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Parkinson Disease: HELP
Articles from Kansas
Based on 68 articles published since 2008
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These are the 68 published articles about Parkinson Disease that originated from Kansas during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review The role of extended-release amantadine for the treatment of dyskinesia in Parkinson's disease patients. 2018

Elkurd, Mazen T / Bahroo, Laxman B / Pahwa, Rajesh. ·Department of Neurology, Medstar Georgetown University Hospital, Georgetown, Washington DC, USA. · Department of Neurology, University of Kansas Medical Center, KS, USA. ·Neurodegener Dis Manag · Pubmed #29564954.

ABSTRACT: Levodopa is the most efficacious treatment for Parkinson's disease (PD). Long-term treatment with levodopa is limited due to dyskinesia. Dyskinesia in PD can be socially and functionally disabling. Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia. When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release. Amantadine ER reduces the severity and duration of dyskinesia during the day, reduces OFF time and increases ON time without troublesome dyskinesia. The most common side effects are hallucination, dizziness, orthostatic hypotension and pedal edema. This review discusses the safety and efficacy of amantadine ER in dyskinesia in PD patients.

2 Review Models of LRRK2-Associated Parkinson's Disease. 2017

Xiong, Yulan / Dawson, Ted M / Dawson, Valina L. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. yulanxiong@ksu.edu. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. yulanxiong@ksu.edu. · Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, 66506, USA. yulanxiong@ksu.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu. · Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu. · Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vdawson@jhmi.edu. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, 70130-2685, USA. vdawson@jhmi.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu. · Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, 70130-2685, USA. tdawson@jhmi.edu. · Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. tdawson@jhmi.edu. ·Adv Neurobiol · Pubmed #28353284.

ABSTRACT: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic causes of Parkinson's disease (PD) and also one of the strongest genetic risk factors in sporadic PD. The LRRK2 protein contains a GTPase and a kinase domain and several protein-protein interaction domains. Both in vitro and in vivo assays in different model systems have provided tremendous insights into the molecular mechanisms underlying LRRK2-induced dopaminergic neurodegeneration. Among all the model systems, animal models are crucial tools to study the pathogenesis of human disease. How do the animal models recapitulate LRRK2-induced dopaminergic neuronal loss in human PD? To answer this question, this review focuses on the discussion of the animal models of LRRK2-associated PD including genetic- and viral-based models.

3 Review Cerium oxide nanoparticles: a 'radical' approach to neurodegenerative disease treatment. 2017

Naz, Shuguftha / Beach, James / Heckert, Blaze / Tummala, Tanuja / Pashchenko, Oleksandra / Banerjee, Tuhina / Santra, Santimukul. ·Department of Chemistry, Kansas Polymer Research Center, Pittsburg State University, 1701 S. Broadway Street, Pittsburg, KS 66762, USA. ·Nanomedicine (Lond) · Pubmed #28181459.

ABSTRACT: Despite advances in understanding the factors that cause many neurodegenerative diseases (NDs), no current therapies have yielded significant results. Cerium oxide nanoparticles (CeONPs) have recently emerged as therapeutics for the treatment of NDs due to their antioxidant properties. This report summarizes the recent findings regarding CeONPs in treatment of various NDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, ischemic stroke and amyotrophic lateral sclerosis. Interest in CeONPs as a potential nanomedicine for NDs has increased due to: their ability to alter signaling pathways, small diameter allowing passage through the blood-brain barrier and scavenging of reactive oxygen species. Due to these properties, CeONPs could eventually revolutionize existing treatments for NDs.

4 Review Clinical utility of DaTscan™ imaging in the evaluation of patients with parkinsonism: a US perspective. 2017

Isaacson, Stuart H / Fisher, Stanley / Gupta, Fiona / Hermanowicz, Neal / Kremens, Daniel E / Lew, Mark F / Marek, Kenneth / Pahwa, Rajesh / Russell, David S / Seibyl, John. ·a Parkinson's Disease and Movement Disorders Center of Boca Raton , FL , USA. · b Saint Luke's Marion Bloch Neuroscience Institute , Kansas City , MO , USA. · c Hackensack University Medical Center, Movement Disorders Center , Hackensack , NJ , USA. · d Irvine Health Movement Disorders Program , University of California , Irvine , CA , USA. · e Thomas Jefferson University, Sidney Kimmel Medical College , Philadelphia , PA , USA. · f University of Southern California Keck School of Medicine , Los Angeles , CA , USA. · g Institute for Neurodegenerative Disorders , New Haven , CT , USA. · h University of Kansas Medical Center , Kansas City , KS , USA. ·Expert Rev Neurother · Pubmed #27813429.

