Use Of Deep Brain Stimulation Research Articles

Analysis of the use of deep brain stimulation in the treatment of Parkinson's disease

The central question of this study was the Analysis of deep brain stimulation (DBS) in the treatment of Parkinson's disease. The need to more deeply understand the benefits and limitations of DBS, especially given its increasing use as the standard treatment for advanced Parkinson's patients, justified this research. Detailed analysis of clinical outcomes and improvements in quality of life provided by DBS could offer valuable information for optimizing treatment protocols and clinical decision-making. This study aimed to address these issues through a comprehensive review of the existing literature, analysis of clinical data, and evaluation of best practices for DBS implementation in Parkinson's disease treatment. The methodology consisted of a qualitative literature review, utilizing sources such as Scielo, Google Scholar, scientific journals, and academic repositories. Relevant studies published in Portuguese, English, and Spanish over the last ten years were included. Inclusion and exclusion criteria ensured the selection of high-quality studies focused on the efficacy of DBS in treating Parkinson's disease. The results demonstrated significant benefits of DBS in improving both motor and non-motor symptoms, with DBS showing superior efficacy compared to other treatments. The study concluded that DBS is a highly effective therapeutic approach for Parkinson's disease, offering substantial improvements in patient quality of life and symptom management, highlighting the need for further research to optimize this treatment modality.

The role of the nucleus basalis of Meynert in neuromodulation therapy: a systematic review from the perspective of neural network oscillations.

As a crucial component of the cerebral cholinergic system and the Papez circuit in the basal forebrain, dysfunction of the nucleus basalis of Meynert (NBM) is associated with various neurodegenerative disorders. However, no drugs, including existing cholinesterase inhibitors, have been shown to reverse this dysfunction. Due to advancements in neuromodulation technology, researchers are exploring the use of deep brain stimulation (DBS) therapy targeting the NBM (NBM-DBS) to treat mental and neurological disorders as well as the related mechanisms. Herein, we provided an update on the research progress on cognition-related neural network oscillations and complex anatomical and projective relationships between the NBM and other cognitive structures and circuits. Furthermore, we reviewed previous animal studies of NBM lesions, NBM-DBS models, and clinical case studies to summarize the important functions of the NBM in neuromodulation. In addition to elucidating the mechanism of the NBM neural network, future research should focus on to other types of neurons in the NBM, despite the fact that cholinergic neurons are still the key target for cell type-specific activation by DBS.

Brain stimulation for patients with multiple sclerosis: an umbrella review of therapeutic efficacy.

Multiple sclerosis patients often experience various symptoms that can greatly impact their quality of life. There are various brain stimulation techniques that have been evaluated for their ability to reduce the symptoms of multiple sclerosis. However, there is inconsistency in the specific stimulation methods used and the symptoms targeted in the existing research. This umbrella review conducted in order to evaluate the effectiveness of brain stimulation and identify limitations and gaps for further research. In this umbrella review, we conducted a searched on Web of Knowledge, PubMed, and Scopus database. We specifically looked for reviews, with or without meta-analyses, that have investigated the effects of brain stimulation methods on symptoms of multiple sclerosis. All articles were examined by AMSTAR 2 (A Measure Tool to Assess Systematic Review 2). We identified 155 articles, of which 14 were eligible for inclusion. Of those, five were qualitative studies and nine were meta-analyses. Among the included studies, four examined the use of deep brain stimulation, while ten investigated the therapeutic potential of noninvasive brain stimulation. Considering the heterogeneity of studies, the current evidence suggests that repetitive transcranial magnetic stimulation may be effective in treating pain and improving motor function, while transcranial direct current stimulation may be useful in alleviating fatigue and enhancing certain aspects of cognitive performance. Deep brain stimulation, on the other hand, appears to be effective in reducing tremors. However, further research is warranted to validate these findings and address the existing limitations in the field.

The use of deep brain stimulation in treatment-refractory Tourette syndrome - a literature review

The use of deep brain stimulation in treatment-refractory Tourette syndrome - a literature review

Neuroethical considerations regarding the use of deep brain stimulation in psychiatry

Neuroethical considerations regarding the use of deep brain stimulation in psychiatry

Clinical practice guidelines on the use of deep brain stimulation for the treatment of obsessive-compulsive disorder: systematic review.

