Impact of deep brain stimulation on gait in Parkinson disease: A kinematic study.

BACKGROUND: The effect of Deep Brain Stimulation (DBS) on gait in Parkinson's Disease (PD) is poorly understood. Kinematic studies utilizing quantitative gait outcomes such as speed, cadence, and stride length have shown mixed results and were done mostly before and after acute DBS discontinuation. OBJECTIVE: To examine longitudinal changes in kinematic gait outcomes before and after DBS surgery. METHOD: We retrospectively assessed changes in quantitative gait outcomes via motion capture in 22 PD patients before and after subthalamic (STN) or globus pallidus internus (GPi) DBS, in on medication state. Associations between gait outcomes and clinical variables were also assessed. RESULT: Gait speed reduced from 110.7 ± 21.3 cm/s before surgery to 93.6 ± 24.9 after surgery (7.7 ± 2.9 months post-surgery, duration between assessments was 15.0 ± 3.8 months). Cadence, step length, stride length, and single support time reduced, while total support time, and initial double support time increased. Despite this, there was overall improvement in the Movement Disorder Society-Unified Parkinson Disease Rating Scale-Part III score "on medication/on stimulation" score (from 19.8 ± 10.7-13.9 ± 8.6). Change of gait speed was not related to changes in levodopa dosage, disease duration, unilateral vs bilateral stimulation, or target nucleus. CONCLUSION: Quantitative gait outcomes in on medication state worsened after chronic DBS therapy despite improvement in other clinical outcomes. Whether these changes reflect the effects of DBS as opposed to ongoing disease progression is unknown.

A systematic review of health disparities research in deep brain stimulation surgery for Parkinson's disease.

Background: Deep brain stimulation (DBS) is the primary surgical intervention for Parkinson's disease (PD) patients with insufficient response to medication, significantly improving motor symptoms and quality of life. Despite FDA approval for over two decades, access to this therapy remains limited. This systematic review aims to evaluate the influence of gender, race/ethnicity, socioeconomic status, and age on health disparities associated with DBS for PD, providing an overview of current research in this field. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, Web of Science and Cochrane databases from 1960 to September 12th, 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Studies that examine the disparities in accessing DBS among patients with PD were included, comparing different demographic factors. Findings were synthesized and presented narratively to identify and understand DBS disparities. Results: After screening for relevance, 25 studies published between 1960 and 2023 were included, with 16 studies meeting full-text review criteria. While reviewing the references of the 16 articles, two additional studies were included, bringing the total number of included studies to 18. Most studies originated from the United States (44%). The identified studies were categorized as identifying disparities, understanding disparities, or reducing disparities. The majority focused on identifying disparities (72%), while fewer studies delved into understanding the underlying factors (28%). No studies evaluated strategies for reducing disparities. The findings indicate that elderly, female, and Black people, as well as those from low socioeconomic backgrounds and developing countries face greater obstacles in accessing DBS for PD. Conclusion: This study highlights factors contributing to disparities in DBS utilization for PD, including race, gender, and socioeconomic status. Public health policymakers, practitioners, and clinicians should recognize these inequalities and work toward reducing disparities, particularly among vulnerable populations.

Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Stimulation: A Case-Control Study.

Background: Deep brain stimulation (DBS) for Parkinson's disease (PD) is generally contraindicated in persons with dementia but it is frequently performed in people with mild cognitive impairment or normal cognition, and current clinical guidelines are primarily based on these cohorts. Objectives: To determine if moderately cognitive impaired individuals including those with mild dementia could meaningfully benefit from DBS in terms of motor and non-motor outcomes. Methods: In this retrospective case-control study, we identified a cohort of 40 patients with PD who exhibited moderate (two or more standard deviations below normative scores) cognitive impairment (CI) during presurgical workup and compared their 1-year clinical outcomes to a cohort of 40 matched patients with normal cognition (NC). The surgery targeted subthalamus, pallidus or motor thalamus, in a unilateral, bilateral or staged approach. Results: At preoperative baseline, the CI cohort had higher Unified Parkinson's Disease Rating Scale (UPDRS) subscores, but similar levodopa responsiveness compared to the NC cohort. The NC and CI cohorts demonstrated comparable degrees of postoperative improvement in the OFF-medication motor scores, motor fluctuations, and medication reduction. There was no difference in adverse event rates between the two cohorts. Outcomes in the CI cohort did not depend on the target, surgical staging, or impaired cognitive domain. Conclusions: Moderately cognitively impaired patients with PD can experience meaningful motor benefit and medication reduction with DBS.

