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Parkinson Disease: HELP
Articles by Carlos Singer
Based on 33 articles published since 2009
(Why 33 articles?)
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Between 2009 and 2019, C. Singer wrote the following 33 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Is levodopa toxic? Insights from a brain bank. 2011

LeWitt, Peter A / Dubow, Jordan / Singer, Carlos. · ·Neurology · Pubmed #21917780.

ABSTRACT: -- No abstract --

2 Review Can 4-aminopyridine modulate dysfunctional gait networks in Parkinson's disease? 2013

Luca, Corneliu C / Singer, Carlos. ·Department of Neurology, Movement Disorders Division, University of Miami Miller School of Medicine, Miami, FL 33136, USA. cluca@med.miami.edu ·Parkinsonism Relat Disord · Pubmed #23706539.

ABSTRACT: Gait dysfunction and postural instability represent a major therapeutic challenge in Parkinson's disease (PD). Gait disability in PD has been historically attributed to striato-nigral degeneration, however there is emerging evidence that multiple neurotransmitter deficits contribute to mobility impairment in PD. 4-aminopyridine (4-AP), a potent neurotransmitter modulator, has a wide range of favorable effects on gait in patients with neurological conditions including multiple sclerosis, spinal cord injury and cerebellar ataxia. In this Review we identify the neurobiological pathways involved in gait dysfunction in PD and discuss the mechanisms of action of 4-AP and its effect on gait related neuronal networks. The proposed mechanisms that may facilitate 4-AP favorable effect on gait in Parkinson's disease include 1) neurotransmitter release (dopamine, glutamate, acetylcholine and noradrenaline) 2) modulation of neuronal network oscillations and 3) increased cortical excitation. Recent clinical trials of 4-AP in neurological conditions associated with gait disorders will be highlighted and the importance of studying non-dopaminergic medications such as 4-AP in PD patients with gait impairment will be emphasized.

3 Review Managing the patient with newly diagnosed Parkinson disease. 2012

Singer, Carlos. ·Center for Parkinson's Disease and Movement Disorders, Clinical Research Building, Leonard M. Miller School of Medicine, University of Miami, 1120 NW 14th Street, 13th Floor, Miami, FL 33136, USA. CSinger@med.miami.edu ·Cleve Clin J Med · Pubmed #22761267.

ABSTRACT: The treatment of early Parkinson disease (PD) is generally symptomatic, although therapy that also offers neuroprotection in early-stage PD would be welcomed. Levodopa remains the most effective agent for relief of PD symptoms, but chronic levodopa therapy is associated with motor fluctuations and dyskinesias, and clinicians may therefore opt to postpone its use. Alternatives to levodopa in early PD include monoamine oxidase (MAO)-B inhibitors, amantadine, and dopamine agonists. MAO-B inhibitors have only mild symptomatic effects. Amantadine is associated with improvement in functional disability and, in a subset of PD patients, a robust symptomatic improvement. Dopamine agonists improve symptoms and may have a neuroprotective effect. Partial dopamine agonists, adenosine A(2A)-receptor antagonists, and safinamide are symptomatic therapies that are under investigation. Neuro protective strategies under study include enhancement of mitochondrial function, antiinflammatory mechanisms, calcium channel blockade, and uric acid elevation. Deep brain stimulation may slow cognitive and motor decline when used in early PD. Stem cell therapy and gene therapy are still under investigation.

4 Review [Parkinsonism: alternative diagnosis beyond idiopathic Parkinson's disease]. 2010

Gutiérrez, José / Singer, Carlos. ·Leonard M. Miller School of Medicine, Department of Neurology, University of Miami, USA. jgutierrez3@med.miami.edu ·Rev Med Inst Mex Seguro Soc · Pubmed #21192900.

ABSTRACT: Parkinsonism is manifested as bradykinesia; tremor with signs and symptoms suggesting Parkinson's disease. The most common cause of Parkinsonism is Idiopathic Parkinson's disease; however, there are other multiple pathologies and situation that have top be considered accordingly in this clinical setting. Since the treatment and outcomes varies widely between these conditions is of paramount importance to work up the Parkinsonism and try to achieve an accurate diagnosis. This review gives a general landscape of Parkinsonism and its most likely differentials.

5 Review Gene-environment interactions in Parkinson's disease and other forms of parkinsonism. 2010

Vance, Jeffery M / Ali, Syed / Bradley, Walter G / Singer, Carlos / Di Monte, Donato A. ·University of Miami, Miami, FL 33101, USA. ·Neurotoxicology · Pubmed #20430055.

ABSTRACT: It is widely recognized that both genetic and environmental factors are likely to contribute to the pathogenesis of human parkinsonism. While the identification of specific predisposing conditions and mechanisms of disease development remain elusive, new discoveries coupled with technological advances over the past decade have provided important clues. From the genetic standpoint, both causal and susceptibility genes have been identified, with some of these genes pointing to gene-environment interactions. The application of emerging genomic technologies, such as Genome Wide Association Studies (GWAS), will certainly further our knowledge of Parkinson's disease (PD)-related genes. From the environmental perspective, toxicant-induced models of parkinsonian syndromes, such as those associated with exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or beta-N-methylamino-l-alanine (BMAA), have revealed potential mechanisms of increased susceptibility based on genetic predisposition. Finally, new hypotheses on mechanisms of disease development include the possibility that exposure to neurotoxicants triggers an upregulation and pathological modifications of alpha-synuclein. Mutations in the alpha-synuclein gene are responsible for rare familial cases of parkinsonism, and polymorphisms in the promoter region of this gene confer a higher susceptibility to idiopathic PD. Thus, toxicant-alpha-synuclein interactions could have deleterious consequences and play a role in pathogenetic processes in human parkinsonism.

6 Clinical Trial Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease. 2018

Elmer, Lawrence W / Juncos, Jorge L / Singer, Carlos / Truong, Daniel D / Criswell, Susan R / Parashos, Sotirios / Felt, Larissa / Johnson, Reed / Patni, Rajiv. ·Department of Neurology, University of Toledo College of Medicine, 3120 Glendale Avenue, Toledo, OH, 43614, USA. Lawrence.Elmer@utoledo.edu. · Department of Neurology and Movement Disorders, Emory University School of Medicine, Atlanta, GA, USA. · Department of Neurology, University of Miami, Miami, FL, USA. · The Parkinson's and Movement Disorder Institute, Fountain Valley, CA, USA. · Department of Neurology, Washington University, St. Louis, MO, USA. · Struthers Parkinson's Center, Golden Valley, MN, USA. · Adamas Pharmaceuticals, Inc., Emeryville, CA, USA. ·CNS Drugs · Pubmed #29532440.

