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NPJ Parkinson's Disease

Sanjeet S Grewal, Karim ReFaey, Amy L Grassle, Ryan J Uitti, Robert E Wharen
Deep brain stimulation (DBS) systems frequently rely on radiofrequency (RF) transmission for patient programming. The potential exists for other devices to interfere with communication between the internal pulse generator (IPG) and the programming device. In this paper, we are reporting a case of programming interference between the IPG and the WaveID device.
2019: NPJ Parkinson's Disease
L M Chahine, A Iranzo, A Fernández-Arcos, T Simuni, N Seedorff, C Caspell-Garcia, A W Amara, C Comella, B Högl, J Hamilton, K Marek, G Mayer, B Mollenhauer, R Postuma, E Tolosa, C Trenkwalder, A Videnovic, W Oertel
REM sleep behavior disorder (RBD) is strongly associated with development of Parkinson's Disease and other α-synuclein-related disorders. Dopamine transporter (DAT) binding deficit predicts conversion to α-synuclein-related disorders in individuals with RBD. In turn, identifying which individuals with RBD have the highest likelihood of having abnormal DAT binding would be useful. The objective of this analysis was to examine if there are basic clinical predictors of DAT deficit in RBD. Participants referred for inclusion in the RBD cohort of the Parkinson Progression Markers Initiative were included...
2019: NPJ Parkinson's Disease
Sneha Mantri, Michelle E Fullard, James Beck, Allison W Willis
State-level variations in disease, healthcare utilization, and spending influence healthcare planning at federal and state levels and should be examined to understand national disparities in health outcomes. This descriptive study examined state-level variations in Parkinson disease (PD) prevalence, patient characteristics, Medicare spending, out-of-pocket costs, and health service utilization using data on 27.5 million Medicare beneficiaries in the US in 2014. We found that 45.8% ( n  = 179,496) of Medicare beneficiaries diagnosed with PD were women; 26...
2019: NPJ Parkinson's Disease
Jonathan Timpka, Örjan Dahlström, Armin Spreco, Maria H Nilsson, Susanne Iwarsson, Toomas Timpka, Per Odin
The importance of understanding the prodromal phase of Parkinson's disease (PD) by systematic recording of prediagnostic symptoms and reductions in body functions has been highlighted. The aim of this study was to investigate whether persons later diagnosed with PD exhibit increased physician-certified sickness absence 1, 2, and 5 years prior to a first sick-leave episode attributed to PD. A case-control study was performed to analyze data from all nontrivial (exceeding 14 days) sick-leave episodes in Sweden between 2008 and 2014...
2018: NPJ Parkinson's Disease
Per Svenningsson, Anders Johansson, Dag Nyholm, Panagiota Tsitsi, Fredrik Hansson, Clas Sonesson, Joakim Tedroff
IRL790 is a novel compound with psychomotor stabilizing properties primarily targeting the dopamine D3 receptor. IRL790 is developed as an experimental treatment for levodopa-induced dyskinesia (LID), impulse control disorder, and psychosis in Parkinson's disease (PD). The primary objective was to investigate the safety and tolerability of IRL790 in PD patients with LID in a randomized controlled trial. PD patients with peak-dose dyskinesia were randomized to placebo or IRL790 treatment (1:3 ratio) for 4 weeks...
2018: NPJ Parkinson's Disease
Belinda Cruse, Hugo Morales-Briceño, Florence C F Chang, Neil Mahant, Ainhi D Ha, Samuel D Kim, Nigel Wolfe, Vu Kwan, David S Tsui, Jane M Griffith, Donna Galea, Victor S C Fung
Levodopa-carbidopa intestinal gel (LCIG) is effective for the control of motor fluctuations in Parkinson's disease (PD). The objective of this study is to report the reduction of dyskinesias after transitioning from 16 to 24-h/day LCIG infusion. From a cohort of 74 PD patients treated with LCIG for motor fluctuations, we identified 12 patients that were treated with 24-h per day infusion with the aim to control troublesome daytime dyskinesia. Clinical, demographic, dyskinesia rating scales were evaluated. Daytime dyskinesia was reduced in 75% (9/12) patients following treatment with 24-h therapy, including 7 who were compared with 16-h therapy and 2 that were transitioned from oral dopaminergic therapy to 24-h LCIG...
2018: NPJ Parkinson's Disease
Paolo Eusebi, Michele Romoli, Federico Paolini Paoletti, Nicola Tambasco, Paolo Calabresi, Lucilla Parnetti
Levodopa-induced dyskinesias (LID) negatively impact on the quality of life of patients with Parkinson's disease (PD). We assessed the risk factors for LID in a cohort of de-novo PD patients enrolled in the Parkinson's Progression Markers Initiative (PPMI). This retrospective cohort study included all PD patients enrolled in the PPMI cohort. Main outcome was the incidence rate of dyskinesia, defined as the first time the patient reported a non-zero score in the item "Time spent with dyskinesia" of the MDS-UPDRS part IV...
