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Parkinson Disease: HELP
Articles by Nikolaus R. McFarland
Based on 31 articles published since 2010
(Why 31 articles?)
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Between 2010 and 2020, Nikolaus McFarland wrote the following 31 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Recognizing Atypical Parkinsonisms: "Red Flags" and Therapeutic Approaches. 2017

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

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

2 Review MRI reveals brain abnormalities in drug-naive Parkinson's disease. 2014

Planetta, Peggy J / McFarland, Nikolaus R / Okun, Michael S / Vaillancourt, David E. ·Departments of 1Applied Physiology and Kinesiology, and 2Neurology, 3Center for Movement Disorders and Neurorestoration, and Departments of 4Neurosurgery, and 5Biomedical Engineering, University of Florida, Gainesville, FL. ·Exerc Sport Sci Rev · Pubmed #24188978.

ABSTRACT: Most brain studies of Parkinson's disease (PD) focus on patients who are already taking antiparkinsonian medication. This makes it difficult to isolate the effects of disease from those of treatment. We review magnetic resonance imaging evidence supporting the hypothesis that early-stage untreated PD patients have structural and functional abnormalities in the brain, some of which are related to motor symptoms.

3 Article A turn for the worse: Turning performance in Parkinson's disease and Essential tremor. 2019

Baudendistel, Sidney T / Schmitt, Abigail C / Rodriguez, Ashley V / McFarland, Nikolaus R / Hass, Chris J. ·Applied Neuromechanics Laboratory, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, USA. Electronic address: sbaudendistel@ufl.edu. · Applied Neuromechanics Laboratory, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, USA. · Department of Neurology, Fixel Institute for Neurological Diseases, Movement Disorders and Neurorestoration Program, University of Florida, Gainesville, FL, USA. ·Clin Biomech (Bristol, Avon) · Pubmed #31669958.

ABSTRACT: BACKGROUND: Turning is an activity of daily living known to elicit falls in older adults and particularly in persons with movement disorders. Specifically, those with Parkinson's disease have marked impairments in forward walking and turning. Although recent work has identified gait impairment in those with Essential tremor, turning has not been extensively evaluated. As the cerebellum is key in the pathophysiology of Essential tremor, complex tasks like turning, may be impaired for this population. The purpose of this study was to investigate turning behavior and falls in those with Essential tremor and Parkinson's disease. METHODS: 15 persons with Essential tremor and 15 persons with Parkinson's disease performed forward walking and turns on an instrumented walkway. t-tests compared groups and a regression was performed to predict fall frequency. FINDINGS: During turning, those with Essential tremor had lower cadence (p = .042) and took more time (p = .05). No other variables, including forward walking variables, differed between groups. When pooling groups, the significant fall frequency predictor model (p = .003) included decreased forward cadence, increased turning cadence, and female sex. Overall, the model explained 40.7% of the variance. INTERPRETATION: While forward gait performance was similar between groups, those with Essential tremor had increased turn time, a measure often associated with turning impairment. Together, these results suggest overall gait impairment in Essential tremor is more prevalent than recognized. Walking performance, both turning and forward, and sex were predictive of fall frequency. Therapeutic interventions in these populations should include both forward walking and turns to mitigate fall risk.

4 Article Progression marker of Parkinson's disease: a 4-year multi-site imaging study. 2017

Burciu, Roxana G / Ofori, Edward / Archer, Derek B / Wu, Samuel S / Pasternak, Ofer / McFarland, Nikolaus R / Okun, Michael S / Vaillancourt, David E. ·University of Florida, Department of Applied Physiology and Kinesiology, Gainesville, FL, USA. · University of Florida, Department of Biostatistics, Gainesville, FL, USA. · Harvard Medical School Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Boston, MA, USA. · University of Florida, Department of Neurology, Gainesville, FL, USA. · University of Florida, Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. · University of Florida, Department of Neurosurgery, Gainesville, FL, USA. · University of Florida, Department of Biomedical Engineering, Gainesville, FL, USA. ·Brain · Pubmed #28899020.

ABSTRACT: Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson's disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson's disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson's disease, which may be used in clinical trials of disease-modifying therapies.

5 Article The ER retention protein RER1 promotes alpha-synuclein degradation via the proteasome. 2017

Park, Hyo-Jin / Ryu, Daniel / Parmar, Mayur / Giasson, Benoit I / McFarland, Nikolaus R. ·Center for Translational Research in Neurodegenerative Disease, Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, United States of America. · Division of Biology of Aging, Department of Aging and Geriatric Research, College of Medicine, University of Florida, Gainesville, FL, United States of America. · Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, United States of America. ·PLoS One · Pubmed #28877262.