ABSTRACT: INTRODUCTION: Single photon emission computed tomography (SPECT) with Ioflupane I123 injection (DaTscan™) was approved by the Food and Drug Administration in 2011 for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. While brain SPECT imaging using DaTscan is a covered service under Medicare policy, there is a lack of consensus on its role in routine clinical practice in the US. Areas covered: To address this issue, an expert group of US-based movement disorders neurologists convened to discuss the clinical utility of DaTscan in movement disorders practices within the US. The group identified and discussed routine clinical scenarios where imaging with DaTscan can provide useful information that may impact management and/or clarify clinical diagnoses. This paper summarizes a consensus reached by the expert group at this meeting. Expert commentary: The major utility of DaTscan imaging is the assistance it provides in distinguishing between nigrostriatal dopaminergic degeneration and non-nigrostriatal degeneration in patients displaying equivocal signs and symptoms of parkinsonism.

5 Review Deep brain stimulation for Parkinson's disease: current status and future outlook. 2016

Smith, Kyle A / Pahwa, Rajesh / Lyons, Kelly E / Nazzaro, Jules M. ·Department of Neurosurgery, University of Kansas Medical Center, 3901 Rainbow Blvd, Mailstop 3021, Kansas City, KS 66160, USA. · Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA. ·Neurodegener Dis Manag · Pubmed #27409150.

ABSTRACT: Parkinson's disease is a neurodegenerative condition secondary to loss of dopaminergic neurons in the substantia nigra pars compacta. Surgical therapy serves as an adjunct when unwanted medication side effects become apparent or additional therapy is needed. Deep brain stimulation emerged into the forefront in the 1990s. Studies have demonstrated improvement in all of the cardinal parkinsonian signs with stimulation. Frameless and 'mini-frame' stereotactic systems, improved MRI for anatomic visualization, and intraoperative MRI-guided placement are a few of the surgical advances in deep brain stimulation. Other advances include rechargeable pulse generators, voltage- or current-based stimulation, and enhanced abilities to 'steer' stimulation. Work is ongoing investigating closed-loop 'smart' stimulation in which stimulation is predicated on neuronal feedback.

6 Review Treatment of early Parkinson's disease. 2014

Pahwa, Rajesh / Lyons, Kelly E. ·A National Parkinson Foundation Center of Excellence, University of Kansas Medical Center, Kansas City, Kansas, USA. ·Curr Opin Neurol · Pubmed #24950010.

ABSTRACT: PURPOSE OF REVIEW: This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. RECENT FINDINGS: The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. SUMMARY: Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

7 Review LRRK2, a puzzling protein: insights into Parkinson's disease pathogenesis. 2014

Esteves, A Raquel / Swerdlow, Russell H / Cardoso, Sandra M. ·CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal. · University of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, KS, USA. · CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address: cardoso.sandra.m@gmail.com. ·Exp Neurol · Pubmed #24907399.

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is a large, ubiquitous protein of unknown function. Mutations in the gene encoding LRRK2 have been linked to familial and sporadic Parkinson's disease (PD) cases. The LRRK2 protein is a single polypeptide that displays GTPase and kinase activity. Kinase and GTPase domains are involved in different cellular signaling pathways. Despite several experimental studies associating LRRK2 protein with various intracellular membranes and vesicular structures such as endosomal/lysosomal compartments, the mitochondrial outer membrane, lipid rafts, microtubule-associated vesicles, the golgi complex, and the endoplasmic reticulum its broader physiologic function(s) remain unidentified. Additionally, the cellular distribution of LRRK2 may indicate its role in several different pathways, such as the ubiquitin-proteasome system, the autophagic-lysosomal pathway, intracellular trafficking, and mitochondrial dysfunction. This review discusses potential mechanisms through which LRRK2 may mediate neurodegeneration and cause PD.

