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Deep brain stimulation (DBS) is a common treatment for motor symptoms of Parkinson disease (PD), a condition associated with increased risk of dysphagia. The effect of DBS on swallowing function has not been comprehensively evaluated using gold-standard imaging techniques, particularly for globus pallidus internus (GPi) DBS. The objective of this retrospective, cross-sectional study was to identify differences in swallowing safety and timing kinematics among PD subjects with and without GPi DBS. We investigated the effects of unilateral and bilateral GPi DBS as well as the relationship between swallowing safety and DBS stimulation parameters, using retrospective analysis of videofluoroscopy recordings (71 recordings from 36 subjects) from electronic medical records. Outcomes were analyzed by surgical status (pre-surgical, unilateral DBS, bilateral DBS). The primary outcome was percent of thin-liquid bolus trials rated as unsafe, with Penetration-Aspiration Scale scores of 3 or higher. Secondary analyses included swallowing timing measures, relationships between swallowing safety and DBS stimulation parameters, and Dynamic Imaging Grade of Swallowing Toxicity ratings. Most subjects swallowed all boluses safely (19/29 in the pre-surgical, 16/26 in the unilateral DBS, and 10/16 in the bilateral DBS conditions). Swallowing safety impairment did not differ among stimulation groups. There was no main effect of stimulation condition on timing metrics, though main effects were found for sex and bolus type. Stimulation parameters were not correlated with swallowing safety. Swallowing efficiency and overall impairment did not differ among conditions. These results provide evidence that GPi DBS does not affect pharyngeal swallowing function. Further, prospective, investigations are needed.
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Clinical Vignette: A 63-year-old man with severe essential tremor underwent staged bilateral ventralis intermedius (Vim) deep brain stimulation (DBS). Left Vim DBS resulted in improved right upper extremity tremor control. Months later, the addition of right Vim DBS to the other brain hemisphere was associated with acute worsening of the right upper extremity tremor. Clinical Dilemma: In staged bilateral Vim DBS, second lead implantation may possibly alter ipsilateral tremor control. While ipsilateral improvement is common, rarely, it can disrupt previously achieved benefit. Clinical Solution: DBS programming, including an increase in left Vim DBS amplitude, re-established and enhanced bilateral tremor control. Gap in Knowledge: The mechanisms underlying changes in ipsilateral tremor control following a second lead implantation are unknown. In this case, worsening and subsequent improvement after optimization highlight the potential impact of DBS implantation on the ipsilateral side. Expert Commentary: After staged bilateral Vim DBS, clinicians should keep an eye on the first or original DBS side and carefully monitor for emergent side effects or worsening in tremor. Ipsilateral effects resulting from DBS implantation present a reprogramming opportunity with a potential to further optimize clinical outcomes. Highlights: This case report highlights the potential for ipsilateral tremor worsening following staged bilateral DBS and provides valuable insights into troubleshooting and reprogramming strategies. The report emphasizes the importance of vigilant monitoring and individualized management in optimizing clinical outcomes for patients undergoing staged bilateral DBS for essential tremor.
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Estimulación Encefálica Profunda , Temblor Esencial , Humanos , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Masculino , Persona de Mediana Edad , Temblor Esencial/terapia , Temblor Esencial/cirugía , Temblor Esencial/fisiopatología , Núcleos Talámicos Ventrales/cirugíaRESUMEN
INTRODUCTION: Parkinson's disease (PD) is characterized by motor symptoms whose progression is typically assessed using clinical scales, namely the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Despite its reliability, the scale is bounded by a 5-point scale that limits its ability to track subtle changes in disease progression and is prone to subjective interpretations. We aimed to develop an automated system to objectively quantify motor symptoms in PD using Machine Learning (ML) algorithms to analyze videos and capture nuanced features of disease progression. METHODS: We analyzed videos of the Finger Tapping test, a component of the MDS-UPDRS, from 24 healthy controls and 66 PD patients using ML algorithms for hand pose estimation. We computed multiple movement features related to bradykinesia from videos and employed a novel tiered classification approach to predict disease severity that employed different features according to severity. We compared our video-based disease severity prediction approach against other approaches recently introduced in the literature. RESULTS: Traditional kinematics features such as amplitude and velocity changed linearly with disease severity, while other non-traditional features displayed non-linear trends. The proposed disease severity prediction approach demonstrated superior accuracy in detecting PD and distinguishing between different levels of disease severity when compared to existing approaches.
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Algoritmos , Progresión de la Enfermedad , Dedos , Aprendizaje Automático , Enfermedad de Parkinson , Grabación en Video , Humanos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/diagnóstico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Reproducibilidad de los Resultados , Fenómenos Biomecánicos , Hipocinesia/fisiopatología , Hipocinesia/diagnóstico , Movimiento/fisiología , Índice de Severidad de la EnfermedadRESUMEN
Clinical vignette: 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. Clinical dilemma: 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. Clinical solution: 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. Gap in knowledge: 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.
