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Movement Disorders: Official Journal of the Movement Disorder Society

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https://www.readbyqxmd.com/read/30644132/sample-enrichment-for-clinical-trials-to-show-delay-of-onset-in-huntington-disease
#1
Jane S Paulsen, Spencer Lourens, Karl Kieburtz, Ying Zhang
BACKGROUND: Disease-modifying clinical trials in persons without symptoms are often limited in methods to assess the impact associated with experimental therapeutics. This study suggests sample enrichment approaches to facilitate preventive trials to delay disease onset in individuals with the dominant gene for Huntington disease. METHODS: Using published onset prediction indexes, we conducted the receiver operating curve analysis for diagnosis within a 3-year clinical trial time frame...
January 14, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30633814/the-usual-suspects-dopamine-and-alpha-synuclein-conspire-to-cause-neurodegeneration
#2
Danielle E Mor, Malcolm J Daniels, Harry Ischiropoulos
Parkinson's disease (PD) is primarily a movement disorder driven by the loss of dopamine-producing neurons in the substantia nigra (SN). Early identification of the oxidative properties of dopamine implicated it as a potential source of oxidative stress in PD, yet few studies have investigated dopamine neurotoxicity in vivo. The discovery of PD-causing mutations in α-synuclein and the presence of aggregated α-synuclein in the hallmark Lewy body pathology of PD revealed another important player. Despite extensive efforts, the precise role of α-synuclein aggregation in neurodegeneration remains unclear...
January 11, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30633810/deep-brain-stimulation-for-pantothenate-kinase-associated-neurodegeneration-a-meta-analysis
#3
Philippe De Vloo, Darrin J Lee, Robert F Dallapiazza, Mohammad Rohani, Alfonso Fasano, Renato P Munhoz, George M Ibrahim, Mojgan Hodaie, Andres M Lozano, Suneil K Kalia
BACKGROUND: Pantothenate kinase-associated neurodegeneration is a rare autosomal-recessive disorder, characterized by progressive neurodegeneration associated with brain iron accumulation. DBS has been trialed to treat related movement disorders, particularly dystonia. The objective of this study was to determine the outcome and safety of DBS for pantothenate kinase-associated neurodegeneration. METHODS: We performed a meta-analysis using independent participant data (n = 99) from 38 articles...
January 11, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30629768/etravirine-in-friedreich-s-ataxia-lessons-from-hiv
#4
EDITORIAL
David R Lynch, Kimberly Schadt, Elizabeth Kichula
No abstract text is available yet for this article.
January 10, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30624809/longitudinal-evaluation-of-iron-concentration-and-atrophy-in-the-dentate-nuclei-in-friedreich-ataxia
#5
Phillip G D Ward, Ian H Harding, Thomas G Close, Louise A Corben, Martin B Delatycki, Elsdon Storey, Nellie Georgiou-Karistianis, Gary F Egan
BACKGROUND: Friedreich ataxia is a recessively inherited, progressive neurological disease characterized by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of abnormalities in these structures. METHODS: Using in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n = 20) and healthy controls (n = 18) over a 2-year period...
January 9, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30624801/drug-repositioning-screening-identifies-etravirine-as-a-potential-therapeutic-for-friedreich-s-ataxia
#6
Giulia Alfedi, Riccardo Luffarelli, Ivano Condò, Giorgia Pedini, Liliana Mannucci, Damiano S Massaro, Monica Benini, Nicola Toschi, Giorgia Alaimo, Luca Panarello, Laura Pacini, Silvia Fortuni, Dario Serio, Florence Malisan, Roberto Testi, Alessandra Rufini
BACKGROUND: Friedreich's ataxia is an autosomal-recessive cerebellar ataxia caused by mutation of the frataxin gene, resulting in decreased frataxin expression, mitochondrial dysfunction, and oxidative stress. Currently, no treatment is available for Friedreich's ataxia patients. Given that levels of residual frataxin critically affect disease severity, the main goal of a specific therapy for Friedreich's ataxia is to increase frataxin levels. OBJECTIVES: With the aim to accelerate the development of a new therapy for Friedreich's ataxia, we took a drug repositioning approach to identify market-available drugs able to increase frataxin levels...