ABSTRACT: Abnormal accumulation of α-synuclein (αSyn) has been linked to endoplasmic-reticulum (ER) stress, defective intracellular protein/vesicle trafficking, and cytotoxicity. Targeting factors involved in ER-related protein processing and trafficking may, therefore, be a key to modulating αSyn levels and associated toxicity. Recently retention in endoplasmic reticulum 1 (RER1) has been identified as an important ER retrieval/retention factor for Alzheimer's disease proteins and negatively regulates amyloid-β peptide levels. Here, we hypothesized that RER1 might also play an important role in retention/retrieval of αSyn and mediate levels. We expressed RER1 and a C-terminal mutant RER1Δ25, which lacks the ER retention/retrieval function, in HEK293 and H4 neuroglioma cells. RER1 overexpression significantly decreased levels of both wild type and A30P, A53T, and E46K disease causal mutants of αSyn, whereas the RER1Δ25 mutant had a significantly attenuated effect on αSyn. RER1 effects were specific to αSyn and had little to no effect on either βSyn or the Δ71-82 αSyn mutant, which both lack the NAC domain sequence critical for synuclein fibrillization. Tests with proteasomal and macroautophagy inhibitors further demonstrate that RER1 effects on αSyn are primarily mediated through the ubiquitin-proteasome system. RER1 also appears to interact with the ubiquitin ligase NEDD4. RER1 in human diseased brain tissues co-localizes with αSyn-positive Lewy bodies. Together, these findings provide evidence that RER1 is a novel and potential important mediator of elevated αSyn levels. Further investigation of the mechanism of RER1 and downstream effectors on αSyn may yield novel therapeutic targets for modulation in Parkinson disease and related synucleinopathies.

6 Article Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study. 2017

Ofori, Edward / Krismer, Florian / Burciu, Roxana G / Pasternak, Ofer / McCracken, Johanna L / Lewis, Mechelle M / Du, Guangwei / McFarland, Nikolaus R / Okun, Michael S / Poewe, Werner / Mueller, Christoph / Gizewski, Elke R / Schocke, Michael / Kremser, Christian / Li, Hong / Huang, Xuemei / Seppi, Klaus / Vaillancourt, David E. ·Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA. · Department of Neuroradiology, Medical University Innsbruck, Innsbruck, Austria. · Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Neurology, Penn State - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. · Department of Pharmacology, Penn State - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, USA. · Department of Neurology, University of Florida, Gainesville, Florida, USA. · Department of Neurosurgery, University of Florida, Gainesville, Florida, USA. · Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. · Department of Public Health Sciences, Medical College of South Carolina, Charleston, South Carolina, USA. · Departments of Neurosurgery, Radiology, and Kinesiology, Penn State - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. · Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA. ·Mov Disord · Pubmed #28714593.

ABSTRACT: BACKGROUND: Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was to evaluate changes in the substantia nigra using single- and bi-tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP. METHODS: The study cohort (n = 425) included 107 healthy controls and 184 PD, 63 MSA, and 71 PSP patients from 3 movement disorder centers. Bi-tensor free water, free-water-corrected fractional anisotropy, free-water-corrected mean diffusivity, single-tensor fractional anisotropy, and single-tensor mean diffusivity were computed for the anterior and posterior substantia nigra. Correlations were computed between diffusion MRI measures and clinical measures. RESULTS: In the posterior substantia nigra, free water was greater for PSP than MSA and PD patients and controls. PD and MSA both had greater free water than controls. Free-water-corrected fractional anisotropy values were greater for PSP patents than for controls and PD patients. PSP and MSA patient single-tensor mean diffusivity values were greater than controls, and single-tensor fractional anisotropy values were lower for PSP patients than for healthy controls. The parkinsonism effect size for free water was 0.145 in the posterior substantia nigra and 0.072 for single-tensor mean diffusivity. The direction of correlations between single-tensor mean diffusivity and free-water values and clinical scores was similar at each site. CONCLUSIONS: Free-water values in the posterior substantia nigra provide a consistent pattern of findings across patients with PD, MSA, and PSP in a large cohort across 3 sites. Free water in the posterior substantia nigra relates to clinical measures of motor and cognitive symptoms in a large cohort of parkinsonism. © 2017 International Parkinson and Movement Disorder Society.

7 Article Parkinson Disease and Autoimmune Disorders-What Can We Learn From Genome-wide Pleiotropy? 2017

McFarland, Nikolaus R / McFarland, Karen N / Golde, Todd E. ·Center for Movement Disorders and Neurorestoration, Department of Neurology, College of Medicine, University of Florida, Gainesville2Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville3McKnight Brain Institute, University of Florida, Gainesville. · Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville3McKnight Brain Institute, University of Florida, Gainesville4Department of Neuroscience, College of Medicine, University of Florida, Gainesville. ·JAMA Neurol · Pubmed #28586798.

ABSTRACT: -- No abstract --

8 Article Striatal and Hippocampal Atrophy in Idiopathic Parkinson's Disease Patients without Dementia: A Morphometric Analysis. 2017

Tanner, Jared J / McFarland, Nikolaus R / Price, Catherine C. ·Clinical and Health Psychology, University of Florida, Gainesville, FL, USA. · Neurology, University of Florida, Gainesville, FL, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA. ·Front Neurol · Pubmed #28450849.