ABSTRACT: BACKGROUND: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRI OBJECTIVE: In this study, we present pooled results from two randomized, double-blind, placebo-controlled, phase III ADS-5102 trials. PATIENTS AND METHODS: The two studies in PD patients with dyskinesia shared design and eligibility criteria, differing only in treatment duration. Results from common assessment time points were pooled. RESULTS: At 12 weeks, the least squares (LS) mean change in total score on the Unified Dyskinesia Rating Scale among 100 patients randomized to ADS-5102 and 96 patients randomized to placebo was - 17.7 (standard error [SE] 1.3) vs. - 7.6 (1.3) points, respectively (- 10.1 points, 95% confidence interval [CI] - 13.8, - 6.5; p < 0.0001). The relative treatment difference between groups was 27.3% (p < 0.0001). At 12 weeks, the LS mean change in OFF time was - 0.59 (0.21) vs. +0.41 (0.20) h/day, a difference of - 1.00 h/day (95% CI - 1.57, - 0.44; p = 0.0006). For both efficacy measures, a significant difference from placebo was attained by two weeks, the first post-baseline assessment, and was maintained throughout 12 weeks. In the pooled ADS-5102 group, the most common adverse events were hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension. CONCLUSIONS: These analyses provide further evidence supporting ADS-5102 as an adjunct to levodopa for treating both dyskinesia and OFF time in PD patients with dyskinesia. Clinicaltrials.gov identifier: NCT02136914 and NCT02274766.

7 Clinical Trial Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores. 2017

Leehey, Maureen / Luo, Sheng / Sharma, Saloni / Wills, Anne-Marie A / Bainbridge, Jacquelyn L / Wong, Pei Shieen / Simon, David K / Schneider, Jay / Zhang, Yunxi / Pérez, Adriana / Dhall, Rohit / Christine, Chadwick W / Singer, Carlos / Cambi, Franca / Boyd, James T. ·From the Department of Neurology (M.L.) and Department of Clinical Pharmacy (J.L.B.), Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora · Department of Biostatistics (S.L., Y.Z.), University of Texas Health Science Center at Houston · Center for Human Experimental Therapeutics (S.S.), University of Rochester, NY · Department of Neurology (A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston · Department of Pharmacy (P.S.W.), Singapore General Hospital · Department of Neurology (D.K.S.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA · Department of Pathology, Anatomy, & Cell Biology (J.S.), Thomas Jefferson University, Philadelphia, PA · Department of Biostatistics (Y.Z.), School of Public Health, University of Texas Health Science Center, Houston · Department of Biostatistics (A.P.), School of Public Health, University of Texas Health Science Center at Houston-UTHealth, Austin · Department of Neurology (R.D.), University of Arkansas for Medical Sciences, Little Rock · Department of Neurology (C.W.C.), University of California San Francisco · Department of Neurology (C.S.), Leonard M. Miller School of Medicine, University of Miami, FL · Department of Neurology (F.C.), University of Pittsburgh, PA · and Department of Neurological Sciences (J.T.B.), Larner College of Medicine, University of Vermont, Burlington. Dr. Luo is currently with the Department of Biostatistics and Bioinformatics, Duke University, Durham, NC. ·Neurology · Pubmed #28972194.

ABSTRACT: OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865.

8 Clinical Trial Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine. 2015

Simon, David K / Wu, Cai / Tilley, Barbara C / Wills, Anne-Marie / Aminoff, Michael J / Bainbridge, Jacquelyn / Hauser, Robert A / Schneider, Jay S / Sharma, Saloni / Singer, Carlos / Tanner, Caroline M / Truong, Daniel / Wong, Pei Shieen. ·*Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; †Department of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX; ‡Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; §Department of Neurology, University of California, San Francisco, CA; ∥Department of Clinical Pharmacy and Neurology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO; ¶Department of Neurology, University of South Florida, Tampa, FL; #Department of Pathology, Anatomy and Cell Biology, Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA; **Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, NY; ††Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL; ‡‡Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, CA; §§The Parkinson's and Movement Disorder Institute, Fountain Valley, CA; and ∥∥Singapore General Hospital, Singapore. ·Clin Neuropharmacol · Pubmed #26366971.

ABSTRACT: OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. RESULTS: Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. CONCLUSIONS: This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD.