2018: NPJ Parkinson's Disease
Stephanie Martin, Iñaki Iturrate, Ricardo Chavarriaga, Robert Leeb, Aleksander Sobolewski, Andrew M Li, Julien Zaldivar, Iulia Peciu-Florianu, Etienne Pralong, Mayte Castro-Jiménez, David Benninger, François Vingerhoets, Robert T Knight, Jocelyne Bloch, José Del R Millán
Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson's Disease (PD) motor symptoms. However, previous works have been inconsistent regarding the functional role of beta activity in untreated Parkinsonian states, questioning such role. We hypothesized that this inconsistency is due to the influence of electrophysiological broadband activity -a neurophysiological indicator of synaptic excitation/inhibition ratio- that could confound measurements of beta activity in STN recordings...
2018: NPJ Parkinson's Disease
Nataliya Titova, Oleg Levin, Elena Katunina, K Ray Chaudhuri
'Levodopa Phobia' is under-recognised in Parkinson's disease but can cause profound detrimental clinical complications if left to continue. Several types can be encountered in clinical practice and can be driven by a misplaced fear of levodopa-induced dyskinesias, other gastrointestinal side effects and also the theoretical notion that levodopa may be toxic to dopaminergic neurons in the brain. The condition can be underpinned by a sense of strong influence from the physicians or carers who are unwilling to prescribe or consider levodopa, and also high levels of anxiety or even impulsive compulsive traits in patients who have been influenced by available literature or social media-based information...
2018: NPJ Parkinson's Disease
L Anselmi, C Bove, F H Coleman, K Le, M P Subramanian, K Venkiteswaran, T Subramanian, R A Travagli
Increasing evidence suggests that environmental neurotoxicants or misfolded α-synuclein generated by such neurotoxicants are transported from the gastrointestinal tract to the central nervous system via the vagus nerve, triggering degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and causing Parkinson's disease (PD). We tested the hypothesis that gastric co-administration of subthreshold doses of lectins and paraquat can recreate the pathology and behavioral manifestations of PD in rats...
2018: NPJ Parkinson's Disease
Robert A Hauser
No abstract text is available yet for this article.
2018: NPJ Parkinson's Disease
Na Feng, Scott Simanski, Kazi Islam, Linda S Hynan, Thomas Kodadek, Dwight C German
Parkinson disease (PD) is a progressive neurodegenerative disease with motor symptoms that result from degeneration of midbrain dopaminergic neurons. Biomarker research seeks to identify the disease during the pre-symptomatic phase, which is a time when therapeutic intervention will be most helpful. Previously, we screened a combinatorial peptoid library to search for antibodies that are present at much higher levels in the serum of PD patients than in control subjects. One such compound, called the PD2 peptoid, was 84% accurate for the identification of de novo PD when employed as the capture agent in an enzyme-linked immunosorbent assay...
2018: NPJ Parkinson's Disease
Stefano Cataldi, Jordan Follett, Jesse D Fox, Igor Tatarnikov, Chelsie Kadgien, Emil K Gustavsson, Jaskaran Khinda, Austen J Milnerwood, Matthew J Farrer
Vacuolar protein sorting 35 (VPS35) is a core component of the retromer trimer required for endosomal membrane-associated protein trafficking. The discovery of a missense mutation, Vps35 p.D620N implicates retromer dysfunction in the pathogenesis of Parkinson's disease (PD). We have characterized a knock-in mouse with a Vps35 p.D620N substitution (hereafter referred to as VKI) at 3 months of age. Standardized behavioral testing did not observe overt movement disorder. Tyrosine hydroxylase (TH)-positive nigral neuron counts and terminal expression in striata were comparable across genotypes...
2018: NPJ Parkinson's Disease
Taylor Chomiak, Alexander Watts, Jacqueline Burt, Richard Camicioli, Sun Nee Tan, Martin J McKeown, Bin Hu
In Parkinson's disease (PD), concurrent declines in cognitive and motor domain function can severely limit an individual's ability to conduct daily tasks. Current diagnostic methods, however, lack precision in differentiating domain-specific contributions of cognitive or motor impairments based on a patients' clinical manifestation. Fear of falling (FOF) is a common clinical manifestation among the elderly, in which both cognitive and motor impairments can lead to significant barriers to a patients' physical and social activities...
