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Parkinson Disease: HELP
Articles from Utah
Based on 68 articles published since 2008
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These are the 68 published articles about Parkinson Disease that originated from Utah during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Motor learning in people with Parkinson's disease: Implications for fall prevention across the disease spectrum. 2018

Paul, Serene S / Dibble, Leland E / Peterson, Daniel S. ·Faculty of Health Sciences, University of Sydney. 75 East St, Lidcombe NSW 2141, Australia. Electronic address: serene.paul@sydney.edu.au. · Department of Physical Therapy and Athletic Training, University of Utah. 520 Wakara Way, Salt Lake City, UT 84108, USA. Electronic address: lee.dibble@hsc.utah.edu. · School of Nutrition and Health Promotion, Arizona State University. 550 N 3rd St, Phoenix, AZ 85004, USA; Phoenix Department of Veterans Affairs, 215 E Indian School Rd, Phoenix, AZ 85012, USA. Electronic address: Daniel.Peterson1@asu.edu. ·Gait Posture · Pubmed #29413803.

ABSTRACT: BACKGROUND: Falls are a significant burden for people with Parkinson's disease (PD), however, individuals across the spectrum of disease severity respond differently to fall prevention interventions. Despite the multifactorial causes of falls in people with PD, recent work has provided insight into interventions that hold promise for fall prevention. Further, studies have begun to identify patient characteristics that may predict responsiveness to such interventions. RESEARCH QUESTION: We discuss (i) the postural motor learning abilities of people with mild versus severe PD that could affect their ability to benefit from fall prevention interventions, (ii) how people with different severity of PD respond to such interventions, and (iii) the practical considerations of providing effective fall prevention interventions for people with PD across the spectrum of disease severity. METHODS: This narrative review consolidates recent work on postural motor learning and fall prevention rehabilitation involving exercise in people with PD. RESULTS: People with PD are able to improve postural motor control through practice, enabling them to benefit from exercise which challenges their gait and balance to reduce falling. Worsening of axial and cognitive symptoms may result in diminished learning, and those with more severe PD may require fully supervised, high intensity programs to reduce falls. SIGNIFICANCE: Understanding how people with PD across the spectrum of disease severity differ in their postural motor learning ability and response to different fall prevention interventions will enable researchers and clinicians to refine such interventions and their delivery to minimize falls and their negative sequelae in people with PD.

2 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.

3 Review Psychosis in Parkinson Disease: A Review of Etiology, Phenomenology, and Management. 2016

Samudra, Niyatee / Patel, Neepa / Womack, Kyle B / Khemani, Pravin / Chitnis, Shilpa. ·Department of Neurology and Neurotherapeutics, Neurology Clinic, University of Texas Southwestern Medical Center, 5303 Harry Hines Blvd, 4th Floor, Suite 108, Dallas, TX, 75390-8869, USA. · Department of Neurology, Henry Ford Hospital, West Bloomfield, MI, USA. · Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA. · Department of Neurology and Neurotherapeutics, Neurology Clinic, University of Texas Southwestern Medical Center, 5303 Harry Hines Blvd, 4th Floor, Suite 108, Dallas, TX, 75390-8869, USA. Shilpa.chitnis@utsouthwestern.edu. ·Drugs Aging · Pubmed #27830568.

ABSTRACT: Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT

4 Review The crucial impact of lysosomes in aging and longevity. 2016

Carmona-Gutierrez, Didac / Hughes, Adam L / Madeo, Frank / Ruckenstuhl, Christoph. ·Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria. · University of Utah, Department of Biochemistry, Salt Lake City, UT 84112-5650, USA. · Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed, Graz, Austria. · Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria. Electronic address: ru.ruckenstuhl@uni-graz.at. ·Ageing Res Rev · Pubmed #27125853.

ABSTRACT: Lysosomes are the main catabolic organelles of a cell and play a pivotal role in a plethora of cellular processes, including responses to nutrient availability and composition, stress resistance, programmed cell death, plasma membrane repair, development, and cell differentiation. In line with this pleiotropic importance for cellular and organismal life and death, lysosomal dysfunction is associated with many age-related pathologies like Parkinson's and Alzheimer's disease, as well as with a decline in lifespan. Conversely, targeting lysosomal functional capacity is emerging as a means to promote longevity. Here, we analyze the current knowledge on the prominent influence of lysosomes on aging-related processes, such as their executory and regulatory roles during general and selective macroautophagy, or their storage capacity for amino acids and ions. In addition, we review and discuss the roles of lysosomes as active players in the mechanisms underlying known lifespan-extending interventions like, for example, spermidine or rapamycin administration. In conclusion, this review aims at critically examining the nature and pliability of the different layers, in which lysosomes are involved as a control hub for aging and longevity.

