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Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, with genetic factors accounting for about 15% of cases. There is a significant challenge in tracking disease progression and treatment response, crucial for developing new therapies. Traditional methods like imaging, clinical monitoring, and biomarker analysis have not conclusively tracked disease progression or treatment response in PD. Our previous research indicated that PD patients with increased dopamine transporter (DAT) and tyrosine hydroxylase (TH) in peripheral blood mononuclear cells (PBMCs) might show disease progression and respond to levodopa treatment. Objective: This study evaluates whether DAT- and TH-expressing PBMCs can monitor motor progression in a PD patient with a heterozygous TH mutation. Methods: We conducted a longitudinal follow-up of a 46-year-old female PD patient with a TH mutation, assessing her clinical features over 18 months through DaT scans and PBMC immunophenotyping. This was compared with idiopathic PD patients (130 subjects) and healthy controls (80 age/sex-matched individuals). Results: We found an increase in DAT+ immune cells concurrent with worsening motor scores (UPDRS-III). Following levodopa therapy, unlike idiopathic PD patients, TH+ immune cell levels in this patient remained high even as her motor scores improved. Conclusions: Longitudinal immunophenotyping in this PD patient suggests DAT+ and TH+ PBMCs as potential biomarkers for tracking PD progression and treatment efficacy, supporting further exploration of this approach in PD research. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of levodopa‐carbidopa intestinal gel (LCIG) as an add‐on rescue therapy following deep brain stimulation (DBS) for treatment of motor fluctuations. Background: Both DBS and LCIG are FDA‐approved therapies for treatment of motor fluctuations in advanced PD. Few studies have examined dual therapy for refractory motor fluctuations and it is unknown what the effect on quality of life will be in advanced PD. Methods: We conducted a retrospective study using a large database of all medical and surgical PD cases at the University of Florida. Six patients were identified with DBS who subsequently received rescue LCIG therapy. The clinical histories, indications for intervention and outcomes were reviewed. Results: All patients were managed initially with DBS (bilateral STN DBS (n = 3), bilateral GPi DBS (n = 1), unilateral GPI DBS (n = 2)). Patients with well‐placed (n = 3) and suboptimally placed DBS leads (n = 3) had significant reduction in their motor fluctuations with improvement in the off‐medication time after rescue LCIG therapy. Improvement in quality of life scores (PDQ‐39) was appreciated in four DBS patients following the addition of LCIG therapy. Conclusions: LCIG is a promising add‐on rescue therapy for select patients with existing DBS devices. The LCIG may possibly reduce motor fluctuations and improve quality of life in advanced PD irrespective of the DBS target or the accuracy of lead placement. Dual therapy may also be ideal for patients who are considered high risk for additional DBS surgeries. [ABSTRACT FROM AUTHOR]

Abstract: Deep brain stimulation is a recognized and effective treatment for several movement disorders. Nevertheless, the efficacy of this intervention on abnormal movements secondary to structural brain pathologies is less consistent. In this report, we describe a case of hemiballism–hemichorea due to a peripartum ischemic stroke‐treated with deep brain stimulation of the globus pallidus internus. Patient observed marked improvement in her symptoms at long‐term follow‐up. Neurophysiologic data revealed lower globus pallidus internus firing rates compared to other hyperkinetic disorders. Pallidal deep brain stimulation is a plausible option for medically refractory hemiballism–hemichorea and cumulative data from multiple centers may be used to fully evaluate its efficacy. [ABSTRACT FROM AUTHOR]

Essential tremor (ET) is a syndrome characterized by the presence of symmetric, moderate to high frequency postural and action tremors of the limbs. Additionally, increasing evidence indicates the occurrence of associated cerebellar features in ET patients including impaired gait and balance. Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been shown to be an effective treatment for medically-refractory ET tremor but its effects on balance remain unclear with conflicting results reported. In this article, we report the effects of frequency modification in four patients with disequilibrium after DBS and review available literature regarding the effects of neurostimulation on balance in ET. Reduction in DBS frequency (10–20 Hz reduction intervals) to the lowest effective settings for tremor control was conducted followed by immediate and 4-week assessment of disequilibrium. All patients reported improvement in balance ranging from mild to marked benefit on clinical global impression scale and in the posture and gait disturbance sub-scores of the International Cooperative Ataxia Rating Scale (ICARS). There was no significant difference in tremor control with DBS frequency adjustments. Our results suggest a relationship between the effects of high-frequency stimulation and disequilibrium in ET patients treated with bilateral or unilateral DBS. Additional larger, prospective studies are warranted to validate these results and discern the relationship between DBS stimulation settings and cerebellar findings in ET. [ABSTRACT FROM AUTHOR]