Deep brain stimulation (DBS) has been proposed to improve symptoms of obsessive-compulsive disorder (OCD) but is not yet an established therapy. To identify relevant guidelines and assess their recommendations for the use of DBS in OCD. Medline, Embase, American Psychiatric Association PsycInfo and Scopus were searched, as were websites of relevant societies and guideline development organisations. The review was based on the PRISMA recommendations, and the search strategy was verified by a medical librarian. The protocol was developed and registered with PROSPERO (CRD42022353715). The guidelines were assessed for quality using the AGREE II instrument. Nine guidelines were identified. Three guidelines scored >80% on AGREE II. 'Scope and Purpose' and 'Editorial Independence' were the highest scoring domains, but 'Applicability' scores were low. Eight guidelines recommended that DBS is used after all other treatment options have failed to alleviate OCD symptoms. One guideline did not recommend DBS beyond a research setting. Only one guideline performed a cost-effectiveness analysis; the other eight did not provide details on safe or effective DBS protocols. Despite a very limited evidence base, eight of the nine identified guidelines supported the use of DBS for OCD as a last line of therapy; however, multiple aspects of DBS provision were not addressed.

Improving Visual Working Memory with Cholinergic Deep Brain Stimulation.

Acetylcholine is a critical modulatory neurotransmitter for cognitive function. Cholinergic drugs improve cognitive performance and enhance neuronal activity in the sensory and association cortices. An alternative means of improving cognitive function is through the use of deep brain stimulation. Prior animal studies have demonstrated that stimulation of the nucleus basalis of Meynert through DBS improves cognitive performance on a visual working memory task to the same degree as cholinesterase inhibitors. Additionally, unlike current pharmacological treatments for neurocognitive disorders, DBS does not lose efficacy over time and adverse effects are rare. These findings suggest that DBS may be a promising alternative for treating cognitive impairments in neurodegenerative disorders such as Alzheimer's disease. Thus, further research and human trials should be considered to assess the potential of DBS as a therapeutic treatment for these disorders.

Deep brain stimulation and digital monitoring for patients with treatment-resistant schizophrenia and bipolar disorder: A case series.

The use of deep brain stimulation (DBS) has been recently extended for treating resistant psychiatric disorders, but the experience in patients with schizophrenia-related disorders and bipolar disorder (BD) is scarce. We conducted an observational, one-year longitudinal study to evaluate the effects of DBS in four treatment-resistant patients with schizophrenia, schizoaffective, and BD, included in a pilot, last-resource protocol. Patients were digitally monitored for objective assessment of behavioral changes. After one year of its initiation, DBS of the nucleus accumbens (in subjects N2, N3, and N4) and subgenual anterior cingulate cortex (in N1) produced a significant clinical improvement, associated with decreases in the Clinical Global Impression (from 5.25±0.5 to 3.5±1, p=0.035) and in the Hamilton Depression Rating Scale (HADRS scores, from 14.5±6.56 to 1.5±1.29, p=0.020). We observed a notable, durable therapeutic response in two patients from this cohort (N1 and N3), a clinically relevant relief in a third (N2), and a lack of a significant response in the last one (N4). Maintenance electroconvulsive therapy sessions could be discontinued in the three patients that responded to DBS (N1-3). There were no side effects or relevant changes in cognitive functioning. There were relevant differences between physical activity and sleep time among the four participants. These results suggest initial evidence that DBS may be an effective and safe alternative for treating complex and resistant forms of schizophrenia-related disorders and BD. Digital monitoring may help to capture objective measures of behavioral changes after the intervention.

Innovative perspectives in limbic surgery using deep brain stimulation.