ABSTRACT: BACKGROUND: Analyses of subcortical gray structure volumes in non-demented idiopathic Parkinson's disease (PD) often, but not always, show volume loss of the putamen, caudate nucleus, nucleus accumbens, and hippocampus. There is building evidence that structure morphometry might be more sensitive to disease-related processes than volume. OBJECTIVE: To assess morphometric differences of subcortical structures (putamen, caudate nucleus, thalamus, globus pallidus, nucleus accumbens, and amygdala) as well as the hippocampus in non-demented individuals with PD relative to age and education matched non-PD peers. METHODS: Prospective recruitment of idiopathic no-dementia PD and non-PD peers as part of a federally funded investigation. T1-weighted isovoxel metrics acquired RESULTS: Group volume differences were observed only for putamen and hippocampi (PD < non-PD) with hippocampal volume significantly associating with disease duration. Group shape differences were observed for bilateral putamen, caudate nucleus, and hippocampus with greater striatal atrophy contralateral to side of motor symptom onset. Hippocampal shape differences disappeared when removing the effects of volume. CONCLUSION: The putamen was the primary structure to show both volume and shape differences in PD, indicating that the putamen is the predominant site of basal ganglia atrophy in early- to mid-stage PD. Side of PD symptom onset associates with contralateral striatal atrophy. Left-onset PD might experience more extensive striatal atrophy than right-onset PD. Hippocampus morphometric results suggest possible primary atrophy of CA3/4 and dentate gyrus.

9 Article Functional MRI of disease progression in Parkinson disease and atypical parkinsonian syndromes. 2016

Burciu, Roxana G / Chung, Jae Woo / Shukla, Priyank / Ofori, Edward / Li, Hong / McFarland, Nikolaus R / Okun, Michael S / Vaillancourt, David E. ·From the Department of Applied Physiology and Kinesiology (R.G.B., J.W.C., P.S., E.O., D.E.V.) and the Departments of Neurology (N.R.M., M.S.O., D.E.V.) and Neurosurgery (M.S.O.), Center for Movement Disorders and Neurorestoration, and Department of Biomedical Engineering (D.E.V.), University of Florida, Gainesville · and Department of Public Health Sciences (H.L.), Medical University of South Carolina, Charleston. ·Neurology · Pubmed #27421545.

ABSTRACT: OBJECTIVE: To explore longitudinal changes in brain activity in patients with Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) using task-based functional MRI (fMRI). METHODS: A total of 112 individuals were scanned 1 year apart while performing a unimanual grip force task: 46 PD, 13 MSA, 19 PSP, and 34 healthy controls. The outcome measure was percent signal change in prespecified regions of interest: putamen, primary motor cortex (M1), supplementary motor area (SMA), and superior motor regions of the cerebellum (lobules V-VI). RESULTS: Patients with PD showed a decline in functional activity over the course of 1 year in the putamen and M1 compared to controls. Changes after 1 year in MSA were exclusively extrastriatal, and included a reduction in functional activity in M1, SMA, and superior cerebellum. In PSP, all regions of interest were less active at 1 year compared to baseline. The functional activity of these regions did not change in the control group. CONCLUSIONS: We provide evidence using task-based fMRI for cortical and striatal functional deterioration in PD over a 1-year period of time. Results also describe more widespread and unique patterns of functional changes in MSA and PSP compared to PD, suggesting distinct rates of disease progression in parkinsonian disorders that may assist in future clinical studies testing the potential efficacy of disease-modifying therapies.

10 Article Free-water and BOLD imaging changes in Parkinson's disease patients chronically treated with a MAO-B inhibitor. 2016

Burciu, Roxana G / Ofori, Edward / Shukla, Priyank / Pasternak, Ofer / Chung, Jae Woo / McFarland, Nikolaus R / Okun, Michael S / Vaillancourt, David E. ·Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida. · Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Neurology, University of Florida, Gainesville, Florida. · Center for Movement Disorders and Neurorestoration, College of Medicine, University of Florida, University of Florida, Gainesville, Florida. · Department of Neurosurgery, University of Florida, Gainesville, Florida. · Department of Biomedical Engineering, University of Florida, Gainesville, Florida. ·Hum Brain Mapp · Pubmed #27089850.

ABSTRACT: Rasagiline is a monoamine oxidase type B inhibitor that possesses no amphetamine-like properties, and provides symptomatic relief in early and late stages of Parkinson's disease (PD). Data in animal models of PD suggest that chronic administration of rasagiline is associated with structural changes in the substantia nigra, and raise the question whether the structure and function of the basal ganglia could be different in PD patients treated chronically with rasagiline as compared with PD patients not treated with rasagiline. Here, we performed a retrospective cross-sectional magnetic resonance imaging (MRI) study at 3 T that investigated nigrostriatal function and structure in PD patients who had taken rasagiline before testing (∼8 months), PD who had not taken rasagiline before testing, and age-matched controls. The two PD groups were selected a priori to not differ significantly in age, sex, disease duration, severity of symptoms, cognitive status, and total levodopa equivalent daily dose of medication. We evaluated percent signal change in the posterior putamen during force production using functional MRI, free-water in the posterior substantia nigra using diffusion MRI, and performance on a bimanual coordination task using a pegboard test. All patients were tested after overnight withdrawal from antiparkinsonian medication. The rasagiline group had greater percent signal change in the posterior putamen, less free-water in the posterior substantia nigra, and better performance on the coordination task than the group not taking rasagiline. These findings point to a possible chronic effect of rasagiline on the structure and function of the basal ganglia in PD. Hum Brain Mapp 37:2894-2903, 2016. © 2016 Wiley Periodicals, Inc.

