Background:Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive, wrist-worn neurostimulation therapy that has demonstrated acute and short-term lasting tremor reduction in patients with essential tremor (ET). However, the longer-term improvement in underlying tremor severity from consistent use of TAPS has not been fully explored. Methods:We conducted a retrospective analysis of the multicenter PROSPECT trial, which evaluated twice-daily TAPS use over three months in patients with ET. Underlying tremor improvement was assessed by comparing pre-stimulation tremor severity at baseline with pre-stimulation tremor severity at 1- and 3-month follow-up visits. Tremor severity was measured using the Bain & Findley Activities of Daily Living (BF-ADL) scale and the Tremor Research Group's Essential Tremor Rating Assessment Scale (TETRAS). Responders were defined as patients demonstrating at least a 1-point improvement on any qualifying task. Results:Among 192 patients with available data, pre-stimulation BF-ADL scores improved significantly by 2.0 points at 1 month and 2.7 points at 3 months compared with baseline (p < 0.001). Pre-stimulation TETRAS scores also showed significant improvements at both time points (p < 0.001). Measurements at 1 and 3 months were made an average of 16.2 hours after the prior stimulation session. Over 80% of patients met responder criteria for underlying tremor improvement on BF-ADL and TETRAS at both follow-up visits. Improvements were observed even among patients using TAPS approximately once daily. Conclusions:Consistent use of TAPS was associated with significant improvement in underlying tremor severity in patients with essential tremor. These findings suggest that regular TAPS use may confer sustained therapeutic benefit.

BACKGROUND:Motor speech disorders are early, common, and functionally limiting features of atypical parkinsonian disorders (APDs) such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA). These impairments are underrecognized and undertreated in neurology clinics. OBJECTIVES:This review aims to characterize speech impairment in APDs, offer practical guidance for clinical evaluation, highlight the role of Speech-Language pathologists (SLPs) in diagnosis and management, and outline current and emerging management strategies. METHODS:A narrative review was conducted by the Diagnosis and Treatment Working Group of CurePSP's Centers of Care, integrating literature and clinical experience to summarize evaluation, diagnosis, and treatment of motor speech disorders in APDs. RESULTS:Speech changes in APDs are often mixed dysarthrias with hypokinetic, spastic, and/or ataxic components, and may include apraxia of speech; these are frequently more severe and progress quicker than in Parkinson's disease. These features can assist in differential diagnosis and should prompt early referral to SLPs. Despite the high prevalence of speech and voice changes, comprehensive assessment of motor speech disorders is uncommon in neurology clinics. Current evidence regarding the efficacy of interventions is mixed. Digital acoustic analysis and neuromodulation offer promising directions for diagnosis and treatment. CONCLUSIONS:Early, collaborative management of motor speech impairment elevates care in APDs. Neurologists and SLPs must work together to improve recognition, diagnosis, and care. Future research should focus on objective biomarkers and personalized therapies to support communication, autonomy, and quality of life for individuals living with APDs.

Background: Urinary symptoms may occur throughout all stages of Parkinson disease (PD) and impair quality of life for patients and caregivers. Lower urinary tract symptoms in PD are multifactorial and may include urinary urgency, frequency, nocturia, incontinence, and voiding dysfunction. Symptoms may be further impacted by mobility impairment, may negatively affect sleep quality, and contribute to falls. There is a lack of evidence-based guidelines to inform management of urinary dysfunction in PD.Objective: To develop consensus statements on screening, diagnosis, and management of urinary dysfunction in PD.Methods: The application of a modified Delphi panel allowed for the synthesis of expert opinions clinical statements. Based upon narrative review of the literature on urological dysfunction in PD, expert panelists developed draft statements that were distributed among movement disorders neurologists, urologists, urogynecologists, and a geriatrician with expertise in lower urinary tract dysfunction and PD. Statements were discussed, edited, and voted on until consensus was achieved. Statements were organized into four sections: A. Common urinary symptoms and in-clinic evaluations. B. PD-specific etiologies for urinary dysfunction. C. Work up for urinary dysfunction in PD. D. Interventions and rehabilitation.Results: Practical consensus-based recommendations were developed for the screening, diagnosis, and management of common urinary symptoms in PD. Statements and a unifying algorithm were developed to guide clinicians involved in the care of patients with PD. Statements address evaluation strategies, PD-specific etiologies, diagnostic work up, and multidisciplinary management.Conclusions: These consensus recommendations offer a practical framework for the diagnosis and treatment of urinary dysfunction in PD.