8 Review Outcomes of rotigotine clinical trials: effects on motor and nonmotor symptoms of Parkinson's disease. 2013

Lyons, Kelly E / Pahwa, Rajesh. ·Department of Neurology, University of Kansas Medical Center, 3599 Rainbow Boulevard, Kansas City, KS 66160, USA. Kelly.lyons@att.net ·Neurol Clin · Pubmed #23931954.

ABSTRACT: Rotigotine transdermal system is a nonergot, 24-hour dopamine agonist approved for the treatment of early and advanced Parkinson's disease (PD). Recent studies have demonstrated significant improvements with rotigotine in motor function in early PD and significant improvements in daily off-time and motor function in advanced PD. In addition to motor improvements, nonmotor symptoms have been shown to be improved with rotigotine in both early and advanced PD. Rotigotine has been shown in large, controlled studies to be safe and efficacious for the treatment of motor and some nonmotor symptoms of early and advanced PD.

9 Review Synucleins: are they two-edged swords? 2013

Surguchov, Andrei. ·VA Medical Center, Kansas City, Missouri, USA. asurguchov@kumc.edu ·J Neurosci Res · Pubmed #23150342.

ABSTRACT: The synuclein family consists of three distinct highly homologous genes, α-synuclein, β-synuclein, and γ-synuclein, which have so far been found only in vertebrates. Proteins encoded by these genes are characterized by an acidic C-terminal region and five or six imperfect repeat motifs (KTKEGV) distributed throughout the highly conserved N-terminal region. Numerous data demonstrate that synucleins are implicated in two groups of the most devastating human disorders, i.e., neurodegenerative diseases (NDDs) and cancer. Mutations in the α-synuclein gene are associated with familial forms of Parkinson's disease (PD), and accumulation of α-synuclein inclusions is a hallmark of this disorder. In breast cancer, increased expression of γ-synuclein correlates with disease progression. Conversely, some results indicate that the members of the synuclein family may have a protective effect. How might these small proteins combine such controversial properties? We present evidence that synuclein's features are basically regulated by two mechanisms, i.e., posttranslational modifications (PTMs) and the level of their expression. We also discuss a new, emerging area of investigation of synucleins, namely, their role in the cell-to-cell propagation of pathology.

10 Review Does mitochondrial DNA play a role in Parkinson's disease? A review of cybrid and other supportive evidence. 2012

Swerdlow, Russell H. ·Departments of Neurology, Biochemistry and Molecular Biology, and Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA. rswerdlow@kumc.edu ·Antioxid Redox Signal · Pubmed #21338319.

ABSTRACT: SIGNIFICANCE: Mitochondria are currently believed to play an important role in the neurodysfunction and neurodegeneration that underlie Parkinson's disease (PD). RECENT ADVANCES: While it increasingly appears that mitochondrial dysfunction in PD can have different causes, it has been proposed that mitochondrial DNA (mtDNA) may account for or drive mitochondrial dysfunction in the majority of the cases. If correct, the responsible mtDNA signatures could represent acquired mutations, inherited mutations, or population-distributed polymorphisms. CRITICAL ISSUES AND FUTURE DIRECTIONS: This review discusses the case for mtDNA as a key mediator of PD, and especially focuses on data from studies of PD cytoplasmic hybrid (cybrid) cell lines.

11 Review The impact and management of nonmotor symptoms of Parkinson's disease. 2011

Lyons, Kelly E / Pahwa, Rajesh. ·Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA. kelly.lyons@att.net ·Am J Manag Care · Pubmed #22087551.

ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disorder diagnosed by the presence of bradykinesia and at least 1 of the symptoms of rigidity, resting tremor, or postural instability. It is increasingly recognized that nonmotor symptoms are common and can adversely affect quality of life, yet they often are not diagnosed and consequently are often untreated. Nonmotor symptoms include neuropsychiatric issues such as anxiety, depression, hallucinations, impulse control disorders, and cognitive impairment, as well as autonomic dysfunction, which may present as gastrointestinal, urinary, and sexual disturbances. Nonmotor symptoms also include excessive sweating, orthostatic hypotension, and sleep disturbances. Management of PD requires recognition of both motor and nonmotor symptoms as well as an understanding of the relationship between these symptoms and how they can be affected by treatments for PD. Therapy should be individualized for each patient, as treatments for the motor symptoms of PD can improve some nonmotor symptoms while they can worsen others. In many cases, symptom-specific treatments are necessary to control nonmotor symptoms of PD.