5 Review Measurement instruments to assess posture, gait, and balance in Parkinson's disease: Critique and recommendations. 2016

Bloem, Bastiaan R / Marinus, Johan / Almeida, Quincy / Dibble, Lee / Nieuwboer, Alice / Post, Bart / Ruzicka, Evzen / Goetz, Christopher / Stebbins, Glenn / Martinez-Martin, Pablo / Schrag, Anette / Anonymous5310860. ·Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Dept. of Neurology, Nijmegen, The Netherlands. bas.bloem@radboudumc.nl. · Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands. · Sun Life Financial Movement Disorders Research & Rehabilitation Centre; Department of Kinesiology & Physical Education, Wilfrid Laurier University, Waterloo, Ontario, Canada. · University of Utah, Department of Physical Therapy, Salt Lake City, Utah, USA. · KU Leuven, University of Leuven, Department of Rehabilitation Sciences, Leuven, Belgium. · Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Dept. of Neurology, Nijmegen, The Netherlands. · 1st Faculty of Medicine and General University Hospital, Dept. of Neurology and Centre of Clinical Neuroscience, Charles University, Prague, Czech Republic. · Department of Neurological Services, Rush University School of Medicine, Chicago, Illinois, USA. · Alzheimer Center Reina Sofia Foundation and CIBERNED, Carlos III Institute of Health, Madrid, Spain. · UCL Institute of Neurology, University College, London, UK. ·Mov Disord · Pubmed #26945525.

ABSTRACT: BACKGROUND: Disorders of posture, gait, and balance in Parkinson's disease (PD) are common and debilitating. This MDS-commissioned task force assessed clinimetric properties of existing rating scales, questionnaires, and timed tests that assess these features in PD. METHODS: A literature review was conducted. Identified instruments were evaluated systematically and classified as "recommended," "suggested," or "listed." Inclusion of rating scales was restricted to those that could be used readily in clinical research and practice. RESULTS: One rating scale was classified as "recommended" (UPDRS-derived Postural Instability and Gait Difficulty score) and 2 as "suggested" (Tinetti Balance Scale, Rating Scale for Gait Evaluation). Three scales requiring equipment (Berg Balance Scale, Mini-BESTest, Dynamic Gait Index) also fulfilled criteria for "recommended" and 2 for "suggested" (FOG score, Gait and Balance Scale). Four questionnaires were "recommended" (Freezing of Gait Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, Survey of Activities, and Fear of Falling in the Elderly-Modified). Four tests were classified as "recommended" (6-minute and 10-m walk tests, Timed Up-and-Go, Functional Reach). CONCLUSION: We identified several questionnaires that adequately assess freezing of gait and balance confidence in PD and a number of useful clinical tests. However, most clinical rating scales for gait, balance, and posture perform suboptimally or have been evaluated insufficiently. No instrument comprehensively and separately evaluates all relevant PD-specific gait characteristics with good clinimetric properties, and none provides separate balance and gait scores with adequate content validity for PD. We therefore recommend the development of such a PD-specific, easily administered, comprehensive gait and balance scale that separately assesses all relevant constructs. © 2016 International Parkinson and Movement Disorder Society.

6 Review Advances in the laboratory evaluation of peripheral neuropathies. 2012

Huan, Mengjing Chloe / Bromberg, Mark. ·Intermountain Health Care Neurosciences Center, 5171 South Cottonwood Street, #810, Murray, UT 84107, USA. chloe.huan@imail.org ·Curr Neurol Neurosci Rep · Pubmed #22147264.

ABSTRACT: Peripheral neuropathy is a common clinical problem in neurology and laboratory testing is an integral part of diagnosis. In the past few years, practice parameters have been published to establish an evidence-based guide to neuropathy testing. There are many tests that are common and accepted in practice, but there is no clear mandate on which tests are necessary. This article reviews recent practice parameter publications as well as other updates in laboratory testing for peripheral neuropathy, including the roles of lipid profile, genetic testing, antibody titers, and B(12) testing in a specific dopamine-treated Parkinson's patients. These can serve as recommendations to help guide laboratory testing.

7 Review Ubiquitin-dependent mitochondrial protein degradation. 2011

Heo, Jin-Mi / Rutter, Jared. ·Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ·Int J Biochem Cell Biol · Pubmed #21683801.

ABSTRACT: Progressive mitochondrial failure is tightly associated with the onset of many age-related human pathologies. This tight connection results from the double-edged sword of mitochondrial respiration, which is responsible for generating both ATP and ROS, as well as from risks that are inherent to mitochondrial biogenesis. To prevent and treat these diseases, a precise understanding of the mechanisms that maintain functional mitochondria is necessary. Mitochondrial protein quality control is one of the mechanisms that protect mitochondrial integrity, and increasing evidence implicates the cytosolic ubiquitin/proteasome system (UPS) as part of this surveillance network. In this review, we will discuss our current understanding of UPS-dependent mitochondrial protein degradation, its roles in diseases progression, and insights into future studies.

8 Review Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors. 2009

Azam, Layla / McIntosh, J Michael. ·Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. layla.azam@utah.edu ·Acta Pharmacol Sin · Pubmed #19448650.

ABSTRACT: Cysteine-rich peptides from the venom of cone snails (Conus) target a wide variety of different ion channels. One family of conopeptides, the alpha-conotoxins, specifically target different isoforms of nicotinic acetylcholine receptors (nAChRs) found both in the neuromuscular junction and central nervous system. This family is further divided into subfamilies based on the number of amino acids between cysteine residues. The exquisite subtype selectivity of certain alpha-conotoxins has been key to the characterization of native nAChR isoforms involved in modulation of neurotransmitter release, the pathophysiology of Parkinson's disease and nociception. Structure/function characterization of alpha-conotoxins has led to the development of analogs with improved potency and/or subtype selectivity. Cyclization of the backbone structure and addition of lipophilic moieties has led to improved stability and bioavailability of alpha-conotoxins, thus paving the way for orally available therapeutics. The recent advances in phylogeny, exogenomics and molecular modeling promises the discovery of an even greater number of alpha-conotoxins and analogs with improved selectivity for specific subtypes of nAChRs.

9 Review The effects of exercise on balance in persons with Parkinson's disease: a systematic review across the disability spectrum. 2009

Dibble, Leland E / Addison, Odessa / Papa, Evan. ·Department of Physical Therapy, University of Utah, Salt Lake City, Utah, USA. Lee.Dibble@hsc.utah.edu ·J Neurol Phys Ther · Pubmed #19265767.

ABSTRACT: BACKGROUND AND PURPOSE: Parkinson's disease is a progressive neurodegenerative disorder that affects neurophysiologic function, movement abilities, and quality of life (QOL). Research examining the effects of exercise has suggested benefits related to a variety of outcomes; however, no reviews have synthesized research findings across the spectrum of disability. This project sought to systematically review studies that examined the impact of exercise interventions on balance outcomes for people with Parkinson's disease, within the categories defined by the World Health Organization in the International Classification of Functioning, Disability, and Health (ICF) model. METHODS: A systematic review of medical literature databases was performed using keywords Parkinson's disease and exercise. Studies were eligible if the intervention included exercise and examined variables within one of the three ICF categories. Following the ICF model, outcomes regarding Body Structure and Function, Activity, and Participation were measured, respectively, in terms of postural instability, balance task performance, and QOL and fall events. RESULTS: Within the Body Structure and Function category, there was moderate evidence that exercise resulted in improvements in postural instability. Within the Activity category, there was moderate evidence that exercise was effective for improving balance task performance. In contrast, within the Participation category, there was limited evidence that exercise resulted in improvements in QOL measures or fall events. DISCUSSION AND CONCLUSIONS: Regardless of the strength of the evidence, the studies reviewed all report that exercise resulted in improvements in postural stability and balance task performance. Despite these improvements, the number and quality of the studies and the outcomes used were limited. There is a need for longer term follow-up to establish trajectory of change and to determine if any gains are retained long term. The optimal delivery and content of exercise interventions (dosing, component exercises) at different stages of the disease are not clear.

10 Clinical Trial Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension. 2016

Isaacson, Stuart / Vernino, Steven / Ziemann, Adam / Rowse, Gerald J / Kalu, Uwa / White, William B. ·Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA. Electronic address: isaacson@ParkinsonsCenter.org. · Department of Neurology & Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA. · Lundbeck LLC, Deerfield, IL, USA. · Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT 06032, USA. ·J Am Soc Hypertens · Pubmed #27614923.

ABSTRACT: The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use.

11 Clinical Trial Outcomes from switching from rotigotine patch to alternate therapies in Parkinson's disease. 2012

Chitnis, Shilpa / Jaffery, Manall / Dewey, Richard B. ·Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas, USA. shilpa.chitnis@utsouthwestern.edu ·Int J Neurosci · Pubmed #21864207.

ABSTRACT: BACKGROUND: When rotigotine patch was withdrawn from the US market, we prospectively gathered data on efficacy, side effects, and daytime sedation on patients while taking rotigotine and following the switch to alternate therapies. METHODS: Patients rated the efficacy of rotigotine on a scale of 0-5 (ineffective to extremely effective) and completed the Epworth Sleepiness Scale. At a follow-up visit a mean of 3 months later, patients rated their change in efficacy and side effects on a scale of -3 to +3 (much worse to much better) and again completed the Epworth Sleepiness Scale. RESULTS: Thirty-three patients were switched to a single alternate treatment. On rotigotine, the average efficacy score was 3.5, and after switching, the average change in efficacy was -0.67 (worsening). Average change scores for efficacy and adverse effects were 0.25 and 0.38 for levodopa, -0.88 and -0.25 for ropinirole IR, -1.2 and -0.83 for ropinirole XL, -0.80 and 1.0 for pramipexole, and -1.0 and 0.50 for rasagiline, respectively. Average change in Epworth score on each alternate agent was -3.9, -2.3, 1.3, 3.0, and 1. CONCLUSION: Rotigotine was an effective treatment with all groups deteriorating after switch except for the levodopa group. Fifty-eight percent of patients preferred rotigotine versus 36% preferring the alternate treatment.

12 Clinical Trial Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity. 2010

Dorval, Alan D / Kuncel, Alexis M / Birdno, Merrill J / Turner, Dennis A / Grill, Warren M. ·Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA. alan.dorval@utah.edu ·J Neurophysiol · Pubmed #20505125.

ABSTRACT: Deep brain stimulation (DBS) of the basal ganglia can alleviate the motor symptoms of Parkinson's disease although the therapeutic mechanisms are unclear. We hypothesize that DBS relieves symptoms by minimizing pathologically disordered neuronal activity in the basal ganglia. In human participants with parkinsonism and clinically effective deep brain leads, regular (i.e., periodic) high-frequency stimulation was replaced with irregular (i.e., aperiodic) stimulation at the same mean frequency (130 Hz). Bradykinesia, a symptomatic slowness of movement, was quantified via an objective finger tapping protocol in the absence and presence of regular and irregular DBS. Regular DBS relieved bradykinesia more effectively than irregular DBS. A computational model of the relevant neural structures revealed that output from the globus pallidus internus was more disordered and thalamic neurons made more transmission errors in the parkinsonian condition compared with the healthy condition. Clinically therapeutic, regular DBS reduced firing pattern disorder in the computational basal ganglia and minimized model thalamic transmission errors, consistent with symptom alleviation by clinical DBS. However, nontherapeutic, irregular DBS neither reduced disorder in the computational basal ganglia nor lowered model thalamic transmission errors. Thus we show that clinically useful DBS alleviates motor symptoms by regularizing basal ganglia activity and thereby improving thalamic relay fidelity. This work demonstrates that high-frequency stimulation alone is insufficient to alleviate motor symptoms: DBS must be highly regular. Descriptive models of pathophysiology that ignore the fine temporal resolution of neuronal spiking in favor of average neural activity cannot explain the mechanisms of DBS-induced symptom alleviation.

13 Clinical Trial High intensity eccentric resistance training decreases bradykinesia and improves Quality Of Life in persons with Parkinson's disease: a preliminary study. 2009

Dibble, Leland E / Hale, Tessa F / Marcus, Robin L / Gerber, J Parry / LaStayo, Paul C. ·University of Utah, Department of Physical Therapy, Salt Lake City, UT 84108, USA. lee.dibble@hsc.utah.edu ·Parkinsonism Relat Disord · Pubmed #19497777.

ABSTRACT: Persons with Parkinson disease (PD) often demonstrate bradykinesia during mobility tasks. Bradykinesia combined with other PD-related movement deficits may contribute to self-reported reductions in quality of life. At this time, no studies have examined the effects of resistance exercise as an intervention to reduce bradykinesia and improve self-reported quality of life. Therefore, we examined changes in muscle force production, clinical measures of bradykinesia, and quality of life following 12 weeks of a high intensity eccentric resistance exercise program in persons with mild to moderate PD. Twenty individuals with idiopathic PD were matched into an experimental or an active control group. All participants were tested prior to and following a 12-week intervention period. The experimental group performed high intensity quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks. The active control group participated in an evidence based exercise program of PD. The outcome variables were quadriceps muscle force, clinical bradykinesia measures (gait speed, timed up and go) and disease specific quality of life (Parkinson's disease questionnaire-39 [PDQ-39]). Data was analyzed using separate 2 (group) x 2 (time period) ANOVAs. Results demonstrated significant time by group interaction effects for gait speed, timed up and go, and the composite PDQ-39 score (p < 0.05). Muscle force, bradykinesia, and QOL were improved to a greater degree in those that performed high intensity eccentric resistance training compared to an active control group. Additional research is needed to determine if this type of training has long-term impact and if it results in an alteration of the natural history of mobility and QOL decline in persons with PD.

14 Article Changes in Timing of Swallow Events in Parkinson's Disease. 2019

Schiffer, Breanne L / Kendall, Katherine. ·1 Division of Otolaryngology, Head & Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA. · 2 Voice Disorders Center, University of Utah Healthcare, Salt Lake City, Utah, USA. ·Ann Otol Rhinol Laryngol · Pubmed #30328706.

ABSTRACT: OBJECTIVES:: The prevalence of Parkinson's disease (PD) increases as the population ages. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. To maximize the benefit of swallowing therapy, protocol design should be based on an understanding of the physiologic swallowing deficits present in the PD population. The aim of this study was to compare the timing of swallow events in a cohort of patients with PD with that in normal age-matched control subjects to characterize variations in the coordination of structural displacement and bolus movement that may contribute to dysphagia. METHODS:: This retrospective study included 68 adults with diagnoses of PD. Liquid bolus swallows during modified barium swallow studies were analyzed and compared with those from an age- and sex-matched cohort of 48 adults without PD. RESULTS:: Patients with PD were significantly slower in initiating and completing airway closure. Hyoid elevation was prolonged in this patient population. CONCLUSIONS:: Patients with PD demonstrate slower initiation of airway closure and a delay in relaxation of hyoid elevation during swallow. Delays increased with larger boluses. These findings may be related to impaired pharyngeal sensation and increased muscular rigidity. The results of this study will be helpful in guiding swallow therapy for patients with PD.

15 Article Lead-DBS v2: Towards a comprehensive pipeline for deep brain stimulation imaging. 2019

Horn, Andreas / Li, Ningfei / Dembek, Till A / Kappel, Ari / Boulay, Chadwick / Ewert, Siobhan / Tietze, Anna / Husch, Andreas / Perera, Thushara / Neumann, Wolf-Julian / Reisert, Marco / Si, Hang / Oostenveld, Robert / Rorden, Christopher / Yeh, Fang-Cheng / Fang, Qianqian / Herrington, Todd M / Vorwerk, Johannes / Kühn, Andrea A. ·Movement Disorders & Neuromodulation Unit, Department for Neurology, Charité - University Medicine Berlin, Germany. Electronic address: andreas.horn@charite.de. · Movement Disorders & Neuromodulation Unit, Department for Neurology, Charité - University Medicine Berlin, Germany. · Department of Neurology, University Hospital of Cologne, Germany. · Wayne State University, Department of Neurosurgery, Detroit, Michigan, USA. · Ottawa Hospital Research Institute, Canada. · Institute of Neuroradiology, Charité - University Medicine Berlin, Germany. · University of Luxembourg, Luxembourg Centre for Systems Biomedicine, Interventional Neuroscience Group, Belvaux, Luxembourg. · Bionics Institute, East Melbourne, Victoria, Australia; Department of Medical Bionics, University of Melbourne, Parkville, Victoria, Australia. · Movement Disorders & Neuromodulation Unit, Department for Neurology, Charité - University Medicine Berlin, Germany; Institute of Neuroradiology, Charité - University Medicine Berlin, Germany. · Medical Physics, Department of Radiology, Faculty of Medicine, University Freiburg, Germany. · Numerical Mathematics and Scientific Computing, Weierstrass Institute for Applied Analysis and Stochastics (WIAS), Germany. · Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, NL, Netherlands; NatMEG, Karolinska Institutet, Stockholm, SE, Sweden. · McCausland Center for Brain Imaging, University of South Carolina, Columbia, SC, USA. · Department of Neurological Surgery, University of Pittsburgh PA, USA. · Department of Bioengineering, Northeastern University, Boston, USA. · Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Scientific Computing & Imaging (SCI) Institute, University of Utah, Salt Lake City, USA. ·Neuroimage · Pubmed #30179717.

ABSTRACT: Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural/functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patient's preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the preprocessing method of choice. This work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.

16 Article Dopamine Replacement Medication Does Not Influence Implicit Learning of a Stepping Task in People With Parkinson's Disease. 2018

Paul, Serene S / Schaefer, Sydney Y / Olivier, Genevieve N / Walter, Christopher S / Lohse, Keith R / Dibble, Leland E. ·1 The University of Sydney, Australia. · 2 University of Utah, Salt Lake City, UT, USA. · 3 Arizona State University, Tempe, AZ, USA. · 4 University of Arkansas for Medical Sciences, Fayetteville, AR, USA. ·Neurorehabil Neural Repair · Pubmed #30409107.

ABSTRACT: INTRODUCTION: Treatment of Parkinson's disease (PD) with exogenous dopamine (ie, levodopa) may positively affect motor symptoms, but may negatively affect other functions such as the learning of motor skills necessary for rehabilitation. This study aimed to determine whether levodopa medication affects general and sequence-specific learning of a stepping task and the transfer of movement skill to untrained balance tasks in people with PD. METHODS: Participants with PD were randomized to practice "on" (n = 14) or "off" (n = 13) levodopa medication. Participants practiced 6 blocks of 6 trials of 24 steps of a stepping task over an acquisition period of 3 consecutive days, followed by single retention blocks of 6 trials 2 and 9 days later. Participants were also assessed on untrained balance (ie, transfer) tasks "on" levodopa before practice and following late retention. RESULTS: There were no between-group differences in general learning, sequence-specific learning, or transfer of skill to untrained balance tasks ( P > .05). Both groups demonstrated general and sequence-specific learning ( P < .001) and trends for improvement in untrained tasks ( P < .001 to P = .26) following practice. Detailed analysis of early acquisition revealed no difference between medication groups. CONCLUSION: People with PD improved performance on the stepping task with practice. The between-group effect sizes were small, suggesting that levodopa medication status ("on" versus "off") during practice did not significantly affect general or sequence-specific learning of the task or components of early acquisition. The practice dose required to optimally result in functional improvements in untrained balance tasks, including reductions in falls, remains to be determined.

17 Article Relating Anticipatory Postural Adjustments to Step Outcomes During Loss of Balance in People With Parkinson's Disease. 2018

Peterson, Daniel S / Lohse, Keith R / Mancini, Martina. ·1 Arizona State University, Phoenix, AZ, USA. · 2 Phoenix Veterans Affairs Medical Center, Phoenix, AZ, USA. · 3 University of Utah, Salt Lake City, UT, USA. · 4 Oregon Health & Science University, Portland, OR, USA. ·Neurorehabil Neural Repair · Pubmed #30198384.