9 Clinical Trial A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. 2014

Anonymous1090789 / Beal, M Flint / Oakes, David / Shoulson, Ira / Henchcliffe, Claire / Galpern, Wendy R / Haas, Richard / Juncos, Jorge L / Nutt, John G / Voss, Tiffini Smith / Ravina, Bernard / Shults, Clifford M / Helles, Karen / Snively, Victoria / Lew, Mark F / Griebner, Brian / Watts, Arthur / Gao, Shan / Pourcher, Emmanuelle / Bond, Louisette / Kompoliti, Katie / Agarwal, Pinky / Sia, Cherissa / Jog, Mandar / Cole, Linda / Sultana, Munira / Kurlan, Roger / Richard, Irene / Deeley, Cheryl / Waters, Cheryl H / Figueroa, Angel / Arkun, Ani / Brodsky, Matthew / Ondo, William G / Hunter, Christine B / Jimenez-Shahed, Joohi / Palao, Alicia / Miyasaki, Janis M / So, Julie / Tetrud, James / Reys, Liza / Smith, Katharine / Singer, Carlos / Blenke, Anita / Russell, David S / Cotto, Candace / Friedman, Joseph H / Lannon, Margaret / Zhang, Lin / Drasby, Edward / Kumar, Rajeev / Subramanian, Thyagarajan / Ford, Donna Stuppy / Grimes, David A / Cote, Diane / Conway, Jennifer / Siderowf, Andrew D / Evatt, Marian Leslie / Sommerfeld, Barbara / Lieberman, Abraham N / Okun, Michael S / Rodriguez, Ramon L / Merritt, Stacy / Swartz, Camille Louise / Martin, W R Wayne / King, Pamela / Stover, Natividad / Guthrie, Stephanie / Watts, Ray L / Ahmed, Anwar / Fernandez, Hubert H / Winters, Adrienna / Mari, Zoltan / Dawson, Ted M / Dunlop, Becky / Feigin, Andrew S / Shannon, Barbara / Nirenberg, Melissa Jill / Ogg, Mattson / Ellias, Samuel A / Thomas, Cathi-Ann / Frei, Karen / Bodis-Wollner, Ivan / Glazman, Sofya / Mayer, Thomas / Hauser, Robert A / Pahwa, Rajesh / Langhammer, April / Ranawaya, Ranjit / Derwent, Lorelei / Sethi, Kapil D / Farrow, Buff / Prakash, Rajan / Litvan, Irene / Robinson, Annette / Sahay, Alok / Gartner, Maureen / Hinson, Vanessa K / Markind, Samuel / Pelikan, Melisa / Perlmutter, Joel S / Hartlein, Johanna / Molho, Eric / Evans, Sharon / Adler, Charles H / Duffy, Amy / Lind, Marlene / Elmer, Lawrence / Davis, Kathy / Spears, Julia / Wilson, Stephanie / Leehey, Maureen A / Hermanowicz, Neal / Niswonger, Shari / Shill, Holly A / Obradov, Sanja / Rajput, Alex / Cowper, Marilyn / Lessig, Stephanie / Song, David / Fontaine, Deborah / Zadikoff, Cindy / Williams, Karen / Blindauer, Karen A / Bergholte, Jo / Propsom, Clara Schindler / Stacy, Mark A / Field, Joanne / Mihaila, Dragos / Chilton, Mark / Uc, Ergun Y / Sieren, Jeri / Simon, David K / Kraics, Lauren / Silver, Althea / Boyd, James T / Hamill, Robert W / Ingvoldstad, Christopher / Young, Jennifer / Thomas, Karen / Kostyk, Sandra K / Wojcieszek, Joanne / Pfeiffer, Ronald F / Panisset, Michel / Beland, Monica / Reich, Stephen G / Cines, Michelle / Zappala, Nancy / Rivest, Jean / Zweig, Richard / Lumina, L Pepper / Hilliard, Colette Lynn / Grill, Stephen / Kellermann, Marye / Tuite, Paul / Rolandelli, Susan / Kang, Un Jung / Young, Joan / Rao, Jayaraman / Cook, Maureen M / Severt, Lawrence / Boyar, Karyn. ·Department of Neurology, Weill Cornell Medical College, New York Hospital, New York. · Department of Biostatistics, University of Rochester Medical Center, Rochester, New York. · Department of Neurology, Georgetown University, Washington, DC. · National Institutes of Health, Bethesda, Maryland. · Department of Neurosciences, University of California, San Diego, La Jolla. · Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia. · Department of Neurology, Oregon Health and Science University, Portland. · Merck, New Jersey. · Biogen Idec, Cambridge, Massachusetts. · Department of Neurosciences, University of California, San Diego, La Jolla10VA Medical Center, San Diego, California. · Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles. · Department of Biostatistics, University of Rochester Medical Center, Rochester, New York12Department of Neurology, University of Rochester, Rochester, New York. · Québec Memory and Motor Skills Disorders Research Center, Clinique Sainte-Anne, Québec, Canada. · Rush University Medical Center, Chicago, Illinois. · Booth Gardner Parkinson's Care Center, EvergreenHealth, Kirkland, Washington. · London Health Sciences Centre, London, Ontario, Canada. · Overlook Medical Center, Atlantic Neuroscience Institute, Summit, New Jersey. · Department of Neurology, University of Rochester, Rochester, New York. · Columbia University Medical Center, Neurological Institute, New York, New York. · Department of Neurology, University of Texas Health Science Center at Houston. · Department of Neurology, Baylor College of Medicine, Houston, Texas. · Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. · The Parkinson's Institute and Clinical Center, Sunnyvale, California. · Department of Neurology, University of Miami School of Medicine, Miami, Florida. · Institute for Neurodegenerative Disorders, New Haven, Connecticut. · Department of Neurology, Butler Hospital, Providence, Rhode Island26Alpert Medical School, Brown University, Providence, Rhode Island. · Department of Neurology, Butler Hospital, Providence, Rhode Island27Port City Neurology, Inc, Scarborough, Maine. · Department of Neurology, University of California, Davis, School of Medicine and Sacramento VA Medical Center, Sacramento. · Port City Neurology, Inc, Scarborough, Maine. · Colorado Neurological Institute, Englewood. · Milton S. Hershey Medical Center, Department of Neurology, Pennsylvania State Hershey College of Medicine, Hershey. · Ottawa Hospital Civic Site, Ottawa, Ontario, Canada. · Avid Radiopharmaceuticals, Philadelphia, Pennsylvania. · Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia33Atlanta VA Medical Center, Atlanta, Georgia. · Muhammad Ali Parkinson Center, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona. · Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville. · Glenrose Rehabilitation Hospital, University of Alberta, Edmonton, Alberta, Canada. · Department of Neurology, University of Alabama at Birmingham. · Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, Ohio. · Department of Neurology, Johns Hopkins University, Baltimore, Maryland. · Feinstein Institute for Medical Research, Center for Neurosciences, Manhasset, New York. · Department of Neurology, New York University Langone Medical Center, New York. · Department of Neurology, Boston University School of Medicine, Boston, Massachusetts. · The Parkinson's and Movement Disorder Institute, Fountain Valley, California. · State University of New York, Downstate Medical Center, Brooklyn, New York. · Department of Neurology, University of South Florida, Tampa. · Department of Neurology, University of Kansas Medical Center, Kansas City. · Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. · Department of Neurology, Georgia Health Science University, Augusta. · Department of Neurology, University of Louisville, Kentucky. · University of Cincinnati College of Medicine, Cincinnati, Ohio. · Department of Neurology, Medical University of South Carolina, Charleston. · Associated Neurologists, PC, Danbury, Connecticut. · Department of Neurology, Washington University in St Louis, Missouri. · Movement Disorders Center, Albany Medical Center, Albany, New York. · Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, Arizona. · Center for Neurological Health, University of Toledo, Toledo, Ohio. · Department of Neurology, Medical University of Ohio at Toledo. · Department of Neurology, University of Colorado Health Science Center, Denver. · Department of Neurology, University of California, Irvine Medical Center, Irvine. · Banner Sun Health Research Institute, Sun City, Arizona. · Department of Neurology, University of Saskatchewan, Royal University Hospital, Saskatchewan, Canada. · Department of Neurology, University of California, San Diego, La Jolla. · Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Neurology, Medical College of Wisconsin, Milwaukee. · Department of Neurology, Duke University, Durham, North Carolina. · State University of New York Upstate Medical Center and Syracuse VA Medical Center, Syracuse. · Department of Neurology, University of Iowa, Iowa City. · Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. · Department of Neurology, University of Vermont College of Medicine, Burlington. · Department of Neurology, Ohio State University, Columbus. · Department of Neurology, Indiana University School of Medicine, Indianapolis. · Department of Neurology, University of Tennessee Health Science Center, Memphis. · Department of Neurology, CHUM-Hôpital Notre-Dame, Montréal, Québec, Canada. · Department of Neurology, University of Maryland School of Science, Baltimore. · Department of Neurology, University of Sherbrooke, Québec, Canada. · Department of Neurology, Louisiana State University Health Science Center, Shreveport. · Lewis Hall Singletary Oncology Center, Thomasville, Georgia. · Parkinson and Movement Disorders Center of Maryland, Elkridge. · Department of Neurology, University of Minnesota, Minneapolis. · Department of Neurology, University of Chicago, Chicago, Illinois. · Department of Neurology, Ochsner Clinic Foundation, New Orleans, Louisiana. · Department of Neurology, Beth Israel Medical Center, New York, New York. ·JAMA Neurol · Pubmed #24664227.

