Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study

OBJECTIVE: To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD). METHODS: One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change. RESULTS: For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] -3.0 [0.45] vs -1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group. CONCLUSIONS: In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores

High-Order Visual Processing, Visual Symptoms, and Visual Hallucinations: A Possible Symptomatic Progression of Parkinson's Disease

Objective: To determine whether Parkinson disease (PD) patients with (VH) have different clinical characteristics and gray-matter volume than those with visual misperceptions (VM) or other visual symptoms (OvS).Background: The spectrum of visual complaints in PD is broad and complex.Methods: We conducted a retrospective chart review of 525 PD patients to identify the frequency of visual symptoms and the association with clinical and radiological features. Brain volumetric MRI data was analyzed using multivariate logistic regression to differentiate cases with and without visual symptoms.Results: Among 525 PD cases, visual complaints were documented in 177 (33.7%). Among these, 83 (46.9%) had VH, 31 (17.5%) had VM, and 63 (35.6%) had OvS (diplopia, blurry vision, photophobia, dry eyes, and eye pain or soreness). When compared to OvS, patients with VH had significantly higher age, duration of disease, rate of REM sleep behavior disorder, and cognitive impairment. Visual hallucinations patients had decreased age-adjusted volumetric averages in 28/30 gray-matter regions when compared to PD without visual symptoms and 30/30 gray-matter regions when compared to VM patients.Conclusions: Visual symptoms in PD may represent a spectrum from OvS to VM to VH, with progression of the latter associated with older age, duration of disease, presence of REM sleep behavior disorder, cognitive impairment, and decreased gray-matter volume

Postsynaptic nigrostriatal dopamine receptors and their role in movement regulation

The article presents the hypothesis that nigrostriatal dopamine may regulate movement by modulation of tone and contraction in skeletal muscles through a concentration-dependent influence on the postsynaptic D1 and D2 receptors on the follow manner: nigrostriatal axons innervate both receptor types within the striatal locus somatotopically responsible for motor control in agonist/antagonist muscle pair around a given joint. D1 receptors interact with lower and D2 receptors with higher dopamine concentrations. Synaptic dopamine concentration increases immediately before movement starts. We hypothesize that increasing dopamine concentrations stimulate first the D1 receptors and reduce muscle tone in the antagonist muscle and than stimulate D2 receptors and induce contraction in the agonist muscle. The preceded muscle tone reduction in the antagonist muscle eases the efficient contraction of the agonist. Our hypothesis is applicable for an explanation of physiological movement regulation, different forms of movement pathology and therapeutic drug effects. Further, this hypothesis provides a theoretical basis for experimental investigation of dopaminergic motor control and development of new strategies for treatment of movement disorders

Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials

Data for: Parkinsonism risk factors in Salt Lake City, Utah: a Community-Based Study

Prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented. A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency for constipation) and 3 exploratory instruments (for hallucinations, cognitive and olfactory complaints.) From June 30th, 2014 to April 30th, 2015 it was sent by mail and email to patients aged 50 and over at two University of Utah community clinics in Salt Lake City

Data for: Parkinsonism risk factors in Salt Lake City, Utah: a Community-Based Study

Prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented. A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency for constipation) and 3 exploratory instruments (for hallucinations, cognitive and olfactory complaints.) From June 30th, 2014 to April 30th, 2015 it was sent by mail and email to patients aged 50 and over at two University of Utah community clinics in Salt Lake City.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV