Wilson disease (WD) is a rare inherited disorder that causes copper accumulation and can be fatal if untreated. This study used real-world data from the US Komodo Health claims database to describe healthcare resource utilization (HCRU) and evaluate direct economic costs among patients with WD. This retrospective observational study identified patients with WD using ICD-9/10 codes (excluding Menkes disease) between 2016 and 2019, with data spanning 2012–2020. Sociodemographic characteristics, HCRU, and costs were analyzed using SPSS v23, SAS v9.4, and R v3.6.0. The study was approved by Pearl Pathways IRB (#20-KANT-224). A total of 2115 patients with prevalent WD, including 360 ever-treated (with reimbursable WD prescriptions), were identified. During the 2-year follow-up, about 25

Perry Syndrome (PS) is a rare autosomal dominant disease caused by mutations in the DCTN1 gene. Clinically it is characterized by a combination of parkinsonism, neuropsychiatric symptoms, weight loss, and central hypoventilation. PS patients exhibit a variable response to dopaminergic medications. Dopaminergic imaging in these patients is rarely reported, but signs of presynaptic dopaminergic deficit are expected. We report a 43-year-old male with genetically confirmed PS who presented with early parkinsonism and relatively preserved response to levodopa, and before developing respiratory problems and weight loss. Ioflupane I-123 SPECT (DaTSCAN) repeatedly demonstrated nearly complete absence of striatal tracer uptake, a severity not previously described in early stages of the disease. This finding suggests that marked dopaminergic denervation may be present at an early clinical stage of Perry syndrome, even in patients who respond to levodopa. Whether this reflects dopaminergic involvement preceding more widespread neurodegeneration in the globus pallidus cannot be determined from a single case, and this possibility needs to be confirmed in larger studies.

Young-onset Parkinson’s disease (YOPD), defined as Parkinson's disease (PD) with onset between 21 and 50 years of age, represents 3–7

The use of chimeric antigen receptor T-cell (CAR-T) therapy has become more widespread in recent years, most commonly for hematologic malignancies. This therapy can be potentially associated with neurotoxic side effects. We present a patient with refractory multiple myeloma who developed diplopia, bilateral upward gaze limitation, abducens palsy, bilateral facial nerve palsy, and thoracic sensory radiculopathy following a course of CAR-T therapy, which were suspected to represent delayed immune effector cell-associated nerve palsies (IEC-NPs). His symptoms progressed despite oral and intravenous steroids. Subsequent intrathecal methotrexate and systemic cyclophosphamide resulted in acute symptomatic improvement and eventual resolution of diplopia and gradual recovery of extraocular movements and facial nerve palsies.

Anti-DPPX encephalitis is a rare form of autoimmune encephalitis characterized antibodies against a subunit of Kv4.2 potassium channels. Characteristic clinical features include cognitive dysfunction, parasomnias, psychosis, and seizures. Motor symptoms typically include myoclonus, tremor, and midline ataxia. DPPX encephalitis presenting as new-onset focal dystonia has not been previously described.