ABSTRACT: IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740714.

10 Article National randomized controlled trial of virtual house calls for Parkinson disease. 2017

Beck, Christopher A / Beran, Denise B / Biglan, Kevin M / Boyd, Cynthia M / Dorsey, E Ray / Schmidt, Peter N / Simone, Richard / Willis, Allison W / Galifianakis, Nicholas B / Katz, Maya / Tanner, Caroline M / Dodenhoff, Kristen / Aldred, Jason / Carter, Julie / Fraser, Andrew / Jimenez-Shahed, Joohi / Hunter, Christine / Spindler, Meredith / Reichwein, Suzanne / Mari, Zoltan / Dunlop, Becky / Morgan, John C / McLane, Dedi / Hickey, Patrick / Gauger, Lisa / Richard, Irene Hegeman / Mejia, Nicte I / Bwala, Grace / Nance, Martha / Shih, Ludy C / Singer, Carlos / Vargas-Parra, Silvia / Zadikoff, Cindy / Okon, Natalia / Feigin, Andrew / Ayan, Jean / Vaughan, Christina / Pahwa, Rajesh / Dhall, Rohit / Hassan, Anhar / DeMello, Steven / Riggare, Sara S / Wicks, Paul / Achey, Meredith A / Elson, Molly J / Goldenthal, Steven / Keenan, H Tait / Korn, Ryan / Schwarz, Heidi / Sharma, Saloni / Stevenson, E Anna / Zhu, William / Anonymous471268. ·From the Department of Biostatistics and Computational Biology (C.A.B.), University of Rochester, NY · National Parkinson Foundation (D.B.B., P.N.S.), Miami, FL · Department of Neurology (K.M.B., E.R.D., I.H.R., H.S.) and The Center for Human Experimental Therapeutics (E.R.D., M.A.A., M.J.E., S.G., H.T.K., R.K., S.S., E.A.S., W.Z.), University of Rochester Medical Center, NY · Division of Geriatric Medicine and Gerontology, Department of Medicine (C.M.B., Z.M., B.D.), Johns Hopkins University School of Medicine, Baltimore, MD · Simone Consulting (R.S.), Sunnyvale, CA · Departments of Neurology and Biostatistics and Epidemiology (A.W.W., M.S., S.R.), University of Pennsylvania Perelman School of Medicine, Philadelphia · University of California San Francisco (N.B.G., M.K., C.M.T., K.D.) · Northwest Neurological, PLLC (J. Aldred), Spokane, WA · Oregon Health and Science University (J.C., A. Fraser), Portland · Baylor College of Medicine (J.J.-S., C.H.), Houston, TX · Augusta University (J.C.M., D.M.), GA · Duke Medical Center (P.H., L.G.), Durham, NC · Massachusetts General Hospital (N.I.M., G.B.), Boston · Struthers Parkinson's Center (M.N.), Minneapolis, MN · Beth Israel Deaconess Medical Center (L.C.S.), Boston, MA · University of Miami (C.S., S.V.-P.), FL · Northwestern University (C.Z., N.O.), Evanston, IL · The Feinstein Institute for Medical Research (A. Feigin, J. Ayan), Northwell Health, Manhasset, NY · Medical University of South Carolina (C.V.), Charleston · University of Kansas Medical Center (R.P.), Kansas City · Parkinson's Institute (R.D.), Sunnyvale, CA · Mayo Clinic (A.H.), Rochester, MN · Center for Information Technology Research in the Interest of Society (CITRIS) (S.D.), University of California, Berkeley · Health Informatics Centre (S.S.R.), Karolinska Institute, Stockholm, Sweden · and PatientsLikeMe (P.W.), Derby, UK. ·Neurology · Pubmed #28814455.

ABSTRACT: OBJECTIVE: To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable. METHODS: In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings. RESULTS: A total of 927 individuals indicated interest, 210 were enrolled, and 195 were randomized. Participants had recently seen a specialist (73%) and were largely college-educated (73%) and white (96%). Ninety-five (98% of the intervention group) completed at least one virtual visit, and 91% of 388 virtual visits were completed. Quality of life did not improve in those receiving virtual house calls (0.3 points worse on a 100-point scale; 95% confidence interval [CI] -2.0 to 2.7 points; CONCLUSIONS: Providing remote neurologic care directly into the homes of people with PD was feasible and was neither more nor less efficacious than usual in-person care. Virtual house calls generated great interest and provided substantial convenience. CLINICALTRIALSGOV IDENTIFIER: NCT02038959. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD, virtual house calls from a neurologist are feasible and do not significantly change quality of life compared to in-person visits. The study is rated Class III because it was not possible to mask patients to visit type.

11 Article Dalfampridine in Parkinson's disease related gait dysfunction: A randomized double blind trial. 2017

Luca, Corneliu C / Nadayil, Gloria / Dong, Chuanhui / Nahab, Fatta B / Field-Fote, Edelle / Singer, Carlos. ·Department of Neurology, University of Miami, Miami, United States. Electronic address: cluca@med.miami.edu. · Florida Atlantic University, Atlanta, United States. · Department of Neurology, University of Miami, Miami, United States. · University of California San Diego, Atlanta, United States. · Shepherd Center, Atlanta, United States. ·J Neurol Sci · Pubmed #28716283.

ABSTRACT: BACKGROUND: Disease-related gait dysfunction causes extensive disability for persons with Parkinson's disease (PD), with no effective therapies currently available. The potassium channel blocker dalfampridine has been used in multiple neurological conditions and improves walking in persons with multiple sclerosis. OBJECTIVES: We aimed to evaluate the effect of dalfampridine extended release (D-ER) 10mg tablets twice daily on different domains of walking in participants with PD. METHODS: Twenty-two participants with PD and gait dysfunction were randomized to receive D-ER 10mg twice daily or placebo for 4weeks in a crossover design with a 2-week washout period. The primary outcomes were change in the gait velocity and stride length. RESULTS: At 4weeks, gait velocity was not significantly different between D-ER (0.89m/s±0.33) and placebo (0.93m/s±0.27) conditions. The stride length was also similar between conditions: 0.96m±0.38 for D-ER versus 1.06m±0.33 for placebo. D-ER was generally well tolerated with the most frequent side effects being dizziness, nausea and balance problems. CONCLUSIONS: D-ER is well tolerated in PD patients, however it did not show significant benefit for gait impairment.