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Estimulación Encefálica Profunda , Neumocéfalo , Humanos , Estimulación Encefálica Profunda/efectos adversos , Neumocéfalo/diagnóstico por imagen , Neumocéfalo/etiología , Neumocéfalo/terapia , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Globo Pálido/diagnóstico por imagen , Globo Pálido/cirugía , MovimientoRESUMEN
BACKGROUND: Evaluation of disease severity in Parkinson's disease (PD) relies on motor symptoms quantification. However, during early-stage PD, these symptoms are subtle and difficult to quantify by experts, which might result in delayed diagnosis and suboptimal disease management. OBJECTIVE: To evaluate the use of videos and machine learning (ML) for automatic quantification of motor symptoms in early-stage PD. METHODS: We analyzed videos of three movement tasks-Finger Tapping, Hand Movement, and Leg Agility- from 26 aged-matched healthy controls and 31 early-stage PD patients. Utilizing ML algorithms for pose estimation we extracted kinematic features from these videos and trained three classification models based on left and right-side movements, and right/left symmetry. The models were trained to differentiate healthy controls from early-stage PD from videos. RESULTS: Combining left side, right side, and symmetry features resulted in a PD detection accuracy of 79 % from Finger Tap videos, 75 % from Hand Movement videos, 79 % from Leg Agility videos, and 86 % when combining the three tasks using a soft voting approach. In contrast, the classification accuracy varied between 40 % and 72 % when the movement side or symmetry were not considered. CONCLUSIONS: Our methodology effectively differentiated between early-stage PD and healthy controls using videos of standardized motor tasks by integrating kinematic analyses of left-side, right-side, and bilateral symmetry movements. These results demonstrate that ML can detect movement deficits in early-stage PD from videos. This technology is easy-to-use, highly scalable, and has the potential to improve the management and quantification of motor symptoms in early-stage PD.
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Deep brain stimulation (DBS) is an effective surgical therapy for carefully selected patients with medication refractory essential tremor (ET). The most popular anatomical targets for ET DBS are the ventral intermedius nucleus (VIM) of the thalamus, the caudal zona incerta (cZI) and the posterior subthalamic area (PSA). Despite extensive knowledge in DBS programming for tremor suppression, it is not uncommon to experience stimulation induced side effects related to DBS therapy. Dysarthria, dysphagia, ataxia, and gait impairment are common stimulation induced side effects from modulation of brain tissue that surround the target of interest. In this review, we explore current evidence about the etiology of stimulation induced side effects in ET DBS and provide several evidence-based strategies to troubleshoot, reprogram and retain tremor suppression.
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Introduction: Charge balancing is used in deep brain stimulation (DBS) to avoid net charge accumulation at the tissue-electrode interface that can result in neural damage. Charge balancing paradigms include passive recharge and active recharge. In passive recharge, each cathodic pulse is accompanied by a waiting period before the next stimulation, whereas active recharge uses energy to deliver symmetric anodic and cathodic stimulation pulses sequentially, producing a net zero charge. We sought to determine differences in stimulation induced side effect thresholds between active vs. passive recharge during the intraoperative monopolar review. Methods: Sixty-five consecutive patients undergoing DBS from 2021 to 2022 were retrospectively reviewed. Intraoperative monopolar review was performed with both active recharge and passive recharge for all included patients to determine side effect stimulation thresholds. Sixteen patients with 64 total DBS contacts met inclusion criteria for further analysis. Intraoperative monopolar review results were compared with the monopolar review from the first DBS programming visit. Results: The mean intraoperative active recharge stimulation threshold was 4.1 mA, while the mean intraoperative passive recharge stimulation threshold was 3.9 mA, though this difference was not statistically significant on t-test (p = 0.442). Mean stimulation threshold at clinic follow-up was 3.2 mA. In Pearson correlation, intraoperative passive recharge thresholds had stronger correlation with follow-up stimulation thresholds (Pearson r = 0.5281, p < 0.001) than intraoperative active recharge (Pearson r = 0.340, p = 0.018), however the difference between these correlations was not statistically significant on Fisher Z correlation test (p = 0.294). The mean difference between intraoperative passive recharge stimulation threshold and follow-up stimulation threshold was 0.8 mA, while the mean difference between intraoperative active recharge threshold and follow-up threshold was 1.2 mA. This difference was not statistically significant on a t-test (p = 0.134). Conclusions: Both intraoperative active recharge and passive recharge stimulation were well-correlated with the monopolar review at the first programming visit. No statistically significant differences were observed suggesting that either passive or active recharge may be utilized intraoperatively.
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[This corrects the article DOI: 10.3389/fnhum.2024.1333183.].
