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Parkinson Disease: HELP
Articles from University of Florida
Based on 333 articles published since 2008
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These are the 333 published articles about Parkinson Disease that originated from University of Florida during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14
1 Guideline Consensus-based clinical practice recommendations for the examination and management of falls in patients with Parkinson's disease. 2014

van der Marck, Marjolein A / Klok, Margit Ph C / Okun, Michael S / Giladi, Nir / Munneke, Marten / Bloem, Bastiaan R / Anonymous4170783. ·Radboud university medical center, Nijmegen Centre for Evidence Based Practice, Department of Neurology, Nijmegen, The Netherlands. · University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. · Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · Radboud university medical center, Nijmegen Centre for Evidence Based Practice, Department of Neurology, Nijmegen, The Netherlands; Radboud university medical center, Nijmegen Centre for Evidence Based Practice, Scientific Institute for Quality of Healthcare, Nijmegen, The Netherlands. · Radboud university medical center, Donders Institute for Brain, Cognition and Behavior, Department of Neurology, Nijmegen, The Netherlands. Electronic address: Bas.Bloem@radboudumc.nl. ·Parkinsonism Relat Disord · Pubmed #24484618.

ABSTRACT: Falls in Parkinson's disease (PD) are common and frequently devastating. Falls prevention is an urgent priority, but there is no accepted program that specifically addresses the risk profile in PD. Therefore, we aimed to provide consensus-based clinical practice recommendations that systematically address potential fall risk factors in PD. We developed an overview of both generic (age-related) and PD-specific factors. For each factor, we specified: best method of ascertainment; disciplines that should be involved in assessment and treatment; and which interventions could be engaged. Using a web-based tool, we asked 27 clinically active professionals from multiple relevant disciplines to evaluate this overview. The revised version was subsequently reviewed by 12 experts. Risk factors and their associated interventions were included in the final set of recommendations when at least 66% of reviewing experts agreed. These recommendations included 31 risk factors. Nearly all required a multidisciplinary team approach, usually involving a neurologist and PD-nurse specialist. Finally, the expert panel proposed to first identify the specific fall type and to tailor screening and treatment accordingly. A routine evaluation of all risk factors remains reserved for high-risk patients without prior falls, or for patients with seemingly unexplained falls. In conclusion, this project produced a set of consensus-based clinical practice recommendations for the examination and management of falls in PD. These may be used in two ways: for pragmatic use in current clinical practice, pending further evidence; and as the active intervention in clinical trials, aiming to evaluate the effectiveness and cost-effectiveness of large scale implementation.

2 Editorial What Would Dr. James Parkinson Think Today? Tau and Other Imaging Possibilities in Parkinson's Disease. 2017

Vaillancourt, David E. ·Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, USA. · Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA. ·Mov Disord · Pubmed #28597559.

ABSTRACT: -- No abstract --

3 Editorial Update on Parkinson's Disease. 2017

Hess, Christopher W / Okun, Michael S. ·Department of Neurology, University of Florida, Center for Movement Disorders and Neurorestoration, Gainesville, Florida. ·Semin Neurol · Pubmed #28511250.

ABSTRACT: -- No abstract --

4 Editorial Neural computation for rehabilitation. 2014

Hu, Xiaoling / Wang, Yiwen / Zhao, Ting / Gunduz, Aysegul. ·Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. · Qiushi Academy for Advanced Studies, Zhejiang University, Zhejiang 310027, China. · Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. · J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA. ·Biomed Res Int · Pubmed #25610868.

ABSTRACT: -- No abstract --

5 Review Subthalamic deep brain stimulation and levodopa in Parkinson's disease: a meta-analysis of combined effects. 2019

Vizcarra, Joaquin A / Situ-Kcomt, Miguel / Artusi, Carlo Alberto / Duker, Andrew P / Lopiano, Leonardo / Okun, Michael S / Espay, Alberto J / Merola, Aristide. ·Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, 260 Stetson St, Suite 2300, Cincinnati, OH, 45267-0525, USA. · Department of Neurology, University of Cincinnati, Cincinnati, OH, USA. · Department of Neuroscience "Rita Levi Montalcini", University of Turin, via Cherasco 15, 10126, Turin, Italy. · Department of Neurology, Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, Gainesville, FL, USA. · Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, 260 Stetson St, Suite 2300, Cincinnati, OH, 45267-0525, USA. merolaae@ucmail.uc.edu. ·J Neurol · Pubmed #29909467.