12 Article Autonomic and electrocardiographic findings in Parkinson's disease. 2017

Gibbons, Christopher H / Simon, David K / Huang, Meilin / Tilley, Barbara / Aminoff, Michael J / Bainbridge, Jacquelyn L / Brodsky, Matthew / Freeman, Roy / Goudreau, John / Hamill, Robert W / Luo, Sheng T / Singer, Carlos / Videnovic, Aleksandar / Bodis-Wollner, Ivan / Wong, Pei S / Anonymous4410906. ·Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: cgibbons@bidmc.harvard.edu. · Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. · Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. · Department of Neurology, School of Medicine, University of California, San Francisco, USA. · Department of Clinical Pharmacy and Neurology, University of Colorado, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. · Department of Neurology, Oregon Health & Science University, USA. · Department of Neurology, Michigan State University, USA. · Department of Neurological Sciences, University of Vermont College of Medicine, USA. · Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. · Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Neurology and Ophthalmology, State University of New York, Downstate Medical Center, USA. · Department of Pharmacy, Singapore General Hospital, Singapore. ·Auton Neurosci · Pubmed #28506500.

ABSTRACT: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P<0.05) between QTcB and PD severity in individuals that were taking QT-interval affecting drugs. A longer QT-interval at baseline was associated with more advanced PD at 5years (P<0.05), and greater disease progression over 5years (P<0.05). There was an association between diminished HRV and an orthostatic decrease in standing blood pressure at baseline in individuals with PD (P<0.05). HRV was not associated with PD severity or progression. In conclusion, we were able to detect measurable associations between the QTcB interval and PD severity, PD severity 5years later, and the change in disease over time. However, routine ECG tracings appear inadequate for the evaluation of autonomic function in PD.

13 Article Caffeine, creatine, GRIN2A and Parkinson's disease progression. 2017

Simon, David K / Wu, Cai / Tilley, Barbara C / Lohmann, Katja / Klein, Christine / Payami, Haydeh / Wills, Anne-Marie / Aminoff, Michael J / Bainbridge, Jacquelyn / Dewey, Richard / Hauser, Robert A / Schaake, Susen / Schneider, Jay S / Sharma, Saloni / Singer, Carlos / Tanner, Caroline M / Truong, Daniel / Wei, Peng / Wong, Pei Shieen / Yang, Tianzhong. ·Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: dsimon1@bidmc.harvard.edu. · Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Cai.Wu@uth.tmc.edu. · Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Barbara.C.Tilley@uth.tmc.edu. · Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany. Electronic address: katja.lohmann@neuro.uni-luebeck.de. · Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany. Electronic address: christine.klein@neuro.uni-luebeck.de. · Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Center for Genomic Medicine, HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA. Electronic address: haydehpayami@uabmc.edu. · Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: AWILLS@mgh.harvard.edu. · Department of Neurology, University of California, San Francisco, USA. Electronic address: Michael.Aminoff@ucsf.edu. · University of Colorado, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy and Neurology, Aurora, CO, USA. Electronic address: Jacci.Bainbridge@ucdenver.edu. · University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: richard.dewey@utsouthwestern.edu. · Department of Neurology, University of South Florida, Tampa, FL, USA. Electronic address: rhauser@health.usf.edu. · Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany. Electronic address: susen.schaake@neuro.uni-luebeck.de. · Department of Pathology, Anatomy and Cell Biology, Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Jay.Schneider@jefferson.edu. · Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: saloni.sharma@chet.rochester.edu. · Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address: csinger@med.miami.edu. · Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: Caroline.Tanner@ucsf.edu. · The Parkinson's and Movement Disorder Institute, Fountain Valley, CA, USA. Electronic address: dtruong@pmdi.org. · Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Peng.Wei@uth.tmc.edu. · University of Colorado, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy and Neurology, Aurora, CO, USA; Singapore General Hospital, Singapore 169608, Singapore. Electronic address: pei.wong@ucdenver.edu. · Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Tianzhong.Yang@uth.tmc.edu. ·J Neurol Sci · Pubmed #28320167.

ABSTRACT: Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD.

14 Article Insomnia, Sleep Quality, and Quality of Life in Mild to Moderate Parkinson's Disease. 2017

Shafazand, Shirin / Wallace, Douglas M / Arheart, Kristopher L / Vargas, Silvia / Luca, Corneliu C / Moore, Henry / Katzen, Heather / Levin, Bonnie / Singer, Carlos. ·1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Miller School of Medicine. · 2 Department of Neurology, Miller School of Medicine, and. · 3 Neurology Service, Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida. · 4 Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miami, Florida; and. ·Ann Am Thorac Soc · Pubmed #28231027.

ABSTRACT: RATIONALE: Sleep disorders are prevalent in Parkinson's disease but underreported in clinical settings. The contribution of sleep disorders to health-related quality of life (HRQOL) for patients with this degenerative neurological disease are not well known. OBJECTIVES: To evaluate the impact of insomnia symptoms, obstructive sleep apnea (OSA), and poor sleep quality on HRQOL in a cohort of patients with idiopathic Parkinson's disease. METHODS: We enrolled a convenience sample of 66 adults seen in the University of Miami Movement Disorders Clinic between July 2011 and June 2013. Participants completed validated questionnaires to determine insomnia symptoms, OSA risk, depression, anxiety, and HRQOL. All patients underwent unattended polysomnography to confirm OSA. Results were compared for those with and without insomnia symptoms. Principal component and regression analyses were performed to evaluate determinants of HRQOL. MEASUREMENTS AND MAIN RESULTS: Participants were predominately Hispanic males with mild to moderate Parkinson's disease. Insomnia symptoms were reported for 46% of the study subjects. OSA (apnea-hypopnea index, ≥5) was noted in 47%, with a mean apnea-hypopnea index of 8.3 ± 11.0. Fairly bad to very bad sleep quality was reported by 21% of the participants. Insomnia (r = 0.71; P < 0.001), daytime sleepiness (r = 0.36; P = 0.003), depression symptoms (r =  0.44; P < 0.001), and anxiety symptoms (r = 0.33; P = 0.006) were significant correlates of poor sleep quality. OSA, severity of Parkinson's disease, and dopaminergic therapy were not. In the principal component analysis, sleep quality was a significant component of the "psychological factor" that in turn was a significant determinant of overall HRQOL. CONCLUSIONS: Insomnia symptoms, OSA, and subsequent poor sleep quality are prevalent in Parkinson's disease. In this single-center, exploratory study, we found that insomnia and poor sleep quality, but not OSA, play important roles in determining overall quality of life for patients with this disease. Clinical trial registered with www.clinicaltrials.gov (NCT02034357).