ABSTRACT Objective Freezing of gait (FOG) in people with Parkinson's disease (PwPD) is debilitating and has limited treatments. Modafinil modulates beta/gamma band activity in the pedunculopontine nucleus (PPN), like PPN deep brain stimulation. We therefore tested the hypothesis that Modafinil would improve FOG in PwPD. Methods PwPD with FOG were randomized to early‐start (24 weeks modafinil) or delayed‐start (12 weeks each, placebo then modafinil) of oral modafinil 50 mg, followed by a 2‐week washout for both arms. Primary outcomes were change in OFF‐levodopa stride length and FOG questionnaire scores; secondary outcomes were change in motor Unified Parkinson's Disease Rating Scale (UPDRS), sleep and quality‐of‐life scores, and post hoc outcome was change in percent freezing time (%FT). Results Early‐ ( n = 12) and delayed‐start ( n = 9) group participants were well matched for age, OFF‐levodopa motor UPDRS and FOG‐Q scores. Primary and secondary outcomes did not reach statistical significance. Limiting the analysis to study completers with quantifiable visualized freezing at the initial visit and collapsing the two study arms ( n = 11), %FT trended to improvement with 50 mg modafinil in 8/11 participants ( p = 0.15) and worsening after 2 weeks washout in 9/11 participants ( p = 0.09). A future cross‐over study with 50 participants would have 0.80 power to detect a 0.5 standard‐deviation improvement in %FT. Interpretation For future therapeutic trials, selecting PwPD with moderate, quantifiable FOG and utilizing appropriate outcome measures like %FT will improve the ability to identify intervention effects. Even for short trials, analyses must account for gait decline. An FOG outcome measure that requires less analysis time burden than video quantification, and the ability for at‐home monitoring is needed.

Background:Parkinson's disease (PD) is the second-most diagnosed age-related neurodegenerative disorder globally. PD pathology causes dysregulation of motor movement and for many, mild or minor cognitive impairment (PD-MCI). The most recommended global screening exam to detect PD-MCI is the Montreal Cognitive Assessment© (MoCA). Traditionally, the MoCA is scored according to guidelines and compared against a standardized cutoff, but clinical professionals additionally draw upon their observations of the patient's performance to determine the score. To better understand how clinicians use the MoCA in real-world clinical settings, we employed the qualitative descriptive approach to identify performance patterns professionals utilize to assess the cognitive health of a person with PD. Methods:We curated retrospective data from nine people with PD-MCI to PD-Dementia. Each patient had one completed MoCA exam and one neuropsychological report containing health data. The assessments were organized into three groups of three and used in semi-structured interviews with six clinical professionals to gather at minimum two clinical opinions for each. Results:Three coders distilled, based on consensus, three clinically meaningful patterns from the interviews composed of features emphasized as vital by the interviewees for determining a person's cognitive health. The derived features were from a patient's performance on sections of the MoCA exam, sociodemographic and health data from the neuropsychological report, and dependent relationships between the assessments. Conclusions:Our study leveraged the popular MoCA exam to explore its real-world clinical use. Extracting these patterns clinicians recognized provides deeper insights into how they interpret cognitive health creating a blueprint for future efforts to tailor the exam for detecting cognitive impairment in people with PD.