ABSTRACT: INTRODUCTION: While subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa improve motor symptoms in Parkinson disease (PD) to a similar magnitude, their combined effect remains unclear. We sought to evaluate whether STN-DBS and levodopa yield differential effects on motor outcomes, dyskinesia, and activities of daily living (ADL) when combined compared to when administered alone. METHODS: We conducted a meta-analysis of all studies reporting motor, dyskinesia, and ADL outcomes after bilateral STN-DBS in PD with presurgical Unified Parkinson's Disease Rating Scale (UPDRS-III) in Medication-OFF and Medication-ON states and postsurgical assessments in four conditions: Stimulation-ON/Medication-ON, Stimulation-ON/Medication-OFF, Stimulation-OFF/Medication-ON, and Stimulation-OFF/Medication-OFF. Dyskinesia duration (UPDRS item 32) and ADL (UPDRS-II) were compared between high and low postsurgical levodopa equivalent daily dose (LEDD) reduction. Random-effects meta-analyses using generic-inverse variance were conducted. Confidence in outcomes effect sizes was assessed. RESULTS: Twelve studies were included (n = 401 patients). Stimulation-ON/Medication-ON was associated with an UPDRS-III improvement of - 35.7 points [95% confidence interval, - 40.4, - 31.0] compared with Stimulation-OFF/Medication-OFF, - 11.2 points [- 14.0, - 8.4] compared with Stimulation-OFF/Medication-ON, and - 9.5 points [- 11.0, - 8.0] compared to Stimulation-ON/Medication-OFF within 5 years. The difference was maintained beyond 5 years by - 28.6 [- 32.8, - 24.4], - 8.1 [- 10.2, - 5.9], and - 8.0 [- 10.3, - 5.6], respectively. No difference was observed between Stimulation-ON/Medication-OFF and Stimulation-OFF/Medication-ON within and beyond 5 years. Dyskinesia duration and ADL outcomes were similar in high vs. low postsurgical LEDD reduction. CONCLUSION: Subthalamic nucleus deep brain stimulation and levodopa independently lessened motor severity in PD to a similar magnitude, but their combined effect was greater than either treatment alone, suggesting therapeutic synergism.

6 Review The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson's Disease. 2018

Mackie, Phillip / Lebowitz, Joe / Saadatpour, Leila / Nickoloff, Emily / Gaskill, Peter / Khoshbouei, Habibeh. ·University of Florida College of Medicine, Department of Neuroscience, Gainesville, FL 32611, United States. · Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States. · University of Florida College of Medicine, Department of Neuroscience, Gainesville, FL 32611, United States. Electronic address: Habibeh@ufl.edu. ·Brain Behav Immun · Pubmed #29551693.

ABSTRACT: The second-most common neurodegenerative disease, Parkinson's Disease (PD) has three hallmarks: dysfunctional dopamine transmission due, at least in part, to dopamine neuron degeneration; intracellular inclusions of α-synuclein aggregates; and neuroinflammation. The origin and interplay of these features remains a puzzle, as does the underlying mechanism of PD pathogenesis and progression. When viewed in the context of neuroimmunology, dopamine also plays a role in regulating peripheral immune cells. Intriguingly, plasma dopamine levels are altered in PD, suggesting collateral dysregulation of peripheral dopamine transmission. The dopamine transporter (DAT), the main regulator of dopaminergic tone in the CNS, is known to exist in lymphocytes and monocytes/macrophages, but little is known about peripheral DAT biology or how DAT regulates the dopaminergic tone, much less how peripheral DAT alters immune function. Our review is guided by the hypothesis that dysfunctional peripheral dopamine signaling might be linked to the dysfunctional immune responses in PD and thereby suggests a potential bidirectional communication between central and peripheral dopamine systems. This review seeks to foster new perspectives concerning PD pathogenesis and progression.