15 Article National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers. 2016

Dorsey, E Ray / Achey, Meredith A / Beck, Christopher A / Beran, Denise B / Biglan, Kevin M / Boyd, Cynthia M / Schmidt, Peter N / Simone, Richard / Willis, Allison W / Galifianakis, Nicholas B / Katz, Maya / Tanner, Caroline M / Dodenhoff, Kristen / Ziman, Nathan / Aldred, Jason / Carter, Julie / Jimenez-Shahed, Joohi / Hunter, Christine / Spindler, Meredith / Mari, Zoltan / Morgan, John C / McLane, Dedi / Hickey, Patrick / Gauger, Lisa / Richard, Irene Hegeman / Bull, Michael T / Mejia, Nicte I / Bwala, Grace / Nance, Martha / Shih, Ludy / Anderson, Lauren / Singer, Carlos / Zadikoff, Cindy / Okon, Natalia / Feigin, Andrew / Ayan, Jean / Vaughan, Christina / Pahwa, Rajesh / Cooper, Jessica / Webb, Sydney / Dhall, Rohit / Hassan, Anhar / Weis, Delana / DeMello, Steven / Riggare, Sara S / Wicks, Paul / Smith, Joseph / Keenan, H Tait / Korn, Ryan / Schwarz, Heidi / Sharma, Saloni / Stevenson, E Anna / Zhu, William. ·1 Department of Neurology, Rochester, New York. · 2 CHET, University of Rochester Medical Center , Rochester, New York. · 3 Duke University School of Medicine , Durham, North Carolina. · 4 Department of Biostatistics, University of Rochester , Rochester, New York. · 5 National Parkinson Foundation , Miami, Florida. · 6 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland. · 7 Simone Consulting , Sunnyvale, California. · 8 Department of Neurology, Philadelphia, Pennsylvania. · 9 Department of Biostatistics and Epidemiology, University of Pennsylvania , Philadelphia, Pennsylvania. · 10 Department of Neurology, University of California San Francisco , San Francisco, California. · 11 Northwest Neurological, PLLC , Spokane, Washington. · 12 Parkinson Center and Movement Disorders Program, Oregon Health and Science University , Portland, Oregon. · 13 Department of Neurology, Baylor College of Medicine , Houston, Texas. · 14 Department of Neurology and Neurosurgery, Johns Hopkins University , Baltimore, Maryland. · 15 Department of Neurology, Georgia Regents University , Augusta, Georgia . · 16 Department of Neurology, Duke Medical Center , Durham, North Carolina. · 17 Department of Neurology, Massachusetts General Hospital , Boston, Massachusetts. · 18 Struthers Parkinson's Center , Golden Valley, Minnesota. · 19 Department of Neurology, Beth Israel Deaconess Medical Center , Boston, Massachusetts. · 20 Department of Neurology, University of Miami , Miami, Florida. · 21 Department of Neurology, Northwestern University , Evanston, Illinois. · 22 The Feinstein Institute for Medical Research, North Shore-LIJ Health System , Manhasset, New York. · 23 Department of Neurology, Medical University of South Carolina , Charleston, South Carolina. · 24 Department of Neurology, University of Kansas Medical Center , Kansas City, Kansas. · 25 Parkinson's Institute , Sunnyvale, California. · 26 Department of Neurology, Mayo Clinic , Rochester, Minnesota. · 27 Center for Information Technology Research in the Interest of Society, University of California , Berkeley, California. · 28 Health Informatics Centre, Karolinska Institute , Stockholm, Sweden . · 29 PatientsLikeMe, Cambridge, Massachusetts . · 30 West Health Institute , La Jolla, California. ·Telemed J E Health · Pubmed #26886406.

ABSTRACT: BACKGROUND: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS: Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. CONCLUSIONS: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

16 Article Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. 2015

Nausieda, Paul A / Hsu, Ann / Elmer, Lawrence / Gil, Ramon A / Spiegel, Joerg / Singer, Carlos / Khanna, Sarita / Rubens, Robert / Kell, Sherron / Modi, Nishit B / Gupta, Suneel. ·Wisconsin Institute for Neurologic and Sleep Disorders, Milwaukee, WI, USA. · Impax Laboratories, Inc., Hayward, CA, USA. · University of Toledo College of Medicine, Toledo, OH, USA. · Charlotte Neurological Services, Port Charlotte, FL, USA. · Saarland University, Homburg/Saar, Germany. · University of Miami, Miami, FL, USA. ·J Parkinsons Dis · Pubmed #26444090.

ABSTRACT: BACKGROUND: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours. OBJECTIVE: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting. METHODS: Patients had ≥2.5 hours/day of "off" time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided. RESULTS: Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily "off" time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE. CONCLUSIONS: Among PD patients with substantial "off" time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.

17 Article Randomized, controlled pilot trial of solifenacin succinate for overactive bladder in Parkinson's disease. 2015

Zesiewicz, Theresa A / Evatt, Marian / Vaughan, Camille P / Jahan, Israt / Singer, Carlos / Ordorica, Raul / Salemi, Jason L / Shaw, Jessica D / Sullivan, Kelly L / Anonymous160825. ·Department of Neurology, University of South Florida, Tampa, FL, USA. Electronic address: tzesiewi@health.usf.edu. · Department of Neurology, Atlanta VA Medical Center and Emory University, Atlanta, GA, USA. · Department of Medicine, Atlanta VA Medical Center and Emory University, Atlanta, GA, USA. · Department of Neurology, University of South Florida, Tampa, FL, USA. · Department of Neurology, University of Miami, Miami, FL, USA. · Department of Urology, University of South Florida, Tampa, FL, USA. · Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX, USA. · Department of Epidemiology, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA. ·Parkinsonism Relat Disord · Pubmed #25814050.

ABSTRACT: OBJECTIVE: To evaluate the efficacy of solifenacin succinate in Parkinson's disease (PD) patients suffering from overactive bladder (OAB). BACKGROUND: Urinary dysfunction is a commonly encountered non-motor feature in PD that significantly impacts patient quality of life. DESIGN/METHODS: This was a double-blind, randomized, placebo-controlled, 3-site study with an open label extension phase to determine the efficacy of solifenacin succinate in idiopathic PD patients with OAB. Patients were randomized to receive solifenacin succinate 5-10 mg daily or placebo for 12 weeks followed by an 8-week open label extension. The primary outcome measure was the change in the mean number of micturitions per 24 h period. Secondary outcome measures included the change in the mean number of urinary incontinence episodes and the mean number of nocturia episodes. RESULTS: Twenty-three patients were randomized in the study. There was no significant improvement in the primary outcome measure in the double-blind phase, but there was an improvement in the number of micturitions per 24 h period in the solifenacin succinate group compared to placebo at a mean dose of 6 mg/day (p = 0.01). In the open label phase, the mean number of urinary incontinence episodes per 24 h period decreased (p = 0.03), as did the number of nocturia episodes per 24 h period (p = 0.01). Adverse events included constipation and xerostomia, which resolved after treatment was discontinued. CONCLUSIONS: In this pilot trial, solifenacin succinate treatment led to an improvement in urinary incontinence, despite persistence in other OAB symptoms.