The subthalamic nucleus is thought to play a crucial role in controlling impulsive actions. Networked among the basal ganglia and receiving input from several cortical areas, the subthalamic nucleus is well positioned to influence action selection when faced with competing and conflicting action outcomes. The purpose of this study was to test the dissociable roles of the dorsal and ventral aspects of the subthalamic nucleus during action conflict in patients with Parkinson's disease undergoing intraoperative neurophysiological recording and to explore a potential mechanism for this inhibitory control. We hypothesized that modulations of neurophysiological activity during action conflict would be more pronounced in the dorsal subthalamic nucleus compared with the ventral subthalamic nucleus, due to the dissociation of cortical afferents to subthalamic nucleus subregions and previous findings of deep brain stimulation targeting subthalamic nucleus subregions in Parkinson's disease. We recorded neurophysiological activity while 10 participants with Parkinson's disease performed the Simon task during deep brain stimulation surgery. Response-locked local field potentials in the theta and beta band (associated with conflict control and movement inhibition, respectively) were analysed across subthalamic nucleus subregions and hemispheres relative to the motor response (ipsilateral/contralateral). In the presence of action conflict, the dorsal subthalamic nucleus, connected to cortical motor regions, exhibited larger theta power relative to the ventral subthalamic nucleus subregion, which is linked to the limbic circuits (P < 0.05). This evidence supports independent subregion function in conflict control. However, both subregions had relatively increased beta power for conflict trials compared with non-conflict in the hemisphere ipsilateral to the motor response. The conflict-related beta modulation was not present in the contralateral hemisphere. This indicates the importance of the ipsilateral hemisphere in the inhibition of incorrect action impulses. Additionally, higher intertrial beta power in the ventral subregion correlated with reduced accuracy on conflict trials, which we propose, could serve as a biomarker for impaired task performance. The results of the study support the existence of a functional dissociation within subthalamic nucleus subregions, emphasizing the role of the dorsal subthalamic nucleus in modulating action conflict.

Background and ObjectivesASPEN-1 was a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, duration of response, and safety of 2 doses of DaxibotulinumtoxinA for Injection (DAXI), a novel botulinum toxin type A formulation in participants with cervical dystonia (CD).MethodsAdults (aged 18–80 years) with moderate-to-severe CD (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] total score ≥20) were enrolled at 60 sites across 9 countries in Europe and North America. Participants were randomized (3:3:1) to single-dose intramuscular DAXI 125U, 250U, or placebo and followed for up to 36 weeks after injection. The primary end point was change from baseline in TWSTRS total score averaged across weeks 4 and 6. Key secondary end points included duration of effect, Clinical and Patient Global Impression of Change (CGIC, PGIC), TWSTRS subscale scores, and safety. Multiplicity-adjusted intent-to-treat hypothesis tests with multiple imputation were performed using ANCOVA and Cochran-Mantel-Haenszel analyses.ResultsOf 444 individuals screened, 301 were randomized to DAXI 125U (n = 125) or 250U (n = 130) or placebo (n = 46). DAXI 125U and 250U significantly improved the mean TWSTRS total score vs placebo (least squares mean [standard error] difference vs placebo: DAXI 125U, −8.5 [1.93], p < 0.0001; DAXI 250U, −6.6 [1.92], p = 0.0006). The median duration of effect (time from treatment until loss of ≥80% of the peak improvement in average TWSTRS total score achieved at weeks 4 and 6) was 24.0 (95% confidence interval 20.3–29.1) weeks with DAXI 125U and 20.3 (16.7–24.0) weeks with DAXI 250U. Significant improvements were also observed with DAXI in CGIC and PGIC responder rates and TWSTRS subscales. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.6% of participants with DAXI 125U, 23.8% with DAXI 250U, and 17.4% with placebo, with injection site pain being the most common overall. The most frequently reported treatment-related TEAEs of interest in DAXI 125U, DAXI 250U, and placebo, respectively, were muscular weakness (4.8%, 2.3%, 0%), musculoskeletal pain (2.4%, 3.1%, 0%), and dysphagia (1.6%, 3.8%, 0%).DiscussionThis study demonstrated that DAXI, at doses of 125U and 250U, is an effective, safe, long-acting, and well-tolerated treatment for CD.Trial Registration InformationClinicalTrials.gov identifier (NCT03608397, submitted July 11, 2018) and EU Clinical Trials Register (ClinicalTrialsRegister.eu EudraCT identifier 2018-000446-19, submitted September 13, 2018). First participant enrolled on June 11, 2018. Trial registration was performed in accordance with the Food and Drug Administration Amendments Act (FDAAA 801), which stipulates that the responsible party register an applicable clinical trial not later than 21 calendar days after enrolling the first human participant (42 CFR 11.24).Classification of EvidenceThis study provides Class I evidence that in adults with moderate-to-severe idiopathic cervical dystonia, DAXI reduces dystonia more effectively than placebo.