Introduction There is limited evidence regarding the precise location and connections of thermoregulatory centers in humans. We present two patients managed with subthalamic nucleus (STN) Deep Brain Stimulation (DBS) for motor fluctuations in PD that developed reproducible hyperhidrosis with high frequency DBS. Objective To describe the clinical features and analyze the location of the electrodes leading to autonomic activation in both patients. Methods We retrospectively assessed the anatomical localization, electrode programming settings and effects of unilateral STN DBS leading to hyperhidrosis. Results Unilateral stimulation of anterior and medially located contacts within the STN and zona incerta (Zi) caused bilateral, consistent, reproducible, and reversible sweating in our patients. Adequate control of motor symptoms without autonomic side effects was accomplished with alternative programming settings. Conclusion Stimulation of the medial Zi and medial and anterior STN causes hyperhidrosis in a pattern similar to that described in primates and rats. We speculate that central autonomic fibers originating in the lateral hypothalamic area project laterally to the ventral/medial Zi and then to brainstem nuclei following an medial and posterior trajectory in relationship to STN. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is a surgical procedure approved for the treatment of select patients with movement disorders, such as Parkinson's disease, essential tremors, and dystonia. DBS uses electricity to neuromodulate abnormal brain circuits found on these disorders to improve patient's symptomatology. In almost 30 years, DBS has shown to be an effective therapy, however, it is not free of side effects. New technological advances have been aimed to improve clinical benefits and at the same time, minimize side effects. In this review, we discuss recent technological innovations in DBS along with the future direction of the field. We describe new DBS systems labeled "smart" devices, promising electrode designs, and newly defined methods to deliver electrical stimulation to the brain. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is a surgical procedure approved for the treatment of select patients with movement disorders, such as Parkinson's disease, essential tremors, and dystonia. DBS uses electricity to neuromodulate abnormal brain circuits found on these disorders to improve patient's symptomatology. In almost 30 years, DBS has shown to be an effective therapy, however, it is not free of side effects. New technological advances have been aimed to improve clinical benefits and at the same time, minimize side effects. In this review, we discuss recent technological innovations in DBS along with the future direction of the field. We describe new DBS systems labeled "smart" devices, promising electrode designs, and newly defined methods to deliver electrical stimulation to the brain. [ABSTRACT FROM AUTHOR]

The cerebellar ataxia syndromes are a heterogeneous group of disorders clinically characterized by the presence of cerebellar dysfunction. Initial assessment of patients with progressive cerebellar ataxia is complex because of an extensive list of potential diagnoses. A detailed history and comprehensive examination are required for an accurate diagnosis and hierarchical diagnostic investigations. Although no cure exists for most of these conditions, a small group of metabolic, hereditary, inflammatory, and immune-mediated etiologies of cerebellar ataxia are amenable to disease-modifying, targeted therapies. Over the past years, disease-specific treatments have emerged. Thus, clinicians must become familiar with these disorders because maximal therapeutic benefit is only possible when done early. In this article, we review disorders in which cerebellar ataxia is a prominent clinical feature requiring targeted treatments along with specific management recommendations. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has emerged as a successful therapy for the treatment of several neurological disorders with potential implications in management of psychiatric disease. A variety of well-characterized hardware and surgical complications have been reported after the procedure, including postoperative hardware infection, system failure, and intracranial hemorrhage. Fortunately, serious surgical complications are rare, but they can lead to immediate or long-term disability. As the number of patients undergoing DBS continues to increase, newer and less common complications continue to emerge. It is imperative that clinicians become familiar with these complications in order to promptly recognize them and institute adequate early treatment. In this report, we examine the occurrence of unusual complications after DBS with emphasis on surgical, hardware, and stimulation-related complications. [ABSTRACT FROM AUTHOR]

Subthalamic nucleus (STN) deep brain stimulation (DBS) is the most common surgical treatment for managing motor complications in Parkinson's disease (PD). Ultimately, outcomes depend on a variety of factors including lead location, access and expertize in programming and PD medical management. Nevertheless, achieving ideal programming settings can be difficult in certain patients, leading to suboptimal control of symptoms and stimulation-induced side effects, notably dysarthria and dyskinesia. Interleaved stimulation (ILS) is a newer programming technique that attempts to optimize the stimulation field, improving control of symptoms while minimizing stimulation-induced adverse effects. A retrospective chart review was performed on PD patients receiving STN DBS over the past 12 months. Clinical and demographic data were collected from patients identified as having received ILS. The rationale and clinical efficacy of ILS was analyzed. Nine patients received ILS due to incomplete PD symptom control or stimulation-induced side effects after attempting multiple programming options. Appropriate lead location was confirmed with postoperative MRI except in one case. Following ILS, patients reported improvement in symptoms and resolution of side effects, while preserving adequate control in Parkinsonism with a mean improvement in UPDRS-MOTOR scores of 51.2 %. ILS continues to emerge as a safe and effective programming strategy for maximizing symptom control in PD while diminishing stimulation-induced side effects. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) may have a disease‐modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results. Objective: The aim was to compare the risk of PD associated with GLP‐1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D). Methods: Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population‐based cohort study comparing the new use of GLP‐1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)–adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP‐1RA and DPP4i users. Results: This study included 89,074 Medicare beneficiaries who initiated either GLP‐1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP‐1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person‐years). An sIPTW‐adjusted Cox model showed that GLP‐1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63–0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP‐1RA. Conclusion: Among Medicare beneficiaries with T2D, the new use of GLP‐1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

• Paraneoplastic cerebellar degeneration (PCD) symptoms include ataxia and nystagmus. • Holmes tremor is a large amplitude, 3–4 Hz tremor associated with PCD. • PCD associated with non-Hodgkin's lymphoma has rarely been reported. • Malignancy workup and repeat biopsy is recommended if suspicion for PCD is high. • Treating the underlying malignancy is the most likely to improve PCD symptoms. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with lower back pain on chronic narcotics who was admitted to hospital due to altered content of consciousness after an attempted suicide. The laboratory investigations and medical examinations reveal the diagnosis of bilateral pallidal and medial temporal lobe ischaemic lesions due to overdose of analgesic oxycodone.

