Modern Deep Brain Stimulation Research Articles

Recommendations for the Prevention and Management of Deep Brain Stimulation Infections Based on 26-Year Single-Center Experience

Introduction: Infections related to deep brain stimulation (DBS) can lead to discontinuation of the treatment and increased morbidity. Various measures of reducing infection rates have been proposed in the literature, but scientific consensus is lacking. The aim of this study was to report a 26-year single center experience of DBS infections and provide recommendations for the prevention and management of them. Methods: The retrospective analysis consisted of 978 DBS surgeries performed at Oulu University Hospital (OUH) from 1997 to 2022. This included 342 primary or reimplantations of DBS electrodes and 559 primary or reimplantations of implantable pulse generator (IPG). Infections within approximately 1 year after the surgery without secondary cause were considered surgical-site infections (SSIs). χ2 test was used to compare infection rates before and after 2013, when the systematic implementation of infection prevention measures was started. Results: A total of 35 DBS implants were found to be infected. The number of SSIs was 30, of which 29 were originally operated in OUH leading to a center-specific infection rate of 3.1%. Of the SSIs, 17.2% occurred after IPG replacement. Staphylococcus aureus was found in 75.0% of cultures and 32.1% were mixed infections. The treatment of SSIs included aggressive surgical revision combined with cefuroxime and vancomycin antibiotics, as most patients in the initial conservative treatment group eventually required surgical revision. A statistically significant difference in infection rates before and after the implementation of preventative measures was not observed (risk ratio 2.20, 95% confidence interval 0.94–5.75, p = 0.051), despite over two-fold difference in the incidence of SSIs. Conclusion: Our findings show that the rates of surgical infections are low in modern DBS, but due to their serious consequences, preventative measures should be implemented. We highlight that mixed infections should be accounted for in the antibiotic selection. Furthermore, our treatment recommendation includes aggressive surgical revision combined with antibiotic treatment.

480 Effect of Chronic DBS on Ventral Capsule Ventral Striatum-Specific Circadian Rhythm in Refractory Obsessive-Compulsive Disorder

INTRODUCTION: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) improves symptoms in ∼66% of patients with treatment-resistant obsessive-compulsive disorder (OCD). However, a common adverse effect of VC/VS DBS is hypomania, marked by decreased need for sleep and increased risk-taking behaviors. Modern DBS devices have enabled 24-hour collection of neural data, allowing for tracking of circadian rhythms reflected by VC/VS local field potentials (LFPs). METHODS: We implanted six patients with treatment-resistant OCD with a DBS device configured for constant VC/VS stimulation and recording. Spectral power in the 9 ± 2.5 Hz band was estimated onboard the device every 10 minutes for a median of 249 days (range 77-608). We assessed the rhythmicity of power in this spectral band by fitting 7-day retrospective rolling windows of per-day normalized LFP power to cosine functions using least-squared regression. Output metrics included acrophase (time of peak activity), amplitude, and fit significance. We quantified trends in acrophase over time using Pearson correlation. RESULTS: All six patients demonstrated consistent 24-hour cyclic LFP activity bilaterally. Two of the six had diurnal peaks which shifted significantly earlier across the study period. The remaining four patients had nocturnal peaks, all shifting significantly later over time. Notably, a patient in the latter group experienced three days of hypomania after DBS initiation associated with circadian disruptions even after clinical symptom resolution. Only after clinical DBS adjustment 2 weeks later did circadian rhythm rapidly return to pre-hypomanic levels. CONCLUSIONS: Study patients demonstrated evolving circadian VC/VS LFP activity across the course of DBS therapy, usually independent of cyclic whole-brain activity (i.e. sleep). Conversely, disruptions to these circadian patterns, as observed here during hypomania, may serve as biomarkers of region-specific stimulation side effects.

Anthropology of Deep Brain Stimulation; the 30th Anniversary of STN DBS in 2023.

The year 2023 marks the 30th anniversary of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD). This procedure prompted a universal interest in DBS for various brain disorders and resulted in a unique expansion of clinical and scientific collaboration between many disciplines, with impact on many aspects of society. To study the anthropology of DBS, that is, its ethno-geographic origins, its evolution, its impact on clinicians and scientists, and its influence on society at large. The authors scrutinized the geo-ethnic origins of the pioneers of modern DBS, and they evaluated, based on the literature and on a long-term praxis, the development of DBS and its impact on clinicians, on healthcare, and on society. Scientists and clinicians from various geo-ethnic origins pioneered modern DBS, leading to worldwide spread of this procedure and to the establishment of large multidisciplinary teams in many centers. Neurologists became actively involved in surgery and took on new laborious tasks of programming ever more complicated DBS systems. Publications sky-rocketed and the global spread of DBS impacted positively on several aspects of society, including healthcare, awareness of neurological diseases, interdisciplinary relations, conferences, patient organizations, unemployment, industry, etc. STN DBS has boosted the field of deep brain electrotherapy for many neurological and psychiatric illnesses, and DBS has generated a global benefit on many aspects of society, well beyond its clinical benefits on symptoms of diseases. With the ever-increasing indications for DBS, more positive global impact is expected.

