Deep Brain Stimulation Surgery Research Articles

Bridging the Gap: Local Field Potentials Offer a Peek Into the Brain of a Person With Parkinson Disease.

Clinically available deep brain recordings in patients with Parkinson disease (PD) offer insights into disease mechanisms and create a pathway for personalized treatment strategies. This case illustrates the transformative potential of recordings of neuronal firing in the form of local field potentials (LFPs) by detailing a patient's clinical trajectory for 6 months after deep brain stimulation (DBS) surgery to treat their PD symptoms. LFPs, obtained easily in clinic with a tablet interface to measure and track brain rhythms across the disease course, enriched the patient's clinical picture. Specifically, strong beta peaks were captured at initial programming, and, as the beta peaks diminished over the course of optimizing settings, symptoms improved. These signals may also reveal insights into the neural dynamics of PD such as hypersynchrony in basal ganglia circuitry. Furthermore, the ability to record chronically may unlock new understanding of neuronal dysfunction in PD, possibly enabling future adaptive DBS. In conclusion, identification, tracking, and modulation of LFPs correlated with subjective and objective clinical improvement in the case presented. The use of neurophysiologic signals in the future may lead to therapeutic innovations for our patients with PD.

Preventing Shift from Pneumocephalus During Deep Brain Stimulation Surgery: Don't Give Up the 'Fork in the Brain'.

We present the case of a patient who developed intra-operative pneumocephalus during left globus pallidus internus deep brain stimulation (DBS) placement for Parkinson's disease (PD). Microelectrode recording (MER) revealed that we were anterior and lateral to the intended target. Clinically, we suspected brain shift from pneumocephalus. Removal of the guide-tube for readjustment of the brain target would have resulted in the introduction of movement resulting from brain shift and from displacement from the planned trajectory. We elected to leave the guide-tube cannula in place and to pass the final DBS lead into a channel that was located posterior-medially from the center microelectrode pass. Surgical techniques which can be employed to minimize brain shift in the operating room setting are critical for reduction in variation of the final DBS lead placement. Pneumocephalus after dural opening is one potential cause of brain shift. The recognition that the removal of a guide-tube cannula could worsen brain shift creates an opportunity for an intraoperative team to maintain the advantage of the 'fork' in the brain provided by the initial procedure's requirement of guide-tube placement.

A Systematic Review of Health Disparities Research in Deep Brain Stimulation Surgery for Parkinson’s Disease (P5-4.001)

A Systematic Review of Health Disparities Research in Deep Brain Stimulation Surgery for Parkinson’s Disease (P5-4.001)

Infection Rates in Rechargeable Cell Implantable Pulse Generators Compared to Primary Cell Implantable Pulse Generators in Patients Undergoing Deep Brain Stimulation Surgery (P2-3.019)

Infection Rates in Rechargeable Cell Implantable Pulse Generators Compared to Primary Cell Implantable Pulse Generators in Patients Undergoing Deep Brain Stimulation Surgery (P2-3.019)

How Women and Men with Parkinson’s Disease Approach Decision-making for Deep Brain Stimulation Surgery (P1-3.011)

How Women and Men with Parkinson’s Disease Approach Decision-making for Deep Brain Stimulation Surgery (P1-3.011)

Risk factors and intervention of caregiver burden in Parkinson's disease: a systematic review and meta-analysis.

This study summarized characteristics and risk factors of caregiver burden in PD patients and used meta-analysis to verify the effectiveness of the intervention on caregiver burden. Systematic review and meta-analysis were conducted. Forty-nine articles that involved 5387 caregivers of patients with PD were included in this study. Results of systematic review indicated that Zarit burden Inventory (ZBI) was the most used scale to measure the caregiver burden. All scales revealed caregivers of PD patients had mild to moderate caregiver burden. For the PD patients with longer disease duration, severer disease severity, more negative emotion and cognition impairment, their caregivers intended to have higher caregiver burden. The caregiver with negative emotion and who spent more time on caregiving indicated higher caregiver burden than the others. The caregiver burden was not improved after deep brain stimulation (DBS). Meta-analysis showed that cognitive behavior therapy and palliative care had no significant effect to reduce caregiver burden in PD patients' caregiver. Caregivers of PD patients experienced mild to moderate caregiver burden. Demographic factor, diseased-related factor and negative emotional factor were the risk factors of caregiver burden. Health education and care support for long-term management after DBS surgery should be provided for patients and caregivers to decrease caregiver burden.