ABSTRACT: BACKGROUND: Effective protective steps are critical for fall prevention, and anticipatory postural adjustments (APAs) after a perturbation but prior to protective steps affect step performance. Although APAs prior to protective steps are altered in people with Parkinson's disease (PD), whether these changes affect subsequent step performance is poorly understood. OBJECTIVE: Characterize the relationship between mediolateral APA size and protective step outcomes in response to anteroposterior balance perturbations in people with PD. METHODS: Twenty-eight individuals with PD completed 25 forward and 25 backward protective steps in response to support surface translations. Multilevel linear models related mediolateral APA size to protective step outcomes. RESULTS: During forward protective stepping, larger mediolateral APAs were associated with delayed ( P < .001) and larger ( P = .004) steps. Larger APAs were also associated with smaller mediolateral ( P < .001) but larger anterior-posterior center of mass movement at foot off ( P < .001). During backward stepping, larger APAs were associated with later steps ( P < .001) and smaller anterior-posterior margin of stability at first foot contact ( P < .001). During backward stepping, larger APAs were also associated with worse clinical (ie, UPDRS [Unified Parkinson's Disease Rating Scale]; P = .005) and balance (ie, MiniBEST [Mini-Balance Evaluation Systems Test]; P = .021) outcomes. CONCLUSIONS: During forward protective stepping, larger APAs were associated with larger and later steps, suggesting APA size may have mixed effects on the subsequent step. During backward stepping, larger APAs were associated with worse stepping outcomes (ie, later steps, smaller anterior-posterior margin of stability, worse clinical outcomes). Interventions aimed at improving APAs in PD should monitor spatial and temporal protective step outcomes to ensure treatment does not negatively affect protective steps, particularly for forward stepping.

18 Article Sleep disturbances and depression severity in patients with Parkinson's disease. 2018

Kay, Daniel B / Tanner, Jared J / Bowers, Dawn. ·Department of Psychology, Brigham Young University, Provo, UT, USA. · Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA. ·Brain Behav · Pubmed #30106239.

ABSTRACT: OBJECTIVES: Parkinson's disease (PD) is a multisystem movement disorder associated with sleep disturbance and depression. Sleep disturbances and depression severity share a bidirectional association. This association may be greater in individuals who are more vulnerable to the deleterious consequences of sleep disturbance and depression severity. We investigated whether the association between sleep disturbances and depression severity is greater in patients with PD than in matched controls (MC). MATERIALS AND METHODS: The study sample (N = 98) included 50 patients with idiopathic PD and 48 age-, race-, sex-, and education-matched controls. Sleep disturbances were assessed using self-reported total sleep time (TST) on the Pittsburgh Sleep Quality Index, the sleep item on the Beck Depression Inventory, 2nd ed. (BDI-II), and the Insomnia Severity Index total score. Depression severity was assessed using the BDI-II total score, excluding the sleep item. Spearman's correlations, chi-squared tests, and multiple regression were used to assess associations between sleep disturbances and depression severity in PD and MC. Fisher's Z transformation was used to test whether the association between sleep disturbances and depression severity was stronger in patients with PD. RESULTS: Shorter TST, sleeping less than usual, and insomnia severity were associated with depression severity in the total sample, r CONCLUSION: Short TST may be an important marker, predictor, or consequence of depression severity in patients with Parkinson's disease.

19 Article Genetic Modifiers of Neurodegeneration in a 2018

Lavoy, Sierra / Chittoor-Vinod, Vinita G / Chow, Clement Y / Martin, Ian. ·Jungers Center for Neurosciences, Oregon Health and Science University, Portland, Oregon 97239. · Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239. · Parkinson Center of Oregon, Oregon Health and Science University, Portland, Oregon 97239. · Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84132. · Jungers Center for Neurosciences, Oregon Health and Science University, Portland, Oregon 97239 martiia@ohsu.edu. ·Genetics · Pubmed #29907646.

ABSTRACT: Disease phenotypes can be highly variable among individuals with the same pathogenic mutation. There is increasing evidence that background genetic variation is a strong driver of disease variability in addition to the influence of environment. To understand the genotype-phenotype relationship that determines the expressivity of a pathogenic mutation, a large number of backgrounds must be studied. This can be efficiently achieved using model organism collections such as the

20 Article Anticipatory postural responses prior to protective steps are not different in people with PD who do and do not freeze. 2018

Peterson, D S / Lohse, K R / Mancini, M. ·Arizona State University, Phoenix, AZ, United States; Phoenix Veterans Affairs Medical Center, Phoenix, AZ, United States. Electronic address: daniel.peterson1@asu.edu. · University of Utah, Salt Lake City, UT, United States. · Oregon Health & Science University, Portland, OR, United States. ·Gait Posture · Pubmed #29902715.