11 Article The relationship between balance confidence and control in individuals with Parkinson's disease. 2016

Lee, Hyo Keun / Altmann, Lori J P / McFarland, Nikolaus / Hass, Chris J. ·Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA. · Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, FL, USA. · Department of Neurology, University of Florida, Gainesville, FL, USA; Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. · Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA; Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. Electronic address: cjhass@hhp.ufl.edu. ·Parkinsonism Relat Disord · Pubmed #26949065.

ABSTRACT: INTRODUCTION: A broad range of subjective and objective assessments have been used to assess balance confidence and balance control in persons with Parkinson's disease (PD). However, little is known about the relationship between self-perceived balance confidence and actual balance control in PD. The purpose of this investigation was to determine the relationship between self-perceived balance confidence and objectively measured static/dynamic balance control abilities. METHODS: Forty-four individuals with PD participated in the study. Patients were stratified into 2 groups based on the modified Hoehn and Yahr (H&Y) disability score: early stage, H&Y ≤ 2.0 and moderate stage, H&Y ≥ 2.5. All participants completed the activities-specific balance confidence (ABC) scale and performed standing balance and gait initiation tasks to assess static and dynamic balance control. The center of pressure (COP) sway (CE95%Sway) during static balance and the peak distance between the projections of the COP and the center of mass (COM) in the transverse plane (COPCOM) during gait initiation were calculated. Pearson correlation analyses were conducted relating the ABC score and CE95%Sway and COPCOM. RESULTS: For early stage PD, there was a moderate correlation between ABC score and CE95%Sway (r = -0.56, R(2) = 0.32, p = 0.002), while no significant correlation was found between ABC score and COPCOM (r = -0.24, R(2) = 0.06, p = 0.227). For moderate stage PD, there was a moderate correlation between ABC score and COPCOM (r = 0.49, R(2) = 0.24, p = 0.044), while no correlation was found between ABC score and CE95%Sway (r = -0.19, R(2) = 0.04, p = 0.478). CONCLUSION: Individuals with different disease severities showed different relationships between balance confidence and actual static/dynamic balance control.

12 Article Free-water imaging in Parkinson's disease and atypical parkinsonism. 2016

Planetta, Peggy J / Ofori, Edward / Pasternak, Ofer / Burciu, Roxana G / Shukla, Priyank / DeSimone, Jesse C / Okun, Michael S / McFarland, Nikolaus R / Vaillancourt, David E. ·1 Department of Applied Physiology and Kinesiology, University of Florida, USA. · 2 Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, USA. · 3 Center for Movement Disorders and Neurorestoration, University of Florida, USA 4 Department of Neurology, University of Florida, USA 5 Department of Neurosurgery, University of Florida, USA. · 3 Center for Movement Disorders and Neurorestoration, University of Florida, USA 4 Department of Neurology, University of Florida, USA. · 1 Department of Applied Physiology and Kinesiology, University of Florida, USA 4 Department of Neurology, University of Florida, USA 6 Department of Biomedical Engineering, University of Florida, USA vcourt@ufl.edu. ·Brain · Pubmed #26705348.

ABSTRACT: Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease group comparisons, the support vector machine 10-fold cross-validation area under the curve was between 0.93-1.00 and there was high sensitivity and specificity. The regions and diffusion measures selected by the model varied across comparisons and are consistent with pathological studies. In conclusion, the current study used a novel bi-tensor diffusion analysis model to indicate that all forms of parkinsonism had elevated free-water in the substantia nigra. Beyond the substantia nigra, both multiple system atrophy and progressive supranuclear palsy, but not Parkinson's disease, showed a broad network of elevated free-water and altered free-water corrected fractional anisotropy that included the basal ganglia, thalamus, and cerebellum. These findings may be helpful in the differential diagnosis of parkinsonian disorders, and thereby facilitate the development and assessment of targeted therapies.

13 Article Abnormal tactile pressure perception in Parkinson's disease. 2015

Kesayan, Tigran / Lamb, Damon G / Falchook, Adam D / Williamson, John B / Salazar, Liliana / Malaty, Irene A / McFarland, Nikolaus R / Okun, Michael S / Shukla, Aparna Wagle / Heilman, Kenneth M. ·a Department of Neurology , University of Florida , Gainesville , FL , USA. ·J Clin Exp Neuropsychol · Pubmed #26313511.