Limbic surgery is one of the most attractive and retaken fields of functional neurosurgery in the last two decades. Psychiatric surgery emerged from the incipient work of Moniz and Lima lesioning the prefrontal cortex in agitated patients. Since the onset of stereotactic and functional neurosurgery with Spiegel and Wycis, the treatment of mental diseases gave attention to refractory illnesses mainly with the use of thalamotomies. Neurosis and some psychotic symptoms were treated by them. Several indications when lesioning the brain were included: obsessive-compulsive disorder, depression, and aggressiveness among others with a diversity of targets. The indiscriminately use of anatomical sites without enough scientific evidence, and uncertainly defined criteria for selecting patients merged with a deficiency in ethical aspects, brought a lack of procedures for a long time: only select clinics allowed this surgery around the world from 1950 to the 1990s. In 1999, Nuttin et al. began a new chapter in limbic surgery with the use of Deep Brain Stimulation, based on the experience of pain, Parkinson's disease, and epilepsy. The efforts were focused on different targets to treat depression and obsessive-compulsive disorders. Nevertheless, other diseases were added to use neuromodulation. The goal of this article is to show the new opportunities to treat neuropsychiatric diseases.

Assess stimulation-induced dyskinesia and its potential physiological mechanism using phase-amplitude coupling

With the increasing use of deep brain stimulation (DBS) on clinical treatment of Parkinsons diseases, stimulation-induced dyskinesia (SID) becomes more and more common. SID was often detected shortly after DBS treatment on patients. However, the pathogenesis of SID and exact region of SID remains unclear. The aim of this paper is to review the studies of stimulation-induced dyskinesia and try to propose a new method to study and quantify SID, which is phase-amplitude coupling. phase-amplitude coupling (PAC) has been widely used in many other studies of brain-related illness and therapies. It is believed to have a profound relationship with our brain activities. Because of the features of PAC itself, the anatomical regions related to SID after pallidal DBS in Parkinson's disease (PD) patients can be possibly found, and the value of PAC can be served as a biomarker for us to assess the stimulation-induced dyskinesia. However, further researches on patients should be done to verify this method. It is very important to understand how SID is formed and its pathogenesis because it may help us find the appropriate parameters of deep brain stimulation and reduce the damage caused by the implant of electrode

Should we offer deep brain stimulation to Parkinson's disease patients with GBA mutations?

Parkinson's disease (PD) patients who are carriers of glucosylceramidase β1 (GBA1) gene mutations typically have an earlier age at onset and a more aggressive disease course, with a higher burden of neuropsychological issues. The use of deep brain stimulation (DBS) in PD patients with disabling motor fluctuations and absence of dementia is a widespread therapeutic option, often with good results in terms of improvement in activities of daily living and quality of life. Although all PD patients, when fulfilling the common selection criteria for DBS, can benefit from this intervention, some studies have raised attention toward the fact that PD patients who are carriers of GBA1 variants may have a worse DBS outcome possibly due to an accelerated progression of cognitive decline. From this viewpoint, we summarize the current literature, highlighting the knowledge gaps and proposing suggestions for further research as well as for clinical practice in this timeframe of uncertainty related to using DBS in PD patients who are carriers of GBA1 variants.

Use of deep brain stimulation for treatment-resistant depression – review of main stimulation targets

Deep brain stimulation (DBS) is an innovative method using neuromodulation in treatment of various diseases, most commonly used in Parkinson’s disease, tremor and dystonia. Due to method’s minimally invasive nature and very low incidence of severe adverse effects, the research upon its use in other indications is conducted. Treatment-resistant depression (TRD) is one of these emerging indications. Currently available data regarding the matter concentrate mainly of electrode placement within seven particular structures of the brain: the subgenual anterior cingulate cortex, the ventral capsule/ventral striatum, the lateral habenula, the nucleus accumbens, the inferior thalamic peduncle, the bed nucleus of the stria terminalis and the medial forebrain bundle. It is yet to be determined which stimulation targets bring the most optimal effect. Published clinical trials give basis to theorize that stimulation of each DBS target results in different neurotransmitter modulation. Antidepressant effects vary also depending on stimulation parameters and overall duration. The aim of this review is to compare various targets for stimulation and underlying physiological mechanisms in therapy of TRD. It is needed to keep in mind that there is still high demand on well-designed, randomized, double-blind trials on bigger groups of patients in order to exclude potential inconsistency between results of clinical research.