7 Review Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review. 2018

Thevathasan, Wesley / Debu, Bettina / Aziz, Tipu / Bloem, Bastiaan R / Blahak, Christian / Butson, Christopher / Czernecki, Virginie / Foltynie, Thomas / Fraix, Valerie / Grabli, David / Joint, Carole / Lozano, Andres M / Okun, Michael S / Ostrem, Jill / Pavese, Nicola / Schrader, Christoph / Tai, Chun-Hwei / Krauss, Joachim K / Moro, Elena / Anonymous621156. ·Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia and the Bionics Institute of Australia, Melbourne, Australia. · Movement Disorders Center, Division of Neurology, Centre Hospitalier Universitaire (CHU) Grenoble, Grenoble Alpes University, Grenoble, France. · Department of Neurosurgery, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. · Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Heidelberg, Germany. · Department of Bioengineering, Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, USA. · Department of Neurology, Institut de Cerveau et de la Moelle épinière, Sorbonne Universités, University Pierre-and-Marie-Curie (UPMC) Université, Paris, France. · Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, United Kingdom. · Department of Neurology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtière University Hospital, Paris, France. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders, Gainesville, Florida, USA. · Department of Neurology, UCSF Movement Disorder and Neuromodulation Center, University of California, San Francisco, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Clinical Medicine, Centre for Functionally Integrative Neuroscience, University of Aarhus, Aarhus, Denmark. · Department of Neurology, Hannover Medical School, Hannover, Germany. · Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. · Department of Neurosurgery, Hannover Medical School, Hannover, Germany. ·Mov Disord · Pubmed #28960543.

ABSTRACT: Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

8 Review Recognizing Atypical Parkinsonisms: "Red Flags" and Therapeutic Approaches. 2017

McFarland, Nikolaus R / Hess, Christopher W. ·Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida College of Medicine, Gainesville, Florida. ·Semin Neurol · Pubmed #28511262.

ABSTRACT: The overlap of signs and symptoms between Parkinson's disease and the atypical parkinsonian syndromes, such as progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome and dementia with Lewy bodies, can render clinical diagnoses challenging. The continued evolution of diagnostic criteria to reflect the increasingly recognized heterogeneous presentations of these diseases further complicates timely recognition and diagnosis. In this review, we provide a diagnostic approach to the classic atypical parkinsonian syndromes, with an emphasis on the key clinical and pathological features of each and the recognition of “red flags” in the setting of recent advances in diagnosis and treatment.

9 Review Current Practice and the Future of Deep Brain Stimulation Therapy in Parkinson's Disease. 2017

Almeida, Leonardo / Deeb, Wissam / Spears, Chauncey / Opri, Enrico / Molina, Rene / Martinez-Ramirez, Daniel / Gunduz, Aysegul / Hess, Christopher W / Okun, Michael S. ·Department of Neurology, University of Florida, Center for Movement Disorders and Neurorestoration, Gainesville, Florida. · Biomedical Engineering, University of Florida, Gainesville, Florida. ·Semin Neurol · Pubmed #28511261.

ABSTRACT: Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease patients experiencing motor fluctuations, medication-resistant tremor, and/or dyskinesia. Currently, the subthalamic nucleus and the globus pallidus internus are the two most widely used targets, with individual advantages and disadvantages influencing patient selection. Potential DBS patients are selected using the few existing guidelines and the available DBS literature, and many centers employ an interdisciplinary team review of the individual's risk-benefit profile. Programmed settings vary based on institution- or physician-specific protocols designed to maximize benefits and limit adverse effects. Expectations should be realistic and clearly defined during the evaluation process, and each bothersome symptom should be addressed in the context of building the risk-benefit profile. Current DBS research is focused on improved symptom control, the development of newer technologies, and the improved efficiency of stimulation delivery. Techniques deliver stimulation in a more personalized way, and methods of adaptive DBS such as closed-loop approaches are already on the horizon.

10 Review Botulinum Toxin Therapy for Parkinson's Disease. 2017

Wagle Shukla, Aparna / Malaty, Irene A. ·Department of Neurology, University of Florida, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, Florida. ·Semin Neurol · Pubmed #28511260.

ABSTRACT: Botulinum toxin (BoNT) therapy is frequently employed in the treatment of Parkinson's disease (PD) symptoms. It can effectively ameliorate the symptoms of cervical dystonia, blepharospasm, sialorrhea, and hyperactive bladder. It is increasingly being used for additional PD-related indications including limb dystonia, oromandibular dystonia, tremors, constipation, dysphagia, gastroparesis, and sweating dysfunction. Botulinum toxin treatment has mostly local side effects and does not interfere with dopaminergic therapies prescribed for PD. With the exception of dystonia and sialorrhea, most evidence for BoNT efficacy is derived from studies conducted in nonparkinsonian populations. Thus, the data to inform typical response pattern and side-effect profile in PD are still evolving. Nevertheless, BoNT is widely used and is an important tool in the PD-treatment arsenal. In this review, the authors discuss the current literature on the use of BoNT in various PD-related motor and nonmotor disorders.