12 Review Diagnosis and initiation of treatment in Parkinson's disease. 2011

Lyons, Kelly E / Pahwa, Rajesh. ·Parkinson's Disease and Movement Disorder Center, Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. Kelly.lyons@att.net ·Int J Neurosci · Pubmed #22035027.

ABSTRACT: Parkinson's disease (PD) is the most common cause of parkinsonism, yet the diagnosis and management can be a challenge. The United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria and dopamine transporter/single-photon emission computed tomography (DaT-SPECT) are diagnostic aids that can improve diagnostic accuracy. Even though PD is a progressive disease, for years, physicians and patients have delayed treatment until functional disability occurs. However, studies of monoamine oxidase-type B (MAO-B) inhibitors, dopamine agonists, and levodopa, all of which can be used as initial therapy, have demonstrated that PD patients receiving treatment do better than those who do not receive treatment, and some studies have shown that those receiving treatment earlier do better long term. Therefore, the management strategy for PD has moved toward earlier initiation of treatment. Although treatment for each patient should be individualized and based on their specific symptoms, severity, and lifestyle, in general MAO-B inhibitors may be used initially to treat mild symptoms, adding a dopamine agonist in younger patients or levodopa in older patients, as symptoms become more severe.

13 Review Management of hallucinations and psychosis in Parkinson's disease. 2010

Eng, Marty L / Welty, Timothy E. ·Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, Kansas 66160, USA. meng@kumc.edu ·Am J Geriatr Pharmacother · Pubmed #20869621.

ABSTRACT: BACKGROUND: Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published. OBJECTIVE: The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD. METHODS: A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. RESULTS: Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years. CONCLUSIONS: Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

14 Review Early diagnosis of Parkinson's disease: recommendations from diagnostic clinical guidelines. 2010

Pahwa, Rajesh / Lyons, Kelly E. ·University of Kansas Medical Center, 3599 Rainbow Blvd., Kansas City, KS 66160, USA. ·Am J Manag Care · Pubmed #20297872.

ABSTRACT: Therapeutic options for Parkinson's disease (PD) are currently limited to symptomatic agents. Levodopa is the most efficacious treatment; however, higher doses and long-term use are associated with adverse effects such as motor fluctuations and dyskinesia. Early treatment of PD with other agents such as dopamine agonists and monoamine oxidase type B inhibitors can provide symptomatic benefit and delay initiation of levodopa therapy. Early treatment of PD is contingent upon early and accurate diagnosis of the disease, which can be challenging because there are no biomarkers or neuroimaging or other clinical tests available to confirm the diagnosis. PD diagnosis is currently based on the presence or absence of various clinical features and the experience of the treating physician. A definitive diagnosis can be made only after autopsy. Moreover, the signs and symptoms present in early PD can resemble those of a number of other movement disorders, particularly other forms of parkinsonism, such as multiple system atrophy, drug-induced parkinsonism, and vascular parkinsonism, as well as diffuse Lewy body disease and essential tremor. Nevertheless, diagnosis of PD based on clinical features and response to antiparkinsonian medication can be achieved with a fairly high level of accuracy, particularly when made by a physician specializing in movement disorders. This article reviews and summarizes published recommendations for the clinical diagnosis of PD.

15 Review The neurodegenerative mitochondriopathies. 2009

Swerdlow, Russell H. ·Department of Neurology, University of Kansas School of Medicine, Kansas City, KS 66160, USA. rswerdlow@kumc.edu ·J Alzheimers Dis · Pubmed #19542616.

ABSTRACT: Mitochondria are physically or functionally altered in many neurodegenerative diseases. This is the case for very rare neurodegenerative disorders as well as extremely common age-related ones such as Alzheimer's disease and Parkinson's disease. In some disorders very specific patterns of altered mitochondrial function or systemic mitochondrial dysfunction are demonstrable. Some disorders arise from mitochondrial DNA mutation, some from nuclear gene mutation, and for some the etiology is not definitively known. This review classifies neurodegenerative diseases using mitochondrial dysfunction as a unifying feature, and in doing so defines a group of disorders called the neurodegenerative mitochondriopathies. It discusses what mitochondrial abnormalities have been identified in various neurodegenerative diseases, what is currently known about the mitochondria-neurodegeneration nexus, and speculates on the significance of mitochondrial function in some disorders not classically thought of as mitochondriopathies.