Reduced Risk of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From a United States Claims Database.

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson's disease (PD) or essential tremor (ET) in the United States.Design: Retrospective, contemporaneous cohort study.Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018.Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, of which 3,869 patients had a de novo implant and primary diagnosis of PD or ET. Follow-up of 3 months was available for 3,810 patients, 12 months for 3,561 patients, and 24 months for 1,812 patients.Intervention: Implantation of a modern directional (MD) or traditional omnidirectional (TO) DBS system.Primary and Secondary Outcome Measures: We hypothesized that MD systems would impact complication rates. Reoperation rate was the primary outcome. Associated diagnoses, patient characteristics, and implanting center details served as covariates. Kaplan–Meier analysis was performed to compare rates of event-free survival and regression models were used to determine covariate influences.Results: Patients implanted with modern systems were 36% less likely to require reoperation, largely due to differences in acute reoperations and intracranial lead reoperations. Risk reduction persisted while accounting for practice differences and implanting center experience. Risk reduction was more pronounced in patients with PD.Conclusions: In the first multicenter analysis of device-related complications including modern DBS systems, we found that modern systems are associated with lower reoperation rates. This risk profile should be carefully considered during device selection for patients undergoing DBS for PD or ET. Prospective studies are needed to further investigate underlying causes.

Technology of deep brain stimulation: current status and future directions.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.

MER based analysis of local field potentials with deep brain stimulation subthalamic nucleus in Parkinson\'s disease using coherence and entropy techniques

Deep brain stimulation (DBS) is a device-based well-developed and well-established innovative frontier surgical-therapeutic method which reduces the symptoms of Parkinson‘s disease (PD) and restores and increases the motor-functioning. DBS gives a unique-opportunity to study the electricaloscillatory( harmonic-ripples) neural-activity of various sub-cortical-structures in PD-subjects. However, the electrically-stimulating local field potentials (LFPs) are fundamentally concerned during subthalamicnuclei (STN) recording. The fluctuations, measured to signify collective neuronal-discharge from neurons surrounding the electrode. The acquisition of extracellular activity of irregular-patterns of STN-activity typically acquired from a population-of-neurons detected as” local field potentials” has discard luminosity on the pathophysiology and seizes the latent to pilot to elegance in modern DBS management. The recordings are often gathered with either intraoperative microelectrode for neuronal-activity and/or DBSleads for chronic-macro-stimulation and reflect oscillatory-activity within nuclei of the basal-ganglia (BG) and thalamic-targets for diagnosing PD. LFP-recordings have numerous clinical implications and presently used to optimize DBS outcomes in closed-loop adaptive-devices/systems. However, the origins of the LFPs are implied softly and implicitly. Thus, the goal of this present study is to analyze LFP recordings within the milieu of clinical-applications for clinical-significancy and this goal is attained with frequency analysis ranging the band from 1Hz-250Hz and coherence band between 0 and 1 level. The results of the study suggest that the spatial-reach of the LFP can extend several millimeters. This study presents a comprehensive investigation into the existing research which gives insights into the origin of LFP-signals and identify the variables that need to be considered when analyzing LFP-signals in clinical settings principally

Improving Safety of MRI in Patients with Deep Brain Stimulation Devices.

MRI is a valuable clinical and research tool for patients undergoing deep brain stimulation (DBS). However, risks associated with imaging DBS devices have led to stringent regulations, limiting the clinical and research utility of MRI in these patients. The main risks in patients with DBS devices undergoing MRI are heating at the electrode tips, induced currents, implantable pulse generator dysfunction, and mechanical forces. Phantom model studies indicate that electrode tip heating remains the most serious risk for modern DBS devices. The absence of adverse events in patients imaged under DBS vendor guidelines for MRI demonstrates the general safety of MRI for patients with DBS devices. Moreover, recent work indicates that-given adequate safety data-patients may be imaged outside these guidelines. At present, investigators are primarily focused on improving DBS device and MRI safety through the development of tools, including safety simulation models. Existing guidelines provide a standardized framework for performing safe MRI in patients with DBS devices. It also highlights the possibility of expanding MRI as a tool for research and clinical care in these patients going forward.

My 25 Stimulating Years with DBS in Parkinson's Disease.