11 Review Motor Complications of Dopaminergic Medications in Parkinson's Disease. 2017

Freitas, Maria Eliza / Hess, Christopher W / Fox, Susan H. ·Division of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida. ·Semin Neurol · Pubmed #28511255.

ABSTRACT: Motor complications are a consequence of the chronic treatment of Parkinson's disease (PD) and include motor fluctuations (wearing-off phenomenon) and levodopa-induced dyskinesia. Both can have a significant impact on functionality and quality of life; thus, proper recognition and management is essential. The phenomenology and temporal relationship of motor complications to the schedule of levodopa dosing can be helpful in characterizing them. There are several therapeutic approaches to motor complications, including pharmacological and surgical options. The authors summarize the different types of motor complications according to phenomenology and the currently available medical treatments, including ongoing trials for the management of this condition.

12 Review The Phenomenology of Parkinson's Disease. 2017

Hess, Christopher W / Hallett, Mark. ·Department of Neurology, University of Florida, Center for Movement Disorders and Neurorestoration, Gainesville, Florida. · Human Motor Control Section, Medical Neurology Branch, NINDS, NIH, Bethesda, Maryland. ·Semin Neurol · Pubmed #28511251.

ABSTRACT: The motor symptoms of Parkinson's disease are not limited to the cardinal symptoms of bradykinesia, rigidity, and resting tremor, but also include a variety of interrelated motor phenomena such as deficits in spatiotemporal planning and movement sequencing, scaling and timing of movements, and intermuscular coordination that can be clinically observed. Although many of these phenomena overlap, a review of the full breadth of the motor phenomenon can aid in the diagnosis and monitoring of disease progression.

13 Review Shaking Up the Debate: Ensuring the Ethical Use of DBS Intervention Criteria for Mid-Stage Parkinson's Patients. 2017

Eijkholt, Marleen / Cabrera, Laura Y / Ramirez-Zamora, Adolfo / Pilitsis, Julie G. ·Center for Ethics & Humanities in the Life Sciences, Michigan State University, Grand Rapids, MI, USA. · Center for Ethics & Humanities in the Life Sciences, Michigan State University, East Lansing, MI, USA. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA. · Department of Neuroscience and Experimental Therapeutics, Albany Medical Center, Albany, NY, USA. ·Neuromodulation · Pubmed #28497554.

ABSTRACT: OBJECTIVES: Deep brain stimulation (DBS) is a well-established treatment for the management of severe motor fluctuations in advanced Parkinson's disease (PD). Until recently, device regulation, medical, and insurance practices limited DBS to patients with advanced stages of PD. In February 2016 this changed, however, when the US Food and Drug Administration (FDA) granted formal approval for the use of brain stimulator in mid-stage PD patients. In this article, we examine whether DBS in mid-stage PD can be ethically justified beyond the FDA approval. MATERIALS AND METHODS: We scrutinize the current risk-benefit profile, the costs-benefit profile, and the capacity for informed consent requirement, to ask if use of subthalamic nucleus (STN) in mid-stage DBS is ethically appropriate. RESULTS: We propose that mid-stage DBS decisions could be appropriate under a shared decision-making model, which embraces a broad quality of life perspective. CONCLUSION: Although it might be too premature to know how the FDA decision will affect medical and insurance practices, we conclude by arguing that revisions to persisting guidelines seems justified both on scientific and ethical grounds.

14 Review Variable frequency stimulation of subthalamic nucleus in Parkinson's disease: Rationale and hypothesis. 2017

Jia, Fumin / Hu, Wei / Zhang, Jianguo / Wagle Shukla, Aparna / Almeida, Leonardo / Meng, Fan-Gang / Okun, Michael S / Li, Luming. ·National Engineering Laboratory for Neuromodulation, Tsinghua University, Beijing, China. · University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. · Beijing Tian Tan Hospital, Capital Medical University, Beijing, China. · Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. · University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. Electronic address: Okun@neurology.ufl.edu. · National Engineering Laboratory for Neuromodulation, Tsinghua University, Beijing, China; Precision Medicine & Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute, Shenzhen, China; Man-machine-environment Engineering Institute, School of Aerospace Engineering, Tsinghua University, Beijing, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China. Electronic address: lilm@tsinghua.edu.cn. ·Parkinsonism Relat Disord · Pubmed #28392298.