ABSTRACT: BACKGROUND/OBJECTIVE: Some of the behavioral disorders associated with Parkinson's disease (PD), such as the reduced magnitude of actions (hypometria) may be related to an impairment in cognitive disengagement. A reduced ability to disengage attention from previous sensory stimuli will alter perception with a reduced range of estimated stimulus magnitudes (contraction to the mean). To test this disengagement hypothesis, participants with PD were tested to learn whether they had abnormal sensory perception with overestimation of the relative magnitude of weaker tactile stimuli and underestimation of the relative magnitude of stronger tactile stimuli in relation to a reference stimulus. DESIGN/METHOD: The participants were 12 people with PD and 12 healthy adults. Test stimuli were applied to the palm using Semmes-Weinstein monofilaments (SWM) of 6 magnitudes, 3 greater and 3 less than a standard stimulus. In each trial, after being stimulated with the reference (standard) stimulus, a test monofilament was applied, and the participant was asked to provide a numerical estimate of the magnitude of the second stimulus relative to the standard. RESULTS: Compared to the control group, participants with PD overestimated the magnitudes of the tactile stimuli below the standard stimulus and underestimated the magnitudes of stimuli above the standard stimulus. CONCLUSIONS: These results demonstrate that people with PD likely have a reduced ability to estimate the relative magnitudes of tactile sensory stimuli. Whereas deafferentation would alter perception in one direction, the impairment of these participants with PD may result from a disorder of disengagement, and disorders of disengagement are often due to frontal-executive dysfunction.

14 Article Distinct patterns of brain activity in progressive supranuclear palsy and Parkinson's disease. 2015

Burciu, Roxana G / Ofori, Edward / Shukla, Priyank / Planetta, Peggy J / Snyder, Amy F / Li, Hong / Hass, Chris J / Okun, Michael S / McFarland, Nikolaus R / Vaillancourt, David E. ·Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA. · Department of Preventive Medicine, Rush University Medical Center, Chicago, Illinois, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, USA. · Department of Neurology, University of Florida, Gainesville, Florida, USA. · Department of Neurosurgery, University of Florida, Gainesville, Florida, USA. · Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA. ·Mov Disord · Pubmed #26148135.

ABSTRACT: The basal ganglia-thalamo-cortical and cerebello-thalamo-cortical circuits are important for motor control. Whether their functioning is affected in a similar or different way by progressive supranuclear palsy (PSP) and Parkinson's disease (PD) is not clear. A functional magnetic resonance imaging (fMRI) force production paradigm and voxel-based morphometry were used to assess differences in brain activity and macrostructural volumes between PSP, PD, and healthy age-matched controls. We found that PSP and PD share reduced functional activity of the basal ganglia and cortical motor areas, but this is more pronounced in PSP than in PD. In PSP the frontal regions are underactive, whereas the posterior parietal and occipital regions are overactive as compared with controls and PD. Furthermore, lobules I through IV, V, and VI of the cerebellum are hypoactive in PSP and PD, whereas Crus I and lobule IX are hyperactive in PSP only. Reductions in gray and white matter volume are specific to PSP. Finally, the functional status of the caudate as well as the volume of the superior frontal gyrus predict clinical gait and posture measures in PSP. PSP and PD share hypoactivity of the basal ganglia, motor cortex, and anterior cerebellum. These patients also display a unique pattern, such that anterior regions of the cortex are hypoactive and posterior regions of the cortex and cerebellum are hyperactive. Together, these findings suggest that specific structures within the basal ganglia, cortex, and cerebellum are affected differently in PSP relative to PD.

15 Article Discriminating features of gait performance in progressive supranuclear palsy. 2015

Amano, Shinichi / Skinner, Jared W / Lee, Hyo Keun / Stegemöller, Elizabeth L / Hack, Nawaz / Akbar, Umer / Vaillancourt, David / McFarland, Nikolaus R / Hass, Chris J. ·Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA; Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH, USA. · Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA. · Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA; Department of Kinesiology, Iowa State University, Ames, IA, USA. · Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA; Department of Neurology, University of Florida, Gainesville, FL, USA. · Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA; Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. Electronic address: cjhass@hhp.ufl.edu. ·Parkinsonism Relat Disord · Pubmed #26032992.

ABSTRACT: INTRODUCTION: Progressive supranuclear palsy (PSP) is the most common form of atypical Parkinsonism; however it is underdiagnosed and often misdiagnosed as Parkinson's disease (PD). METHODS: We investigated gait initiation (GI) and gait performance in a total of 36 participants (12 PSP, 12 PD and 12 healthy age- and gender-matched controls) to gain further insight into specific motor deficits that characterize dynamic postural control and gait in PSP. Anticipatory postural adjustments (APAs), quantified by center of pressure (COP) displacement and speed prior to an initial heel off, and the maximum distance (COPCOM) between COP and center of mass (COM) during all three GI phases were calculated to evaluate dynamic postural control. Steady-state gait performance was also evaluated and compared across the groups. RESULTS: APAs in PSP were significantly altered such that the posterior COP shift is profoundly diminished when compared to PD (p < 0.05). Moreover, proper velocity control during GI in PSP was affected, particularly in the mediolateral direction, when compared to PD (p < 0.05). The diminished COPCOM distance is further indicative of more severe dynamic postural instability in PSP than in PD (p < 0.05). Significant differences in spatiotemporal parameters, inter-step variability, and asymmetry during gait in PSP, in comparison with PD were also identified (all p's < 0.05). CONCLUSION: The present study reveals that the compensatory GI strategy in PSP is distinct from PD and paradoxically induces lateral instability. Further, gait performance in PSP is slower and more variable which could be the consequence of lateral instability and fear of falling.