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Deep brain stimulation (DBS) is a neuromodulatory therapy that has been FDA approved for the treatment of various disorders, including but not limited to, movement disorders (e.g., Parkinson's disease and essential tremor), epilepsy, and obsessive-compulsive disorder. Computational methods for estimating the volume of tissue activated (VTA), coupled with brain imaging techniques, form the basis of models that are being generated from retrospective clinical studies for predicting DBS patient outcomes. For instance, VTA models are used to generate target-and network-based probabilistic stimulation maps that play a crucial role in predicting DBS treatment outcomes. This review defines the methods for calculation of tissue activation (or modulation) including ones that use heuristic and clinically derived estimates and more computationally involved ones that rely on finite-element methods and biophysical axon models. We define model parameters and provide a comparison of commercial, open-source, and academic simulation platforms available for integrated neuroimaging and neural activation prediction. In addition, we review clinical studies that use these modeling methods as a function of disease. By describing the tissue-activation modeling methods and highlighting their application in clinical studies, we provide the neural engineering and clinical neuromodulation communities with perspectives that may influence the adoption of modeling methods for future DBS studies.
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BACKGROUND: Natural killer (NK) cells are important innate immunity players and have unique abilities to recognize and eliminate cancer cells, particularly in settings of antibody-opsonization and antibody-dependant cellular cytotoxicity (ADCC). However, NK cell-based responses in bladder cancers to therapeutic antibodies are typically immunosuppressed, and these immunosuppressive mechanisms are largely unknown. METHODS: Single cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry were used to investigate the phenotype of tumour-infiltrating NK cells in patients with bladder cancer. Further, in vitro, and in vivo models of this disease were used to validate these findings. FINDINGS: NK cells within bladder tumours displayed reduced expression of FcγRIIIa/CD16, the critical Fc receptor involved in ADCC-mediated cytotoxicity, on both transcriptional and protein levels. Transcriptional signatures of transforming growth factor (TGF)-ß-signalling, a pleiotropic cytokine known for its immunosuppressive and tissue residency-inducing effects, were upregulated in tumour-infiltrating NK cells. TGF-ß mediated CD16 downregulation on NK cells, was further validated in vitro, which was accompanied by a transition into a tissue residency phenotype. This CD16 downregulation was also abrogated by TGF-ßR signalling inhibition, which could also restore the ADCC ability of NK cells subject to TGF-ß effects. In a humanized mouse model of bladder cancer, mice treated with a TGF-ß inhibitor exhibited increased ADCC activity compared to mice treated only with antibodies. INTERPRETATION: This study highlights how TGF-ß-rich bladder cancers inhibit NK cell-mediated ADCC by downregulating CD16. TGF-ß inhibition represents new avenues to reverse immunosuppression and enhance the tumoricidal capacity of NK cells in bladder cancer. FUNDING: The Guimaraes Laboratory is funded by a US Department of Defense-Breast Cancer Research Program-Breakthrough Award Level 1 (#BC200025), a grant (#2019485) awarded through the Medical Research Future Fund (MRFF, with the support of the Queensland Children's Hospital Foundation, Microba Life Sciences, Richie's Rainbow Foundation, Translational Research Institute (TRI) and UQ), and a grant (#RSS_2023_085) funded by a Metro South Health Research Support Scheme. J.K.M.W. is funded by a UQ Research Training Program PhD Scholarship and N.O. is funded by a NHMRC Postgraduate Scholarship (#2021932).
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Células Asesinas Naturales , Receptores de IgG , Transducción de Señal , Factor de Crecimiento Transformador beta , Neoplasias de la Vejiga Urinaria , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , Animales , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Receptores de IgG/metabolismo , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis de la Célula Individual , FemeninoRESUMEN
Circadian rhythms have been shown in the subthalamic nucleus (STN) in Parkinson's disease (PD), but only a few studies have focused on the globus pallidus internus (GPi). This retrospective study investigates GPi circadian rhythms in a large cohort of subjects with PD (130 recordings from 93 subjects) with GPi activity chronically recorded in their home environment. We found a significant change in GPi activity between daytime and nighttime in most subjects (82.4%), with a reduction in GPi activity at nighttime in 56.2% of recordings and an increase in activity in 26.2%. GPi activity in higher frequency bands ( > 20 Hz) was more likely to decrease at night and in patients taking extended-release levodopa medication. Our results suggest that circadian fluctuations in the GPi vary across individuals and that increased power at night might be due to the reemergence of pathological neural activity. These findings should be considered to ensure successful implementation of adaptive neurostimulation paradigms in the real-world.
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Ritmo Circadiano , Estimulación Encefálica Profunda , Globo Pálido , Levodopa , Enfermedad de Parkinson , Humanos , Globo Pálido/fisiopatología , Enfermedad de Parkinson/fisiopatología , Ritmo Circadiano/fisiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Levodopa/uso terapéutico , Núcleo Subtalámico/fisiopatologíaRESUMEN
The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.