ABSTRACT: -- No abstract --

15 Review Preclinical and Potential Applications of Common Western Herbal Supplements as Complementary Treatment in Parkinson's Disease. 2017

Morgan, Luke A / Grundmann, Oliver. ·a Department of Medicinal Chemistry , College of Pharmacy, University of Florida , Gainesville , FL , USA. ·J Diet Suppl · Pubmed #28095073.

ABSTRACT: Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system. The complementary use of green tea (Camellia sinensis), red wine (Vitis vinifera), arctic root (Rhodiola rosea), and dwarf periwinkle (Vinca minor) may have a greater therapeutic effect than current pharmaceutical drugs, such as monoamine oxidase inhibitors or dopamine agonists alone. The bioactive components of these plants have been shown to have neuroprotective, antioxidant, anti-proteinopathies, neural-vasodilation, anti-inflammatory, and iron chelating potential. They may treat the disease at the cellular level by decreasing microglia activation, attenuating damage from radical oxygen species, supporting correct protein folding, chelating iron, increasing the substantia nigra blood flow, and promoting dopaminergic cell growth. Although these alternative medicines appear to have potential, further human clinical trials need to be conducted to determine whether they could have a greater therapeutic effect than conventional medicines alone.

16 Review Parkinson's disease psychosis: therapy tips and the importance of communication between neurologists and psychiatrists. 2016

Martinez-Ramirez, Daniel / Okun, Michael S / Jaffee, Michael S. ·Department of Neurology, University of Florida College of Medicine, Center for Movement Disorders & Neurorestoration, Gainesville, FL 32607, USA. ·Neurodegener Dis Manag · Pubmed #27408981.

ABSTRACT: Parkinson's disease (PD) is a chronic and complex neurodegenerative disorder resulting in a mixture of motor and nonmotor symptoms. Psychosis develops in around 60% of PD patients during and can be one of the most challenging nonmotor symptoms. PD psychosis is considered the single greatest precipitant for nursing home placement. PD psychosis is an independent predictor of increased mortality, and there is no 'ideal' or universal treatment strategy. The treatment approach to PD psychosis should be tailored and individualized for each patient. In this review, we will discuss PD psychosis and provide practical treatment considerations for neurologists, psychiatrists and other healthcare professionals. We stress the importance of real-time communication between members of the healthcare team.

17 Review Deep brain stimulation improves gait velocity in Parkinson's disease: a systematic review and meta-analysis. 2016

Roper, Jaimie A / Kang, Nyeonju / Ben, Juliana / Cauraugh, James H / Okun, Michael S / Hass, Chris J. ·Department of Applied Physiology and Kinesiology, University of Florida, 100 Florida Gym, PO Box 118205, Gainesville, FL, 32611-8205, USA. jaimier@ufl.edu. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, USA. jaimier@ufl.edu. · Department of Applied Physiology and Kinesiology, University of Florida, 100 Florida Gym, PO Box 118205, Gainesville, FL, 32611-8205, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, USA. · Department of Neurology, University of Florida, Gainesville, USA. · Department of Neurosurgery, University of Florida, Gainesville, USA. ·J Neurol · Pubmed #27126451.

ABSTRACT: In Parkinson's disease (PD), slow gait speed is significantly related to clinical ratings of disease severity, impaired performance of daily activities, as well as increased overall disability. Conducting a meta-analysis on gait speed is an objective and quantitative technique to summarize the effectiveness of DBS and to determine the effect sizes for future studies. We conducted a systematic review and meta-analysis that analyzed the effects of deep brain stimulation (DBS) surgery on gait speed in patients with PD to gain fundamental insight into the nature of therapeutic effectiveness. A random effects model meta-analysis on 27 studies revealed a significant overall standardized mean difference medium effect size equal to 0.60 (SE = 0.06; p < 0.0001; Z = 10.58). Based on our synthesis of the 27 studies, we determined the following: (1) a significant and medium effect size indicating DBS improves gait speed; (2) DBS improved gait speed regardless of whether the patients were tested in the on or off medication state; (3) both bilateral and unilateral DBS led to gait speed improvement; (4) the effects of DBS on gait speed in the data collection sessions after surgery (DBS on vs. off) were comparable with data collection before surgery (before surgery vs. DBS after surgery); and (5) when evaluating the effects of DBS and medication on gait speed suprathreshold doses were comparable to normal dosages of medication and DBS. The current analysis provides objective evidence that both unilateral and bilateral DBS provide a therapeutic benefit on gait speed in persons with PD.