1136 Risk Factors for Postoperative Urinary Retention After Deep Brain Stimulation Surgery: The Role of the Subthalamic Nucleus

INTRODUCTION: Deep brain stimulation (DBS) is a widely used neurosurgical procedure for treating Parkinson's disease (PD) and essential tremor (ET). Lower urinary tract dysfunction is a common complication in PD, and this study examines the risk factors for postoperative urinary retention (POUR) after DBS surgery in PD and ET patients to improve patient outcomes. METHODS: This retrospective study analyzed data from patients who underwent DBS surgery for PD and ET at the University of Florida between 2010 and 2021. Data on patient characteristics and surgical details were collected and analyzed using univariate and mixed-linear models. RESULTS: 350 patients underwent 1086 DBS or IPG surgeries, with 153 of them having PD and 197 having ET. The rate of POUR was 79/477 (16.6%), 19/295 (5.2%), and 1/246 (0.4%) for Part 1, Part 2, and IPG replacement. Optimal mixed linear modeling revealed history of urinary retention (OR = 10.2, p = .002), Part 1 surgery (OR = 3.6 compared to Part 2, p < .0003), male sex (OR = 2.5, p = .011), having an electrode placed or connected for the first time (OR = 1.8, p = .046), surgical time (OR 1.5 for each 30 min increase, p < .0001), CCI (OR = 1.4 per comorbidity, p= .006), and preoperative opioid use (OR 1.4 for each additional 10 MME, p = .022) to be significant risk factors for POUR. Having an electrode in STN was found to be protective of POUR (OR = 0.4, p = .030). CONCLUSIONS: While most identified risk factors for POUR in DBS are non-modifiable, they remain important for preoperative planning. Reducing opioid use and minimizing surgical time may help mitigate POUR risk. Targeting the STN during DBS may lead to decreased POUR rates, indicating the potential benefits of STN-targeted DBS for PD and ET patients.

Demographics of focused ultrasound thalamotomy for essential tremor and trends in deep brain stimulation surgery after its introduction in the USA

BackgroundEssential tremor (ET) is a movement disorder that affects 4%–5% of adults >65 years. For patients with medically refractory ET, neurosurgical interventions such as deep brain stimulation (DBS) and unilateral...

489 Increase in Broadband Power Is an Electrophysiologic Marker of Focal Thalamic Activity During Movement

INTRODUCTION: The architecture of the human thalamus is currently indirectly inferred from human histopathologic and non-human animal studies. Given that movement-related increases in broadband power from electrocorticography recording have been previously shown to identify specific motor cortical subregions involved with a particular movement, we explored whether this phenomenon can also be used to localize motor subregions of thalamus. METHODS: We performed serial human thalamic local field potentials recordings using an electrode moved through the lateral thalamusduring deep brain stimulation surgery in 10 subjects. During the recording at each location, subjects alternated between 5 second epochs of rest and 5 second periods of contralateral hand movement. Power spectra were generated for each epoch using Welch’s overlapping periodogram method (1 second window, 50% overlap). Spectra from all movement and rest epochs were separately averaged. The difference between the power in the 65 to 95 Hz band during movement versus rest was used as a proxy for task-related change in broadband activity. Task-related differences in prominent low-frequency oscillations (patient-specific sub-ranges within 5 to 30 Hz) were analyzed per individual oscillation and in aggregate. Significance was determined using unpaired T tests at a threshold of p = 0.05. RESULTS: We find that recording sites showing statistically significant increases in broadband power during movement tend to tightly cluster in areas predicted to represent motor thalamus, whereas sites showing statistically significant reduction in the power (desynchronization) of low frequency oscillations are more diffusely distributed. This finding is replicated across all subjects. CONCLUSIONS: These results suggest that a task-dependent increase in broadband power is an electrophysiologic marker of focal thalamic activity and may be useful to delineate specific thalamic subregions on an individual subject basis.