Treatment of tardive dystonia: A review

Tardive dystonia (TD), the second most common but most disabling form of tardive syndrome, was initially described in 1982. It is caused by exposure to dopamine receptor blocking agents including antipsychotics and antiemetics. It most commonly presents as cranial or cervical dystonia. Characteristics suggestive of a TD diagnosis include a young age of onset, male predominance, and the higher prevalence of phasic cervical dystonia and retrocollis. Treatment of TD is limited. In this paper we review the literature on treatment options for TD as well as discussing a strategic approach. Options include use of clozapine which appears to have anti-dystonia properties. Other medications reported on with limited evidence include VMAT2 inhibitors, anticholinergics, clonazepam, and baclofen. Botulinum toxin has been shown to provide relief in TD in a manner similar to primary dystonia. The largest literature is on the use of deep brain stimulation (DBS) of the globus pallidus pars interna which includes blinded studies. We finish with providing an algorithm based on current knowledge.

Translational aspects of deep brain stimulation for chronic pain.

The use of deep brain stimulation (DBS) for the treatment of chronic pain was one of the first applications of this technique in functional neurosurgery. Established brain targets in the clinic include the periaqueductal (PAG)/periventricular gray matter (PVG) and sensory thalamic nuclei. More recently, the anterior cingulum (ACC) and the ventral striatum/anterior limb of the internal capsule (VS/ALIC) have been investigated for the treatment of emotional components of pain. In the clinic, most studies showed a response in 20%-70% of patients. In various applications of DBS, animal models either provided the rationale for the development of clinical trials or were utilized as a tool to study potential mechanisms of stimulation responses. Despite the complex nature of pain and the fact that animal models cannot reliably reflect the subjective nature of this condition, multiple preparations have emerged over the years. Overall, DBS was shown to produce an antinociceptive effect in rodents when delivered to targets known to induce analgesic effects in humans, suggesting a good predictive validity. Compared to the relatively high number of clinical trials in the field, however, the number of animal studies has been somewhat limited. Additional investigation using modern neuroscience techniques could unravel the mechanisms and neurocircuitry involved in the analgesic effects of DBS and help to optimize this therapy.

Dopamine and Beyond: Implications of Psychophysical Studies of Intracranial Self-Stimulation for the Treatment of Depression.

Major depressive disorder is a leading cause of disability and suicide worldwide. Consecutive rounds of conventional interventions are ineffective in a significant sub-group of patients whose disorder is classified as treatment-resistant depression. Significant progress in managing this severe form of depression has been achieved through the use of deep brain stimulation of the medial forebrain bundle (MFB). The beneficial effect of such stimulation appears strong, safe, and enduring. The proposed neural substrate for this promising clinical finding includes midbrain dopamine neurons and a subset of their cortical afferents. Here, we aim to broaden the discussion of the candidate circuitry by exploring potential implications of a new “convergence” model of brain reward circuitry in rodents. We chart the evolution of the new model from its predecessors, which held that midbrain dopamine neurons constituted an obligatory stage of the final common path for reward seeking. In contrast, the new model includes a directly activated, non-dopaminergic pathway whose output ultimately converges with that of the dopaminergic neurons. On the basis of the new model and the relative ineffectiveness of dopamine agonists in the treatment of depression, we ask whether non-dopaminergic circuitry may contribute to the clinical efficacy of deep brain stimulation of the MFB.

Long-term comparative effectiveness of deep brain stimulation in severe obsessive-compulsive disorder

BackgroundTwenty years after the first use of Deep Brain Stimulation (DBS) in obsessive-compulsive disorder (OCD), our knowledge of the long-term effects of this therapeutic option remains very limited. ObjectiveOur study aims to assess the long-term effectiveness and tolerability of DBS in OCD patients and to look for possible predictors of long-term response to this treatment. MethodsWe studied the course of 25 patients with severe refractory OCD treated with DBS over an average follow-up period of 6.4 years (±3.2) and compared them with a control group of 25 patients with severe OCD who refused DBS and maintained their usual treatment. DBS was implanted at the ventral anterior limb of the internal capsule and nucleus accumbens (vALIC-Nacc) in the first six patients and later at the bed nucleus of stria terminalis (BNST) in the rest of patients. Main outcome was change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score between the two groups assessed using mixed models. Secondary effectiveness outcomes included Hamilton Depression Rating Scale (HDRS) and Global Assessment of Functioning (GAF) scores. ResultsObsessive symptoms fell by 42.5% (Y-BOCS score) in patients treated with DBS and by 4.8% in the control group. Fifty-six per cent of DBS-treated patients could be considered responders at the end of follow-up and 28% partial responders. Two patients among those who rejected DBS were partial responders (8%), but none of the non-DBS group achieved criteria for complete response. HDRS and GAF scores improved significantly in 39.2% and 43.6% among DBS-treated patients, while did not significantly change in those who rejected DBS (improvement limited to 6.2% in HDRS and 4.2% in GAF scores). No statistically significant predictors of response were found. Mixed models presented very large comparative effect sizes for DBS (4.29 for Y-BOCS, 1.15 for HDRS and 2.54 for GAF). Few patients experienced adverse effects and most of these effects were mild and transitory. ConclusionsThe long-term comparative effectiveness and safety of DBS confirm it as a valid option for the treatment of severe refractory OCD.

