Aspects opératoires et péri-opératoires de la stimulation cérébrale profonde [Operative and perioperative aspects of deep brain stimulation].

La stimulation cérébrale profonde (SCP) nécessite l'implantation chirurgicale d'un système comprenant électrodes cérébrales et boîtier(s) de stimulation. Les noyaux cérébraux visés par la méthodologie stéréotaxique d'implantation doivent être visualisés au mieux par une imagerie à haute résolution. La procédure chirurgicale d'implantation des électrodes se fait si possible en anesthésie locale pour faire des mesures électro-physiologiques et tester en peropératoire l'effet de la stimulation, afin d'optimiser la position de l'électrode définitive. Dans un deuxième temps, le ou les générateur(s) d'impulsions sont implantés en anesthésie générale. La SCP pour les mouvements anormaux a une très bonne efficacité et un risque de complications graves faible quoique non nul. Les complications liées au matériel sont les plus fréquentes. Deep brain stimulation (DBS) requires the surgical implantation of a system including brain electrodes and impulsion generator(s). The nuclei targeted by the stereotaxic implantation methodology have to be visualized at best by high resolution imaging. The surgical procedure for implanting the electrodes is performed if possible under local anaesthesia to make electro-physiological measurements and to test intra-operatively the effect of the stimulation, in order to optimize the position of the definitive electrode. In a second step, the impulsion generator(s) are implanted under general anaesthesia. DBS for movement disorders has a very good efficacy and a low albeit non-zero risk of serious complications. Complications related to the material are the most common.

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND: Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES: The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS: We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS: There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION: There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.

Bilateral deep brain stimulation : the placement of the second electrode is not necessarily less accurate than that of the first one

Introduction La stimulation cérébrale profonde est reconnue comme étant un traitement efficace des pathologies du mouvement. Nous avons récemment modifié notre technique chirurgicale, en limitant le nombre de pénétrations intracérébrales à trois par hémisphère. Objectif Le premier objectif de cette étude est d'évaluer la précision de l'électrode implantée des deux côtés de la chirurgie, depuis l'implémentation de cette technique chirurgicale. Le deuxième objectif est d'étudier si l'emplacement de l'électrode implantée était amélioré grâce à l'électrophysiologie. Matériel et méthode Il s'agit d'une étude rétrospective reprenant les protocoles opératoires et imageries à résonnance magnétique (IRM) cérébrales de 30 patients ayant subi une stimulation cérébrale profonde bilatérale. Pour l'électrophysiologie, nous avons utilisé trois canules parallèles du « Ben Gun », centrées sur la cible planifiée grâce à l'IRM. Les IRM pré- et post-opératoires ont été fusionnées. La distance entre la cible planifiée et le centre de l'artéfact de l'électrode implantée a été mesurée. Résultats Il n'y a pas eu de différence significative concernant la précision du ciblage des deux côtés (hémisphères) de la chirurgie. Il y a eu plus d'ajustements peropératoires du deuxième côté de la chirurgie, basé sur l'électrophysiologie, ce qui a permis d'approcher de manière significative la cible planifiée grâce à l'IRM, sur l'axe médio- latéral. Conclusion Il y a plus d'ajustements nécessaires de la position de la deuxième électrode, possiblement en lien avec le « brain shift ». Nous suggérons de ce fait d'utiliser une trajectoire d'électrode centrale accompagnée par de l'électrophysiologie, associé à une évaluation clinique. En cas de résultat clinique sub-optimal, nous proposons d'effectuer une exploration multidirectionnelle.

Subthalamic (STN) Deep Brain Stimulation (DBS) in Parkinson's Disease (PD): Correlation Between the Location of the Stimulated Contacts and the Clinical Effects in 14 Patients

Objectives: To correlate the chronic stimulated electrode position on postoperative MRI with the clinical response obtained in PD patients. Material and Method: We retrospectively reviewed 14 consecutive parkinsonian patients who were selected for STN-DBS surgery. Coordinates were determined on an IR T2 MRI coronal section per pendicular to AC-PC plane 3 mm posterior to midcommissural point (MCP) and 12 mm lateral to the midline the inferior aspect of subthalamic region. A CRW stereotactic frame was used for the surgical procedure. A 3D IR T2 MRI was performed postoperatively to determine the location of the stimulated contact in each patient. The clinical results were assessed independently by the neurological team. Results: All but 2 patients had monopolar stimulation. The mean coordinates of the stimulated contacts were: AP ^ ÿ4:23G1:4, Lat ^ 1:12G0:15, Vert ^ ÿ4:1 G2:7 to the MCP. With a mean follow-up of 8 months, all stimulated patients had a significant clinical improvement (preop/postop «ON» UPDRS: 25:8G7:0= 23:3 G8:6; preop/postop «OFF» UPDRS: 50:2G11:4=26:0 G7:8), 60% of them without any antiparkinsonian drug. Conclusion: According to the stereotactic atlas of Schaltenbrand and Warren and the 3D shape of the STN, our results show that our targetting is accurate and almost all the stimulated contacts are comprised in the STN volume. This indicates that MRI is a safe, precise and reproducible procedure for targetting the STN. The location of the stimulated contact within the STN volume is a good predictor of the clinical results.

Parkinson's disease.

In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, although whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting the motor cortex. Current studies suggest a possible therapeutic potential for rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible with regard to functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters that derive their rationale from studies on brain physiology. These novel parameters are intended to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia with regard to motor control and its contribution to the pathogenesis of motor disorders. Noninvasive brain stimulation studies will enhance our understanding of PD pathophysiology and might provide further evidence for potential therapeutic applications.

