrgicos realizados a lo largo de la historia. Se detalla la perspectiva de tratamiento quirúrgico actual, así como los aspectos éticos que se han de considerar en relación con el surgimiento de estas nuevas terapias (AU)

Given the advances experienced in neurosurgical techniques, and because the diagnosis and classifi cation of psychiatric diseases has evolved over the past decades, new experimental treatments are arising to treat a greater number of medication-resistant psychiatric patients. Among psychiatric diseases, anorexia nervosa has the highest mortality rate, and approximately 20% of patients experience torpid outcomes. For these patients who do not respond to conservative management, deep brain stimulation has arisen as an alternative option, although studies are still scarce. We review the pathophysiology of anorexia nervosa, as well as the various neurosurgical treatments that have been performed throughout history. The prospect of current surgical treatments is detailed, as well as the ethical aspects to consider regarding the emergence of these new therapies (AU)

Estimulación cerebral para el trastorno obsesivo-compulsivo resistente a tratamiento médico / Deep brain stimulation for drug-resistant obsessive-compulsive disorder

Aproximadamente un 10% de los pacientes con trastorno obsesivo-compulsivo tienen formas crónicas muy incapacitantes de la enfermedad, resistentes a las terapias conservadoras actuales, lo que conlleva un deterioro significativo para su calidad de vida y altas tasas de suicidio. Para estos pacientes se dispone de nuevas terapias efectivas mediante tratamiento neuroquirúrgico. A continuación revisamos de forma exhaustiva las técnicas neuroquirúrgicas actuales y las tasas de remisión y efectos adversos, con sus aspectos metodológicos fundamentales. La realización de pequeñas lesiones en dianas específicas del circuito límbico, como la cingulotomía, la capsulotomía, la tractotomía subcaudada o la leucotomía límbica, está siendo sustituida por la estimulación cerebral profunda mediante electrodos en estas dianas, lo que permite efectuar una terapia reversible y adaptable a las necesidades del paciente. Además, el desarrollo de la neuroimagen y el mejor conocimiento de los circuitos cerebrales han permitido la identificación de nuevas dianas para la neuroestimulación en este trastorno, con buenos resultados. La investigación debe continuar progresando para mejorar el tratamiento de los pacientes con trastorno obsesivo-compulsivo resistente (AU)

Approximately 10% of patients with obsessive-compulsive disorder have very disabling chronic forms of the disease, which are resistant to all current conservative therapies. These patients experience a significant deterioration in their quality of life and high rates of suicide. The development of new effective neurosurgical treatments has led to an improvement in a significant percentage of patients that would otherwise have remained severely disabled. We comprehensively review remission rates, adverse effects and fundamental methodological aspects of the current neurosurgical techniques for medication resistant obsessive-compulsive disorder. The making of small lesions in specific targets of the limbic circuit, such as cingulotomy, capsulotomy, limbic leucotomy and subcaudate tractotomy, is being replaced by deep brain stimulation through electrodes located in these targets, which is reversible and adaptable to every patient's need. Furthermore, the development of neuroimaging techniques and a better understanding of brain circuits in the last decades, have allowed the identification of new targets for neurostimulation in this disorder, with good results. Research must continue in order to help in the treatment of medication-resistant obsessive-compulsive disorder (AU)

Bilateral pallidal stimulation for x-linked dystonia parkinsonism.

OBJECTIVE: To report the clinical benefits of bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) in a patient with X-linked dystonia parkinsonism (XDP). DESIGN: Case report. SETTING: Tertiary referral center. Patient A 40-year-old Filipino man with genetically confirmed XDP and severely disabling generalized dystonia. Intervention Bilateral GPi DBS. MAIN OUTCOME MEASURES: The primary outcome measures were the Burke-Fahn-Marsden Dystonia Scale (BFMDS) severity and disability scores, and the secondary outcome measure was the Unified Parkinson Disease Rating Scores. RESULTS: At the 1-year postoperative follow-up, there was 80.4% improvement in the BFMDS severity score and 66.7% improvement in the BFMDS disability score. CONCLUSION: Bilateral GPi DBS seems to be very effective in improving dystonia in XDP.