Pallidal multifractal complexity is a new potential physiomarker of dystonia

ObjectiveLow-frequency 4–12 Hz pallidal oscillations are being considered as potential physiomarkers for dystonia. We suggest investigating the multifractal properties of pallidal activity as an additional marker. MethodsWe employed local field potentials (LFP) recordings from 23 patients with dystonia who were undergoing deep brain stimulation (DBS) surgery to explore the connection between disease severity and the multifractal characteristics of pallidal activity. Furthermore, we performed an analysis of LFP recordings from four patients, following the externalization of DBS lead electrodes, to investigate the impact of DBS and neck muscle vibration on multifractal parameters. ResultsGreater dystonia severity exhibited a correlation with a narrower multifractal spectrum width but higher multifractal spectral asymmetry. Both GPi DBS and muscle vibration in dystonia patients expanded the multifractal spectrum width while restoring multifractal spectral symmetry. Notably, the threshold peak intensities for an increase in multifractal spectrum width substantially overlapped with the optimal volume of tissue activated. A broader multifractal spectrum during DBS corresponded to more favorable clinical outcomes. ConclusionsMultifractal properties of pallidal neuronal activity serve as indicators of neural dysfunction in dystonia. SignificanceThese findings suggest the potential of utilizing multifractal characteristics as predictive factors for the DBS outcome in dystonia.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Asymptomatic cable twisting in a patient with impending Twiddler syndrome detected during deep brain stimulation surgery for Parkinson’s disease: A case report

Background: Deep brain stimulation (DBS) has consistently demonstrated high efficacy and safety in patients with Parkinson’s disease. Twiddler’s syndrome is a rare occurrence of hardware failure in patients undergoing neuromodulation. We report here a case of subclinical cable twisting jeopardizing Twiddler’s syndrome in a patient with Parkinson’s disease who underwent DBS surgery targeting the globus pallidus internus (GPI). Case Description: A 70-year-old woman with a 7-year history of Parkinson’s disease refractory to medication was referred to our department for treatment of involuntary movements of the left hand and leg. She underwent right GPI DBS implantation. Left GPI DBS implantation was subsequently planned to manage resting tremors that developed in the right leg after the first surgery at around one year after the first surgery. During a routine check-up before the second surgery, we incidentally detected Twiddler’s syndrome. The patient showed no neurological deficits in the left extremities, the same as before right GPI DBS. We performed left GPI DBS concomitantly with the revision of the implantable pulse generator and extension wire. Conclusion: Twiddler’s syndrome is a rare complication of DBS. Subclinical risk of cable twisting jeopardizing Twiddler’s syndrome is rarely detected without clinical indications of hardware failure. Neurosurgeons should be cognizant of and regularly monitor the implanted device in case serious complications occur.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

The association between motor and non-motor symptoms in essential tremor patients being evaluated for deep brain stimulation surgery

BackgroundNon-motor symptoms, including depression and cognitive impairment, are common in essential tremor (ET), but associations between these symptoms and tremor are poorly understood. MethodsA retrospective, single-institution, cohort study evaluated 140 patients with ET undergoing evaluation for deep brain stimulation (DBS) surgery. The Fahn-Tolosa-Marin (FTM) or Washington Heights-Inwood Genetic Study of ET (WHIGET) scale was used to grade tremor. Tremor scores were divided into quartiles. Patients underwent clinical neuropsychological evaluations that included a comprehensive cognitive test battery and Beck Depression Inventory-II (BDI-II). Subgroup analysis was performed with groups who met criteria for depression (BDI-II > 14) or overall cognitive impairment (<9th percentile on at least two dissimilar cognitive tests). Independent samples t-tests were used for continuous variables and chi square tests for categorical variables. Univariable and multivariable regressions were used to determine relationships between tremor and non-motor scores. ResultsTremor quartile was correlated with language domain performance (p = 0.044) but not depression scores. FTM score was associated with BDI-II (β = 0.940, p = 0.010), language (β = −0.936, p = 0.012), and visuospatial domain (β = −0.836, p = 0.025) scores, such that worse tremor was associated with more depression and worse language and visuospatial function. WHIGET score was not associated with any neuropsychological scores on multivariable regression. ConclusionFTM score was associated with language, visuospatial, and mood symptoms, suggesting a relationship between the severity of these symptom types. Different tremor scores capture different motor symptoms and relationships with nonmotor symptoms.

Effects of subthalamic nucleus deep brain stimulation using different frequency programming paradigms on axial symptoms in advanced Parkinson's disease.