• Tremor dominant, postural instability/gait dominant, and intermediate type categories are reproducible subtypes of Parkinson's disease. • Parkinson's disease subtypes continuously vary with disease duration. • Intermediate subtypes require further delineation. [ABSTRACT FROM AUTHOR]

Background: The association between newer classes of glucose‐lowering drugs (GLDs) and the risk of Parkinson's disease (PD) remains unclear. Objective: The aim was to examine the effect of newer GLDs on the risk of PD through a meta‐analysis of randomized outcome trials. Methods: The methods included randomized placebo‐controlled outcome trials that reported PD events associated with three newer classes of GLDs (ie, dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 receptor agonists, and sodium‐glucose co‐transporter‐2 inhibitors) in participants with or without type 2 diabetes. The pooled odds ratio (OR) and 95% confidence interval (CI) were estimated using Peto's method. Results: The study included 24 trials involving 33 PD cases among 185,305 participants during a median follow‐up of 2.2 years. Newer GLDs were significantly associated with a lower PD risk (OR: 0.50; 95% CI: 0.25–0.98) than placebo. Conclusion: Newer GLDs may possibly be associated with a decreased risk of PD; however, larger datasets are required to confirm or refute this notion. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Impulse control disorders (ICDs) are common among patients with Parkinson's disease (PD). Risk factors identified for developing ICDs include young age, family history, and impulsive personality traits. However, the association of these potentially disabling disorders with nondopaminergic drugs and sleep disorders has been understudied. Our objective was to examine the association between ICDs and nondopaminergic medications and sleep disorders. Methods: We conducted an observational study of 53 patients with PD from the National Institute of Neurology and Neurosurgery. ICDs were diagnosed using the Questionnaire for Impulsive–Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP‐RS). Patients underwent polysomnography screening to diagnose the presence of sleep disorders. We documented the presence of dopaminergic and nondopaminergic medications, including monoamine oxidase type B inhibitors (MAOBIs), antidepressants, sleep inductors, and antipsychotics. Results: ICDs were reported in 18.9% of the patients (n = 10), and sleep disorders were diagnosed in 81.1% of patients (n = 43). 32.1% of the patients were on antidepressants, 17% on MAOBIs, 15.1% on sleep inductors, and 1.9% on antipsychotics. We observed that QUIP‐RS A–D subscore depended on the presence of antidepressants (p = .03) and sleep inductors (p = .02). Sleep disorders were not associated with the total QUIP‐RS score (p = .93) or QUIP‐RS A–D subscore (p = .81). Conclusion: Antidepressants and sleep inductors were significant predictors for individual QUIP‐RS items and subscores. Our results suggest that nondopaminergic drugs commonly used for PD may be associated with impulse control disorders. We did not identify a relationship between ICDs and polysomnography‐confirmed sleep disorders in patients with PD. Larger and longitudinal studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) is a complex, chronic inflammatory condition affecting the gastrointestinal tract. IBD has been associated with a variety of neurologic manifestations including peripheral nerve involvement, increased risk of thrombotic, demyelinating and events. Furthermore, an evolving association between IBD and neurodegenerative disorders has been recognized, and early data suggests an increased risk of these disorders in patients diagnosed with IBD. The relationship between intestinal inflammatory disease and neuroinflammation is complex, but the bidirectional interaction between the brain-gut-microbiome axis is likely to play an important role in the pathogenesis of these disorders. Identification of common mechanisms and pathways will be key to developing potential therapies. In this review, we discuss the evolving interface between IBD and neurological conditions, with a focus on clinical, mechanistic, and potentially therapeutic implications. [ABSTRACT FROM AUTHOR]

The prefrontal cortex and the amygdala are critical for the emotional guidance of behavior and are believed to be a site of action for many anxiolytics and anxiogenics. Despite extensive studies examining how these drugs affect behavior, there is little information regarding their effects on neuronal activity. Additionally, with recent recognition of anxiety as a non-motor symptom of Parkinson’s disease, it is unknown if activity in the cortex and the amygdala is altered. Previously, we reported that hemiparkinsonian rats had higher baseline anxiety-like behavior and diminished responsiveness to the acute anxiolytic, diazepam. In contrast, sham-lesioned rats exhibited anxiolytic behavior to diazepam. In this study, we monitored in vivo single-unit spiking activity simultaneously from the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA) in anesthetized sham-lesioned and hemiparkinsonian rats to unmask neuro-circuits underpinning the difference in diazepam responsiveness. We found that baseline spiking activity in the ACC was the same in both sham and hemiparkinsonian rats. We also noted a similar phenomenon for baseline activity in the BLA between sham and hemiparkinsonian rats. However, neuronal spiking activity after diazepam administration (1.5 mg/kg, SubQ) was lower than in controls in the ACC of sham-lesioned rats whereas no difference was noted after diazepam treatment in hemiparkinsonian rats. BLA neuronal spiking activity was unaffected by diazepam administration in either animal group. On the other hand, yohimbine treatment (5 mg/kg, SubQ) coincided with lower neuronal spiking activity compared to controls in the BLA of sham-lesioned rats, but was unchanged from controls in hemiparkinsonian rats. Yohimbine did not affect ACC neuronal spiking activity in either group. Overall, the lack of ACC responsiveness to diazepam in hemiparkinsonian, but not sham-lesioned rats underscores a plausible fundamental difference in anxiety-related neural signaling between animal groups. [ABSTRACT FROM AUTHOR]