Identifying the Sources of Racial Disparity in the Treatment of Parkinson's Disease With Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficacious treatment for appropriately selected patients with advanced, medically refractory Parkinson's disease (PD). It is severely underutilized in Black patients-constituting a major treatment gap. The source of this disparity is unknown, but its identification and correction are necessary to provide equitable care. OBJECTIVE: To identify sources of racial disparity in DBS for PD. METHODS: We predicted the demographics of potential DBS candidates by synthesizing published data on PD and race. We retrospectively examined the clinical course of a cohort including all patients with PD evaluated for DBS at our center from 2016 to 2020, testing whether the rate of DBS use and time from evaluation to surgery differed by race. We also tested whether the geographic distribution of patient catchment was biased relative to racial demographics. RESULTS: Far fewer Black patients were evaluated for DBS than would be expected, given regional demographics. There was no significant difference in the rate at which Black patients evaluated in our clinic were treated with DBS, compared with White patients. Fewer patients were recruited from portions of the surrounding area with larger Black populations. CONCLUSION: The known underuse of DBS in Black patients with PD was replicated in this sample from a center in a racially diverse metropolitan area, but was not attributable to the presurgical workup. Future work should examine the transition from medical management to surgical evaluation where drivers of disparity are potentially situated. Surgical practices should increase outreach to physicians managing PD in underserved areas.

Recommendations for Deep Brain Stimulation Device Management During a Pandemic.

Most medical centers are postponing elective procedures and deferring non-urgent clinic visits to conserve hospital resources and prevent spread of COVID-19. The pandemic crisis presents some unique challenges for patients currently being treated with deep brain stimulation (DBS). Movement disorder (Parkinson's disease, essential tremor, dystonia), neuropsychiatric disorder (obsessive compulsive disorder, Tourette syndrome, depression), and epilepsy patients can develop varying degrees of symptom worsening from interruption of therapy due to neurostimulator battery reaching end of life, device malfunction or infection. Urgent intervention to maintain or restore stimulation may be required for patients with Parkinson's disease who can develop a rare but potentially life-threatening complication known as DBS-withdrawal syndrome. Similarly, patients with generalized dystonia can develop status dystonicus, patients with obsessive compulsive disorder can become suicidal, and epilepsy patients can experience potentially life-threatening worsening of seizures as a result of therapy cessation. DBS system infection can require urgent, and rarely emergent surgery. Elective interventions including new implantations and initial programming should be postponed. For patients with existing DBS systems, the battery status and electrical integrity interrogation can now be performed using patient programmers, and employed through telemedicine visits or by phone consultations. The decision for replacement of the implantable pulse generator to prevent interruption of DBS therapy should be made on a case-by-case basis taking into consideration battery status and a patient's tolerance to potential therapy disruption. Scheduling of the procedures, however, depends heavily on the hospital system regulations and on triage procedures with respect to safety and resource utilization during the health crisis.

Clinical outcomes of globus pallidus deep brain stimulation for Parkinson disease: a comparison of intraoperative MRI- and MER-guided lead placement.

OBJECTIVE: Deep brain stimulation (DBS) lead placement is increasingly performed with the patient under general anesthesia by surgeons using intraoperative MRI (iMRI) guidance without microelectrode recording (MER) or macrostimulation. The authors assessed the accuracy of lead placement, safety, and motor outcomes in patients with Parkinson disease (PD) undergoing DBS lead placement into the globus pallidus internus (GPi) using iMRI or MER guidance. METHODS: The authors identified all patients with PD who underwent either MER- or iMRI-guided GPi-DBS lead placement at Emory University between July 2007 and August 2016. Lead placement accuracy and adverse events were determined for all patients. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor scores for patients completing 12 months of follow-up. The authors also assessed the levodopa-equivalent daily dose (LEDD) and stimulation parameters. RESULTS: Seventy-seven patients were identified (MER, n = 28; iMRI, n = 49), in whom 131 leads were placed. The stereotactic accuracy of the surgical procedure with respect to the planned lead location was 1.94 ± 0.21 mm (mean ± SEM) (95% CI 1.54-2.34) with frame-based MER and 0.84 ± 0.007 mm (95% CI 0.69-0.98) with iMRI. The rate of serious complications was similar, at 6.9% for MER-guided DBS lead placement and 9.4% for iMRI-guided DBS lead placement (RR 0.71 [95% CI 0.13%-3.9%]; p = 0.695). Fifty-seven patients were included in clinical outcome analyses (MER, n = 16; iMRI, n = 41). Both groups had similar characteristics at baseline, although patients undergoing MER-guided DBS had a lower response on their baseline levodopa challenge (44.8% ± 5.4% [95% CI 33.2%-56.4%] vs 61.6% ± 2.1% [95% CI 57.4%-65.8%]; t = 3.558, p = 0.001). Greater improvement was seen following iMRI-guided lead placement (43.2% ± 3.5% [95% CI 36.2%-50.3%]) versus MER-guided lead placement (25.5% ± 6.7% [95% CI 11.1%-39.8%]; F = 5.835, p = 0.019). When UPDRS III motor scores were assessed only in the contralateral hemibody (per-lead analyses), the improvements remained significantly different (37.1% ± 7.2% [95% CI 22.2%-51.9%] and 50.0% ± 3.5% [95% CI 43.1%-56.9%] for MER- and iMRI-guided DBS lead placement, respectively). Both groups exhibited similar reductions in LEDDs (21.2% and 20.9%, respectively; F = 0.221, p = 0.640). The locations of all active contacts and the 2D radial distance from these to consensus coordinates for GPi-DBS lead placement (x, ±20; y, +2; and z, -4) did not differ statistically by type of surgery. CONCLUSIONS: iMRI-guided GPi-DBS lead placement in PD patients was associated with significant improvement in clinical outcomes, comparable to those observed following MER-guided DBS lead placement. Furthermore, iMRI-guided DBS implantation produced a similar safety profile to that of the MER-guided procedure. As such, iMRI guidance is an alternative to MER guidance for patients undergoing GPi-DBS implantation for PD.