BackgroundIPX203 is a novel oral extended-release formulation of carbidopa/levodopa (CD/LD) developed to address the short half-life of immediate-release CD/LD. In the phase 3 RISE-PD trial, IPX203 significantly improved "Good On" time in patients with Parkinson's disease compared with immediate-release CD/LD.ObjectivesTo evaluate the safety and efficacy of IPX203 in an open-label extension of the pivotal phase 3 study.MethodsThis 9-month extension enrolled patients who completed the randomized, double-blind trial. Key efficacy endpoints included Movement Disorder Society-Unified Parkinson's Disease Rating Scale and Patient and Clinical Global Impression scores. Adverse events (AEs) were recorded.ResultsImprovements in efficacy were maintained and dosing frequency and total daily dose remained stable through the trial. A total of 52.7% of patients experienced >= 1 treatment-emergent AE, mostly mild or moderate and occurred within the first 90 days of treatment.ConclusionsIn this phase 3 open-label extension, IPX203 exhibited a favorable safety and tolerability profile and sustained efficacy of comparable magnitude to the end of the double-blind study. (c) 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BACKGROUND:There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.OBJECTIVES:The objective was to determine if P2B001 (a fixed, low-dose, extended-release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole-ER.METHODS:This was a 12-week, double-blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or commercial doses of pramipexole-ER titrated to optimal dose (1.5-4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole-ER.RESULTS:P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were -2.66 (95% CI, -4.33 to -1.00) versus pramipexole-ER 0.6 mg (P = 0.0018) and - 3.30 (95% CI, -4.96 to -1.63) versus rasagiline-ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole-ER (mean, 3.2 mg), but significantly less worsening in daytime-sleepiness (ESS treatment difference: -2.66 [95% CI, -3.50 to -1.81]; P < 0.0001). P2B001 was well-tolerated with fewer sleep-related and dopaminergic adverse events than titrated doses of pramipexole-ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects.CONCLUSIONS:P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole-ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once-daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society.

Background Converging lines of evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, justifying exploration of therapeutic agents thought to attenuate pathogenic microglial function. We sought to test the safety and efficacy of NLY01-a brain-penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation-in Parkinson's disease. Methods We report a 36-week, randomised, double-blind, placebo-controlled study of NLY01 in participants with early untreated Parkinson's disease conducted at 58 movement disorder clinics in the USA. Participants meeting UK Brain Bank or Movement Disorder Society research criteria for Parkinson's disease were randomly allocated (1:1:1) to one of two active treatment groups (2 center dot 5 mg or 5 center dot 0 mg NLY01) or matching placebo, based on a central computer-generated randomisation scheme using permuted block randomisation with varying block sizes. All participants, investigators, coordinators, study staff, and sponsor personnel were masked to treatment assignments throughout the study. The primary efficacy endpoint for the primary analysis population (defined as all randomly assigned participants who received at least one dose of study drug) was change from baseline to week 36 in the sum of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III. Safety was assessed in the safety population (all randomly allocated participants who received at least one dose of the study drug) with documentation of adverse events, vital signs, electrocardiograms, clinical laboratory assessments, physical examination, and scales for suicidality, sleepiness, impulsivity, and depression. This trial is complete and registered at ClinicalTrials.gov, NCT04154072. Findings The study took place between Jan 28, 2020, and Feb 16, 2023. 447 individuals were screened, of whom 255 eligible participants were randomly assigned (85 to each study group). One patient assigned to placebo did not receive study treatment and was not included in the primary analysis. At 36 weeks, 2 center dot 5 mg and 5 center dot 0 mg NLY01 did not differ from placebo with respect to change in sum scores on MDS-UPDRS parts II and III: difference versus placebo -0 center dot 39 (95% CI -2 center dot 96 to 2 center dot 18; p=0 center dot 77) for 2 center dot 5 mg and 0 center dot 36 (-2 center dot 28 to 3 center dot 00; p=0 center dot 79) for 5 center dot 0 mg. Treatment-emergent adverse events were similar across groups (reported in 71 [84%] of 85 patients on 2 center dot 5 mg NLY01, 79 [93%] of 85 on 5 center dot 0 mg, and 73 [87%] of 84 on placebo), with gastrointestinal disorders the most commonly observed class in active groups (52 [61%] for 2 center dot 5 mg, 64 [75%] for 5 center dot 0 mg, and 30 [36%] for placebo) and nausea the most common event overall (33 [39%] for 2 center dot 5 mg, 49 [58%] for 5 center dot 0 mg, and 16 [19%] for placebo). No deaths occurred during the study. Interpretation NLY01 at 2 center dot 5 and 5 center dot 0 mg was not associated with any improvement in Parkinson's disease motor or non-motor features compared with placebo. A subgroup analysis raised the possibility of motor benefit in younger participants. Further study is needed to determine whether these exploratory observations are replicable.