Introduction Chronic pain is one of the most common non-motor symptoms of Parkinson's disease (PD) affecting up to 85% of patients. Previous studies have established that reduced mechanical and thermal thresholds occur in both idiopathic PD patients and animal models of PD, suggesting that changes may occur in sensory processing circuits. Improvements in sensory thresholds are achieved using subthalamic nucleus (STN) deep brain stimulation (DBS), however the mechanism by which this occurs remains unresolved. Materials and methods We examined unilateral medial forebrain bundle 6-hydroxydopamine (6OHDA) rat model of PD to determine whether STN DBS alters neuronal firing rates in brain areas involved in ascending and descending pain processing. Specifically, single unit in vivo recordings were conducted in the anterior cingulate cortex (ACC), the periaqueductal grey (PAG), and the ventral posteriolateral nucleus of the thalamus (VPL), before, during and after stimulation was applied to the STN at 50 or 150 Hz. Results Sham and 6OHDA lesioned animals have similar neuronal firing activity in the VPL, ACC and PAG before stimulation was applied (p > 0.05). In 6OHDA lesioned rats, both low frequency stimulation (LFS) (p < 0.01) and high frequency stimulation (HFS) (p < 0.05) attenuated firing frequency in the ACC. In shams, only LFS decreased firing frequency. A subset of neurons in the PAG was significantly attenuated in both sham and 6OHDA lesioned animals during HFS and LFS (p < 0.05), while another subset of PAG neuronal activity significantly increased in 6OHDA lesioned rats during HFS (p < 0.05). Finally, low or high frequency STN DBS did not alter neuronal firing frequencies in the VPL. Conclusions Our results suggest that STN DBS alters neuronal firing in descending pain circuits. We hypothesize that STN DBS attenuates excitatory projections from the ACC to the PAG in 6OHDA lesioned rats. Following this, neurons in the PAG respond by either increasing (during HFS only) or decreasing (during both LFS and HFS), which may modulate descending facilitation or inhibition at the level of the spinal cord. Future work should address specific neuronal changes in the ACC and PAG that occur in a freely moving parkinsonian animal during a pain stimulus treated with STN DBS. [ABSTRACT FROM AUTHOR]

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. To evaluate the use of videos and machine learning (ML) for automatic quantification of motor symptoms in early-stage PD. 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. 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. 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. • Automated detection of early-stage PD using video-based kinematic analysis. • Integration of left-side, right-side, and symmetry movements enhances automatic early-PD detection. • Non-invasive, cost-effective tool for remote monitoring of motor symptoms in PD. • Objective measures from video analysis support early diagnosis and treatment strategies. [ABSTRACT FROM AUTHOR]

Chronic pain is a major complaint for up to 85% of Parkinson's disease patients; however, it often not identified as a symptom of Parkinson's disease. Adequate treatment of motor symptoms often provides analgesic effects in Parkinson's patients but how this occurs remains unclear. Studies have shown both Parkinson's patients and 6-hydroxydopamine-lesioned rats exhibit decreased sensory thresholds. In humans, some show improvements in these deficits after subthalamic deep brain stimulation, while others report no change. Differing methods of testing and response criteria may explain these varying results. We examined this effect in 6-hydroxydopamine-lesioned rats. Sprague-Dawley rats were unilaterally implanted with subthalamic stimulating electrodes in the lesioned right hemisphere and sensory thresholds were tested using von Frey, tail-flick and hot-plate tests. Tests were done during and off subthalamic stimulation at 50 and 150 Hz to assess its effects on sensory thresholds. The 6-hydroxydopamine-lesioned animals exhibited lower mechanical (left paw, P < 0.01) and thermal thresholds than shams (hot plate, P < 0.05). Both 50 and 150 Hz increased mechanical (left paw; P < 0.01) and thermal thresholds in 6-hydroxydopamine-lesioned rats (hot-plate test: 150 Hz, P < 0.05, 50 Hz, P < 0.01). Interestingly, during von Frey testing, low-frequency stimulation provided a more robust improvement in some 6OHDA lesioned rats, while in others, the magnitude of improvement on high-frequency stimulation was greater. This study shows that subthalamic deep brain stimulation improves mechanical allodynia and thermal hyperalgesia in 6-hydroxydopamine-lesioned animals at both high and low frequencies. Furthermore, we suggest considering using low-frequency stimulation when treating Parkinson's patients where pain remains the predominant complaint. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson's disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-Ⅲ) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006). [ABSTRACT FROM AUTHOR]

Over the past two decades, animal models of Parkinson's disease (PD) have helped to determine the plausible underlying mechanism of levo-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia following l-DOPA treatment. However, our understanding of the mechanisms related to this phenomenon remains incomplete. The purpose of this manuscript is to provide a comprehensive review of treatment protocols used for assessing the occurrence of l-DOPA-induced dyskinesia, l-DOPA absorption, distribution, drug/food interaction, and discuss current strategies and future directions. This review offers a historical perspective using l-DOPA in animal models of PD and the occurrence of l-DOPA-induced dyskinesia. [ABSTRACT FROM AUTHOR]