16 Article Unexpected dual task benefits on cycling in Parkinson disease and healthy adults: a neuro-behavioral model. 2015

Altmann, Lori J P / Stegemöller, Elizabeth / Hazamy, Audrey A / Wilson, Jonathan P / Okun, Michael S / McFarland, Nikolaus R / Wagle Shukla, Aparna / Hass, Chris J. ·Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, Florida, United States of America; Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America. · Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States of America; Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America; Department of Kinesiology, Iowa State University, Ames, Iowa, United States of America. · Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, Florida, United States of America; Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America; Department of Speech-Language Pathology, Midwestern University, Downers Grove, Illinois, United States of America. · Department of Neurology and Neurosurgery, University of Florida, Gainesville, Florida, United States of America; Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America. · Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States of America; Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America. ·PLoS One · Pubmed #25970607.

ABSTRACT: BACKGROUND: When performing two tasks at once, a dual task, performance on one or both tasks typically suffers. People with Parkinson's disease (PD) usually experience larger dual task decrements on motor tasks than healthy older adults (HOA). Our objective was to investigate the decrements in cycling caused by performing cognitive tasks with a range of difficulty in people with PD and HOAs. METHODS: Twenty-eight participants with Parkinson's disease and 20 healthy older adults completed a baseline cycling task with no secondary tasks and then completed dual task cycling while performing 12 tasks from six cognitive domains representing a wide range of difficulty. RESULTS: Cycling was faster during dual task conditions than at baseline, and was significantly faster for six tasks (all p<.02) across both groups. Cycling speed improved the most during the easiest cognitive tasks, and cognitive performance was largely unaffected. Cycling improvement was predicted by task difficulty (p<.001). People with Parkinson's disease cycled slower (p<.03) and showed reduced dual task benefits (p<.01) than healthy older adults. CONCLUSIONS: Unexpectedly, participants' motor performance improved during cognitive dual tasks, which cannot be explained in current models of dual task performance. To account for these findings, we propose a model integrating dual task and acute exercise approaches which posits that cognitive arousal during dual tasks increases resources to facilitate motor and cognitive performance, which is subsequently modulated by motor and cognitive task difficulty. This model can explain both the improvement observed on dual tasks in the current study and more typical dual task findings in other studies.

17 Article Weight loss and impact on quality of life in Parkinson's disease. 2015

Akbar, Umer / He, Ying / Dai, Yunfeng / Hack, Nawaz / Malaty, Irene / McFarland, Nikolaus R / Hess, Christopher / Schmidt, Peter / Wu, Samuel / Okun, Michael S. ·Department of Neurology, Brown University, Providence, Rhode Island, United States of America. · Department of Mathematics, Clarkson University, Potsdam, New York, United States of America. · Department of Biostatistics, University of Florida, Gainesville, Florida, United States of America. · Department of Neurology, University of Florida, Gainesville, Florida, United States of America. · National Parkinson Foundation, Miami, Florida, United States of America. ·PLoS One · Pubmed #25938478.

ABSTRACT: INTRODUCTION: Weight loss is common in Parkinson's Disease (PD) and sometimes may precede the diagnosis. Weight loss is associated with multiple factors but its impact on health-related quality of life (HRQL) in PD remains unknown. We sought to investigate the factors associated with weight change and to quantify its effect on HRQL. METHODS: The National Parkinson Foundation Quality Improvement Initiative (NPF-QII) data was used to analyze PD patients longitudinally between two visits, separated by 12 ± 6 months. Multiple linear regression analyses were used to assess the associations between baseline covariates and body weight change per month, and to evaluate whether, and to what degree, Parkinson's Disease Questionnaire (PDQ-39) scores were affected. RESULTS: A higher Hoehn & Yahr stage, higher number of comorbidities, older age, lower MOCA estimate, and higher rate of levodopa usage were observed in patients who lost weight. Multivariate regression analysis indicated that age and levodopa usage were significantly associated with weight loss. Furthermore, monthly body weight loss was significantly associated with HRQL decline in PD patients. Loss of 1 lb (0.45 kg) per month was associated with a decline in QOL: an increase of 0.5% in PDQ-39 Summary Index score (p=0.004), and 1.1% and 1.5% increases in the mobility and ADL dimensions, respectively. CONCLUSION: Weight loss in PD is common and seems to correlate with worsened HRQL. Awareness of factors associated with weight loss and its relation to HRQL may help practitioners improve patient management and expectations.