Purpose of Review:The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP). APDs also include conditions of structural, genetic, vascular, toxic/metabolic, infectious, and autoimmune origin. Their differential diagnosis can be challenging early in the course, if the presentation is atypical, or if a rare or non-neurodegenerative condition is present. This review equips community general neurologists to make an early provisional diagnosis before, or in place of, referral to a tertiary center. Early diagnosis would allay diagnostic uncertainty, allow prompt symptomatic management, provide disease-specific information and support resources, avoid further pointless testing and treatments, and create the possibility of trial referral. Recent Findings:We address 64 APDs using one over-arching flow diagram and a series of detailed tables. Most instances of APDs can be diagnosed with a careful history and neurological exam, along with a non-contrast brain MRI. Additional diagnostic tests are rarely needed but are delineated where applicable. Our diagnostic algorithm encourages referral to a tertiary center whenever the general neurologist feels it would be in the patient's best interest. Our algorithm emphasizes that the diagnosis of APDs is an iterative process, refined with the appearance of new diagnostic features, availability of new technology, and advances in scientific understanding of the disorders. Clinicians' proposals for all diagnostic tests for the APDs, including repeat visits, should be discussed with patients and their families to ensure that the potential information to be gained aligns with their larger clinical goals. Summary:We designed this differential diagnostic algorithm for the APDs to enhance general neurologists' diagnostic skills and confidence and to help them address the less common or more ambiguous cases.

Objective: To assess the long-term safety and efficacy of IPX203. Background: IPX203 is an investigational oral extended-release (ER) carbidopa-levodopa (CD-LD) that contains immediate-release (IR) granules, ER beads, and mucoadhesive polymers to prolong therapeutic LD plasma concentrations. In a Phase 3 study, IPX203 was shown to be superior to IR CD-LD for "Good On" time. Design/Methods: This was a 9-month, multicenter, open-label safety extension study. Parkinson's patients with motor fluctuations who had successfully completed the Phase 3 double-blind study comparing the safety and efficacy of IPX203 with IR CD-LD were invited to enroll in this study. Results: Between April 3, 2019, and March 21, 2022, 419 patients were enrolled and received treatment; 352 (84%) patients completed the study; 67 (16%) discontinued. The primary reasons for discontinuation were patient withdrawal (22 [32.8%]), adverse events (AEs) (20 [29.9%]), and lack of efficacy (14 [20.9%)]. IPX203 was generally safe and well tolerated. Overall, 221 (52.7%) patients experienced treatment-emergent AEs (TEAEs). The most frequent TEAEs (≥2% patients) were dyskinesia (21 [5.0%]), fall (21 [5.0%]), urinary tract infection (21 [5.0%]), back pain (15 [3.6%]), constipation (11 [2.6%]), and COVID-19 (10 [2.4%]). The majority of TEAEs were mild or moderate in severity and occurred within the first 90 days of treatment. All efficacy measures were stable throughout the study period of 9 months. Most patients reached a stable dosing regimen by 3 months of treatment; the average daily dosing frequency of IPX203 was generally stable over the 9-month period. The average (mean [SD]) daily dosing frequency of IPX203 was 3.1 (0.45) times/day, the mean±SD daily dose of IPX203 was 1539.61±630.837 (range: 420.0, 4458.9) mg and the median (range) treatment duration was 271.0 (16, 369) days. Conclusions: In this 9-month open-label extension study, IPX203 exhibited a favorable safety and tolerability profile, and efficacy was maintained from baseline to the end of the study. Disclosure: Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acorda. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sunovion. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Herantis Pharma. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus (formerly USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AskBio. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Supernus (formerly, USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avion Pharmaceuticals. The institution of Dr. Espay has received research support from NIH. The institution of Dr. Espay has received research support from Michael J Fox Foundation for Parkinson's Research. Dr. Espay has received intellectual property interests from a discovery or technology relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Adamas Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aptinyx. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Britannia. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CAVR. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ClearView Healthcare Partners. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Decision Resource Group (DRG). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Enterin. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FirstWord. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Kinetics Consulting (GKC). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GuidePoint Global. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Huron. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for InSearch Consulting. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Insignia Strategies. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KeiferRX LLC. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KeyQuest. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KX Advisors. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Kyowa Kirin Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for L.E.K. Consulting. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck A/S. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NOVUS. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Perception OpCo (Cerevel Therapeutics LLC). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE . Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion Neurostim LLC. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tolmar Inc.. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for US World Meds. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pharmather. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Global Life Sciences. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus Pharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inhibikase. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LifeSciences Consultants. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Research Catalyst . Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curium Pharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Syneos. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevance. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pharma 2 B. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vivifi Biotech. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sio Gene Therapies. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alterity. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ameal. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Projects in Knowledge. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DDB Health. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BRACKET/Signant. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Efficient CME. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kansas City Southwest Clinical Society. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Triangle Insights. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clarity Science, LLC. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioMedical Insights. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Coleman Research. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Deallus. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EPI-Q. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orion. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Advances. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ovid Therapeutics. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Amneal. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inhibikase. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vivifi Biotech. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for ADAMAS . Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ameal . Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurochallenge. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kansas City Southwest Clinical Society. Dr. Hauser has stock in Inhibikase. Dr. Hauser has stock in Axial Therapeutics. The institution of Dr. Hauser has received research support from Biogen, Inc.. The institution of Dr. Hauser has received research support from Cavion, Inc. The institution of Dr. Hauser has received research support from Centogene. The institution of Dr. Hauser has received research support from Cerevel. The institution of Dr. Hauser has received research support from Cynapsus Therapeutics. The institution of Dr. Hauser has received research support from Enterin. The institution of Dr. Hauser has received research support from Global Kinetics Corporation. The institution of Dr. Hauser has received research support from Impax Laboratory. The institution of Dr. Hauser has received research support from Intec Pharma. The institution of Dr. Hauser has received research support from Jazz Pharmaceuticals, Inc.. The institution of Dr. Hauser has received research support from Neuro Derm. The institution of Dr. Hauser has received research support from Northwestern University. The institution of Dr. Hauser has received research support from Pfizer. The institution of Dr. Hauser has received research support from Pharma 2 B. The institution of Dr. Hauser has received research support from Revance Therapeutics. The institution of Dr. Hauser has received research support from Roche. The institution of Dr. Hauser has received research support from Sun Pharma Advanced Research. The institution of Dr. Hauser has received research support from Sunovion. The institution of Dr. Hauser has received research support from AbbVie. The institution of Dr. Hauser has received research support from Axovant Sciences Ltd.. The institution of Dr. Hauser has received research support from Cerevance. The institution of Dr. Hauser has received research support from MJFF. The institution of Dr. Hauser has received research support from Neuraly. The institution of Dr. Hauser has received research support from Sanofi US Services, Inc.. The institution of Dr. Hauser has received research support from Bukwang Pharmaceuticals. The institution of Dr. Hauser has received research support from Integrative Research Laboratories Sweden AB. The institution of Dr. Hauser has received research support from Genentech, Inc.. The institution of Dr. Hauser has received research support from UCB Biopharma SPRL. Dr. Hauser has received intellectual property interests from a discovery or technology relating to health care. Dr. Dhall has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cala Health. Dr. Dhall has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Best Doctors Inc. Dr. Dhall has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pharma2B. Dr. Dhall has stock in Atea Pharmaceuticals. Dr. Dhall has stock in Armata Pharmaceuticals. Dr. Dhall has stock in Gilead Health Science. Dr. Dhall has stock in Compass Pathway. Dr. Dhall has stock in Imara Pharmaceuticals. The institution of Dr. Dhall has received research support from Amneal. The institution of Dr. Dhall has received research support from Neuroderm. The institution of Dr. Dhall has received research support from Cerevel Therapeutics. The institution of Dr. Dhall has received research support from Neurocrine. The institution of Dr. Dhall has received research support from Neuraly. The institution of Dr. Dhall has received research support from SPARC. The institution of Dr. Dhall has received research support from Pharma2B. The institution of Dr. Dhall has received research support from Alexion. The institution of Dr. Dhall has received research support from Parkinsons Foundation. Dr. Thakkar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for abbvie. Dr. Thakkar has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for abbvie. Dr. Thakkar has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for neurocrine. Dr. Thakkar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for teva. Dr. Thakkar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for medtronic. The institution of Dr. Cloud has received research support from NIH. Dr. Cloud has received personal compensation in the range of $500-$4,999 for serving as a Community leader with Paltown. Dr. Banisadr has nothing to disclose. Dr. Fisher has received personal compensation for serving as an employee of Amneal Pharmaceuticals. Hester Visser has received personal compensation for serving as an employee of Amneal Pharmaceuticals LLC. Hester Visser has received stock or an ownership interest from Amneal Pharmaceuticals LLC.