Introduction: The optimal timing for physical therapy (PT) delivery in Parkinson's disease (PD) is unknown. Our objective was to determine whether spacing physical therapy visits over a longer period of time is beneficial for maintenance of physical function in PD.Methods: A single center, single-blinded, randomized controlled trial of PD participants. Participants (n = 30) were randomized to either burst (two PT sessions weekly for 6 weeks) or spaced (one PT session every 2 weeks for 6 months) PT. 11 participants in each arm completed the study and were analyzed. The primary outcome measure was the Timed Up and Go (TUG) test at baseline and 6 months. The burst group had an additional outcome measure timepoint at the completion of PT at 6 weeks.Results: Neither group achieved a minimal clinically significant benefit in the TUG score (3.5s) at 6 months. The spaced PT TUG scores were maintained when comparing baseline (7.8 ± 1.5s) and 6 month timepoints (7.8 ± 2.6s, p = 0.594). The burst group TUG scores comparing baseline (9.8 ± 3.8s) to 6 weeks (9.1 ± 3.0s) also was maintained (p = 0.365). The burst group worsened, however, when measuring the period from 6 weeks to 6 months (12.1 ± 7.6s, p = 0.034).Conclusions: The spaced PT group had stability of the TUG mobility measure at 6 months, while the burst group had a significant worsening once PT was discontinued after 6 weeks. It is feasible to test these approaches in a future larger comparative effectiveness study. [ABSTRACT FROM AUTHOR]

Aim We describe a child with severe generalized choreoathetosis and anti–N-methyl- d -aspartate receptor encephalitis after herpes simplex virus type 1 encephalitis. Recent evidence supports an autoimmune trigger for anti–N-methyl- d -aspartate receptor encephalitis following a viral infection. This is emerging as a common and potentially treatable autoimmune condition in the pediatric population. Patient description A 6-month-old girl presented with fever, diarrhea, and partial seizures and was subsequently treated for proven herpes simplex virus type 1 encephalitis. Shortly thereafter, she developed irritability, insomnia, dysautonomia, orolingual and facial choreodystonic movements, spontaneous vocalizations, and choreoathetoid movements of her trunk and limbs. Cerebrospinal fluid analysis confirmed anti–N-methyl- d -aspartate receptor antibodies. Management of her movements required titrated doses of clobazam, valproate, tetrabenazine, and immunotherapy. At 3 months' follow-up, her abnormal movements had completely resolved. Conclusions Our patient adds to recent evidence linking a viral trigger for brain autoimmunity. Movement disorders appear early, leading to severe patient and family distress, and pose a serious management dilemma because of a paucity of clinical trials assessing treatments in the pediatric population. Abnormal hyperkinetic movements present early and prominently, requiring a combination of symptomatic and immune-modulating therapies for successful treatment. [ABSTRACT FROM AUTHOR]

Introduction: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. Methods: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. Results: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. Conclusion: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages. [ABSTRACT FROM AUTHOR]

The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to identify anatomical regions related to stimulation‐induced dyskinesia (SID) after pallidal deep brain stimulation (DBS) in Parkinson's disease (PD) patients and to analyze connectivity associated with SID. Methods: This retrospective study analyzed the clinical and imaging data of PD patients who experienced SID during the monopolar review after pallidal DBS. We analyzed structural and functional connectivity using normative connectivity data with the volume of tissue activated (VTA) modeling. Each contact was assigned to either that producing SID (SID VTA) or that without SID (non‐SID VTA). Structural and functional connectivity was compared between SID and non‐SID VTAs. "Optimized VTAs" were also estimated using the DBS settings at 6 months after implantation. Results: Of the 68 consecutive PD patients who underwent pallidal implantation, 20 patients (29%) experienced SID. SID VTAs were located more dorsally and anteriorly compared with non‐SID and optimized VTAs and were primarily in the dorsal globus pallidus internus (GPi) and dorsal globus pallidus externus (GPe). SID VTAs showed significantly higher structural connectivity than non‐SID VTAs to the associative cortex and supplementary motor area/premotor cortex (P < 0.0001). Simultaneously, non‐SID VTAs showed greater connectivity to the primary sensory cortex, cerebellum, subthalamic nucleus, and motor thalamus (all P < 0.0004). Functional connectivity analysis showed significant differences between SID and non‐SID VTAs in multiple regions, including the primary motor, premotor, and prefrontal cortices and cerebellum. Conclusion: SID VTAs were primarily in the dorsal GPi/GPe. The connectivity difference between the motor‐related cortices and subcortical regions may explain the presence and absence of SID. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Although earlier studies reported variable speech changes following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients, the effects of globus pallidus internus (GPi) DBS on speech performance in PD remain largely unknown. Objective: We aimed to characterize speech changes following PD GPi-DBS. Methods: We retrospectively analyzed clinical and speech outcomes of 25 PD patients treated with bilateral GPi-DBS at a single center. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), speech subsystem domains (respiratory, laryngeal, resonance, orofacial, rate, prosody, rhythm, and naturalness), and overall speech intelligibility. Scores at baseline were compared with those at 6 months, 1 year, and the longest clinical follow-up available. Results: In the off-medication state, activities of daily living and motor function based on UPDRS II and III significantly improved postoperatively. We observed unique patterns of speech changes in patients with PD following GPi-DBS in the short- (n = 25) and longer-term (n = 8) follow-up periods. Velopharyngeal (resonance), laryngeal components, and prosody worsened after bilateral GPi-DBS (p < 0.015). Speech intelligibility did not worsen after GPi-DBS in the short-term, but there was a trend to deteriorate at long-term follow-up (e.g., one year and beyond). We observed worsening of hypokinetic dysarthria in individual patients. Also, a minority of patients developed stuttering, spastic dysarthria, or ataxic dysarthria. Conclusion: Bilateral GPi-DBS worsened several modalities of parkinsonian speech without compromising overall speech intelligibility. GPi-DBS can potentially worsen or induce hypokinetic dysarthria, stuttering, spastic dysarthria, or ataxic dysarthria. GPi-DBS may have different and variable effects on speech function when compared to STN-DBS. [ABSTRACT FROM AUTHOR]