18 Article Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. 2015

Anonymous2041224 / Kieburtz, Karl / Tilley, Barbara C / Elm, Jordan J / Babcock, Debra / Hauser, Robert / Ross, G Webster / Augustine, Alicia H / Augustine, Erika U / Aminoff, Michael J / Bodis-Wollner, Ivan G / Boyd, James / Cambi, Franca / Chou, Kelvin / Christine, Chadwick W / Cines, Michelle / Dahodwala, Nabila / Derwent, Lorelei / Dewey, Richard B / Hawthorne, Katherine / Houghton, David J / Kamp, Cornelia / Leehey, Maureen / Lew, Mark F / Liang, Grace S Lin / Luo, Sheng T / Mari, Zoltan / Morgan, John C / Parashos, Sotirios / Pérez, Adriana / Petrovitch, Helen / Rajan, Suja / Reichwein, Sue / Roth, Jessie Tatsuno / Schneider, Jay S / Shannon, Kathleen M / Simon, David K / Simuni, Tanya / Singer, Carlos / Sudarsky, Lewis / Tanner, Caroline M / Umeh, Chizoba C / Williams, Karen / Wills, Anne-Marie. ·University of Rochester, Rochester, New York. · University of Texas Health Science Center at Houston. · Medical University of South Carolina, Charleston. · National Institutes of Health, Bethesda, Maryland. · University of South Florida, Tampa. · Pacific Health Research and Education Institute, Honolulu, Hawaii. · University of California, San Francisco. · State University of New York Downstate Medical Center, Brooklyn. · University of Vermont, Burlington. · University of Kentucky, Lexington. · University of Michigan, Ann Arbor. · University of Maryland School of Medicine, Baltimore. · University of Pennsylvania, Philadelphia. · University of Calgary, Calgary, Alberta, Canada. · University of Texas Southwestern Medical Center, Dallas. · University of Southern California, Los Angeles. · Ochsner Medical Center, New Orleans, Louisiana. · University of Colorado Denver, Aurora. · The Parkinson's Institute and Clinical Center, Sunnyvale, California. · Johns Hopkins University, Baltimore, Maryland. · Georgia Regents University, Augusta. · Struthers Parkinson's Center, Golden Valley, Minnesota. · Thomas Jefferson University, Philadelphia, Pennsylvania. · Rush University Medical Center, Chicago, Illinois. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Northwestern University, Chicago, Illinois. · University of Miami, Miami, Florida. · Brigham and Women's Hospital, Boston, Massachusetts. ·JAMA · Pubmed #25668262.

ABSTRACT: IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

19 Article Assessing the non-motor symptoms of Parkinson's disease: MDS-UPDRS and NMS Scale. 2015

Martinez-Martin, P / Chaudhuri, K R / Rojo-Abuin, J M / Rodriguez-Blazquez, C / Alvarez-Sanchez, M / Arakaki, T / Bergareche-Yarza, A / Chade, A / Garretto, N / Gershanik, O / Kurtis, M M / Martinez-Castrillo, J C / Mendoza-Rodriguez, A / Moore, H P / Rodriguez-Violante, M / Singer, C / Tilley, B C / Huang, J / Stebbins, G T / Goetz, C G. ·Alzheimer Center Reina Sofia Foundation and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Eur J Neurol · Pubmed #23607783.

ABSTRACT: BACKGROUND AND PURPOSE: Although Parkinson's disease (PD) is characterized by typical motor manifestations, non-motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part I - Non-Motor Aspects of Experiences of Daily Living (nM-EDL) compared with the Non-Motor Symptoms Scale (NMSS). METHODS: To this purpose, 434 consecutive patients with PD were included in an international, observational, cross-sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin's Concordance Correlation Coefficient (LCCC) and Bland-Altman plot. RESULTS: As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (r(S) > 0.60). The total score correlation of the MDS-UPDRS Part I with the NMSS was high (r(S) = 0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60-64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland-Altman plot; LCCC < 0.60 for severe patients). CONCLUSIONS: (i) MDS-UPDRS Part I (nM-EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant.

20 Article Severity of depression and anxiety are predictors of response to antidepressant treatment in Parkinson's disease. 2014

Moonen, A J H / Wijers, A / Leentjens, A F G / Christine, C W / Factor, S A / Juncos, J / Lyness, J M / Marsh, L / Panisset, M / Pfeiffer, R / Rottenberg, D / Serrano Ramos, C / Shulman, L / Singer, C / Slevin, J / McDonald, W / Auinger, P / Richard, I H. ·Department of Psychiatry, Maastricht University, Maastricht, The Netherlands. Electronic address: anja.moonen@maastrichtuniversity.nl. · Department of Psychiatry, Maastricht University, Maastricht, The Netherlands. · Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. · Department of Neurology, Emory University, Atlanta, GA, USA. · University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. · Mental Health Care Line, Michael E. DeBakey Veterans Administration Medical Center, Houston, USA; Department of Psychiatry, Baylor College of Medicine, Houston, USA; Department of Neurology, Baylor College of Medicine, Houston, USA. · Department of Neurology, University of Montreal, Montreal, Canada. · Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA. · Department of Neurology, University of Minnesota, Minneapolis, MN, USA; Department of Radiology, University of Minnesota, Minneapolis, MN, USA. · University of Puerto Rico School of Medicine, Puerto Rico. · Department of Neurology, University of Maryland School of Medicine, Baltimore, USA. · Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA. · Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, USA. · Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA. ·Parkinsonism Relat Disord · Pubmed #24679737.

ABSTRACT: BACKGROUND: Antidepressants have appeared to be more effective than placebo treatment in treating depressive syndromes in patients with Parkinson's disease (PD). OBJECTIVE: To identify factors that predict improvement in depressive symptoms during antidepressant treatment in depressed PD patients. METHODS: A secondary analysis was performed on the dataset of the Randomized Placebo-controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received active treatment with either paroxetine or venlafaxine extended release (XR), and 39 patients received placebo treatment. Backward stepwise regression analyses were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24) score between assessments at baseline and week 12 as the main outcome measure, and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the Clinical Anxiety Scale (CAS) as independent variables. RESULTS: In both the active treatment and placebo groups, higher baseline HAMD-24 score and lower UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher anxiety scores predicted less response in the active treatment group. Higher MMSE scores predicted greater response only in the placebo-treated group. Sex and age were no predictors of response. CONCLUSIONS: Higher pre-treatment depression scores and lower pre-treatment anxiety scores are the two most important predictors for improvement during antidepressant treatment in depressed PD patients, which is in line with those found in treatment studies of depressed non-PD patients. Furthermore, our results indicate the requirement for different or more intensive treatment for depressed PD patients with more severe anxiety symptoms.

21 Article Relationship between the MDS-UPDRS domains and the health-related quality of life of Parkinson's disease patients. 2014

Martínez-Martín, P / Rodríguez-Blázquez, C / Forjaz, M J / Alvarez-Sánchez, M / Arakaki, T / Bergareche-Yarza, A / Chade, A / Garretto, N / Gershanik, O / Kurtis, M M / Martínez-Castrillo, J C / Mendoza-Rodríguez, A / Moore, H P / Rodríguez-Violante, M / Singer, C / Tilley, B C / Huang, J / Stebbins, G T / Goetz, C G. ·Alzheimer Center Reina Sofia Foundation and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Eur J Neurol · Pubmed #24447695.