18 Article Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy. 2015

Planetta, Peggy J / Kurani, Ajay S / Shukla, Priyank / Prodoehl, Janey / Corcos, Daniel M / Comella, Cynthia L / McFarland, Nikolaus R / Okun, Michael S / Vaillancourt, David E. ·Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida. ·Hum Brain Mapp · Pubmed #25413603.

ABSTRACT: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1 -weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp.

19 Article Global attentional neglect of segmented lines in Parkinson's disease. 2015

Falchook, Adam D / Salazar, Liliana / Neal, Dan / Kesayan, Tigran / Williamson, John B / Malaty, Irene A / McFarland, Nikolaus R / Okun, Michael S / Rodriguez, Ramon L / Wagle Shukla, Aparna / Heilman, Kenneth M. ·a Department of Neurology , University of Florida , Gainesville , FL , USA. ·Neurocase · Pubmed #25073971.

ABSTRACT: Global attention requires disengagement from focal elements of stimuli. Since people with Parkinson's disease (PD) may reveal impaired disengagement, this study attempted to learn if people with PD may be impaired at allocating global attention. Healthy adults and people with PD attempted to bisect lines of uniform thickness and lines composed of two segments of unequal thickness and length. When the longer line segment was to the right of the shorter segment, the group with PD demonstrated an increased deviation toward the longer segment, supporting the postulate that people with PD have an impaired ability to disengage focal attention and engage global spatial attention.

20 Article Defining the clinically meaningful difference in gait speed in persons with Parkinson disease. 2014

Hass, Chris J / Bishop, Mark / Moscovich, Mariana / Stegemöller, Elizabeth L / Skinner, Jared / Malaty, Irene A / Wagle Shukla, Aparna / McFarland, Nikolaus / Okun, Michael S. ·Department of Applied Physiology and Kinesiology (CJH, JS), Center for Movement Disorders and Neurorestoration, Department of Neurology, (CJH, MM, JS, IAM, AWS, NM, MSO), Department of Physical Therapy (MB), University of Florida, Gainesville · and Department of Kinesiology, Iowa State University, Ames (ELS). ·J Neurol Phys Ther · Pubmed #25198866.

ABSTRACT: BACKGROUND AND PURPOSE: Gait dysfunction is a common target for pharmacological, behavioral, and surgical interventions in persons with Parkinson disease. However, the responsiveness of gait speed, that is, clinically important difference, is not well described in the literature for this population. The purpose of this study was to determine the magnitude of meaningful difference in gait speed using multiple methods of assessment and utilizing a large sample of participants inclusive of various stages of disease severity. METHODS: Gait speed was measured using an instrumented walkway in 324 ambulatory persons with idiopathic Parkinson disease. Cross-sectional analysis of the clinically important difference for gait speed was performed using distribution- and anchor-based approaches: disability (Schwab and England Activities of Daily Living Scale), disease stage (Modified Hoehn and Yahr Scale), and severity (Unified Parkinson's Disease Rating Scale). RESULTS: Using distribution-based analyses and effect size metrics, the small important difference in gait speed was 0.06 m/s, moderate was 0.14 m/s, and large was 0.22 m/s. Applying previously established cut-points for small, moderate, and large change in the motor scale score, the associated changes in gait speed that might be expected are 0.02, 0.06, and 0.10 m/s. DISCUSSION AND CONCLUSIONS: Our data revealed that the clinically important difference in gait speed among persons with Parkinson disease on medication ranged from 0.05 m/s to 0.22 m/s by distribution-based analysis and ranged from 0.02 m/s to 0.18 m/s per level within the anchor-based metrics. These data will aid in evaluating the effectiveness of interventions to improve gait speed in persons with Parkinson disease.Video Abstract available. See video (Supplemental Digital Content 1, http://links.lww.com/JNPT/A77) for more insights from the authors.

21 Article The "brittle response" to Parkinson's disease medications: characterization and response to deep brain stimulation. 2014

Martinez-Ramirez, Daniel / Giugni, Juan / Vedam-Mai, Vinata / Shukla, Aparna Wagle / Malaty, Irene A / McFarland, Nikolaus R / Rodriguez, Ramon L / Foote, Kelly D / Okun, Michael S. ·Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America; Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America. · Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, United States of America. ·PLoS One · Pubmed #24733172.