Objective: To discuss the development and implementation of a training program of a neurology-naïve Advanced Practice Registered Nurse (APRN) into a small academic movement practice in the US from both the training physician and nurse practitioner ’ s perspective, highlighting the differences between the training of an APRN versus an MD movement disorders fellow. Background: There is a growing shortage of neurologists in the US that cannot keep up with an aging population. An APRN was hired to help the only movement disorders specialist in an academic practice in the Midwest improve access to care. However, the APRN had no experience or training in neurology or movement disorders. The training program in place at the institution was more appropriate for primary care and needed modi fi cations to be suitable for the development of a competent movement disorders APRN with the potential to eventually practice independently. Methods: This case study involves a single dyad of MD and APRN. By completion of a survey, the MD and APRN explored their experiences integrating the APRN into a movement disorders practice after 18 months of training. Each person was initially blinded to the other ’ s answers. After survey completion, answers were shared and, through open discussion, the dyad determined the best practices for the future training of neurology APRN ’ s at that institution. Results: Training an APRN is most effective when the training MD appreciates the differences in the prerequisite skills of APRNs versus MD ’ s. For example, MD movement fellows have several thousand more hours of training than newly graduated APRNs, who may not have any neurology training at all. Pertinent knowledge gaps include neuroanatomy, neurophysiology, pharmacology, and interpretation of the neurological exam. Addressing those knowledge gaps in a formalized manner using available online and in-person resources creates a favorable training experience. Conclusions: Through the integration of online learning courses, supervised on-the-job training, and an adaptive approach to education, an APRN can learn movement

BACKGROUND Deep brain stimulation (DBS) is a well-established neurosurgical intervention for a growing number of neurological and psychiatric diseases. Patients who are affected by Parkinson’s disease may benefit from DBS of either the subthalamic nucleus or the globus pallidus internus. Patients who undergo DBS often notice a significant reduction in their clinical symptoms; however, the procedure is not without risks. Multicenter studies have reported postoperative complications such as hardware infection, intracranial hemorrhage, and perielectrode edema. OBSERVATIONS The authors report a case of a perielectrode cyst managed conservatively. Tracking the impedance trend was a novel approach to monitor for changes within the cyst and to herald a clinical change in the patient. Perielectrode cystic formation can be a transient process that resolves spontaneously or with conservative, nonoperative management, and all diagnostic information is valuable in making clinical decisions. LESSONS Impedance values have provided an appropriate estimation of this patient’s clinical picture. The authors suggest treatment of edema and a cyst after DBS lead implantation through conservative management and observation, avoiding the removal of hardware if a patient’s clinical picture is either stable or improving and forgoing additional clinical imaging if the impedance values are trending in an appropriate direction.