18 Review Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects. 2016

Mestre, Tiago A / Lang, Anthony E / Okun, Michael S. ·Parkinson's Disease and Movement Disorders Clinic, Division of Neurology, Department of Medicine, University of Ottawa, The Ottawa Hospital Research Institute, Ottawa, Canada. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida Health, Gainesville, Florida, USA. ·Mov Disord · Pubmed #26952118.

ABSTRACT: Deep brain stimulation (DBS) is a well-established treatment option for movement disorders, especially for Parkinson's disease (PD). There is a need to determine the role of expectation of benefit and the use of placebo to better understand the effects of electrode placement including the (micro)lesion effect. These factors must be understood to better interpret and attribute the therapeutic value of DBS. In this review, we critically present currently available data on the placebo, nocebo, lessebo, and lesion effects in the context of DBS. We provide a discussion of strategies that have the potential for controlling these effects in the setting of future DBS trials. We conclude that there is a need to standardize definitions for nocebo and (micro)lesion effects and that there are intrinsic limitations in defining the effect of expectation of benefit in DBS. These issues will be challenging to overcome especially with current technology and available study designs. New stimulation paradigms, better study designs, and the use of adaptive closed-loop DBS devices may facilitate a more accurate assessment of the placebo, nocebo, and lessebo effects in future DBS trials.

19 Review Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies. 2016

Uchihara, Toshiki / Giasson, Benoit I. ·Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. uchihara-ts@igakuken.or.jp. · Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKinght Brain Institute, University of Florida, 1275 Center Drive, PO Box 100159, Gainesville, FL, 32610-0159, USA. bgiasson@ufl.edu. ·Acta Neuropathol · Pubmed #26446103.

ABSTRACT: Progressive aggregation of alpha-synuclein (αS) through formation of amorphous pale bodies to mature Lewy bodies or in neuronal processes as Lewy neurites may be the consequence of conformational protein changes and accumulations, which structurally represents "molecular template". Focal initiation and subsequent spread along anatomically connected structures embody "structural template". To investigate the hypothesis that both processes might be closely associated and involved in the progression of αS pathology, which can be observed in human brains, αS amyloidogenic precursors termed "seeds" were experimentally injected into the brain or peripheral nervous system of animals. Although these studies showed that αS amyloidogenic seeds can induce αS pathology, which can spread in the nervous system, the findings are still not unequivocal in demonstrating predominant transsynaptic or intraneuronal spreads either in anterograde or retrograde directions. Interpretation of some of these studies is further complicated by other concurrent aberrant processes including neuroimmune activation, injury responses and/or general perturbation of proteostasis. In human brain, αS deposition and neuronal degeneration are accentuated in distal axon/synapse. Hyperbranching of axons is an anatomical commonality of Lewy-prone systems, providing a structural basis for abundance in distal axons and synaptic terminals. This neuroanatomical feature also can contribute to such distal accentuation of vulnerability in neuronal demise and the formation of αS inclusion pathology. Although retrograde progression of αS aggregation in hyperbranching axons may be a consistent feature of Lewy pathology, the regional distribution and gradient of Lewy pathology are not necessarily compatible with a predictable pattern such as upward progression from lower brainstem to cerebral cortex. Furthermore, "focal Lewy body disease" with the specific isolated involvement of autonomic, olfactory or cardiac systems suggests that spread of αS pathology is not always consistent. In many instances, the regional variability of Lewy pathology in human brain cannot be explained by a unified hypothesis such as transsynaptic spread. Thus, the distribution of Lewy pathology in human brain may be better explained by variable combinations of independent focal Lewy pathology to generate "multifocal Lewy body disease" that could be coupled with selective but variable neuroanatomical spread of αS pathology. More flexible models are warranted to take into account the relative propensity to develop Lewy pathology in different Lewy-prone systems, even without interconnections, compatible with the expanding clinicopathological spectra of Lewy-related disorders. These revised models are useful to better understand the mechanisms underlying the variable progression of Lewy body diseases so that diagnostic and therapeutic strategies are improved.