Abstract Background Wilson disease (WD) is a rare disorder of copper metabolism, causing copper accumulation mainly in the liver and the brain. The prevalence of WD was previously estimated around 20 to 33.3 patients per million for the United States, Europe, and Asia, but data on the prevalence of WD in Germany are limited. Objectives To describe patient characteristics and to assess prevalence of WD in Germany using a representative claims database. Methods WD patients were identified in the WIG2 (Wissenschaftliches Institut für Gesundheitsökonomie und Gesundheitssystemforschung; Scientific Institute for Health Economics and Health Systems Research) benchmark database of 4.5 million insured Germans by combining ICD-10-coding with WD-specific lab tests and treatments. The study period ranged from 2013 to 2016 for assessing patient characteristics, and to 2018 for prevalence, respectively. Results Seventy unique patients were identified. Most patients (86%) were between 18 and 64 years of age and more often male (60%) than female. Two patients (3%) younger than 18 years were included, as well as 8 patients (11%) older than 64 years. Most common WD subtypes were hepatic (57%), psychiatric (49%), and neurologic (44%). Average prevalence was 20.3 patients per million (range: 17.8–24.4), with similar results for two-year prevalence. Generally, prevalence increased steadily over the study period. Observed mortality was low, with only one death during the study period. Conclusions This study adds valuable real-world data on the prevalence and patient characteristics of WD in Germany. Generally, our findings align with other reports and contribute to the global understanding of WD epidemiology. Still, regional and temporal trends remain to be investigated more thoroughly to further the understanding of the natural history and epidemiology of this rare disease.

OBJECTIVES:To describe the epidemiology, patient characteristics and comorbidities in patients with Wilson disease (WD) in the USA. DESIGN:Retrospective, population-based study. SETTING:The study used the US Komodo claims database containing records regarding medical claims for over 120 million individuals. PARTICIPANTS:Patients with WD were identified via ICD-10 (10th revision of the International Classification of Diseases) code during the study period 2016-2019 and no age restriction was applied. A further stratification by disease subtype ('hepatic', 'neurologic' and 'psychiatric') was performed. MAIN OUTCOME MEASURES:WD prevalence was reported by age, sex and US census regions/divisions. Adjusted prevalence was calculated using age-specific prevalence standardised to the USA (2010 US census) and to the world (WHO 2000-2025) to enable comparisons across countries, using direct standardisation of prevalence estimates by age group. RESULTS:Overall, 2115 patients with WD were identified during the study period. Among them, 56.8% had hepatic symptoms, 57.0% neurologic symptoms and 47.4% psychiatric symptoms. The most frequent manifestations in hepatic patients were liver signs and symptoms (90.8%), in neurologic patients cognitive defects (50.7%) and in psychiatric patients mood disorders (86.4%). The mean age in the overall cohort was 39.9 years. Prevalence estimation was based on 1481 patients with WD between 2017 and 2019. The 2017-2019 crude period prevalence was 21.2 patients per million (95% CI: 20.1 to 22.3), with similar prevalence observed for both sexes. CONCLUSIONS:This study provides important real-world data on the diagnosed prevalence of WD in the USA and revealed the comorbidities associated with various disease subtypes, thereby providing a comprehensive basis for guiding physicians and policy makers in the management of this chronic disease.