Dystonic tremor (DT) is defined as the tremor in body parts affected by dystonia. Although deep brain stimulation (DBS) has been used to manage medically-refractory DT patients, its efficacy has not been well established. The objective of this study is to provide an up-to-date systematic review of DBS outcomes for DT patients. We conducted a literature search using Medline, Embase, and Cochrane Library databases in February 2020 according to the PRISMA guidelines. From 858 publications, we identified 30 articles involving 89 DT patients who received DBS of different targets. Thalamic DBS was the most common (n = 39) and improved tremor by 40-50% potentially in the long-term over five years with variable effects on dystonic symptoms. Globus pallidus internus (GPi), subthalamic, and subthalamic nucleus (STN) DBS improved both tremor and dystonic symptoms; however, data were limited. A few studies have reported better tremor and dystonia outcomes with combinations of different targets. Concerning adverse effects, gait/balance disorders, and ataxia seemed to be more common among patients treated with thalamic or subthalamic DBS, whereas parkinsonian adverse effects were observed only in patients treated with subthalamic or GPi DBS. Comparative benefits and limitations of these targets remain unclear because of the lack of randomized controlled trials. In conclusion, DBS of these targets may improve tremor with a variable effect on dystonia with different adverse effect profiles. The shortcomings in the literature include long-term motor outcomes, quality of life outcomes, optimal DBS targeting, and DBS programming strategy. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making.Methods: This single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes.Results: For the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes.Conclusion: Bilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied. [ABSTRACT FROM AUTHOR]

Objective: To analyze deep brain stimulation (DBS) outcomes in patients with cervical dystonia (CD), the relationships between motor and disability/pain outcomes, and the differences in outcomes between globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS, and to identify potential outcome predictors. Methods: A systematic literature search identified individual patient data of CD patients who underwent DBS and whose outcomes were assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Then, we performed a pooled meta-analysis on this cohort. Results: A review of 39 papers yielded 208 patients with individual TWSTRS scores and demographic information. At a mean follow-up period of 23.3 months after either GPi or STN DBS, the TWSTRS total (58.8%), severity (53.9%), disability (61.3%), and pain (46.6%) scores significantly improved compared to baseline status (all p < 0.001). There were no significant outcome differences between short-term (< 23.3 months) and long-term (≥ 23.3 months). The TWSTRS outcomes after GPi and STN DBS were comparable, whereas these two targets showed different adverse effect profiles. The rates of responders to DBS according to the TWSTRS total and severity (defined as ≥ 25% improvement) were both 89%. Regression analyses demonstrated motor benefits associated with disability improvement more than pain relief (R2 = 0.345 and 0.195, respectively). No clinically meaningful predictors for DBS outcomes were identified. Conclusion: DBS improves motor symptoms, disability, and pain in CD patients and may provide sustained benefits over 2 years. GPi and STN appear to be equally effective targets with different adverse effect profiles. [ABSTRACT FROM AUTHOR]