16 Review A review of ropinirole prolonged release in Parkinson's disease. 2009

Nashatizadeh, Muhammad M / Lyons, Kelly E / Pahwa, Rajesh. ·Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. ·Clin Interv Aging · Pubmed #19503779.

ABSTRACT: Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson's disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily "off" time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD.

17 Review Levodopa-related wearing-off in Parkinson's disease: identification and management. 2009

Pahwa, Rajesh / Lyons, Kelly E. ·Department of Neurology, University of Kansas Medical Center, 3599 Rainbow Blvd., Kansas City, KS 66160, USA. ·Curr Med Res Opin · Pubmed #19228103.

ABSTRACT: BACKGROUND: Levodopa is currently the most effective treatment for Parkinson's disease (PD); however, long-term levodopa therapy often results in motor complications, such as motor fluctuations and dyskinesia. The initial complication is commonly wearing-off, which is the re-emergence of motor and non-motor symptoms before the next scheduled levodopa dose. OBJECTIVE: The purpose of this article was to review published literature that discusses wearing-off, focusing on the role of the healthcare professional, including the primary care physician, in the effective management of wearing-off. METHODS: An electronic literature search was conducted using MEDLINE and EMBASE to find articles discussing wearing-off and its management using the following keywords: 'Parkinson's disease'; 'wearing-off'; 'levodopa'; 'primary care'. FINDINGS AND CONCLUSIONS: Current evidence indicates that a consistent delivery of levodopa should improve long-term symptomatic efficacy and may prevent or delay motor complications. A number of therapeutic options are available to optimize therapeutic outcome, including modification of the levodopa dose or dosing schedule,switching to another levodopa formulation and the use of adjunct therapies, such as catechol-O-methyl transferase inhibitors, dopamine agonists and monoamine oxidase-B inhibitors. The management of wearing-off is dependent upon the early identification of symptoms and the initiation of effective treatment. Key issues are the need to educate patients and to facilitate good communication with both primary and secondary healthcare professionals. In most cases, patients with PD initially present to primary healthcare professionals who may refer the patient to a neurologist once disease management becomes more complex. However, in many cases, especially in rural areas where neurologists may not be widely available, the primary healthcare professionals may manage the patient throughout the disease course. Limitations of this review include the restricted search criteria and selected search period.

18 Clinical Trial Randomized, placebo-controlled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson's disease (EASE LID 3). 2017

Oertel, Wolfgang / Eggert, Karla / Pahwa, Rajesh / Tanner, Caroline M / Hauser, Robert A / Trenkwalder, Claudia / Ehret, Reinhard / Azulay, Jean Philippe / Isaacson, Stuart / Felt, Larissa / Stempien, Mary Jean. ·Philipps University, Marburg, Germany. · University of Kansas Medical Center, Kansas City, Kansas, USA. · University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · University of South Florida, Tampa, Florida, USA. · Paracelsus-Elena-Klinik, Kassel and Clinic Neurosurgery, University Medical Center, Goettingen, Germany. · Praxis Neurologie, Berlin, Germany. · Hôpital de la Timone, Marseille, France. · Parkinson's Disease and Movement Disorders Center, Boca Raton, Florida, USA. · Adamas Pharmaceuticals, Inc., Emeryville, California, USA. ·Mov Disord · Pubmed #28833562.