Introduction: Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus pallidus. Such disorders are commonly neurodegenerative or neurometabolic conditions which produce varied neurologic as well as systemic manifestations other than dystonia. Chemo-denervation with botulinum toxin has been successfully used for focal or segmental dystonia. However, studies evaluating the effect of BoNT therapy on patients with secondary dystonia are sparse, given the heterogeneity in etiology and presentation. Methods: We present a series of patients with secondary dystonia who were managed with botulinum toxin therapy. Patients included in this series had a confirmed neurometabolic cause of dystonia. Results: A total of 14 patients, with ages ranging from 17 to 36 years, with disorders including Wilson’s disease, pantothenate kinase-associated neurodegeneration (PKAN), Niemann–Pick disease type C (NPC), glutaric aciduria type 1, Sanfilippo syndrome (Mucopolysaccharidosis Type IIIb), and GM2 gangliosidosis (Sandhoff disease) are presented. Most patients experienced a mild to moderate improvement in treated dystonia with benefits ranging from 6 to 12 weeks, with the median length of the benefits lasting approximately eight weeks, without any significant adverse effects. Conclusion: Although the secondary causes of dystonia are complex and diverse, our presented data and the available reports of the use of botulinum toxin support the conclusion that chemo-denervation plays an important role in symptom alleviation.

ABSTRACT 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 trial. Objective To test whether stimulation of this site is associated with improvements of long-term motor outcomes in advanced-stage PD. Methods Active contacts of the early DBS cohort (N=14) were analyzed. Sweet spot and connectivity models derived from this cohort were then used to estimate long-term motor outcomes in an independent DBS cohort of advanced-stage PD patients (N=29). Results In early-stage PD, proximity of stimulation to the dorsolateral STN associated with slower motor progression. In advanced-stage PD, stimulation proximity to the same site associated with better long-term motor outcomes (R=0.60, P<0.001). Conclusions Results suggest stimulation of a specific site in the dorsolateral STN associates with both slower motor progression and long-term motor improvements in PD.

Background: Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson's Disease (PD) [1], based on data from the deep brain stimulation (DBS) in early-stage PD pilot trial [2]. This study's objective was to test whether stimulation of this site is also associated with optimal improvements of long-term motor symptoms in advanced-stage PD.

Objective: This study aims to evaluate factors associated with episodes of delirium in a large single-institution cohort of patients with Parkinson's Disease (PD). Background: Literature suggests patients with Parkinson's Disease (PD) are at increased risk of delirium. Despite being at an apparent increased risk and worse health outcomes, there is a paucity of information on predictive factors for delirium in patients with PD. Design/Methods: This was a single-center, IRB-approved retrospective cohort study. Patients with ICD-10 diagnoses of Parkinson's Disease in the University of Louisville Hospital system were identified via billing tracing. Patient records were reviewed for diagnoses of delirium/encephalopathy, or for neuropsychiatric episodes meeting the DSM-V criteria for delirium. Data at time of episode(s) was collected, including demographics, ICD-10 coding, medications, and neuropsychiatric co-morbidities at time of episode, and date of PD diagnosis. Results: 40/625 (6.5%) pts with PD diagnosis met inclusion criteria for an episode of delirium, of which 18/40 (45%) carried an ICD-10 code of delirium or encephalopathy at time of episode. Average age of first episode was 70.72, mean 3.67 years following PD diagnosis. Average number of medications was 8.2, and average dose of PD medication in levodopa equivalents at first episode was 656.3 mg. Most common presenting symptoms of first episode were altered mental status (18%) and hallucinations (18%). Most common identifiable etiologies were medication changes (25%) and UTI/urosepsis (20%). 14/40 (35%) patients had pre-existing mood disorder and 9/40 (23%) had PD dementia. Zero patients had neurostimulators. Conclusions: In this retrospective study of a PD population, factors more associated with episodes of delirium include pre-existing mood disorder, PD dementia, UTI and medication changes. Many episodes did not include an ICD-10 code of delirium/encephalopathy in their diagnosis, reinforcing that delirium is under-diagnosed in patients with PD. Disclosure: Mr. Schmitt has nothing to disclose. Ms. Coghlan has nothing to disclose. Mr. Johnson has nothing to disclose. Ms. Fulkerson has nothing to disclose. Mr. Alluri has nothing to disclose. Dr. Holiday has nothing to disclose. Dr. Hedera has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Hedera has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Hedera has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for University of Louisville.