Dystonia is an incurable movement disorder which can cause not only physical but also mental problems, leading to impaired health-related quality of life (HRQoL). For patients with dystonia refractory to medical treatment, deep brain stimulation (DBS) is a well-established surgical treatment. The objective of this systematic review is to provide a better understanding of HRQoL outcomes after DBS for dystonia. A search of the literature was conducted using Medline (PubMed), Embase, and Cochrane Library databases in May 2019. HRQoL outcomes after DBS along with motor outcomes were reported in a total of 36 articles involving 610 patients: 21 articles on inherited or idiopathic isolated dystonia, 5 on tardive dystonia, 3 on cerebral palsy, 2 on myoclonus-dystonia, 1 on X-linked dystonia-parkinsonism, and 3 on mixed cohorts of different dystonia subtypes. DBS improved motor symptoms in various subtypes of dystonia. Most studies on patients with inherited or idiopathic isolated dystonia showed significant improvement in physical QoL, whereas gains in mental QoL were less robust and likely related to the complexity of associated neuropsychiatric problems. HRQoL outcomes beyond 5 years remain scarce. Although the studies on patients with other subtypes of dystonia also demonstrated improvement in HRQoL after DBS, the interpretation is difficult because of a limited number of articles with small cohorts. Most articles employed generic measures (e.g. Short Form Health Survey-36) and this highlights the critical need to develop and to utilize sensitive and disease-specific HRQoL measures. Finally, long-term HRQoL outcomes and predictors of HRQoL should also be clarified. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on reducing levodopa‐induced dyskinesia (LID) in Parkinson's disease, and to explore the potential underlying mechanisms. Methods: We retrospectively assessed clinical outcomes in 43 patients with preoperative LID who underwent DBS targeting the STN (20/43) or GPi (23/43). The primary clinical outcome was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) and secondary outcomes included changes in the total daily levodopa equivalent dose, the drug‐off Unified Parkinson Disease Rating Scale Part Ⅲ at the last follow‐up (median, 18 months), adverse effects, and programming settings. Correlation analysis was used to find potential associated factors that could be used to predict the efficacy of DBS for dyskinesia management. Results: Compared to baseline, both the STN group and the GPi group showed significant improvement in LID with 60.73 ± 40.29% (mean ± standard deviation) and 93.78 ± 14.15% improvement, respectively, according to the UDysRS score. Furthermore, GPi‐DBS provided greater clinical benefit in the improvement of dyskinesia (P < 0.05) compared to the STN. Compared to the GPi group, the levodopa equivalent dose reduction was greater in the STN group at the last follow‐up (43.81% vs. 13.29%, P < 0.05). For the correlation analysis, the improvement in the UDysRS outcomes were significantly associated with a reduction in levodopa equivalent dose in the STN group (r = 0.543, P = 0.013), but not in the GPi group (r = −0.056, P = 0.801). Interpretation: Both STN and GPi‐DBS have a beneficial effect on LID but GPi‐DBS provided greater anti‐dyskinetic effects. Dyskinesia suppression for STN‐DBS may depend on the reduction of levodopa equivalent dose. Unlike the STN, GPi‐DBS might exert a direct and independent anti‐dyskinesia effect. [ABSTRACT FROM AUTHOR]

Objective: To compare subthalamic nucleus (STN) deep brain stimulation (DBS) with globus pallidus interna (GPi) DBS for tremor suppression in Parkinson disease (PD).Background: DBS is an effective surgical therapy that has been shown to provide significant benefit for motor symptoms in PD. Currently, two main structures targeted to treat motor complications in PD are the STN and GPi. Although some groups traditionally favor STN over GPi for tremor suppression, evidence demonstrating superiority in long-term tremor control is limited.Methods: We performed a systematic review for all randomized trials comparing STN vs GPi DBS in PD that were published before March 2017. Five studies were examined in a random effects model meta-analysis. We conducted moderator variable analysis to determine if there was a treatment effect difference for STN versus GPi.Results: We compared DBS ON versus OFF and found a significant overall standardized difference mean effect: Effect Size = 0.36; 95% CI = 0.316-0.395; P < 0.0001. These findings indicate that DBS reduced tremor symptoms in PD patients with a medium effect size. Moderator variable analysis of STN vs GPI revealed two significant standardized effect sizes: STN effect size = 0.38 and GPi effect size = 0.35. A Z-test showed that effect sizes between the STN and GPi were not significantly different (P = 0.56).Conclusions: DBS is effective in reducing tremor in PD patients regardless of stimulation target. However, the degree of tremor suppression in STN DBS versus GPi DBS was equivalent. [ABSTRACT FROM AUTHOR]

Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear. To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight. This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses. There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0–12 months after the first or 0–36 months after the second surgery) was positively associated with survival (R2 = 0.14, p < 0.001). Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts. • There was a decline in body weight predating motor symptom onset. • Weight decline accelerated in the decade preceding death. • The bilateral STN DBS group gained the most weight after surgery. • Post-DBS weight was positively associated with survival. [ABSTRACT FROM AUTHOR]

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes. [ABSTRACT FROM AUTHOR]