Cortical Potentials Evoked by Subthalamic Stimulation Demonstrate a Short Latency Hyperdirect Pathway in Humans.

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact.SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.

Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

Cystic Lesions as a Rare Complication of Deep Brain Stimulation.

DBS is a typically well-tolerated operation for treatment of Parkinson's disease, dystonia, and essential tremor (ET). Complications related to the surgical procedure and implanted hardware may occur. More commonly reported complications include hemorrhage, seizure, confusion, and infection. In this article, we report on a rare, but important, complication of DBS surgery, a brain cyst formation at the tip of the implanted ventralis intermedius nucleus (VIM) DBS lead in 2 patients who underwent the procedure at 2 different centers. The indication for surgery was debilitating ET, and in both cases, there was development of a delayed-onset neurological deficit associated with an internal capsule/thalamic cystic lesion formation located at the tip of the DBS lead. Case 1 presented within a few months post-DBS, whereas case 2 had a 10-mo delay to onset of symptoms. No clinical and radiological signs of infection were observed and both DBS systems were explanted with uneventful recovery.

Neuromyelitis Optica Spectrum Disorder Associated With Autoimmune Hemolytic Anemia and Lymphoma.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder characterized by monophasic or recurrent attacks of optic neuritis (ON) and transverse myelitis. NMO spectrum disorders include patients who are seropositive for NMO-IgG antibody and have experienced at least 1 demyelinating attack. NMO has been associated with other autoimmune conditions. We describe a patient diagnosed with autoimmune hemolytic anemia and marginal zone lymphoma, who later developed NMO-IgG seropositive ON. The coexistence of multiple immunologic abnormalities in this patient points to a generalized dysfunction of the humoral immune system. History of autoimmunity should alert the clinician to the possibility of NMO spectrum disorder in a patient presenting with isolated ON.

Stereotactic neurosurgical planning, recording, and visualization for deep brain stimulation in non-human primates.

Methodologies for stereotactic neurosurgery and neurophysiological microelectrode recordings (MER) in non-human primate research typically rely on brain atlases that are not customized to the individual animal, and require paper records of MER data. To address these limitations, we developed a software tool (Cicerone) that enables simultaneous interactive 3D visualization of the neuroanatomy, neurophysiology, and neurostimulation data pertinent to deep brain stimulation (DBS) research studies in non-human primates. Cicerone allows for analysis of co-registered magnetic resonance images (MRI), computed tomography (CT) scans, 3D brain atlases, MER data, and DBS electrode(s) with predictions of the volume of tissue activated (VTA) as a function of the stimulation parameters. We used Cicerone to aid the implantation of DBS electrodes in two parkinsonian rhesus macaques, targeting the subthalamic nucleus in one monkey and the globus pallidus in the other. Cicerone correctly predicted the anatomical position of 79% and 73% of neurophysiologically defined MER sites in the two animals, respectively. In contrast, traditional 2D print atlases achieved 61% and 48% accuracy. Our experience suggests that Cicerone can improve anatomical targeting, enhance electrophysiological data visualization, and augment the design of stimulation experiments.