20 Review Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Parkinson Disease: A Meta-Analysis. 2016

Wagle Shukla, Aparna / Shuster, Jonathan J / Chung, Jae Woo / Vaillancourt, David E / Patten, Carolynn / Ostrem, Jill / Okun, Michael S. ·Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, 3450 Hull Road, Gainesville, FL 32607(∗). Electronic address: aparna.shukla@neurology.ufl.edu. · Department of Health Outcomes and Policy, Clinical and Translational Science Institute, University of Florida, Gainesville, FL(†). · Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL(‡). · Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL(§). · Brain Rehabilitation Research Center of Excellence and Department of Physical Therapy, University of Florida, Gainesville, FL(‖). · Department of Neurology and Surgical Movement Disorders, University of California, San Francisco, CA(¶). · Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL(#). ·PM R · Pubmed #26314233.

ABSTRACT: OBJECTIVE: Several studies have reported repetitive transcranial magnetic stimulation (rTMS) therapy as an effective treatment for the control of motor symptoms in Parkinson disease. The objective of the study is to quantify the overall efficacy of this treatment. TYPES: Systematic review and meta-analysis. LITERATURE SURVEY: We reviewed the literature on clinical rTMS trials in Parkinson disease since the technique was introduced in 1980. We used the following databases: MEDLINE, Web of Science, Cochrane, and CINAHL. PATIENTS AND SETTING: Patients with Parkinson disease who were participating in prospective clinical trials that included an active arm and a control arm and change in motor scores on Unified Parkinson's Disease Rating Scale as the primary outcome. We pooled data from 21 studies that met these criteria. We then analyzed separately the effects of low- and high-frequency rTMS on clinical motor improvements. SYNTHESIS: The overall pooled mean difference between treatment and control groups in the Unified Parkinson's Disease Rating Scale motor score was significant (4.0 points, 95% confidence interval, 1.5, 6.7; P = .005). rTMS therapy was effective when low-frequency stimulation (≤ 1 Hz) was used with a pooled mean difference of 3.3 points (95% confidence interval 1.6, 5.0; P = .005). There was a trend for significance when high-frequency stimulation (≥ 5 Hz) studies were evaluated with a pooled mean difference of 3.9 points (95% confidence interval, -0.7, 8.5; P = .08). rTMS therapy demonstrated benefits at short-term follow-up (immediately after a treatment protocol) with a pooled mean difference of 3.4 points (95% confidence interval, 0.3, 6.6; P = .03) as well as at long-term follow-up (average follow-up 6 weeks) with mean difference of 4.1 points (95% confidence interval, -0.15, 8.4; P = .05). There were insufficient data to statistically analyze the effects of rTMS when we specifically examined bradykinesia, gait, and levodopa-induced dyskinesia using quantitative methods. CONCLUSION: rTMS therapy in patients with Parkinson disease results in mild-to-moderate motor improvements and has the potential to be used as an adjunct therapy for the treatment of Parkinson disease. Future large, sample studies should be designed to isolate the specific clinical features of Parkinson disease that respond well to rTMS therapy.

21 Review The Subthalamic Nucleus, Limbic Function, and Impulse Control. 2015

Rossi, P Justin / Gunduz, Aysegul / Okun, Michael S. ·Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA. pjrossi@ufl.edu. · Department of Neurology, University of Florida College of Medicine, HSC Box 100236, Gainesville, FL, 32610-0236, USA. pjrossi@ufl.edu. · J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA. ·Neuropsychol Rev · Pubmed #26577509.

ABSTRACT: It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.

22 Review The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson's disease. 2015

Barboza, Jose L / Okun, Michael S / Moshiree, Baharak. ·a 1 University of South Florida , Tampa, FL, USA. · b 2 University of Florida, Center for Movement Disorders and Neurorestoration , Gainesville, FL, UK. · c 3 University of Miami , Miami, FL, USA +1 30 5243 2515 , bmoshiree@med.miami.edu. ·Expert Opin Pharmacother · Pubmed #26374094.

ABSTRACT: INTRODUCTION: Parkinson's disease (PD) affects the nerves of the entire gastrointestinal (GI) tract and may result in profound gastrointestinal (GI) dysfunction leading to poor patient outcomes. Common GI disturbances in patients with PD include gastroparesis (GP), constipation and small intestinal bacterial overgrowth syndrome (SIBO). In particular, GP is difficult to treat due to the limited options available and precautions, contraindications and adverse effects associated with the approved treatments. Moreover, some commonly used medications can worsen pre-existing PD. AREAS COVERED: Our review will focus on treatment options for GP and SIBO with motilin agonists, dopamine receptor antagonists, Ghrelin agonists muscarinic agonists, 5-HT4 receptor agonists, antibiotics, probiotics and herbal formulation such as iberogast. Constipation occurs in the majority of patients with PD and fortunately many treatments are now available. Our review is based on original papers or reviews selected from PUBMED search and Cochrane reviews. EXPERT OPINION: Motility disorders of the GI tract are found frequently in patients with PD and treating the underlying GI disorders caused by PD with various prokinetics and laxatives is paramount in achieving improvements in patient's motor function. Various prokinetics and laxatives are now available to provide some relief of the GI morbidity caused by PD leading even to better absorption of even the PD treatments.