2018: NPJ Parkinson's Disease
Diptaman Chatterjee, Mansi Bhatt, David Butler, Erwin De Genst, Christopher M Dobson, Anne Messer, Jeffrey H Kordower
Therapeutics designed to target α-synuclein (α-syn) aggregation may be critical in halting the progression of pathology in Parkinson's disease (PD) patients. Nanobodies are single-domain antibody fragments that bind with antibody specificity, but allow readier genetic engineering and delivery. When expressed intracellularly as intrabodies, anti-α-syn nanobodies fused to a proteasome-targeting proline, aspartate or glutamate, serine, and threonine (PEST) motif can modulate monomeric concentrations of target proteins...
2018: NPJ Parkinson's Disease
Katharine M von Herrmann, Lucas A Salas, Eileen M Martinez, Alison L Young, Joseph M Howard, Mary S Feldman, Brock C Christensen, Owen M Wilkins, Stephen L Lee, William F Hickey, Matthew C Havrda
Neuroinflammation is a well-characterized pathophysiology occurring in association with the progression of Parkinson's disease. Characterizing the cellular and molecular basis of neuroinflammation is critical to understanding its impact on the incidence and progression of PD and other neurologic disorders. Inflammasomes are intracellular pro-inflammatory pattern-recognition receptors capable of initiating and propagating inflammation. These cellular complexes are well characterized in the innate immune system and activity of the NLRP3 inflammasome has been reported in microglia...
2018: NPJ Parkinson's Disease
Erica J Melief, Jonathan W McKinley, Jonathan Y Lam, Nicole M Whiteley, Alec W Gibson, John F Neumaier, Charles W Henschen, Richard D Palmiter, Nigel S Bamford, Martin Darvas
Parkinson's disease (PD) is primarily associated with the degeneration of midbrain dopamine neurons, but it is now appreciated that pathological processes like Lewy-body inclusions and cell loss affect several other brain regions, including the central lateral (CL) and centromedian/parafascicular (CM/PF) thalamic regions. These thalamic glutamatergic neurons provide a non-cortical excitatory input to the dorsal striatum, a major projection field of dopamine neurons. To determine how thalamostriatal signaling may contribute to cognitive and motor abnormalities found in PD, we used a viral vector approach to generate mice with loss of thalamostriatal glutamate signaling specifically restricted to the dorsal striatum (CAV2Cre - Slc17a6 lox/lox mice)...
2018: NPJ Parkinson's Disease
Jeanette M Metzger, Colleen F Moore, Carissa A Boettcher, Kevin G Brunner, Rachel A Fleddermann, Helen N Matsoff, Henry A Resnikoff, Viktoriya Bondarenko, Timothy J Kamp, Timothy A Hacker, Todd E Barnhart, Patrick J Lao, Bradley T Christian, R Jerry Nickles, Catherine L Gallagher, James E Holden, Marina E Emborg
Loss of cardiac postganglionic sympathetic innervation is a characteristic pathology of Parkinson's disease (PD). It progresses over time independently of motor symptoms and is not responsive to typical anti-parkinsonian therapies. Cardiac sympathetic neurodegeneration can be mimicked in animals using systemic dosing of the neurotoxin 6-hydroxydopamine (6-OHDA). As in PD, 6-OHDA-induced neuronal loss is associated with increased inflammation and oxidative stress. To assess the feasibility of detecting changes over time in cardiac catecholaminergic innervation, inflammation, and oxidative stress, myocardial positron emission tomography with the radioligands [11 C] meta -hydroxyephedrine (MHED), [11 C]PBR28 (PBR28), and [61 Cu]diacetyl- bis ( N (4))-methylthiosemicarbazone (ATSM) was performed in 6-OHDA-intoxicated adult, male rhesus macaques ( n  = 10; 50 mg/kg i...
2018: NPJ Parkinson's Disease
C Marras, J C Beck, J H Bower, E Roberts, B Ritz, G W Ross, R D Abbott, R Savica, S K Van Den Eeden, A W Willis, C M Tanner
Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1)...
2018: NPJ Parkinson's Disease
Pablo Martinez-Martin, Jaime Kulisevsky, Pablo Mir, Eduardo Tolosa, Pilar García-Delgado, María-Rosario Luquin
Early clinical diagnosis of advanced Parkinson's disease (APD) may be difficult. This study aimed to validate a simple screening tool, the CDEPA questionnaire ("Cuestionario De Enfermedad de Parkinson Avanzada" [Questionnaire for Advanced Parkinson's Disease]), for the identification of APD in daily practice. The study included 173 consecutively selected patients with PD (40% were women, mean age was 68.4 ± 10.5 years), stratified according to the Hoehn and Yahr (HY) scale. The CDEPA questionnaire defined APD as the presence of severe disability requiring help for activities of daily living (ADL), motor fluctuations with limitation or inability to perform ADL, severe dysphagia, recurrent falls, or dementia...
2018: NPJ Parkinson's Disease
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