Brain energy consumption induced by electrical stimulation promotes systemic glucose uptake.

BACKGROUND: Controlled transcranial stimulation of the brain is part of clinical treatment strategies in neuropsychiatric diseases such as depression, stroke, or Parkinson's disease. Manipulating brain activity by transcranial stimulation, however, inevitably influences other control centers of various neuronal and neurohormonal feedback loops and therefore may concomitantly affect systemic metabolic regulation. Because hypothalamic adenosine triphosphate-sensitive potassium channels, which function as local energy sensors, are centrally involved in the regulation of glucose homeostasis, we tested whether transcranial direct current stimulation (tDCS) causes an excitation-induced transient neuronal energy depletion and thus influences systemic glucose homeostasis and related neuroendocrine mediators.METHODS: In a crossover design testing 15 healthy male volunteers, we increased neuronal excitation by anodal tDCS versus sham and examined cerebral energy consumption with (31)phosphorus magnetic resonance spectroscopy. Systemic glucose uptake was determined by euglycemic-hyperinsulinemic glucose clamp, and neurohormonal measurements comprised the parameters of the stress systems.RESULTS: We found that anodic tDCS-induced neuronal excitation causes an energetic depletion, as quantified by (31)phosphorus magnetic resonance spectroscopy. Moreover, tDCS-induced cerebral energy consumption promotes systemic glucose tolerance in a standardized euglycemic-hyperinsulinemic glucose clamp procedure and reduces neurohormonal stress axes activity.CONCLUSIONS: Our data demonstrate that transcranial brain stimulation not only evokes alterations in local neuronal processes but also clearly influences downstream metabolic systems regulated by the brain. The beneficial effects of tDCS on metabolic features may thus qualify brain stimulation as a promising nonpharmacologic therapy option for drug-induced or comorbid metabolic disturbances in various neuropsychiatric diseases.

Transcranial Magnetic Stimulation Combined with EEG Reveals Covert States of Elevated Excitability in the Human Epileptic Brain.

BACKGROUND: Transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a stochastic occurrence despite constant stimulation parameters. This observation raises the possibility that the pre-stimulation period contains multiple covert states of brain excitability some of which are associated with the generation of EDs. OBJECTIVE: To investigate whether the interictal period contains "high excitability" states that upon brain stimulation produce EDs and can be differentiated from "low excitability" states producing normal appearing TMS-EEG responses. METHODS: In a cohort of 25 patients with Genetic Generalized Epilepsies (GGE) we identified two subjects characterized by the intermittent development of TMS-induced EDs. The high-excitability in the pre-stimulation period was assessed using multiple measures of univariate time series analysis. Measures providing optimal discrimination were identified by feature selection techniques. The "high excitability" states emerged in multiple loci (indicating diffuse cortical hyperexcitability) and were clearly differentiated on the basis of 14 measures from "low excitability" states (accuracy = 0.7). CONCLUSION: In GGE, the interictal period contains multiple, quasi-stable covert states of excitability a class of which is associated with the generation of TMS-induced EDs. The relevance of these findings to theoretical models of ictogenesis is discussed.

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy.

PURPOSE: To study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location. METHODS: Eight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction. RESULTS: The distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3mm from the subiculum (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm to the subiculum. CONCLUSION: Decrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

Cerebellar transcranial direct current stimulation modulates verbal working memory.

BACKGROUND: Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. OBJECTIVE: We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. METHOD: We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. RESULTS: In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. CONCLUSION: Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions.

Brain tissue properties differentiate between motor and limbic basal ganglia circuits.

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome.

Effects of amygdala-hippocampal stimulation on interictal epileptic discharges.

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.

Traitement des epilepsies réfractaires: rôle de la stimulation electrique [Treatment of pharmacoresistant epilepsy: stimulated refractoriness].

Antiepileptic drugs allow controlling seizures in 70% of patients. For the others, a presurgical work-up should be undertaken, especially if a focal seizure origin is suspected; however, only a fraction of pharmacoresistant patients will be offered resective (curative) surgery. In the last 15 years, several palliative therapies using extra- or intracranial electrical stimulations have been developed. This article presents the vagal nerve stimulation, the deep brain stimulation (targeting the mesiotemporal region or the thalamus), and the cortical stimulation "on demand". All show an overall long-term responder rate between 30-50%, but less than 5% of patients becoming seizure free. It is to hope that a better understanding of epileptogenic mechanisms and of the implicated neuronal networks will lead to an improvement of these proportions.

Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Confirmation of functional zones within the human subthalamic nucleus: patterns of connectivity and sub-parcellation using diffusion weighted imaging.

The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery.

Neurologie [Neurology].

In 2011, new oral anticoagulants for atrial fibrillation are available and the ABCD3-I score predicting stroke after TIA updates the ABCD2 score. New McDonald criteria allow faster MS diagnosis and the first oral treatment (fingolimod) for MS can be prescribed. A new anti-antiepileptic drug (retigabine) is available and sodium valproate has long term neurological adverse effects after in utero exposure. Among Parkinson disease treatments, deep brain stimulation is extending applications and dopamine agonists with extended release are as efficient and well tolerated as standard forms at long term scale. Monoclonal antibodies and immunosuppressant agents are proposed as good alternatives in the treatment of chronic dysimmune polyneuropathies. Gene therapy for the treatment of genetic myopathies is progressing.