ABSTRACT: BACKGROUND: The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy. OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of 274 mg ADS-5102 (amantadine) extended-release capsules (equivalent to 340-mg amantadine HCl) for levodopa-induced dyskinesia in a randomized controlled trial. METHODS: PD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS-5102 once daily at bedtime for 13 weeks. The primary efficacy analysis was based on change from baseline to week 12 on the Unified Dyskinesia Rating Scale total score in the modified intent-to-treat population. OFF time was a key secondary measure. RESULTS: At week 12, least-squares mean change in the Unified Dyskinesia Rating Scale was -20.7 (standard error 2.2) for ADS-5102 (n = 37) and -6.3 (standard error 2.1) for placebo (n = 38; treatment difference -14.4, 95% confidence interval -20.4 to -8.3, P < .0001), indicating improvement in levodopa-induced dyskinesia. OFF time decreased 0.5 hours (standard error 0.3) for ADS-5102 from a baseline mean of 2.6 hours and increased 0.6 hours (standard error 0.3) for placebo from a baseline mean of 2.0 hours (treatment difference -1.1 hours, 95% confidence interval -2.0 to -0.2, P = .0199). The most common adverse events (ADS-5102 versus placebo) included dry mouth (13.5% versus 2.6%), nausea (13.5% versus 2.6%), decreased appetite (10.8% versus 0%), insomnia (10.8% versus 0%), orthostatic hypotension (10.8% versus 0%), constipation (8.1% versus 0%), falls (8.1% versus 5.3%), and visual hallucinations (8.1% versus 5.3%). Adverse events led to treatment discontinuation in 19% versus 8%, respectively. CONCLUSION: ADS-5102 274 mg is an oral pharmacotherapy demonstrating a significant decrease in levodopa-induced dyskinesia and improving OFF time. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

19 Clinical Trial ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study): A Randomized Clinical Trial. 2017

Pahwa, Rajesh / Tanner, Caroline M / Hauser, Robert A / Isaacson, Stuart H / Nausieda, Paul A / Truong, Daniel D / Agarwal, Pinky / Hull, Keith L / Lyons, Kelly E / Johnson, Reed / Stempien, Mary Jean. ·Department of Neurology, University of Kansas Medical Center, Kansas City. · Department of Neurology, University California-San Francisco. · Parkinson's Disease Research, Education and Clinic Center, San Francisco Veterans Affairs Medical Center, San Francisco, California. · Health Byrd Parkinson's Disease and Movement Disorders Center of Excellence, University of South Florida, Tampa. · Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida. · Wisconsin Institute for Neurologic and Sleep Disorders, Milwaukee. · The Parkinson's and Movement Disorder Institute, Fountain Valley, California. · Booth Gardner Parkinson's Care Center, Evergreen Health, Kirkland, Washington. · Raleigh Neurology Associates, Raleigh, North Carolina. · Adamas Pharmaceuticals Inc, Emeryville, California. ·JAMA Neurol · Pubmed #28604926.

ABSTRACT: Importance: Medical treatment of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) is an unmet need. Objective: To evaluate the efficacy and safety of ADS-5102 (amantadine) extended-release 274-mg capsules for treatment of LID in patients with PD. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled clinical trial was conducted between May 7, 2014, and July 22, 2015, at 44 North American sites among patients with PD treated with levodopa who experienced at least 1 hour of troublesome dyskinesia per day with at least mild functional impact. Interventions: Patients were randomized to receive placebo or 274 mg of ADS-5102 administered orally at bedtime for up to 25 weeks. Main Outcomes and Measures: The primary efficacy analysis was the change from baseline to week 12 in the Unified Dyskinesia Rating Scale total score for ADS-5102 vs placebo in the modified intent-to-treat population. OFF time (amount of time the PD medication is not controlling motor symptoms) was a key secondary end point. Safety analyses included all patients who received the study drug (ADS-5102 or placebo). Results: A total of 189 patients were screened, and 126 were randomized; the modified intent-to-treat population included 121 patients (51 women and 70 men; mean [SD] age, 64.7 [9.1] years). At week 12, the least-squares mean (SE) change in the Unified Dyskinesia Rating Scale score was -15.9 (1.6) for ADS-5102 (n = 63) and -8.0 (1.6) for placebo (n = 58) (treatment difference, -7.9; 95% CI, -12.5 to -3.3; P < .001). OFF time decreased by a mean (SE) of 0.6 (0.3) hours for ADS-5102 and increased by 0.3 (0.3) hours for placebo (treatment difference, -0.9 hours; 95% CI, -1.6 to -0.2; P = .02). Common adverse events for ADS-5102 vs placebo included visual hallucinations (15 [23.8%] vs 1 [1.7%]), peripheral edema (15 [23.8%] vs 0), and dizziness (14 [22.2%] vs 0). Adverse events led to treatment discontinuation for 13 patients receiving ADS-5102 (20.6%) vs 4 patients receiving placebo (6.9%). Conclusions and Relevance: ADS-5102, 274 mg at bedtime, may be an effective treatment for LID. An additional benefit is reduced OFF time. To our knowledge, this is the first demonstration of an oral treatment reducing both LID and OFF time in patients with PD with dyskinesia. Trial Registration: clinicaltrials.gov Identifier: NCT02136914.