Introduction: IPX203 is a novel oral extended-release (ER) formulation of carbidopa (CD) and levodopa (LD) developed to address the short half-life and limited area for absorption of LD in the gastrointestinal tract. This paper presents the formulation strategy of IPX203 and its relationship to the pharmacokinetics (PK) and pharmacodynamic profile of IPX203 in Parkinson's disease (PD) patients.Methods: IPX203 was developed with an innovative technology containing immediate-release (IR) granules and ER beads that provides rapid LD absorption to achieve desired plasma concentration and maintaining it within the therapeutic range for longer than can be achieved with current oral LD formulations. The PK and pharmacodynamics of IPX203 were compared with IR CD-LD in a Phase 2, open-label, rater-blinded, multicenter, crossover study in patients with advanced PD.Results: Pharmacokinetic data showed that on Day 15, LD concentrations were sustained above 50% of peak for 6.2 h with IPX203 vs. 3.9 h with IR CD-LD (P = 0.0002). Pharmacodynamic analysis demonstrated that mean MDS-UPDRS Part III scores prior to administration of the first daily dose were significantly lower among patients receiving IPX203 than IR CD-LD (LS mean difference -8.1 [25.0], P = 0.0255). In a study conducted in healthy volunteers, a high-fat, high-calorie meal delayed plasma LD Tmax by 2 h, and increased Cmax and AUCtau by approximately 20% compared with a fasted state. Sprinkling capsule contents on applesauce did not affect PK parameters.Conclusion: These data confirm that the unique design of IPX203 addresses some of the limitations of oral LD delivery.

For more than 25 years since its inception, a single-source programmable implantable pulse generator (IPG) was the mainstay technology of modern deep brain stimulation (DBS) systems used for medication-refractory movement disorders. However, multiple independent current control (MICC) was a recent innovation in IPG design, which was approved by the United States Food and Drug Administration. MICC attempts to control current fluctuations and enhance precision delivery by using an independent current source directed to each contact on the electrode lead. Current-control should also allow for the delivered therapy to remain more stable, at least in relation to fluctuations in impedance. Stimulation-induced side effects are commonly reported and these may be related to inherent DBS device limitations. This often leads to the dilemma of administering suboptimal stimulation parameters to avoid side effects. Hence, we postulated that converting a precursor, optimized system with an MICC-ready DBS IPG would be feasible and yield additional therapeutic benefits. This retrospective chart review consisted of 50 adult Parkinson’s disease and essential tremor patients, from which three additional study subsamples were statistically analyzed. All patients presented with single-source, voltage-controlled Medtronic IPG devices and subsequently underwent single conversion to a hybrid DBS system with a Boston Scientific MICC-enabled IPG. Differences in side-effect thresholds (SETs) were retrospectively assessed using Wilcoxon signedrank tests and Shapiro–Wilk tests were used to test normality assumptions. Statistical significance was determined using an alpha of 0.05 (two-tailed). All conversions were successfully undertaken with no surgical complications (eg, infections, reoperations, hardware malfunctions) or complications related to reprogramming. Moreover, there was no adverse effect (eg, unexpected pain, cosmetic deformity, infection, hematoma, wound erosion) in any patient following conversion. Among the Study Subsample patients, there was a statistically significant median difference in SETs at the first postoperative clinic visit compared to before conversion (median 11 days after conversion; left electrode: median 4.0 mA vs. 3.7 mA, P = 0.017; right electrode: 4.2 mA vs. 3.7 mA, P = 0.030; Fig. 1). Nearly 91% of patients received fractionation at the first postoperative visit. Approximately 68% of patients improved in at least one symptom or adverse event at the first postoperative visit. The accompanying supplemental information provides additional details regarding the study methodology, results, and limitations. Among the limitations of our study are the retrospective design and lack of objective movement disorder scales (eg, Unified Parkinson’s Disease Rating Scale), which may have introduced bias. Additionally, the possible restrictions to magnetic resonance imaging of hybrid DBS systems, a possible increase in study-wide error rate, use of a convenience sample at one clinical site, and the unintentional lack of Black/African American patients in our study may have further biased our findings. Our study preliminarily demonstrated that conversion from a single-source system to a hybrid DBS system using an MICCenabled IPG is safe and feasible. The most common reason for conversion was battery depletion. Some patients desired a rechargeable DBS system, which was achievable with the MICC-enabled device. Improvements in SETs evidenced in our