Project description:Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.
Project description:Deep brain stimulation (DBS) is a neurosurgical technique, which consists of continuous delivery of an electrical pulse through chronically implanted electrodes connected to a neurostimulator, programmable in amplitude, pulse width, frequency, and stimulation channel. DBS is a promising treatment option for addressing severe and drug-resistant movement disorders. The success of DBS therapy is a combination of surgical implantation techniques, device technology, and clinical programming strategies. Changes in device settings require highly trained and experienced clinicians to achieve maximal therapeutic benefit for each targeted symptom, and optimization of stimulation parameters can take many visits. Thus, the development of innovative DBS technologies that can optimize the clinical implementation of DBS will lead to wider scale utilization. This review aims to present engineering approaches that have the potential to improve clinical outcomes of DBS, focusing on the development novel temporal patterns, innovative electrode designs, computational models to guide stimulation, closed-loop DBS, and remote programming.
Project description:Deep brain stimulation (DBS) therapy requires extensive patient-specific planning prior to implantation to achieve optimal clinical outcomes. Collective analysis of patient's brain images is promising in order to provide more systematic planning assistance. In this paper the design of a normalization pipeline using a group specific multi-modality iterative template creation process is presented. The focus was to compare the performance of a selection of freely available registration tools and select the best combination. The workflow was applied on 19 DBS patients with T1 and WAIR modality images available. Non-linear registrations were computed with ANTS, FNIRT and DRAMMS, using several settings from the literature. Registration accuracy was measured using single-expert labels of thalamic and subthalamic structures and their agreement across the group. The best performance was provided by ANTS using the High Variance settings published elsewhere. Neither FNIRT nor DRAMMS reached the level of performance of ANTS. The resulting normalized definition of anatomical structures were used to propose an atlas of the diencephalon region defining 58 structures using data from 19 patients.
Project description:BackgroundFunctional movement disorders (FMD) are a commonly under-recognized diagnosis in patients with underlying neurodegenerative diseases. FMD have been observed in patients undergoing deep brain stimulation (DBS) for Parkinson's disease (PD) and other movement disorders. The prevalence of coexisting FMD among movement disorder-related DBS patients is unknown, and it may occur more often than previously recognized.MethodsWe retrospectively assessed the relative prevalence and clinical characteristics of FMD occurring post-DBS, in PD and dystonia patients (FMD+, n = 29). We compared this cohort with age at surgery-, sex-, and diagnosis-matched subjects without FMD post-DBS (FMD-, n = 29).ResultsBoth the FMD prevalence (0.2%-2.1%) and the number of cases/DBS procedures/year varied across centers (0.15-3.65). A total of nine of 29 FMD+ cases reported worse outcomes following DBS. Although FMD+ and FMD- manifested similar features, FMD+ showed higher psychiatric comorbidity.ConclusionsDBS may be complicated by the development of FMD in a subset of patients, particularly those with pre-morbid psychiatric conditions.
Project description:Deep brain stimulation (DBS) represents one of the major clinical breakthroughs in the age of translational neuroscience. In 1987, Benabid and colleagues demonstrated that high-frequency stimulation can mimic the effects of ablative neurosurgery in Parkinson's disease (PD), while offering two key advantages to previous procedures: adjustability and reversibility. Deep brain stimulation is now an established therapeutic approach that robustly alleviates symptoms in patients with movement disorders, such as Parkinson's disease, essential tremor, and dystonia, who present with inadequate or adverse responses to medication. Currently, stimulation electrodes are implanted in specific target regions of the basal ganglia-thalamic circuit and stimulation pulses are delivered chronically. To achieve optimal therapeutic effect, stimulation frequency, amplitude, and pulse width must be adjusted on a patient-specific basis by a movement disorders specialist. The finding that pathological neural activity can be sampled directly from the target region using the DBS electrode has inspired a novel DBS paradigm: closed-loop adaptive DBS (aDBS). The goal of this strategy is to identify pathological and physiologically normal patterns of neuronal activity that can be used to adapt stimulation parameters to the concurrent therapeutic demand. This review will give detailed insight into potential biomarkers and discuss next-generation strategies, implementing advances in artificial intelligence, to further elevate the therapeutic potential of DBS by capitalizing on its modifiable nature. Development of intelligent aDBS, with an ability to deliver highly personalized treatment regimens and to create symptom-specific therapeutic strategies in real-time, could allow for significant further improvements in the quality of life for movement disorders patients with DBS that ultimately could outperform traditional drug treatment.
Project description:Theta-burst stimulation (TBS) can be a non-invasive technique to modulate cognitive functions, with promising therapeutic potential, but with some contradictory results. Event related potentials are used as a marker of brain deterioration and can be used to evaluate TBS-related cognitive performance, but its use remains scant. This study aimed to study bilateral inhibitory and excitatory TBS effects upon neurocognitive performance of young healthy volunteers, using the auditory P300' results. Using a double-blind sham-controlled study, 51 healthy volunteers were randomly assigned to five different groups, two submitted to either excitatory (iTBS) or inhibitory (cTBS) stimulation over the left dorsolateral pre-frontal cortex (DLPFC), two other actively stimulated the right DLPFC and finally a sham stimulation group. An oddball based auditory P300 was performed just before a single session of iTBS, cTBS or sham stimulation and repeated immediately after. P300 mean latency comparison between the pre- and post-TBS stimulation stages revealed significantly faster post stimulation latencies only when iTBS was performed on the left hemisphere (p = 0.003). Right and left hemisphere cTBS significantly delayed P300 latency (right p = 0.026; left p = 0.000). Multiple comparisons for N200 showed slower latencies after iTBS over the right hemisphere. No significant difference was found in amplitude variation. TBS appears to effectively influence neural networking involved in P300 formation, but effects seem distinct for iTBS vs cTBS and for the right or the left hemisphere. P300 evoked potentials can be an effective and practical tool to evaluate transcranial magnetic stimulation related outcomes.
Project description:Background:Movement disorders (MDs) are increasingly being managed with deep brain stimulation (DBS). High-quality economic evaluations (EEs) are necessary to evaluate the cost-effectiveness of DBS. We conducted a systematic review of published EEs of the treatment of MDs with DBS. The review compares and contrasts the reported incremental cost-effectiveness ratios (ICERs) and methodology employed by trial-based evaluations (TBEs) and model-based evaluations (MBEs). Methods:MeSH and search terms relevant to "MDs," "DBS," and "EEs" were used to search biomedical and economics databases. Studies that used a comparative design to evaluate DBS, including before-after studies, were included. Quality and reporting assessments were conducted independently by 2 authors. Seventeen studies that targeted Parkinson's disease (PD), dystonia, and essential tremor (ET), met our selection criteria. Results:Mean scores for methodological and reporting quality were 73% and 76%, respectively. The ICERs for DBS compared with best medical therapy to treat PD patients obtained from MBEs had a lower mean and range compared with those obtained from TBEs ($55,461-$735,192 per quality-adjusted life-year [QALY] vs. $9,301-$65,111 per QALY). Pre-post ICER for DBS to treat dystonia was $64,742 per QALY. DBS was not cost-effective in treating ET compared with focused-ultrasound surgery. Cost-effectiveness outcomes were sensitive to assumptions in health utilities, surgical costs, battery life-span, model time horizons, and the discount rate. Conclusions:The infrequent use of randomized, controlled trials to evaluate DBS efficacy, the paucity of data reporting the long-term effectiveness and/or utility of DBS, and the uncertainty surrounding cost data limit our ability to report cost-effectiveness summaries that are robust.
Project description:Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.
Project description:To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities.Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients.Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients.The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality.The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.
Project description:IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).