January 9, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30615804/-18-f-av-1451-uptake-differs-between-dementia-with-lewy-bodies-and-posterior-cortical-atrophy
#7
Zuzana Nedelska, Keith A Josephs, Jonathan Graff-Radford, Scott A Przybelski, Timothy G Lesnick, Bradley F Boeve, Daniel A Drubach, David S Knopman, Ronald C Petersen, Clifford R Jack, Val J Lowe, Jennifer L Whitwell, Kejal Kantarci
BACKGROUND: Posterior cortical atrophy and dementia with Lewy bodies are 2 distinct clinical syndromes, yet they can overlap in symptoms and occipital hypometabolism. Patients with dementia with Lewy bodies often have overlapping Alzheimer's disease pathology. Similarly, Lewy bodies can be found in patients with posterior cortical atrophy. We investigated differences in the distribution and magnitude of F18-AV-1451 uptake in patients with these 2 syndromes. METHODS: Consecutive patients with probable dementia with Lewy bodies (n = 33), posterior cortical atrophy (n = 18), and cognitively unimpaired controls (n = 100) underwent 18 F-AV-1451 positron emission tomography...
January 7, 2019: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30597635/reproducible-detection-of-nigral-iron-deposition-in-2-parkinson-s-disease-cohorts
#8
Jason Langley, Naying He, Daniel E Huddleston, Shengdi Chen, Fuhua Yan, Bruce Crosson, Stewart Factor, Xiaoping Hu
BACKGROUND: Previous studies investigating nigral iron accumulation used T2 or T2 *-weighted contrasts to define the regions of interest (ROIs) in the substantia nigra with mixed results. Because these contrasts are not sensitive to neuromelanin, ROIs may have inadvertently missed the SNpc. An approach sensitive to neuromelanin should yield consistent results. We examine iron deposition in ROIs derived from neuromelanin-sensitive and T2 *-weighted contrasts, respectively. METHODS: T1 -weighted and multiecho gradient echo imaging data were obtained in 2 cohorts...
December 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30597623/the-democratic-aspect-of-machine-learning-limitations-and-opportunities-for-parkinson-s-disease
#9
EDITORIAL
Laura Bonanni
No abstract text is available yet for this article.
December 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30597616/the-appendix-and-the-risk-of-parkinson-s-disease-appended-notes-on-correlation-and-causation
#10
Jonggeol Jeffrey Kim, Sara Bandres-Ciga
No abstract text is available yet for this article.
December 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30597610/lrrk2-mediated-rab10-phosphorylation-in-immune-cells-from-parkinson-s-disease-patients
#11
Farzaneh Atashrazm, Deborah Hammond, Gayathri Perera, Marc F Bolliger, Elie Matar, Glenda M Halliday, Birgitt Schüle, Simon J G Lewis, R Jeremy Nichols, Nicolas Dzamko
BACKGROUND: Leucine-rich repeat kinase 2 is a potential therapeutic target for the treatment of Parkinson's disease, and clinical trials of leucine-rich repeat kinase 2 inhibitors are in development. The objective of this study was to evaluate phosphorylation of a new leucine-rich repeat kinase 2 substrate, Rab10, for potential use as a target engagement biomarker and/or patient enrichment biomarker for leucine-rich repeat kinase 2 inhibitor clinical trials. METHODS: Peripheral blood mononuclear cells and neutrophils were isolated from Parkinson's disease patients and matched controls, and treated ex vivo with a leucine-rich repeat kinase 2 inhibitor...
December 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30597605/association-of-brain-heptachlor-epoxide-and-other-organochlorine-compounds-with-lewy-pathology
#12
G Webster Ross, Robert D Abbott, Helen Petrovitch, John E Duda, Caroline M Tanner, Chris Zarow, Jane H Uyehara-Lock, Kamal H Masaki, Lenore J Launer, William B Studabaker, Lon R White
BACKGROUND: Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study...
December 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30597596/lrp10-a-novel-disease-gene-bridging-parkinson-s-disease-and-dementia-with-lewy-body
#13
Francesca Morgante, Enza Maria Valente
No abstract text is available yet for this article.
December 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30589955/glucocerebrosidase-mutations-and-synucleinopathies-toward-a-model-of-precision-medicine
#14
REVIEW
Fabio Blandini, Roberto Cilia, Silvia Cerri, Gianni Pezzoli, Anthony H V Schapira, Stephen Mullin, José L Lanciego
Glucocerebrosidase is a lysosomal enzyme. The characterization of a direct link between mutations in the gene coding for glucocerebrosidase (GBA1) with the development of Parkinson's disease and dementia with Lewy bodies has heightened interest in this enzyme. Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α-synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α-synuclein burden, thereby slowing down or even preventing neuronal death...
December 27, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30589953/the-long-term-direct-and-indirect-economic-burden-among-parkinson-s-disease-caregivers-in-the-united-states
#15
Pablo Martinez-Martin, Dendy Macaulay, Yash J Jalundhwala, Fan Mu, Erika Ohashi, Thomas Marshall, Kavita Sail
BACKGROUND: Parkinson's disease is a progressive, disabling neurodegenerative disorder associated with significant economic burden for patients and caregivers. The objective of this study was to compare the direct and indirect economic burden of Parkinson's patients' caregivers with demographically matched controls in the United States, in the 5 years after first diagnosis of Parkinson's disease. METHODS: Policyholders (18-64 years old) linked to a Parkinson's disease patient (≥2 diagnoses of Parkinson's disease; first diagnosis is the index date) from January 1, 1998 to March 31, 2014, were selected from a private-insurer claims database and categorized as Parkinson's caregivers...
