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Parkinson Disease: HELP
Articles by Dr. M Okun
Based on 232 articles published since 2010
(Why 232 articles?)
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Between 2010 and 2020, M. Okun wrote the following 232 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
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 / Anonymous4210783. ·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 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 --

3 Editorial The emerging field of palliative care for Parkinson's disease. Letter from the guest editors. 2012

Miyasaki, Janis M / Okun, Michael S. · ·Parkinsonism Relat Disord · Pubmed #23206368.

ABSTRACT: -- No abstract --

4 Editorial Personalized medicine in deep brain stimulation through utilization of neural oscillations. 2012

Wagle Shukla, Aparna / Okun, Michael S. · ·Neurology · Pubmed #22592364.

ABSTRACT: -- No abstract --

5 Review Diagnosis and Treatment of Parkinson Disease: A Review. 2020

Armstrong, Melissa J / Okun, Michael S. ·Department of Neurology, University of Florida College of Medicine, Gainesville. · Fixel Institute for Neurologic Diseases, University of Florida, Gainesville. ·JAMA · Pubmed #32044947.

ABSTRACT: Importance: Parkinson disease is the most common form of parkinsonism, a group of neurological disorders with Parkinson disease-like movement problems such as rigidity, slowness, and tremor. More than 6 million individuals worldwide have Parkinson disease. Observations: Diagnosis of Parkinson disease is based on history and examination. History can include prodromal features (eg, rapid eye movement sleep behavior disorder, hyposmia, constipation), characteristic movement difficulty (eg, tremor, stiffness, slowness), and psychological or cognitive problems (eg, cognitive decline, depression, anxiety). Examination typically demonstrates bradykinesia with tremor, rigidity, or both. Dopamine transporter single-photon emission computed tomography can improve the accuracy of diagnosis when the presence of parkinsonism is uncertain. Parkinson disease has multiple disease variants with different prognoses. Individuals with a diffuse malignant subtype (9%-16% of individuals with Parkinson disease) have prominent early motor and nonmotor symptoms, poor response to medication, and faster disease progression. Individuals with mild motor-predominant Parkinson disease (49%-53% of individuals with Parkinson disease) have mild symptoms, a good response to dopaminergic medications (eg, carbidopa-levodopa, dopamine agonists), and slower disease progression. Other individuals have an intermediate subtype. For all patients with Parkinson disease, treatment is symptomatic, focused on improvement in motor (eg, tremor, rigidity, bradykinesia) and nonmotor (eg, constipation, cognition, mood, sleep) signs and symptoms. No disease-modifying pharmacologic treatments are available. Dopamine-based therapies typically help initial motor symptoms. Nonmotor symptoms require nondopaminergic approaches (eg, selective serotonin reuptake inhibitors for psychiatric symptoms, cholinesterase inhibitors for cognition). Rehabilitative therapy and exercise complement pharmacologic treatments. Individuals experiencing complications, such as worsening symptoms and functional impairment when a medication dose wears off ("off periods"), medication-resistant tremor, and dyskinesias, benefit from advanced treatments such as therapy with levodopa-carbidopa enteral suspension or deep brain stimulation. Palliative care is part of Parkinson disease management. Conclusions and Relevance: Parkinson disease is a heterogeneous disease with rapidly and slowly progressive forms. Treatment involves pharmacologic approaches (typically with levodopa preparations prescribed with or without other medications) and nonpharmacologic approaches (such as exercise and physical, occupational, and speech therapies). Approaches such as deep brain stimulation and treatment with levodopa-carbidopa enteral suspension can help individuals with medication-resistant tremor, worsening symptoms when the medication wears off, and dyskinesias.

6 Review A Review of Cognitive Outcomes Across Movement Disorder Patients Undergoing Deep Brain Stimulation. 2019

Cernera, Stephanie / Okun, Michael S / Gunduz, Aysegul. ·J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States. · Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL, United States. ·Front Neurol · Pubmed #31133956.

ABSTRACT:

7 Review Emerging therapies in Parkinson disease - repurposed drugs and new approaches. 2019

Elkouzi, Ahmad / Vedam-Mai, Vinata / Eisinger, Robert S / Okun, Michael S. ·Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA. ahmad.elkouzi@neurology.ufl.edu. · Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA. · Department of Neurosurgery, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA. ·Nat Rev Neurol · Pubmed #30867588.

ABSTRACT: Parkinson disease (PD) treatment options have conventionally focused on dopamine replacement and provision of symptomatic relief. Current treatments cause undesirable adverse effects, and a large unmet clinical need remains for treatments that offer disease modification and that address symptoms resistant to levodopa. Advances in high-throughput drug screening methods for small molecules, developments in disease modelling and improvements in analytical technologies have collectively contributed to the emergence of novel compounds, repurposed drugs and new technologies. In this Review, we focus on disease-modifying and symptomatic therapies under development for PD. We review cellular therapies and repurposed drugs, such as nilotinib, inosine, isradipine, iron chelators and anti-inflammatories, and discuss how their success in preclinical models has paved the way for clinical trials. We provide an update on immunotherapies and vaccines. In addition, we review non-pharmacological interventions targeting motor symptoms, including gene therapy, adaptive deep brain stimulation (DBS) and optogenetically inspired DBS. Given the many clinical phenotypes of PD, individualization of therapy and precision of treatment are likely to become important in the future.

8 Review Medications, Deep Brain Stimulation, and Other Factors Influencing Impulse Control Disorders in Parkinson's Disease. 2019

Eisinger, Robert S / Ramirez-Zamora, Adolfo / Carbunaru, Samuel / Ptak, Brandon / Peng-Chen, Zhongxing / Okun, Michael S / Gunduz, Aysegul. ·Department of Neuroscience, University of Florida, Gainesville, FL, United States. · Hospital Padre Hurtado, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile. · Department of Neurology, Fixel Center for Neurological Diseases, University of Florida, Gainesville, FL, United States. · Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States. ·Front Neurol · Pubmed #30863353.