In advanced Parkinson's disease (PD), axial symptoms are common and can be debilitating. Although deep brain stimulation (DBS) significantly improves motor symptoms, conventional high-frequency stimulation (HFS) has limited effectiveness in improving axial symptoms. In this study, we investigated the effects on multiple axial symptoms after DBS surgery with three different frequency programming paradigms comprising HFS, low-frequency stimulation (LFS), and variable-frequency stimulation (VFS). This study involved PD patients who had significant preoperative axial symptoms and underwent bilateral subthalamic nucleus (STN) DBS. Axial symptoms, motor symptoms, medications, and quality of life were evaluated preoperatively (baseline). One month after surgery, HFS was applied. At 6months post-surgery, HFS assessments were performed, and HFS was switched to LFS. A further month later, we conducted LFS assessments and switched LFS to VFS. At 8months after surgery, VFS assessments were performed. Of the 21 PD patients initially enrolled, 16 patients were ultimately included in this study. Regarding HFS, all axial symptoms except for the Berg Balance Scale (p < 0.0001) did not improve compared with the baseline (all p > 0.05). As for LFS and VFS, all axial symptoms improved significantly compared with both the baseline and HFS (all p < 0.05). Moreover, motor symptoms and medications were significantly better than the baseline (all p < 0.05) after using LFS and VFS. Additionally, the quality of life of the PD patients after receiving LFS and VFS was significantly better than at the baseline and with HFS (all p < 0.0001). Our findings indicate that HFS is ineffective at improving the majority of axial symptoms in advanced PD. However, both the LFS and VFS programming paradigms exhibit significant improvements in various axial symptoms.

Single neurons in the thalamus and subthalamic nucleus process cardiac and respiratory signals in humans

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

Prescribing medications for Parkinson's disease

Around 10 million people worldwide have Parkinson's disease and in the UK the estimated figure is 153000. The condition is characterised by motor symptoms including tremors, stiffness, slowness, balance problems and/or gait disorders, but sufferers can develop a wide range of associated psychological and physical problems. Treatment includes a combination of pharmacological and supportive physical therapies, supplied by a multidisciplinary team. As the condition progresses, medication regimens expand to include a combination of drug therapies. For those who do not benefit from pharmacological therapy deep brain stimulation surgery can be considered. Some people find that alternative therapies such as homeopathy, music and massage are useful additions to standard medical treatments. This article will give an overview of Parkinson's disease, including symptoms and diagnosis, and explore issues for consideration when prescribing common first-line Parkinson's medications.

Clinical evaluation of a stereotactic system for single-stage deep brain stimulation surgery under general anesthesia: technical note.

Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Auditory oddball responses in the human subthalamic nucleus and substantia nigra pars reticulata

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

Intracerebral hemorrhage after deep brain stimulation surgery guided with microelectrode recording: analysis of 297 procedures

ObjectivesReport the incidence of symptomatic and asymptomatic intracerebral hemorrhage (ICH) in patients submitted to deep brain stimulation (DBS) guided with microelectrode recording (MER) with further analysis of potential risk factors, both inherent to the patient and related to the pathology and surgical technique. MethodsWe performed a retrospective observational study. 297 DBS procedures were concluded in 277 patients in a single hospital centre between January 2010 and December 2020. All surgeries were guided with MER. We analysed the incidence of symptomatic and asymptomatic ICH and its correlation to age, sex, diagnosis, hypertension and perioperative hypertension, diabetes, dyslipidaemia, antiplatelet drugs, anatomic target, and number of MER trajectories. ResultsThere were a total of 585 electrodes implanted in 277 patients. 16 ICH were observed, of which 6 were symptomatic and 10 asymptomatic, none of which incurred in permanent neurological deficit. The location of the hemorrhage varied between cortical and subcortical plans, always in relation with the trajectory or the final position of the electrode. The incidence of symptomatic ICH per lead-implantation was 1%, and the CT-scan demonstrated asymptomatic ICH in 1.7% more patients. Male patients or with hypertension are 2.7 and 2.2 times more likely to develop ICH, respectively. However, none of these characteristics has been shown to have a statistically significant association with the occurrence of ICH, as well as age, diagnosis, diabetes, dyslipidaemia, antiplatelet drugs, anatomic target, number of MER trajectories and perioperative hypertension. ConclusionsMER-guided DBS is a safe technique, with low incidence of ICH and no permanent deficits in our study. Hypertension and male sex seem to be risk factors for the development of ICH in this surgery. Nevertheless, no statistically significant factors were found for the occurrence of this complication.