Application Of Deep Brain Stimulation Research Articles

How to carry out the clinical application of deep brain stimulation

How to carry out the clinical application of deep brain stimulation

Recent advances in Essential Tremor: Surgical treatment

While no real breakthrough in the medical treatment of Essential Tremor (ET) has recently emerged, surgical field is expanding exponentially. Purpose of this review is to examine the recent and future developments of the surgical treatments for ET.Technological advances are shaping the present and the future application of deep brain stimulation (DBS) in ET. New electrode configurations as well as new implantable pulse generators are now available. Application of closed-loop or adaptive stimulation in clinical practice will allow DBS to deliver stimulation in a truly physiological way to restore aberrant neurological circuits on demand, thus avoiding side effects, tolerance and also saving the battery life.Besides DBS and standard thalamotomy, novel surgical approaches for ET are on the horizon. The development of MRI-guided focused ultrasound technique has been the new frontier of deep brain lesional therapies. Although the benefit of motor cortex stimulation is yet to be defined, this minimally invasive approach remains intriguing.Although the advances of surgical treatments along the clinical and technological directions described in this review will certainly contribute to a successful management of ET patients, future studies need to consider critical issues such as the heterogeneity of ET and the development of tolerance.

Chemical and Physical Approaches for the Treatment of Alzheimer's Disease

Alzheimer’s disease (AD) is a destructive neurodegenerative disorder, which threatens elderly people in their mental health irreversibly, causing cognitive deficit such as learning difficulties and memory loss. Neurobiological pathogenesis leading to the neuronal dysfunction in AD are mainly rationalized by two hypotheses: 1) extracellular aggregation of the β-amyloid (Aβ) peptide, which impacts on the normal neuronal pathways through excessive oxidative stress and damages neurons; and 2) intracellular hyperphosphorylation of tau protein, which forms the paired helical filaments, then gravely impacts axonal transport. In this review, we firstly introduce the neurobiological concept of AD, and its pathogenesis. Then we review the chemical approaches pointedly directing at Aβ peptide and tau protein, and the clinical reality of these pharmacological strategies. Thirdly, we discuss a physical approach, deep brain stimulation (DBS), which is receiving considerable attention in recent years due to its success in treating Parkinson disease clinically. DBS delivers current pulses, which are generated by a implanted pacemaker, through electrodes into dysfunctional brain structures to influence neural activities with the possibility to improve the cognitive function. We will summarize the clinical applications of DBS to restore cognitive impairments due to AD, and animal studies related with DBS. Finally, we will discuss the current study obstacles and future research development of DBS in preclinical and clinical investigations of AD.

Chemical and Physical Approaches for the Treatment of Alzheimer's Disease

Alzheimer’s disease (AD) is a destructive neurodegenerative disorder, which threatens elderly people in their mental health irreversibly, causing cognitive deficit such as learning difficulties and memory loss. Neurobiological pathogenesis leading to the neuronal dysfunction in AD are mainly rationalized by two hypotheses: 1) extracellular aggregation of the β-amyloid (Aβ) peptide, which impacts on the normal neuronal pathways through excessive oxidative stress and damages neurons; and 2) intracellular hyperphosphorylation of tau protein, which forms the paired helical filaments, then gravely impacts axonal transport. In this review, we firstly introduce the neurobiological concept of AD, and its pathogenesis. Then we review the chemical approaches pointedly directing at Aβ peptide and tau protein, and the clinical reality of these pharmacological strategies. Thirdly, we discuss a physical approach, deep brain stimulation (DBS), which is receiving considerable attention in recent years due to its success in treating Parkinson disease clinically. DBS delivers current pulses, which are generated by a implanted pacemaker, through electrodes into dysfunctional brain structures to influence neural activities with the possibility to improve the cognitive function. We will summarize the clinical applications of DBS to restore cognitive impairments due to AD, and animal studies related with DBS. Finally, we will discuss the current study obstacles and future research development of DBS in preclinical and clinical investigations of AD.