P 32 Stereotactically guided brain modulation of the frontostriatal circuits for Huntington's disease: current state

Introduction: Huntingtońs disease (HD) is a genetically determined, rare neurodegenerative disorder with pathological motor, behavioral and cognitive neurological characteristics. In light of the lack of disease-modifying therapies, stereotactically assisted intracranial therapies targeting the pallidal area (globus pallidus) and the frontostriatal circuits, such as deep-brain stimulation (DBS), stereotactic lesioning (pallidotomy), and brain-grafting approaches have gained increased recognition for the treatment of Huntington’s disease-associated motor symptoms. Material and Methods: We conducted a narrative review of in-human studies targeting the globus pallidus and adjunct structures (nucleus caudatus and putamen) using stereotactically guided intracranial approaches, such as ablative procedures (pallidotomy) and deep-brain stimulation of the internal/external globus pallidus, as well as intracranial brain-graft injection. We assessed the terms Huntingtońs disease, chorea, parkinsonism, dystonia, globus pallidus externus/internus, deep brain stimulation, lesioning, ablation, pallidotomy, brain grafts, fetal neural grafts, unified Huntingtońs disease rating scale (UHDRS), safety, efficacy and quality of life in data sources derived through searches of PubMed, Ovid MEDLINE, and Scopus, and through manual searches of the bibliographies of known primary and review articles covering the period 1990-2021. Results: Stereotactic lesioning (pallidotomy) was performed on a few HD patients (70 subjects). The outcome of this approach is similar to brain-grafting strategies, with inconsistent findings and mild-to-moderate clinical responsiveness. We also identified a total of 19 in-human DBS trials targeting the globus pallidus internus/externus for HD-associated motor symptoms (chorea, dystonia, and parkinsonism). The majority comprised case reports, along with a few prospective observational cohort studies. At the end of the average observation period, we did not detect any significant changes in the UHDRS total score after pallidotomy and restorative injections, while in contrast, the use of deep-brain stimulation resulted in a significant reduction in chorea symptoms, with the global UHDRS remaining unchanged. Conclusions: Currently, stereotactically guided treatment strategies (DBS, pallidotomy, and brain grafts) should be considered in cases where selective HD-related treatment resistance (chorea, dystonia, and parkinsonism/hyperkinesia) is present. In contrast to the case for PD, the experience of using DBS for HD is currently very limited, as the majority of published trials consist of uncontrolled observational cohort studies. The comparison of UHDRS scores pre- and post-pallidal DBS in a large proportion of HD patients demonstrated the meaningful impact of DBS on chorea symptoms without any worsening of the overall UHDRS score, due, for example, to an increase in bradykinesia.

338 Disparate Use of Deep Brain Stimulation for Parkinson’s Disease in Black Patients is Driven by Barriers to Access that Arise Before Surgical Referral

