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Background Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson’s Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot clinical trial. Here, subject-level visualizations are presented of this early-stage PD dataset to further describe the relationship between active contacts and motor progression. This study also evaluates whether stimulation of the sweet spot and connectivity model associated with slower motor progression is also associated with improvements in long-term motor outcomes in patients with advanced-stage PD. Methods Active contacts of the early-stage PD cohort (N = 14) were analyzed alongside the degree of two-year motor progression. Sweet spot and connectivity models derived from the early-stage PD cohort were then used to determine how well they can estimate the variance in long-term motor outcomes in an independent STN-DBS cohort of advanced-stage PD patients (N = 29). Results In early-stage PD, proximity of stimulation to the dorsolateral STN was associated with slower motor progression. In advanced-stage PD, stimulation proximity to the early PD connectivity model and sweet spot were associated with better long-term motor outcomes (R = 0.60, P < 0.001; R = 0.37, P = 0.046, respectively). Conclusions Results suggest stimulation of a specific site in the dorsolateral STN is associated with both slower motor progression and long-term motor improvements in PD.

Disease outcomes are heterogeneous in Parkinson's disease and may be predicted by gene variants. This study investigated if the BDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the “NIH Exploratory Trials in PD Long-term Study 1” (NET-PD LS-1, n = 540). DNA samples were genotyped for the rs6265 SNP and others (rs11030094, rs10501087, rs1491850, rs908867, and rs1157659). The primary measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and its motor component (UPDRS-III). Groups were divided by genotype and treatment regimen (levodopa monotherapy vs levodopa with other medications vs no levodopa). T allele carriers were associated with worse UPDRS outcomes compared to C/C subjects when treated with levodopa monotherapy (+ 6 points, p = 0.02) and to T allele carriers treated with no levodopa treatment strategies (UPDRS: + 8 points, p = 0.01; UPDRS-III: + 6 points, p = 0.01). Similar effects of worse outcomes associated with levodopa monotherapy were observed in the BDNF rs11030094, rs10501087, and rs1491850 SNPs. This study suggests the levodopa monotherapy strategy is associated with worse disease outcomes in BDNF rs6265 T carriers. Pending prospective validation, BDNF variants may be precision medicine factors to consider for symptomatic treatment decisions for early-stage PD patients.

The deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot trial began more than a decade ago and remains the only investigation of DBS in mildly symptomatic patients. Patients completed therapeutic washouts biannually for two years, outpatient assessments through five years, and a longitudinal washout assessment after 11 years. Here, the patient experience of participating in the early DBS pilot trial is described. Semi-structured interviews were audio-recorded and transcribed. Transcripts were coded, analyzed using an iterative inductive-deductive approach, and used to develop a conceptual framework. Ten participants (n = 6 early optimal drug therapy (ODT), n = 4 early DBS + ODT) were interviewed. Motivations for participation included benefit to future PD patients and potential personal benefit, while hesitations included risk of surgical complications. While early ODT patients who received standard-of-care DBS described significant changes in their functional capacities after surgery, early DBS patients described a maintenance of quality of life that made PD less impactful over an extended period. Patients expressed high satisfaction with trial participation and early DBS. This study suggests that the PD experience with early DBS may notably differ from standard-of-care DBS. The FDA has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016).

The current study evaluated the prevalence of comorbid spasticity and urinary incontinence (UI) in a long-term care facility. Medical history, presence of UI, and activities of daily living (ADL) dependency were obtained from medical records and Minimum Data Set 3.0. Quality of life was assessed with the EuroQoL-5D-5L (EQ-5D). Comorbid spasticity and UI presented in 29% of participants (14 of 49). Participants with spasticity and UI had higher ADL dependency and lower EQ-5D than participants without both conditions (4.9, 95% confidence interval [CI] [1.6, 80.], p = 0.003; −0.17, 95% CI [−0.33, 0.00], p = 0.044; respectively). More than one half of participants with lower limb spasticity had severe UI, compared to only 10% without lower limb spasticity (relative risk = 5.5; 95% CI [1.9, 15.9]; p = 0.006). Comorbid spasticity and UI may be common in the long-term care setting and negatively associated with ADL and quality of life. Further investigation is needed to confirm these findings. [ Journal of Gerontological Nursing, 46 (10), 35–42.]