ABSTRACT: BACKGROUND AND PURPOSE: The Movement Disorder Society sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument for assessing Parkinson's disease (PD). The present study was aimed at determining the relationships between MDS-UPDRS components and health-related quality of life (HRQoL) evaluations in PD patients. METHODS: An international, multicenter, cross-sectional study was carried out of 435 PD patients assessed with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ-5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation coefficients, exploratory factor analysis and multiple linear regression models (dependent variables EQ-5D and PDQ-8) were performed. RESULTS: The participants' age was 66.71 ± 10.32 years (51.5% men). PD duration was 8.52 ± 6.14, and median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS-UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from 0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS-UPDRS domains as independent variables, the main determinant for both the EQ-5D index and the PDQ-8 was Part II followed by Part I. After factorial grouping of the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes. CONCLUSIONS: The MDS-UPDRS component most tightly related with the HRQoL measures was a combination of motor and non-motor experiences of daily living.

22 Article Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. 2013

Schenck, C H / Montplaisir, J Y / Frauscher, B / Hogl, B / Gagnon, J-F / Postuma, R / Sonka, K / Jennum, P / Partinen, M / Arnulf, I / Cochen de Cock, V / Dauvilliers, Y / Luppi, P-H / Heidbreder, A / Mayer, G / Sixel-Döring, F / Trenkwalder, C / Unger, M / Young, P / Wing, Y K / Ferini-Strambi, L / Ferri, R / Plazzi, G / Zucconi, M / Inoue, Y / Iranzo, A / Santamaria, J / Bassetti, C / Möller, J C / Boeve, B F / Lai, Y Y / Pavlova, M / Saper, C / Schmidt, P / Siegel, J M / Singer, C / St Louis, E / Videnovic, A / Oertel, W. ·Minnesota Regional Sleep Disorders Center, Department of Psychiatry, Hennepin County Medical Center and University of Minnesota Medical School, Minneapolis, MN, USA. schen010@umn.edu ·Sleep Med · Pubmed #23886593.

ABSTRACT: OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

23 Article The MDS-UPDRS Part II (motor experiences of daily living) resulted useful for assessment of disability in Parkinson's disease. 2013

Rodriguez-Blazquez, Carmen / Rojo-Abuin, Jose Manuel / Alvarez-Sanchez, Mario / Arakaki, Tomoko / Bergareche-Yarza, Alberto / Chade, Anabel / Garretto, Nelida / Gershanik, Oscar / Kurtis, Monica M / Martinez-Castrillo, Juan Carlos / Mendoza-Rodriguez, Amelia / Moore, Henry P / Rodriguez-Violante, Mayela / Singer, Carlos / Tilley, Barbara C / Huang, Jing / Stebbins, Glenn T / Goetz, Christopher G / Martinez-Martin, Pablo. ·National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Parkinsonism Relat Disord · Pubmed #23791519.

ABSTRACT: OBJECTIVE: To evaluate the motor experiences of daily living section of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS M-EDL) for assessing disability in PD patients; to determine the association between disability and quality of life; and to identify cut-off score ranges for no, mild, moderate and severe disability with this measure. METHODS: International, observational, cross-sectional study of 435 PD patients, assessed with: MDS-UPDRS, Hoehn and Yahr staging, Rapid Assessment of Disability Scale, Clinical Impression of Severity Index for PD, Parkinson's Disease Questionnaire-8 and EQ-5D. Descriptive statistics, Spearman's rank correlation coefficients, Kruskal-Wallis test for group comparisons, ordinal logistic regression analysis for setting cut-off values and a step-wise multiple linear regression model were calculated. RESULTS: MDS-UPDRS M-EDL correlated 0.70-0.80 with other disability measures, and -0.46 to 0.74 with quality of life scales. Scores significantly increased with higher disease duration and severity (p < 0.001). Cut-off values for the M-EDL were: 0-2 points, no disability; 3-16, mild; 17-31, moderate; and 32 points or more, severe. Linear regression analysis identified the MDS-UPDRS nM-EDL section as the main determinant of M-EDL, followed by the rest of MDS-UPDRS sections (explained variance: 59%). CONCLUSIONS: MDS-UPDRS M-EDL proved to be useful for assessing disability in PD.

24 Article An accelerometry-based study of lower and upper limb tremor in Parkinson's disease. 2013

Scanlon, Blake K / Levin, Bonnie E / Nation, Daniel A / Katzen, Heather L / Guevara-Salcedo, Alexandra / Singer, Carlos / Papapetropoulos, Spiridon. ·Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA. bscanlon@stanford.edu ·J Clin Neurosci · Pubmed #23639618.

ABSTRACT: Over the past two decades, several studies have aimed to quantify the kinetic properties of tremor with primary focus on the upper limbs. However, there is a lack of investigation into the properties of tremor in the lower limbs. The objective of this preliminary study was to investigate the properties of oscillatory movement, at rest and in posture, in both the upper and lower limbs of Parkinson's disease (PD) patients with clinically undetectable to modest rest/postural tremor and healthy controls. PD patients (N = 16) and controls (N = 8) were examined clinically by a movement disorders specialist and oscillatory movements in all four extremities were evaluated using a portable biaxial accelerometer. While tremor intensity and frequency did not differ between groups, the intraindividual variability of rest and postural tremor frequency in the dexterity-dominant lower limb was lower in people living with PD than in healthy adults. Additionally, rest tremor frequency was discrepant between upper and lower limbs in PD. Our work introduces the possibility that minute variations in lower limb movements, which are imperceptible upon expert clinical exam, can be used to differentiate a diseased sample from a healthy one. These preliminary findings suggest that additional work using objective tremor measurement may improve our understanding of lower limb motor dysfunction in PD and lead to the refinement of current, and the development of new, metrics to enhance early diagnosis, differential diagnosis, and symptom quantification.

25 Article Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. 2013

Boeve, B F / Silber, M H / Ferman, T J / Lin, S C / Benarroch, E E / Schmeichel, A M / Ahlskog, J E / Caselli, R J / Jacobson, S / Sabbagh, M / Adler, C / Woodruff, B / Beach, T G / Iranzo, A / Gelpi, E / Santamaria, J / Tolosa, E / Singer, C / Mash, D C / Luca, C / Arnulf, I / Duyckaerts, C / Schenck, C H / Mahowald, M W / Dauvilliers, Y / Graff-Radford, N R / Wszolek, Z K / Parisi, J E / Dugger, B / Murray, M E / Dickson, D W. ·Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. bboeve@mayo.edu ·Sleep Med · Pubmed #23474058.

ABSTRACT: OBJECTIVE: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. METHODS: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. RESULTS: 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. CONCLUSIONS: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

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