INTRODUCTION: Deep brain stimulation (DBS) is an effective therapy for Parkinson’s disease (PD) that can provide substantial improvements in quality of life for patients inadequately controlled with medication. However, there is severe racial disparity in its use, with Black PD patients being much less likely to be treated with DBS than White patients. We hypothesized that the extensive process of patient selection and workup limits access to DBS, and we analyzed the records of a major movement disorder and DBS center to determine if this barrier to access was apparent. METHODS: We reviewed a database that includes every patient considered for DBS between 2016 and February of 2021. We cross-tabulated the patients by race, as documented in the medical record, and progression to surgical intervention. We determined whether there was a significant difference in the proportion of patients who were not treated with DBS via Fisher’s exact test. RESULTS: Out of 211 PD patients evaluated by a DBS movement specialist and referred for preoperative workup since 2016, 10 (5%) were indicated to be Black, compared to 160 (76%) White, 7 (3%) Asian, and 34 (16%) Unknown. Of those, 7/10 (70%) Black patients were treated with surgery, compared to 123/160 (77%) White, 5/7 (71%) Asian, and 23/34 (68%) Unknown (p = 0.61, Fisher’s Exact Test). CONCLUSION: While very few Black patients were referred to DBS Clinic, there was no significant difference between racial groups in the likelihood of receiving surgery once referred. This suggests that the disparity arises before preoperative workup, with potential candidates for treatment never reaching DBS clinic. Future work should attempt to identify factors driving this disparity, with particular attention paid to referral patterns. Notably, these results do not exclude the possibility that the general burden of preoperative evaluation and postoperative management might influence decisions on whether to refer patients.

Parkinson's Disease - What is New?

The prevalence of Parkinson's disease (PD) will double by 2030. PD is no longer regarded as a single disease entity. Monogenetic forms may appear clinically identical to sporadic PD. The corona pandemic has caused a deterioration in a great proportion of patients due to concerns of accessing medical care. During this time, teleconsultations emerged as a helpful service for many PD patients as they can reliably administer parts of the neurological examination remotely. New studies address the ongoing controversy about whether the use of levodopa should be delayed. The conclusion is that physicians should not be afraid of using levodopa to treat patients early in the course of PD. Furthermore, the role of dopamine agonists is changing. Besides their known high rates of edema, somnolence and hallucinations dopamine agonists are associated with the development of impulse control disorders in approx. half of the treated patients. During the last 10 years, only two new substances (safinamide, opicapone) have come onto the market in Germany, both with the indication as add on therapy to levodopa in patients with fluctuations. The use of deep brain stimulation and drug pumps in patients with levodopa effect fluctuations is growing, because at this point in the course of the disease, patients also accept invasive therapies that can prolong and optimize independence. Patients who need levodopa more than 5 times a day and who have severe, disturbing OFF phases (> 2 hours a day) despite optimal non-levodopa-based treatment can consider these options. PD stage and symptom-focused, guideline-based physiotherapy has a positive effect on the course of the disease, everyday performance and quality of life and reduces the risk of falling. Multidisciplinary networks are proving effective in reducing falls and hospital admissions.

Comparison of Shod and Unshod Gait in Patients With Parkinson's Disease With Subthalamic and Nigral Stimulation

Background: The Parkinsonian [i.e., Parkinson's disease (PD)] gait disorder represents a therapeutical challenge with residual symptoms despite the use of deep brain stimulation of the subthalamic nucleus (STN DBS) and medical and rehabilitative strategies. The aim of this study was to assess the effect of different DBS modes as combined stimulation of the STN and substantia nigra (STN+SN DBS) and environmental rehabilitative factors as footwear on gait kinematics.Methods: This single-center, randomized, double-blind, crossover clinical trial assessed shod and unshod gait in patients with PD with medication in different DBS conditions (i.e., STIM OFF, STN DBS, and STN+SN DBS) during different gait tasks (i.e., normal gait, fast gait, and gait during dual task) and compared gait characteristics to healthy controls. Notably, 15 patients participated in the study, and 11 patients were analyzed after a dropout of four patients due to DBS-induced side effects.Results: Gait was modulated by both factors, namely, footwear and DBS mode, in patients with PD. Footwear impacted gait characteristics in patients with PD similarly to controls with longer step length, lower cadence, and shorter single-support time. Interestingly, DBS exerted specific effects depending on gait tasks with increased cognitive load. STN+SN DBS was the most efficient DBS mode compared to STIM OFF and STN DBS with intense effects as step length increment during dual task.Conclusion: The PD gait disorder is a multifactorial symptom, impacted by environmental factors as footwear and modulated by DBS. DBS effects on gait were specific depending on the gait task, with the most obvious effects with STN+SN DBS during gait with increased cognitive load.