Implementation of a smartphone wireless accelerometer platform for establishing deep brain stimulation treatment efficacy of essential tremor with machine learning.

Essential tremor (ET) is a highly prevalent movement disorder. Patients with ET exhibit a complex progressive and disabling tremor, and medical management often fails. Deep brain stimulation (DBS) has been successfully applied to this disorder, however there has been no quantifiable way to measure tremor severity or treatment efficacy in this patient population. The quantified amelioration of kinetic tremor via DBS is herein demonstrated through the application of a smartphone (iPhone) as a wireless accelerometer platform. The recorded acceleration signal can be obtained at a setting of the subject's convenience and conveyed by wireless transmission through the Internet for post-processing anywhere in the world. Further post-processing of the acceleration signal can be classified through a machine learning application, such as the support vector machine. Preliminary application of deep brain stimulation with a smartphone for acquisition of a feature set and machine learning for classification has been successfully applied. The support vector machine achieved 100% classification between deep brain stimulation in `on' and `off' mode based on the recording of an accelerometer signal through a smartphone as a wireless accelerometer platform.

Deep Brain Stimulation of Thalamic Nuclei for Treatment of Intractable Epilepsy

Context: Epilepsy is one of the most common serious neurological disorders. Antiepileptic drugs are effective in most of patients, but one third of them are poorly controlled or their seizures are refractory to drug treatment. Resective surgery is the most common form of surgical treatment for uncontrolled seizures, but it can be associated with profound complications that limit its use. Hence, alternative therapeutic options are required. Evidence Acquisition: Deep brain stimulation (DBS) is increasingly used for the treatment of neurological and psychiatric diseases in patients who do not respond to conventional treatment. Significant improvement of well-being (i.e. quality of life) has been observed in patients with Parkinson’s disease and obsessive compulsive disorder. As a result of these observations, DBS is now performed in small patient groups for the treatment of many disorders including epilepsy. However, despite its broad therapeutic potential, the appropriate targets for DBS are poorly understood and the application of DBS is most often based on case-reports rather than basic research derived from the laboratory. There are studies suggesting that intractable epileptic seizures can be modified or interrupted by electrical stimulation of subcortical structures including thalamic nuclei. In this review article, we focused on DBS in thalamus to highlight the recent developments and address the perspectives of this approach for the treatment of refractory epilepsy. Results: Anterior and centromedian thalamic nuclei have a potential role in reducing seizure frequency, particularly in patients with partial and generalized tonic clonic seizures, respectively. Stimulus parameters, especially frequency is an essential factor in determination of the effects of stimulation. Moreover, bilateral stimulation of thalamic nuclei in most experimental and clinical studies appeared to be protective against the incidence of seizure. Conclusions: Electrical stimulation of anterior and centromedian thalamic nuclei represents a new alternative option in the treatment of patients with refractory epilepsy, particularly in those with partial and generalized tonic clonic seizures who are not candidates for surgery or do not respond to surgery. Although most studies suggest that bilateral high frequency stimulation of thalamic nuclei is effective in reducing seizure activity, further studies are required to determine optimal parameters and risk/benefit ratio of thalamic nuclei DBS for the treatment of intractable epilepsy.

Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments.

Modern deep brain stimulation (DBS) has become a routine therapy for patients with movement disorders such as Parkinson's disease, generalized or segmental dystonia and for multiple forms of tremor. Growing numbers of publications also report beneficial effects in other movement disorders such as Tourette's syndrome, various forms of chorea and DBS is even being studied for Parkinson's-related dementia. While exerting remarkable effects on many motor symptoms, DBS does not restore normal neurophysiology and therefore may also have undesirable side effects including speech and gait deterioration. Furthermore, its efficacy might be compromised in the long term, due to progression of the underlying disease. Various programming strategies have been studied to try and address these issues, e.g., the use of low-frequency rather than high-frequency stimulation or the targeting of alternative brain structures such as the pedunculopontine nucleus. In addition, further technical developments will soon provide clinicians with an expanded choice of hardware such as segmented electrodes allowing for a steering of the current to optimize beneficial effects and reduce side effects as well as the possibility of adaptive stimulation systems based on closed-loop concepts with or without accompanying advances in programming and imaging software. In the present article, we will provide an update on the most recent achievements and discoveries relevant to the application of DBS in the treatment of movement disorder patients and give an outlook on future clinical and technical developments.