December 27, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30589951/cost-effectiveness-of-magnetic-resonance-guided-focused-ultrasound-for-essential-tremor
#16
Chunmei Li, Olga Gajic-Veljanoski, Alexis K Schaink, Caroline Higgins, Alfonso Fasano, Nancy Sikich, Irfan Dhalla, Vivian Ng
BACKGROUND: Radiofrequency thalamotomy and deep brain stimulation are current treatments for moderate to severe medication-refractory essential tremor. However, they are invasive and thus carry risks. Magnetic resonance-guided focused ultrasound is a new, less invasive surgical option. The objective of the present study was to determine the cost-effectiveness of magnetic resonance-guided focused ultrasound compared with standard treatments in Canada. METHODS: We conducted a cost-utility analysis using a Markov cohort model...
December 27, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30589467/evaluation-of-myorg-mutations-as-a-novel-cause-of-primary-familial-brain-calcification
#17
You Chen, Feng Fu, Si Chen, Zhidong Cen, Haiyan Tang, Jinxiu Huang, Fei Xie, Xiaosheng Zheng, Dehao Yang, Haotian Wang, Xuerong Huang, Yun Zhang, Yongji Zhou, Jing-Yu Liu, Wei Luo
BACKGROUND: Very recently, the MYORG gene was identified as a novel causative gene for autosomal-recessive primary familial brain calcification. OBJECTIVE: To investigate the clinical, genetic, and neuroradiological characteristics of primary familial brain calcification patients with biallelic MYORG mutations in China. METHODS: We collected clinical and neuroradiological data of 169 Chinese patients with primary familial brain calcification, including 151 sporadic patients and 18 patients from 13 families compatible with an autosomal-recessive mode of inheritance...
December 27, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30576008/unraveling-gut-microbiota-in-parkinson-s-disease-and-atypical-parkinsonism
#18
Michela Barichella, Marco Severgnini, Roberto Cilia, Erica Cassani, Carlotta Bolliri, Serena Caronni, Valentina Ferri, Raffaella Cancello, Camilla Ceccarani, Samanta Faierman, Giovanna Pinelli, Gianluca De Bellis, Luigi Zecca, Emanuele Cereda, Clarissa Consolandi, Gianni Pezzoli
BACKGROUND: Although several studies have suggested that abnormalities in gut microbiota may play a critical role in the pathogenesis of PD, data are still extremely heterogeneous. METHODS: 16S gene ribosomal RNA sequencing was performed on fecal samples of 350 individuals, subdivided into idiopathic PD (n = 193, of whom 39 were drug naïve) stratified by disease duration, PSP (n = 22), MSA (n = 22), and healthy controls (HC; n = 113). Several confounders were taken into account, including dietary habits...
December 21, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30576007/statin-use-and-delayed-onset-of-huntington-s-disease
#19
Jordan L Schultz, Peg C Nopoulos, Annie Killoran, John A Kamholz
BACKGROUND: There is evidence to suggest that 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) may be beneficial in Huntington's disease (HD). OBJECTIVE: This study aimed to determine if statin use was associated with delayed motor diagnosis in participants with premotor HD. METHODS: Among premotor HD participants from the Enroll-HD database, statin users were propensity score matched with statin nonusers based on cytosine-adenine-guanine-age product score, cytosine-adenine-guanine repeat length, baseline age, sex, and region...
December 21, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/30575996/pridopidine-a-clinic-ready-compound-reduces-3-4-dihydroxyphenylalanine-induced-dyskinesia-in-parkinsonian-macaques
#20
Tom H Johnston, Michal Geva, Lilach Steiner, Aric Orbach, Spyros Papapetropoulos, Juha-Matti Savola, Ian J Reynolds, Paula Ravenscroft, Michael Hill, Susan H Fox, Jonathan M Brotchie, Ralph Laufer, Michael R Hayden
BACKGROUND: Pridopidine, in development for Huntington's disease, may modulate aberrant l-dopa-induced effects including l-dopa-induced dyskinesia (LID). OBJECTIVE: This study investigated whether pridopidine could reduce LID in the MPTP macaque model of Parkinson's disease and characterized the observed behavioral effects in terms of receptor occupancy. METHODS: The pharmacokinetic profile and effects of pridopidine (15-30 mg/kg) on parkinsonism, dyskinesia, and quality of on-time, in combination with l-dopa, were assessed in MPTP macaques with LID...
December 21, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
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