Spasticity is common in long-term care facilities; however, this often-disabling condition is largely underdiagnosed in this setting and therefore left untreated. This study aimed to test the ability of a three-question flowchart used at the bedside by primary care providers in the long-term care setting to identify residents in need of referral to a specialist for spasticity consultation. All residents of a single long-term care facility were approached for participation in this cross-sectional, observational study. Spasticity diagnostic evaluations by a movement disorders specialist neurologist (reference standard) were compared with referral determinations made by two primary care providers [a primary care physician (PCP) and a nurse practitioner (NP)] using the simple flowchart. The analysis included 49 residents (80% male, age 78.2±9.0 years) who were evaluated by the reference standard neurologist and at least one primary care provider. The bedside referral tool demonstrated high sensitivity and moderate specificity when used by the PCP (92% and 78%, respectively; AUC=0.84) and NP (80% and 53%, respectively; AUC=0.67). This simple tool may be useful for primary care providers to identify residents to be referred to a specialist for evaluation and treatment of spasticity. These results warrant further investigation of the potential utility of this screening tool across multiple long-term care facilities and various types of care providers.

Mitochondria are key regulators of cell viability and provide essential functions that protect against neurodegenerative disease. To develop a model for mitochondrial-dependent neurodegeneration in Caenorhabditis elegans, we used RNA interference (RNAi) and genetic ablation to knock down expression of enzymes in the Coenzyme Q (CoQ) biosynthetic pathway. CoQ is a required component of the ATP-producing electron transport chain in mitochondria. We found that reduced levels of CoQ result in a progressive uncoordinated (Unc) phenotype that is correlated with the appearance of degenerating GABA neurons. Both the Unc and degenerative phenotypes emerge during late larval development and progress in adults. Neuron classes in motor and sensory circuits that use other neurotransmitters (dopamine, acetylcholine, glutamate, serotonin) and body muscle cells were less sensitive to CoQ depletion. Our results indicate that the mechanism of GABA neuron degeneration is calcium-dependent and requires activation of the apoptotic gene, ced-4 (Apaf-1). A molecular cascade involving mitochondrial-initiated cell death is also consistent with our finding that GABA neuron degeneration requires the mitochondrial fission gene, drp-1. We conclude that the cell selectivity and developmental progression of CoQ deficiency in C. elegans indicate that this model may be useful for delineating the role of mitochondrial dysfunction in neurodegenerative disease.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is recognized as a safe and effective treatment in mid- and advanced-staged Parkinson’s disease (PD) that decreases the need for PD medications and their associated costs. This study reports medication costs from the only clinical trial to evaluate DBS in patients with early-stage PD and projects costs through advanced-stage disease. The DBS in early-stage PD pilot was a prospective, single-blind clinical trial that randomized 30 patients with early-stage PD 1:1 to receive bilateral STN-DBS plus optimal drug therapy (ODT) or ODT alone. Subjects who completed the trial participated in an observational follow-up study and were evaluated annually for five years after randomization. PD medication data collected at each study visit were used to calculate and project medication costs (n = 28). Five-year cumulative medication cost reduction with early DBS+ODT was $28,246. Mean annual medication cost for early DBS+ODT subjects was 2.4 times lower than early ODT subjects (β = 2.4, 95%CI:1.5–3.7, p = 0.0004). Early DBS+ODT is projected to reduce cumulative medication costs by $104,958 over 15 years of disease duration. DBS in early-stage PD may provide long-term medication cost reduction compared to standard care. •Deep brain stimulation (DBS) in early Parkinson’s disease reduces PD medication use.•Early DBS provides long-term PD medication cost savings versus standard care.•Medication cost savings do not outweigh, but may partly offset, DBS-associated costs.

Spasticity is common in long-term care settings (affecting up to one in three residents), yet it remains under-treated despite safe and effective, Food and Drug Administration (FDA)-approved therapies. One barrier to treatment may be lack of awareness of available therapies for long-term care residents living with spasticity. A standardized spasticity treatment awareness and interest interview was conducted with 18 nursing home residents and 11 veterans’ home residents in this cross-sectional study. Veterans’ home residents were also asked about potential barriers to receiving spasticity treatment. Many residents across both long-term care facilities were unaware of most of the treatment options for spasticity. Participants were most aware of physical/occupational therapy (83%, 95% CI: 65–93%) and least aware of intrathecal baclofen (21%, 95% CI: 9–39%). After learning about treatments, only 7% of participants (95% CI: 0–23%) were not interested in receiving any form of spasticity treatment. Among residents previously unaware of spasticity treatments, at least one quarter became interested in receiving treatment and at least one-fifth indicated possibly being interested in the treatment after learning about it. Potential barriers to receiving treatment included traveling to see a doctor and limited knowledge of insurance coverage of spasticity treatments. These results suggest that patient-centered approaches, including education and discerning patient preferences, may improve spasticity treatment in long-term care settings.

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson’s disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50–75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n=15) or ODT (n=14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t-tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (p>0.05). BMI change over two years was not different between the groups (p=0.62, ODT = −0.89; DBS+ODT = −0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).