ABSTRACT: BACKGROUND: Protective stepping after a loss of balance is related to falls. Anticipatory postural responses (APAs) prior to protective stepping can impact step performance, may be larger in people with PD, and have been suggested to be related to freezing of gait (FOG). However, whether people with PD and FOG (PD + FOG) exhibit larger APAs than people with PD and no FOG (PD-FOG) is unknown. RESEARCH QUESTION: Determine the impact of freezing status on APAs prior to protective steps, thus providing a better understanding of the link between FOG and APAs. METHODS: Twenty-eight people with PD (13 PD + FOG) were exposed to 50 support surface translations (25 forward, 25 backward, random order) resulting in protective steps. The size of medio-lateral weight shifts prior to the protective step (i.e. APAs), and the percentage of trials with an APA were calculated via force-plates. FOG status was assessed at the time of testing as well as 3.25(+/-0.43) years later. Participants without FOG at testing, but with FOG at follow-up were identified as "converters". RESULTS AND SIGNIFICANCE: For both forward and backward protective stepping, size and percentage trials with an APA were not statistically different between PD + FOG and PD-FOG, even after excluding converters from the PD-FOG group (p > 0.27 for all). No group by direction interactions were observed. These data suggest that, in mild to moderate PD, an inability to couple APAs with stepping, rather than an inappropriately sized APA, may be most related to freezing of gait.

21 Article Dual-task interference during gait on irregular terrain in people with Parkinson's disease. 2018

Xu, Hang / Merryweather, Andrew / Foreman, K Bo / Zhao, Jie / Hunt, MaryEllen. ·Jiangsu Province Keylab of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA. Electronic address: h_xu@xzhmu.edu.cn. · Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA. Electronic address: a.merryweather@utah.edu. · Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA. Electronic address: bo.foreman@hsc.utah.edu. · School of Medical Imaging, Xuzhou Medical University, Xuzhou, China. Electronic address: zhaojiecumt@163.com. · Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA. ·Gait Posture · Pubmed #29702370.

ABSTRACT: BACKGROUND: Gait impairments in people with Parkinson's disease (PD) are accentuated in dual-task conditions. Most PD studies on dual-task gait have measured only straight line walking and treadmill gait. Gait alterations on irregular terrain are poorly understood. RESEARCH QUESTION: To what extent does walking on irregular terrain exacerbate dual-task interference in people with PD, compared to age-matched control participants? METHODS: Gait data were collected for nine participants with mild to moderate PD and nine healthy age-matched participants on regular and irregular terrains. Gait was tested as a single task and in dual-task conditions with serial 7 subtractions. The spatiotemporal variables (speed, cadence, single limb support, step length and width), kinematic variables (range of motion for hip, knee and ankle joints) and stability variables (trunk range of motion and center of mass acceleration RMS) were compared across conditions. RESULTS: People with PD showed reduced gait speed and cadence and increased mediolateral center of mass acceleration when walking on irregular terrain with dual-tasks. Surface irregularity was associated with increased ankle transverse motion in both groups. Increased hip and knee sagittal motion was observed in the control participants when terrain changed from regular to irregular under dual-task conditions. This was not statistically significant for the PD group. SIGNIFICANCE: Dual-task walking on irregular terrain exacerbated the gait deficits, particularly for people with PD. Gait speed, cadence and mediolateral body stability were compromised when people with PD walked on irregular terrain whilst performing dual-tasks. There was an increase in ankle transverse motion in both groups when traversing irregular terrain. This might have been an adaptive strategy, to prevent tripping.

22 Article Home-based step training using videogame technology in people with Parkinson's disease: a single-blinded randomised controlled trial. 2018

Song, Jooeun / Paul, Serene S / Caetano, Maria Joana D / Smith, Stuart / Dibble, Leland E / Love, Rachelle / Schoene, Daniel / Menant, Jasmine C / Sherrington, Cathie / Lord, Stephen R / Canning, Colleen G / Allen, Natalie E. ·1 Faculty of Health Sciences, The University of Sydney, Sydney, NSW, Australia. · 2 Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia. · 3 Musculoskeletal Health Sydney, School of Public Health, The University of Sydney, Sydney, NSW, Australia. · 4 Falls, Balance and Injury Research Centre, Neuroscience Research Australia, The University of New South Wales, Sydney, NSW, Australia. · 5 Southern Cross University, Coffs Harbour, NSW, Australia. · 6 Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA. · 7 Institute for Biomedicine of Ageing, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. ·Clin Rehabil · Pubmed #28745063.

ABSTRACT: OBJECTIVES: To determine whether 12-week home-based exergame step training can improve stepping performance, gait and complementary physical and neuropsychological measures associated with falls in Parkinson's disease. DESIGN: A single-blinded randomised controlled trial. SETTING: Community (experimental intervention), university laboratory (outcome measures). SUBJECTS: Sixty community-dwelling people with Parkinson's disease. INTERVENTIONS: Home-based step training using videogame technology. MAIN MEASURES: The primary outcomes were the choice stepping reaction time test and Functional Gait Assessment. Secondary outcomes included physical and neuropsychological measures associated with falls in Parkinson's disease, number of falls over six months and self-reported mobility and balance. RESULTS: Post intervention, there were no differences between the intervention ( n = 28) and control ( n = 25) groups in the primary or secondary outcomes except for the Timed Up and Go test, where there was a significant difference in favour of the control group ( P = 0.02). Intervention participants reported mobility improvement, whereas control participants reported mobility deterioration-between-group difference on an 11-point scale = 0.9 (95% confidence interval: -1.8 to -0.1, P = 0.03). Interaction effects between intervention and disease severity on physical function measures were observed ( P = 0.01 to P = 0.08) with seemingly positive effects for the low-severity group and potentially negative effects for the high-severity group. CONCLUSION: Overall, home-based exergame step training was not effective in improving the outcomes assessed. However, the improved physical function in the lower disease severity intervention participants as well as the self-reported improved mobility in the intervention group suggest home-based exergame step training may have benefits for some people with Parkinson's disease.

23 Article Preserving Self: Theorizing the Social and Psychological Processes of Living With Parkinson Disease. 2017

Vann-Ward, Terrie / Morse, Janice M / Charmaz, Kathy. ·1 University of Utah, Salt Lake City, Utah, USA. · 2 Sonoma State University, Rohnert Park, California, USA. ·Qual Health Res · Pubmed #28818020.

ABSTRACT: The purpose of this constructivist grounded theory article is to identify, explore, and theorize the social and psychological processes used by people with Parkinson disease. Analytic procedures generated the five-stage theory of Preserving self of people with Parkinson disease: (a) making sense of symptoms, (b) defining turning points, (c) experiencing identity dilemmas, (d) reconnecting the self, and (e) envisioning a future. Reminders of former selves and capabilities were painful; participants desperately sought normalcy. Participants developed creative methods for maintaining independence but frequently overestimated their abilities and took risks. Participants were 15 men and 10 women (ages 40-95), most of whom lived with their families. Disease status was ascertained through medication logs and two scales: Hoehn and Yahr staging and Activities of Daily Living. Data included 62 in-depth interviews, nonparticipant observation, and participant photos, videos, and related documents. Recommendations were derived from the theory to support processes of Preserving Self as interventions designed to reduce the loss of self and to enhance Preserving self. These recommendations included developing relationships, teaching expected and unexpected feelings and behaviors, and involvement with sensory integrating activities.

24 Article Adaptation of postural recovery responses to a vestibular sensory illusion in individuals with Parkinson disease and healthy controls. 2017

Lester, Mark E / Cavanaugh, James T / Foreman, K Bo / Shaffer, Scott W / Marcus, Robin / Dibble, Leland E. ·Army-Baylor University Doctoral Physical Therapy Program, Joint Base San Antonio, Ft. Sam Houston, TX, USA. Electronic address: mark.e.lester4.mil@mail.mil. · Department of Physical Therapy, University of New England Portland, ME, USA. · Department of Physical Therapy, University of Utah Salt Lake City, UT, USA. · Army-Baylor University Doctoral Physical Therapy Program, Joint Base San Antonio, Ft. Sam Houston, TX, USA. ·Clin Biomech (Bristol, Avon) · Pubmed #28783491.

ABSTRACT: BACKGROUND: The ability to adapt postural responses to sensory illusions diminishes with age and is further impaired by Parkinson disease. However, limited information exists regarding training-related adaptions of sensory reweighting in these populations. METHODS: This study sought to determine whether Parkinson disease or age would differentially affect acute postural recovery or adaptive postural responses to novel or repeated exposure to sensory illusions using galvanic vestibular stimulation during quiet stance. FINDINGS: Acutely, individuals with Parkinson disease demonstrated larger center of pressure coefficient of variation compared to controls. Unlike individuals with Parkinson disease and asymptomatic older adults, healthy young adults acutely demonstrated a reduction in Sample Entropy to the sensory illusion. Following a period of consolidation Sample Entropy increased in the healthy young group, which coincided with a decreased center of pressure coefficient of variation. Similar changes were not observed in the Parkinson disease or older adult groups. INTERPRETATION: Taken together, these results suggest that young adults learn to adapt to vestibular illusion in a more robust manner than older adults or those with Parkinson disease. Further investigation into the nature of this adaptive difference is warranted.

25 Article Connectivity Predicts deep brain stimulation outcome in Parkinson disease. 2017

Horn, Andreas / Reich, Martin / Vorwerk, Johannes / Li, Ningfei / Wenzel, Gregor / Fang, Qianqian / Schmitz-Hübsch, Tanja / Nickl, Robert / Kupsch, Andreas / Volkmann, Jens / Kühn, Andrea A / Fox, Michael D. ·Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. · Department of Neurology, Movement Disorder and Neuromodulation Unit, Charité-Universitätsmedizin, Berlin, Germany. · Department of Neurology, Würzburg University Hospital, Würzburg, Germany. · Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah. · Institute of Software Engineering and Theoretical Computer Science, Neural Information Processing Group, Berlin Technical University, Berlin, Germany. · Department of Bioengineering, Northeastern University, Boston, MA. · NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany. · Department of Neurosurgery, Würzburg University Hospital, Würzburg, Germany. · Clinic of Neurology and Stereotactic Neurosurgery, Otto von Guericke University, Magdeburg, Germany. · Neurology Moves, Berlin, Germany. · Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA. ·Ann Neurol · Pubmed #28586141.

ABSTRACT: OBJECTIVE: The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. METHODS: A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. RESULTS: In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. INTERPRETATION: Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. Ann Neurol 2017;82:67-78.

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