Neurosurgical Approaches in Demyelinating Disorders; Where are We Now?

Demyelinating diseases of the central nervous system (CNS) are a group of autoimmune disorders affecting the myelin sheets of CNS neurons resulting in different neurological deficits and disability. Multiple sclerosis (MS), Devic’s disease, progressive multifocal leukoencephalopathy, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO) are among the most common types of demyelinating disorders. Currently MS is the leading cause of neurological disability in young population after trauma . The incidence and prevalence of MS is increasing worldwide primarily due to increase the incidence in female population. Globally, the median estimated incidence of MS is 5.2 (range: 0.5-20.6) per 100,000 p-yrs, the median estimated prevalence of MS is 112.0 (with a range of 5.2-335) per 100,000 p-yrs, and the average disease duration is 20.2 years (range: 7.6-36.2). In Iran, the prevalence and incidence of MS is estimated to be 54.51 and 5.87 per 100,000. Diagnosis of demyelinating disorders is a controversial issue and several criteria has been introduced for the aforementioned subject. Diagnostic criteria for clinically definite MS require documentation of two or more episodes of symptoms and two or more signs that reflect pathology in anatomically noncontiguous white matter tracts of the CNS. The second may be documented by abnormal paraclinical tests such as MRI or evoked potentials (EPs).
 The standard treatment for patients with demyelinating disorders and especially MS is the medical management. Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis have shown efficacy of new oral disease-modifying drugs, teriflunomide and dimethyl fumarate, with similar or better efficacy than the injectable disease-modifying drugs, IFN-β and glatiramer acetate. In addition, the new oral drugs seem to have a favorable safety profile. Further, the monoclonal antibody alemtuzumab, which in clinical trials has shown superiority to subcutaneous IFN-β 1a, has been approved in Europe. In acute exacerbation and flare up of the disease, methylprednisolone pulse is the only approved treatment.
 Although the standard of treatment of MS and other demyelinating disorders is medical, but neurosurgical procedures especially the functional neurosurgical interventions has found their way in management of patients with demyelinating disorders. These interventions are used to treat the complications of MS and demyelinating disorders such as tremor, trigeminal neuralgia, movement disorders and neuropathic pains. Most of these interventions are stereotactic in order to obtain precise targeting of a special deep brain nucleus. The first application of deep brain stimulation (DBS) in patients with MS was for treatment of tremor. Recently it has been demonstrated that DBS of ventral intermediate (VIM) nucleus of thalamus results in alleviation of severe, disabling tremor in patients with MS. Other experiments have also demonstrated decreased tremor and improved quality of life in MS patients responsive to DBS.
 Neuropathic pain and trigeminal neuralgia are among the other complications of demyelinating disorders which are associated with disability and decreased quality of life. Several investigations have shown that DBS of thalamic nuclei would be effective in treatment of neuropathic pain in patients with MS, although the results are controversial and need further investigations. The trigeminal neuralgia is often treated by microsurgical decompression of the trigeminal nerve. However this approach is not effective in patients with demyelinating disorders as they have different pathology. Case series have shown that Gamma Knife surgery (GKS) is an effective and safe treatment for trigeminal neuralgia in patients with MS. No clinical trial is available for comparing the results and outcome between GKS and microsurgical approach. However results of case series are favorable.
 There are still other field that could be approached surgically in patients with demyelinating disorders. Recent bodies of evidence have demonstrated a link between cervical cord plaques and discopathy in those with MS which needs further investigation. Tumefactive demyelinating lesions (TDL) are another issues observed in patients with MS which have unknown course and pathology. The link between demyelinating disorders and brain tumors is also another issues which deserves further investigation. To take a long story short, although the role of functional neurosurgical procedures in management of patients with demyelinating disorders especially MS is still limited, but there is optimistic horizons for growing role of neurosurgical procedures in management of different complications of demyelinating disorders refractory to medical therapy.Â

Deep brain stimulation for psychiatric disorders: where we are now

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation.

Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders.

Deep brain stimulation for psychiatric diseases: what are the risks?

Despite the application of deep brain stimulation (DBS) as an efficient treatment modality for psychiatric disorders, such as obsessive-compulsive disorder (OCD), Gilles de la Tourette Syndrome (GTS), and treatment refractory major depression (TRD), few patients are operated or included in clinical trials, often for fear of the potential risks of an approach deemed too dangerous. To assess the surgical risks, we conducted an analysis of publications on DBS for psychiatric disorders. A PubMed search was conducted on reports on DBS for OCD, GTS, and TRD. Forty-nine articles were included. Only reports on complications related to DBS were selected and analyzed. Two hundred seventy-two patients with a mean follow-up of 22 months were included in our analysis. Surgical mortality was nil. The overall mortality was 1.1 %: two suicides were unrelated to DBS and one death was reported to be unlikely due to DBS. The majority of complications were transient and related to stimulation. Long-term morbidity occurred in 16.5 % of cases. Three patients had permanent neurological complications due to intracerebral hemorrhage (2.2 %). Complications reported in DBS for psychiatric diseases appear to be similar to those reported for DBS in movement disorders. But class I evidence is lacking. Our analysis was based mainly on small non-randomized studies. A significant number of patients (approximately 150 patients) who were treated with DBS for psychiatric diseases had to be excluded from our analysis as no data on complications was available. The exact prevalence of complications of DBS in psychiatric diseases could not be established. DBS for psychiatric diseases is promising, but remains an experimental technique in need of further evaluation. A close surveillance of patients undergoing DBS for psychiatric diseases is mandatory.

Deep Brain Stimulation for Substance Abuse

Substance abuse represents a significant public health issue, yet current standard treatments are largely ineffective. Deep brain stimulation (DBS) surgery may offer an effective interventional approach to treat substance abuse by enabling direct manipulation of neural circuits. DBS has been successfully used in patients with movement disorders and, more recently, in select psychiatric conditions. The ability of DBS surgery to address addictive behavior, however, critically relies upon fundamental knowledge of reward pathways within the brain. Recent evidence has provided insight into those pathways, and studies using DBS surgery in animal models of addiction and reports describing the successful use of DBS in humans with substance abuse disorders provide encouraging support for the feasibility of DBS in treating addiction. Here, we review the pathophysiological mechanisms of addiction and the currently available literature on the application of DBS for substance abuse.

Uncommon Applications of Deep Brain Stimulation in Hyperkinetic Movement Disorders

Uncommon Applications of Deep Brain Stimulation in Hyperkinetic Movement Disorders

Uncommon applications of deep brain stimulation in hyperkinetic movement disorders.

BackgroundIn addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study.MethodsA Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus.ResultsWe identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi) DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies.DiscussionDespite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.

Deep brain stimulation: current status.

In the last two decades, applications of deep brain stimulation (DBS) have expanded rapidly in the field of neurosciences. The most common indications for DBS are Parkinson's disease, medically refractory seizures, essential tremors, and primary dystonia. This device has also been used as an investigational tool in patients having Tourette's syndrome, tardive dyskinesia, and refractory seizures. In the field of psychiatry, DBS has been used for the treatment of refractory obsessive compulsive disorder and depression. The complications are mainly related to surgery, the device, and its stimulation. This article provides an overview of the current status and recent advances in the field of DBS.

Deep Brain Stimulation: Expanding Applications.

For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models.