23 Review Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline. 2015

Gunduz, Aysegul / Morita, Hokuto / Rossi, P Justin / Allen, William L / Alterman, Ron L / Bronte-Stewart, Helen / Butson, Christopher R / Charles, David / Deckers, Sjaak / de Hemptinne, Coralie / DeLong, Mahlon / Dougherty, Darin / Ellrich, Jens / Foote, Kelly D / Giordano, James / Goodman, Wayne / Greenberg, Benjamin D / Greene, David / Gross, Robert / Judy, Jack W / Karst, Edward / Kent, Alexander / Kopell, Brian / Lang, Anthony / Lozano, Andres / Lungu, Codrin / Lyons, Kelly E / Machado, Andre / Martens, Hubert / McIntyre, Cameron / Min, Hoon-Ki / Neimat, Joseph / Ostrem, Jill / Pannu, Sat / Ponce, Francisco / Pouratian, Nader / Reymers, Donnie / Schrock, Lauren / Sheth, Sameer / Shih, Ludy / Stanslaski, Scott / Steinke, G Karl / Stypulkowski, Paul / Tröster, Alexander I / Verhagen, Leo / Walker, Harrison / Okun, Michael S. ·University of Florida , Gainesville, FL , USA. ·Int J Neurosci · Pubmed #25526555.

ABSTRACT: The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

24 Review Functional outcomes associated with expiratory muscle strength training: narrative review. 2014

Laciuga, Helena / Rosenbek, John C / Davenport, Paul W / Sapienza, Christine M. ·336 Dauer Hall, University of Florida, Gainesville, FL 32611. hlaciuga@ufl.edu. ·J Rehabil Res Dev · Pubmed #25144167.

ABSTRACT: This review presents the available evidence for the effects of expiratory muscle strength training (EMST) with the use of a pressure threshold device. The investigators used computerized database searches for studies reporting the outcomes of pressure threshold EMST published after 1994. A total of 24 selected articles presented outcomes related but not limited to respiratory function, such as speech, swallow, voice, and cough function in persons with neurologic conditions such as Parkinson disease, multiple sclerosis, and Lance-Adams syndrome; in persons with respiratory diseases, such as chronic obstructive pulmonary disease; and in healthy young adults and sedentary and active elderly. Several studies demonstrated promising outcomes of EMST as a non-task-specific training for airway protection in persons with dysphagia secondary to neuromuscular impairments; however, further research is needed to confirm and generalize the reported findings.

25 Review Treatment of advanced Parkinson's disease. 2014

Giugni, Juan C / Okun, Michael S. ·Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, Florida, USA. ·Curr Opin Neurol · Pubmed #24978634.

ABSTRACT: PURPOSE OF REVIEW: Later stage Parkinson's disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinson's disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinson's disease. RECENT FINDINGS: We will discuss the latest pharmacological strategies (e.g., inhibitors of dopamine-metabolizing enzymes, dopamine agonists, and extended release dopamine formulations) for addressing motor dysfunction. We will summarize the risks and benefits of current invasive treatments. Finally, we will address the current evidence supporting the treatment of nonmotor symptoms in the advanced Parkinson's disease patient. We will conclude by detailing the potential nonpharmacological and multidisciplinary approaches for advanced stage Parkinson's disease. SUMMARY: The optimization of levodopa is, in most cases, the most powerful therapeutic option available; however, medication optimization requires an advanced understanding of Parkinson's disease. Failure of conventional pharmacotherapy should precipitate a discussion of the potential risks and benefits of more invasive treatments. Currently, there are no comparative studies of invasive treatment. Among the invasive treatments, deep brain stimulation has the largest amount of existing evidence, but also has the highest individual per patient risk. Nonmotor symptoms will affect quality of life more than the motor Parkinson's disease symptoms, and these nonmotor symptoms should be aggressively treated. Many advanced Parkinson's disease patients will likely benefit from multi and interdisciplinary Parkinson's disease teams with multiple professionals collaborating to develop a collective and tailored strategy for an individual patient.

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