ABSTRACT: Impulse control disorders (ICDs) in Parkinson's disease (PD) have a high cumulative incidence and negatively impact quality of life. ICDs are influenced by a complex interaction of multiple factors. Although it is now well-recognized that dopaminergic treatments and especially dopamine agonists underpin many ICDs, medications alone are not the sole cause. Susceptibility to ICD is increased in the setting of PD. While causality can be challenging to ascertain, a wide range of modifiable and non-modifiable risk factors have been linked to ICDs. Common characteristics of PD patients with ICDs have been consistently identified across many studies; for example, males with an early age of PD onset and dopamine agonist use have a higher risk of ICD. However, not all cases of ICDs in PD can be directly attributable to dopamine, and studies have concluded that additional factors such as genetics, smoking, and/or depression may be more predictive. Beyond dopamine, other ICD associations have been described but remain difficult to explain, including deep brain stimulation surgery, especially in the setting of a reduction in dopaminergic medication use. In this review, we will summarize the demographic, genetic, behavioral, and clinical contributions potentially influencing ICD onset in PD. These associations may inspire future preventative or therapeutic strategies.

9 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.

10 Review The Emerging Evidence of the Parkinson Pandemic. 2018

Dorsey, E Ray / Sherer, Todd / Okun, Michael S / Bloem, Bastiaan R. ·Department of Neurology and Center for Health+Technology, University of Rochester Medical Center, Rochester, NY, USA. · Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA. · Fixel Center for Neurological Diseases, Program for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville, FL, USA. · Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Neurology, Nijmegen, The Netherlands. ·J Parkinsons Dis · Pubmed #30584159.

ABSTRACT: Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.

11 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 / Anonymous640921. ·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.

12 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.

13 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 --

14 Review Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging. 2016

Hamani, Clement / Lozano, Andres M / Mazzone, Paolo A M / Moro, Elena / Hutchison, William / Silburn, Peter A / Zrinzo, Ludvic / Alam, Mesbah / Goetz, Laurent / Pereira, Erlick / Rughani, Anand / Thevathasan, Wesley / Aziz, Tipu / Bloem, Bastiaan R / Brown, Peter / Chabardes, Stephan / Coyne, Terry / Foote, Kelly / Garcia-Rill, Edgar / Hirsch, Etienne C / Okun, Michael S / Krauss, Joachim K. ·Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ont., Canada. ·Stereotact Funct Neurosurg · Pubmed #27728909.

ABSTRACT: The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss shortcomings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS.

15 Review Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology. 2016

Hamani, Clement / Aziz, Tipu / Bloem, Bastiaan R / Brown, Peter / Chabardes, Stephan / Coyne, Terry / Foote, Kelly / Garcia-Rill, Edgar / Hirsch, Etienne C / Lozano, Andres M / Mazzone, Paolo A M / Okun, Michael S / Hutchison, William / Silburn, Peter / Zrinzo, Ludvic / Alam, Mesbah / Goetz, Laurent / Pereira, Erlick / Rughani, Anand / Thevathasan, Wesley / Moro, Elena / Krauss, Joachim K. ·Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ont., Canada. ·Stereotact Funct Neurosurg · Pubmed #27723662.

ABSTRACT: Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues.

16 Review Diagnosing Parkinson Disease. 2016

Hess, Christopher W / Okun, Michael S. · ·Continuum (Minneap Minn) · Pubmed #27495197.

ABSTRACT: PURPOSE OF REVIEW: While establishing the diagnosis of Parkinson disease (PD) can be straightforward, it can be challenging in some patients, even for the experienced neurologist. The misdiagnosis rate ranges from 10% to 20% or greater depending on clinician experience. RECENT FINDINGS: Despite promise in the search for a biomarker that can establish the presence of PD and act as a marker of its progression, the diagnosis of PD continues to be based on clinical examination. Core criteria, exclusion criteria, and supportive criteria have been developed to aid the clinician in establishing the diagnosis. Nonmotor symptoms of PD are usually present at the time of diagnosis, may precede motor symptoms, and should be specifically sought during evaluation. Ancillary testing can be appropriate, but its indications and utility must be clearly understood. SUMMARY: The diagnosis of PD requires the recognition of the core features of PD and the differentiation of its clinical presentation from other entities with similar and potentially overlapping symptoms. A careful history and examination guided by clinical diagnostic criteria will usually establish the diagnosis of PD or uncover red flags for the possibilities of other diagnoses. Appropriate selection and interpretation of ancillary testing is critical to avoid misdiagnosis and unnecessary tests.

17 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.

18 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.

19 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.

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 Novel targets and stimulation paradigms for deep brain stimulation. 2015

De Jesus, Sol / Almeida, Leonardo / Peng-Chen, Zhongxing / Okun, Michael S / Hess, Christopher W. ·a 1 Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, Florida, USA. ·Expert Rev Neurother · Pubmed #26312646.

ABSTRACT: Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.

24 Review Management of impulse control disorders in Parkinson's disease: Controversies and future approaches. 2015

Samuel, Michael / Rodriguez-Oroz, Maria / Antonini, Angelo / Brotchie, Jonathan M / Ray Chaudhuri, Kallol / Brown, Richard G / Galpern, Wendy R / Nirenberg, Melissa J / Okun, Michael S / Lang, Anthony E. ·Department of Neurology, National Parkinson Foundation International Centre of Excellence, King's College Hospital, King's Health Partners, London, UK. ·Mov Disord · Pubmed #25607799.

ABSTRACT: Impulse control disorders in Parkinson's disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies.

25 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.

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