The year 2017 marks the 30th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid, Pollak et al. in 1987, initially targeting the motor thalamus to treat tremor, and subsequently targeting the subthalamic nucleus (STN) for treatment of symptoms of advanced Parkinson’s disease (PD). STN DBS is undoubtedly “the most important discovery since levodopa”, as stated by David Marsden in 1994. In 2014, The Lasker– DeBakey Clinical Medical Research Award to “honor two scientists who developed deep brain stimulation of the subthalamic nucleus”, was bestowed upon Benabid and DeLong. STN DBS remains today the main surgical procedure for PD, due to its effectiveness in ameliorating PD symptoms and because it is the only surgical procedure for PD that allows a radical decrease in medication. Future improvements of DBS include the possibility to deliver a “closed-loop”, “on demand” stimulation, as highly preliminary studies suggest that it may improve both axial and appendicular symptoms and reduce side effects such as dysarthria. Even though DBS of the subthalamic nucleus is the main surgical procedure used today for patients with PD, all patients are not suitable for STN DBS; as a functional neurosurgeon performing since more than 25 years various surgical procedures the aim of which is not to save life but to improve the patient’s quality of life, I consider that the surgery should be tailored to the patient’s individual symptoms and needs, and that its safety is paramount.

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.

The present indication and future of deep brain stimulation.

The use of electrical stimulation to treat pain in human disease dates back to ancient Rome or Greece. Modern deep brain stimulation (DBS) was initially applied for pain treatment in the 1960s, and was later used to treat movement disorders in the 1990s. After recognition of DBS as a therapy for central nervous system (CNS) circuit disorders, DBS use showed drastic increase in terms of adaptability to disease and the patient’s population. More than 100,000 patients have received DBS therapy worldwide. The established indications for DBS are Parkinson’s disease, tremor, and dystonia, whereas global indications of DBS expanded to other neuronal diseases or disorders such as neuropathic pain, epilepsy, and tinnitus. DBS is also experimentally used to manage cognitive disorders and psychiatric diseases such as major depression, obsessive-compulsive disorder (OCD), Tourette’s syndrome, and eating disorders. The importance of ethics and conflicts surrounding the regulation and freedom of choice associated with the application of DBS therapy for new diseases or disorders is increasing. These debates are centered on the use of DBS to treat new diseases and disorders as well as its potential to enhance ability in normal healthy individuals. Here we present three issues that need to be addressed in the future: (1) elucidation of the mechanisms of DBS, (2) development of new DBS methods, and (3) miniaturization of the DBS system. With the use of DBS, functional neurosurgery entered into the new era that man can manage and control the brain circuit to treat intractable neuronal diseases and disorders.

Twenty‐five years of deep brain stimulation: Celebrations and apprehensions

The year 2012 marks the 25th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid et al in 1987, initially to treat tremor with DBS of the ventral intermediate nucleus of the thalamus. The subsequent extension of DBS to the subthalamic nucleus (STN), demonstrating its efficacy on virtually all symptoms of advanced Parkinson's disease (PD), sparked an era of intense clinical and research activities, eventually transcending PD and movement disorders to encompass mood and mind. Investigations of the role of DBS in a variety of neurological, psychiatric, cognitive, and behavioral conditions is ongoing. Serendipitous discoveries and advances in functional imaging are providing "new" brain targets for an increasing number of pathologies. Toward the end of this quarter of a century of DBS, there have been some indications that the field may be at risk of gliding down a slippery slope, reminiscent of the excesses of the old-era DBS. Although there are many reasons this year to celebrate the achievements of 25 years of modern DBS, there are also reasons to fear the opening of a new Pandora's box.

The evolution of deep brain stimulation for neuropsychiatric disorders

Deep brain stimulation (DBS) is the most focal method for stimulating the human brain. In contrast to lesions, DBS is nonablative, with the advantages of reversibility and adjustability. Thus, therapeutic effectiveness can be enhanced and stimulation-related side effects minimized during long-term patient management. While DBS is an approved adjunct therapy for severe, medication-refractory movement disorders, it remains investigational in neuropsychiatry. However, experience to date, though limited, suggests that DBS may offer a degree of hope to patients with severe and treatment-resistant neuropsychiatric illness. Thus far, work in obsessive-compulsive disorder (OCD), the first psychiatric condition studied using modern DBS devices, has shown consistently positive results across multiple small-scale studies. Work in treatment-resistant Major Depressive Disorder (MDD) also suggests therapeutic potential in preliminary studies, generating cautious optimism for this indication. With the increase in potential applications, a number of clinical and preclinical research efforts have now focused on understanding the mechanisms of action of DBS. Further development of DBS for these and other illnesses with primarily behavioral symptoms will require thoughtful collaboration among multiple disciplines.