20 Clinical Trial Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis. 2015

Ballard, Clive / Isaacson, Stuart / Mills, Roger / Williams, Hilde / Corbett, Anne / Coate, Bruce / Pahwa, Rajesh / Rascol, Olivier / Burn, David J. ·Wolfson Centre for Age-Related Diseases, King's College London, London, UK. Electronic address: clive.ballard@kcl.ac.uk. · Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL. · ACADIA Pharmaceuticals, San Diego, CA. · Wolfson Centre for Age-Related Diseases, King's College London, London, UK. · University of Kansas Medical Center, Kansas City, KS. · Department of Clinical Pharmacology and Neurosciences, University UPS of Toulouse III, Toulouse, France. · Institute of Neuroscience, Newcastle University, Newcastle, UK. ·J Am Med Dir Assoc · Pubmed #26239690.

ABSTRACT: OBJECTIVES: To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. DESIGN: Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. SETTING: Primary and secondary care medical centers in the United States, Canada, Europe, and India. PARTICIPANTS: A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. INTERVENTIONS: Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. MAIN OUTCOME MEASURES: Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. CONCLUSIONS: This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality.

21 Clinical Trial Tolerance of the VocaLog™ Vocal Monitor by Healthy Persons and Individuals With Parkinson Disease. 2015

Searl, Jeff / Dietsch, Angela M. ·University of Kansas Medical Center, Hearing and Speech Department, Kansas City, KS. · University of Kansas Medical Center, Hearing and Speech Department, Kansas City, KS. Electronic address: angela.m.dietsch.ctr@mail.mil. ·J Voice · Pubmed #25726068.

ABSTRACT: OBJECTIVE: To assess subject tolerance of extended use of the VocaLog™ vocal monitor (VM), a device marketed to log calibrated decibel sound pressure level. STUDY DESIGN: Prospective between-subjects design including two age- and sex-matched groups: individuals with Parkinson disease (IWPD) and healthy persons. METHODS: After an initial session to calibrate the device and demonstrate its use, participants wore the VM during waking hours for five consecutive days. At a second visit to return the VM, participants completed a survey and a short interview regarding their experience with and perceptions of the device. RESULTS: Those with PD and control subjects reported relatively few issues with use of the VM. There were no group differences regarding convenience, others' reactions, technical issues, or future participation in similar studies. Participants with PD indicated similar frequency of discomfort issues but higher severity ratings for discomfort during VM use compared with healthy participants. CONCLUSIONS: The VocaLog™ offers a method to monitor vocal loudness during everyday activities for several consecutive days. The device was well tolerated by participants from both groups. IWPD reported greater discomfort than controls, possibly reflecting altered sensory perceptions associated with PD. The current data offer some reassurance that this VM can be tolerated by both healthy persons and those with PD for clinical and research purposes.

22 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.

23 Clinical Trial Feasibility of group voice therapy for individuals with Parkinson's disease. 2011

Searl, Jeff / Wilson, Kristel / Haring, Karen / Dietsch, Angela / Lyons, Kelly / Pahwa, Rajesh. ·Hearing and Speech Department, University of Kansas Medical Center, Kansas City, KS, USA. jsearl@kumc.edu ·J Commun Disord · Pubmed #21889774.