Abstract: Background: The ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS). Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long‐term reduction of benefit seen with VIM‐DBS. Objectives: To compare clinical outcomes and DBS programming in the long‐term between VIM and cZI neurostimulation in ET‐DBS patients. Materials and Methods: A retrospective review of 53 DBS leads from 47 patients was performed. Patients were classified into VIM or cZI groups according to the location of the activated DBS contact. Demographics, DBS settings, and Tremor Rating Scale scores were compared between groups at baseline and yearly follow‐up to 4 years after DBS. Student t‐tests and analysis of variance (ANOVA) were used to compare variables between groups. Results: Relative to baseline, an improvement in ON‐DBS tremor scores was observed in both groups from 6 months to 4 years post‐DBS (p < 0.05). Although improvement was still significant at 4 years, scores from month 6 to 2 years were comparable between groups but at 3 and 4 years post‐DBS the outcome was better in the VIM group (p < 0.01). Stimulation settings were similar across groups, although we found a lower voltage in the VIM group at 3 years post‐DBS. Conclusions: More ventral DBS contacts in the cZI region do improve tremor, however, VIM‐DBS provided better long‐term outcomes. Randomized controlled trials comparing cZI vs VIM targets should confirm these results. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming. We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six expert centers across the United States. The primary outcome was time spent DBS programming and secondary outcomes measured changes in motor symptoms, caregiver strain and medication requirements. We found a significant reduction in initial visit time (SOC: 43.8 ± 28.9 min n = 37, MAP DBS: 27.4 ± 13.0 min n = 35, p = 0.001). We did not find a significant difference in total programming time between the groups over the 6-month study duration. MAP DBS-aided patients experienced a significantly larger reduction in UPDRS III on-medication scores (−7.0 ± 7.9) compared to SOC (−2.7 ± 6.9, p = 0.01) at six months. MAP DBS was well tolerated and improves key aspects of DBS programming time and clinical efficacy. • This study is the first to evaluate model-based DBS programming in a randomized controlled clinical trial. • This study shows the utility of the MAP DBS platform with multiple anatomical targets, DBS systems, and clinical workflows. • The results suggest the utility of MAP DBS in the programming process, and will be further explored to develop new clinical practices that reduce the burden of therapy optimization. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) employing high-frequency stimulation (HFS) is commonly used in the globus pallidus interna (GPi) and the subthalamic nucleus (STN) for treating motor symptoms of patients with Parkinson's disease (PD). Although DBS improves motor function in most PD patients, disease progression and stimulation-induced nonmotor complications limit DBS in these areas. In this study, we assessed whether stimulation of the substantia nigra pars reticulata (SNr) improved motor function. Hemiparkinsonian rats predominantly touched with their unimpaired forepaw >90% of the time in the stepping and limb-use asymmetry tests. After SNr-HFS (150 Hz), rats touched equally with both forepaws, similar to naive and sham-lesioned rats. In vivo, SNr-HFS decreased beta oscillations (12–30 Hz) in the SNr of freely moving hemiparkinsonian rats and decreased SNr neuronal spiking activity from 28 ± 1.9 Hz before stimulation to 0.8 ± 1.9 Hz during DBS in anesthetized animals; also, neuronal spiking activity increased from 7 ± 1.6 to 18 ± 1.6 Hz in the ventromedial portion of the thalamus (VM), the primary SNr efferent. In addition, HFS of the SNr in brain slices from normal and reserpine-treated rat pups resulted in a depolarization block of SNr neuronal activity. We demonstrate improvement of forelimb akinesia with SNr-HFS and suggest that this motor effect may have resulted from the attenuation of SNr neuronal activity, decreased SNr beta oscillations, and increased activity of VM thalamic neurons, suggesting that the SNr may be a plausible DBS target for treating motor symptoms of DBS. [ABSTRACT FROM AUTHOR]

As the second most common progressive neurodegenerative disorder with increased prevalence in the aging population, Parkinson's disease (PD) affects more than 10 million individuals worldwide with approximately 60,000 new cases occurring each year only in the US. While daily living abilities deteriorate in people with PD, they spend a significant amount of time in their homes. Unfortunately, most existing guidelines for home modification design reflect a standardized, singular plan. This study aimed to demonstrate the feasibility of using a virtual reality (VR) system for persons with PD to virtually walk through different home modifications and to adapt and personalize interior features. A sample of 15 participants with idiopathic PD and 24 healthy adults ambulated on a pressure mat, while using a VR headset and hand controller. Both groups envisioned walking through a virtual doorway from a simulated bedroom into its attached bathroom. Design features for the intervention included doorway width and door-frame color. Each participant was randomly assigned to one of three intervention conditions: (1) standard design, (2) enhanced design, and (3) co-design. The codesign module allowed participants to manipulate design features using a hand controller. We recorded 4 movement variables. Participants completed three questionnaires assessing anxiety, system usability, and satisfaction. Healthy control adults revealed no differences in movement or subjective assessment between the three intervention conditions. However, there were significant differences in the PD group between co-design and the other conditions. The changes were appreciated in the baseline measures of gait distance and strikes as well as in the composite gait component score. This study showed that using VR as a participatory design tool for persons with PD is safe and feasible. Additionally, the self-determination of interior design conditions may possibly affect movement performance measures and merits additional controlled trials. • People with Parkinson's can experience a virtual environment and choose home modifications. • The developed virtual reality tool was satisfying and user-friendly. • The virtual reality tool did not increase anxiety over baseline levels. • Choice of virtual interior features may result in improved movement performance. [ABSTRACT FROM AUTHOR]

R3180 --> Neuromodulators, such as norepinephrine and dopamine, regulate immune responses. In addition to receptor competency, select immune cells express machinery to engage in active neurotransmitter transmission. Specifically, macrophages express the norepinephrine (NET) and dopamine transporters (DAT). However, how these transporters ‐ classically studied in central neurons ‐ affect immunity remains poorly understood. To this end, we investigated the expression and function of NET and DAT in human macrophages. We found that monocyte‐derived macrophages express functional NET and DAT in vitro. A subset of human intestinal macrophages were further confirmed to express DAT in situ. Interestingly, we discovered that inhibiting DAT, but not NET, enhanced the pro‐inflammatory macrophage program in response to an immune challenge. We attribute this modulation to an observed LPS‐induced efflux of dopamine through DAT that engages an autocrine dopamine signaling loop. Collectively, we propose that DAT actively regulates dopamine signaling on immune cells, and, in this context, DAT on macrophages is a novel, dynamic immunomodulator. [ABSTRACT FROM AUTHOR]