Estimulação Cerebral Profunda: Nova Fronteira no Tratamento das Doenças do Sistema Nervoso Central

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. 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. 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). 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.

Simultaneous Trial of Deep Brain and Motor Cortex Stimulation in Chronic Intractable Neuropathic Pain

Background/Objectives: Both motor cortex stimulation (MCS) and deep brain stimulation (DBS) of the ventralis caudalis (Vc) thalamus have been shown to be effective in chronic neuropathic pain, and the modulation of thalamic and thalamocortical activity is regarded as a possible mechanism. Although Vc DBS and MCS have a common analgesic mechanism, the application of MCS and DBS is still considered empirical, and there is no consensus on which method is better. Methods: We performed a simultaneous trial of thalamic Vc DBS and MCS in 9 patients with chronic neuropathic pain and investigated the results of the stimulation trial and long-term pain relief. Results: Of the 9 patients initially implanted with both DBS and MCS electrodes, 8 (89%) had a successful trial; 6 of these 8 patients (75%) responded to MCS, and the remaining 2 responded to Vc DBS. During the long-term follow-up, the mean numeric rating scale score decreased significantly (p < 0.05). The percentages of pain relief in the chronic MCS group and the chronic DBS group were 37.9 ± 16.5 and 37.5%, respectively, and there was no statistically significant difference (p = 0.157). Conclusion: Considering the initial success rate and the less invasive nature of epidural MCS compared with DBS, we think that MCS would be a more reasonable initial means of treatment for chronic intractable neuropathic pain.

Robust deep brain stimulation functional MRI procedures in rats and mice using an MR-compatible tungsten microwire electrode.

To develop a series of robust and readily adoptable protocols for the application of deep brain stimulation (DBS)-functional MRI (fMRI) in rodents. DBS-fMRI procedures were conducted in rat and mouse under varying anesthetic conditions (isoflurane in rat and mouse, α-chloralose in rat). A homemade two-channel tungsten microwire electrode was used to minimize magnetic susceptibility artifacts, and was targeted to the ventral posteromedial (VPM) thalamus for DBS-fMRI scanning procedures. Compared with a commercially available MR-compatible electrode, the tungsten microwire generated greatly reduced magnetic-susceptibility artifacts. In the rat, VPM-DBS using the microwire electrode resulted in robust positive blood-oxygen-level-dependent signal changes in somatosensory cortex that were relatively independent of anesthetic type. In the mouse, VPM-DBS similarly generated large, positive neurovascular responses in somatosensory cortex that were detected using cerebral blood volume measurements. Collectively, this work describes reasonable and easily adoptable procedures for conducting DBS-fMRI studies in rodent models. The protocols developed herein may be extended to study DBS effects under numerous experimental conditions and at varying stimulation targets.

Neuroradiology, Anesthesia, Bioengineering, and Hardware Programming in the Clinical Applications of Deep Brain Stimulation

Deep brain stimulation (DBS) is an interventional surgical procedure used to treat an array of sensorimotor, cognitive, and psychiatric diseases originating in distinct brain regions. Although the Food and Drug Adminstration has approved DBS for the treatment of essential tremor and Parkinson disease, this technique is currently being used to treat major depression, dystonia, and obsessive compulsive disorder. Pathophysiological brain areas responsible for abnormal functions are targeted with implanted electrodes that are subsequently attached to battery packs to provide targeted electrical stimulation within the necessary parameters of stimulation required to decrease the phenotypic expressions of these debilitating diseases. DBS regularly targets the stimulation of the ventral thalamic nuclei, subthalamic nucleus, globus pallidus and the basal ganglion in an attempt to diminish symptoms of tremor, Parkinson disease, Tourette syndrome, and pain. Herein, we aim to address the bioengineering that dictates the limitations of current DBS treatments, as well as the history, current use, and potential of DBS as it relates to a variety of motor and neuropsychiatric diseases. This will serve as an insightful analysis about the current landscape of DBS and its potential for more widespread applications in the clinical arena.