ABSTRACT: PURPOSE: The primary purpose was to demonstrate the feasibility of executing treatment tasks focused on increasing loudness in a group format for individuals with Parkinson's disease (PD). A second purpose was to report preliminary pre-to-post treatment outcomes for individuals with PD immediately after they complete the group program. METHODS: The group intervention is described. Fifteen adults with PD who participated in the group and three clinicians leading the group provided feedback about the execution of the intervention. The participants also provided voice samples and self-ratings of voice handicap once before completing the 8-week voice group and once immediately after completing the voice group. Outcome measures included voice intensity, fundamental frequency (F0) mean, standard deviation and range, maximum phonation time, and listener judgment of loudness. RESULTS: Feedback from the clinicians suggested that many, but not all, of the voice activities could be executed within a group setting. Participants with PD indicated they understood the focus of the group and that subjectively they felt the group was helpful for increasing loudness. Statistically significant increases occurred for voice intensity, F0 maximum, and F0 range. Voice handicap scores decreased significantly and 80% of the participants were judged louder post intervention. CONCLUSIONS: Clinician and participant feedback indicated that it was feasible to execute most LSVT(®) tasks in a group format with some modifications. The preliminary outcome data indicate that the targeted behavior (voice dB and loudness) did change in the predicted direction as did several other measures. Future studies comparing outcomes of group intervention to the gold standard LSVT(®), and exploring retention of treatment gains over time, are needed. LEARNING OUTCOMES: After reading the manuscript, readers will be able to: (1) Describe previous attempts at group intervention to improve voice for individuals with Parkinson's disease. (2) List three ways that the group intervention tried in this study differed from LSVT(®). (3) Identify three limitations to this study that must be addressed before advocating implementation of the group approach in clinical situations.

24 Clinical Trial Orally disintegrating selegiline in Parkinson patients with dopamine agonist-related adverse effects. 2010

Lyons, Kelly E / Friedman, Joseph H / Hermanowicz, Neal / Isaacson, Stuart H / Hauser, Robert A / Hersh, Bonnie P / Silver, Dee E / Tetrud, James W / Elmer, Lawrence W / Parashos, Sotirios A / Struck, Lynn K / Lew, Mark F / Pahwa, Rajesh. ·University of Kansas Medical Center, Kansas City, KS 66160, USA. lyons.kelly@att.net ·Clin Neuropharmacol · Pubmed #19855267.

ABSTRACT: OBJECTIVE: To determine whether adding orally disintegrating selegiline (ODS) while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations, and impulse control disorders (ICDs) without compromising efficacy in Parkinson disease (PD) patients. METHODS: This was a 12-week open-label study of 60 PD patients with motor fluctuations and DA-related AEs of EDS, pedal edema, hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25 mg once daily, and down titration of the DA was started with a goal of a 50% reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further reductions of the DA were allowed if the AEs were not resolved. RESULTS: The addition of ODS allowed a reduction in the mean daily dose of pramipexole from 2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73% with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n = 25). Mean activities of daily living and motor scores from the Unified Parkinson's Disease Rating Scale as well as quality-of-life scores were significantly improved without an increase in daily "off" time. The most common AEs, most of which resolved after titration, were worsening of PD, nausea/vomiting, dyskinesia, increased off time, body aches, insomnia, orthostatic hypotension, and increased anxiety and depression. CONCLUSIONS: In most subjects, the addition of ODS with decreasing dosages of DAs substantially reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.

25 Clinical Trial An open-label conversion study of pramipexole to ropinirole prolonged release in Parkinson's disease. 2009

Lyons, Kelly E / Pahwa, Rajesh. ·Department of Neurology, Parkinson's Disease and Movement Disorder Center, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. lyons.kelly@att.net ·Mov Disord · Pubmed #19768728.

ABSTRACT: Ropinirole prolonged release (PR) is a once daily oral dopamine agonist approved for the treatment of Parkinson's disease (PD). The goal of this 4 week, open-label study was to determine the most effective conversion ratio with the fewest adverse effects (AEs) when switching from pramipexole to ropinirole PR. Sixty patients with PD taking pramipexole were converted overnight to ropinirole PR at ratios of 1:3, 1:4, or 1:5 such that 20 consecutive subjects were enrolled in each group. Ropinirole PR dose adjustments were allowed to maintain efficacy or to reduce AEs. An overnight switch from pramipexole to ropinirole PR was found to be well tolerated and AEs were typical for a dopamine agonist. The most common AEs were worsening of PD symptoms, dizziness, somnolence, and nausea, the majority of which resolved after dose adjustments. Thirteen subjects discontinued ropinirole PR before 4 weeks. These subjects were taking a significantly greater dose of pramipexole, the majority greater than 4 mg/day, and tended to have longer disease durations. A conversion ratio of 1 mg of pramipexole to 4 mg of ropinirole PR resulted in the fewest discontinuations of ropinirole PR, the fewest dose adjustments and the largest percentage of subjects that preferred ropinirole PR.

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