ABSTRACT: OBJECTIVE: Formulate a definition and describe the clinical characteristics of PD patients with a "brittle response" (BR) to medications versus a "non-brittle response" (NBR), and characterize the use of DBS for this population. METHODS: An UF IRB approved protocol used a retrospective chart review of 400 consecutive PD patients presenting to the UF Center for Movement Disorders and Neurorestoration. Patient records were anonymized and de-identified prior to analysis. SPSS statistics were used to analyze data. RESULTS: Of 345 included patients, 19 (5.5%) met criteria for BR PD. The BR group was comprised of 58% females, compared to 29% in the NBR group (P = .008). The former had a mean age of 63.4 compared to 68.1 in the latter. BR patients had lower mean weight (63.5 vs. 79.6, P = <.001), longer mean disease duration (12.6 vs. 8.9 years, P = .003), and had been on LD for more years compared to NBR patients (9.8 vs. 5.9, P = .001). UPDRS motor scores were higher (40.4 vs. 30.0, P = .001) in BR patients. No differences were observed regarding the Schwab and England scale, PDQ-39, and BDI-II. Sixty-three percent of the BR group had undergone DBS surgery compared to 18% (P = .001). Dyskinesias were more common, severe, and more often painful (P = <.001) in the BR group. There was an overall positive benefit from DBS. CONCLUSION: BR PD occurred more commonly in female patients with a low body weight. Patients with longer disease duration and longer duration of LD therapy were also at risk. The BR group responded well to DBS.

22 Article An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting. 2014

Hack, Nawaz / Fayad, Sarah M / Monari, Erin H / Akbar, Umer / Hardwick, Angela / Rodriguez, Ramon L / Malaty, Irene A / Romrell, Janet / Shukla, Aparna A Wagle / McFarland, Nikolaus / Ward, Herbert E / Okun, Michael S. ·Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, Florida, United States of America. · Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, Florida, United States of America; Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America. ·PLoS One · Pubmed #24646688.

ABSTRACT: BACKGROUND: To examine our eight year clinic-based experience in a Parkinson's disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). METHODS: The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. RESULTS: There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45-87 years (mean 68.3±10.15), disease duration of 17-240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = -0.36, p<0.01) and H&Y score (r = -0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). CONCLUSIONS: This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting.

23 Article Chronic treatment with novel small molecule Hsp90 inhibitors rescues striatal dopamine levels but not α-synuclein-induced neuronal cell loss. 2014

McFarland, Nikolaus R / Dimant, Hemi / Kibuuka, Laura / Ebrahimi-Fakhari, Darius / Desjardins, Cody A / Danzer, Karin M / Danzer, Michael / Fan, Zhanyun / Schwarzschild, Michael A / Hirst, Warren / McLean, Pamela J. ·Center for Translational Research in Neurodegenerative Disease, Department of Neurology, University of Florida, Gainesville, Florida, United States of America. · MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America. · Division of Neurology and Inherited Metabolic Diseases, Children's Hospital, Heidelberg University Hospital, Ruprecht-Karls University Heidelberg, Heidelberg, Germany. · Deparment of Neurology, Universitatsklinikum Ulm, Ulm, Germany. · Pfizer Neuroscience Research Unit, Cambridge, Massachusetts, United States of America. · Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America. ·PLoS One · Pubmed #24465863.

ABSTRACT: Hsp90 inhibitors such as geldanamycin potently induce Hsp70 and reduce cytotoxicity due to α-synuclein expression, although their use has been limited due to toxicity, brain permeability, and drug design. We recently described the effects of a novel class of potent, small molecule Hsp90 inhibitors in cells overexpressing α-synuclein. Screening yielded several candidate compounds that significantly reduced α-synuclein oligomer formation and cytotoxicity associated with Hsp70 induction. In this study we examined whether chronic treatment with candidate Hsp90 inhibitors could protect against α-synuclein toxicity in a rat model of parkinsonism. Rats were injected unilaterally in the substantia nigra with AAV8 expressing human α-synuclein and then treated with drug for approximately 8 weeks by oral gavage. Chronic treatment with SNX-0723 or the more potent, SNX-9114 failed to reduce dopaminergic toxicity in the substantia nigra compared to vehicle. However, SNX-9114 significantly increased striatal dopamine content suggesting a positive neuromodulatory effect on striatal terminals. Treatment was generally well tolerated, but higher dose SNX-0723 (6-10 mg/kg) resulted in systemic toxicity, weight loss, and early death. Although still limited by potential toxicity, Hsp90 inhibitors tested herein demonstrate oral efficacy and possible beneficial effects on dopamine production in a vertebrate model of parkinsonism that warrant further study.

24 Article Driving errors in Parkinson's disease: moving closer to predicting on-road outcomes. 2014

Classen, Sherrilene / Brumback, Babette / Monahan, Miriam / Malaty, Irene I / Rodriguez, Ramon L / Okun, Michael S / McFarland, Nikolaus R. ·Sherrilene Classen, PhD, MPH, OTR/L, is Professor and Director, School of Occupational Therapy, Elborn College, Room 2555B, 1201 Western Road, Western University, London, Ontario N6G 1H1 Canada. At the time of the study, she was Director, Institute for Mobility, Activity and Participation, and Associate Professor, Department of Occupational Therapy, College of Public Health and Health Professions, University of Florida, Gainesville; sclassen@uwo.ca. · Babette Brumback, PhD, is Professor and Program Director, Department of Biostatistics, University of Florida, Gainesville. · Miriam Monahan, MS OT, CDRS, is Occupational Therapist and Certified Driving Rehabilitation Specialist, Department of Occupational Therapy and Institute for Mobility, Activity and Participation, University of Florida, Gainesville. · Irene I. Malaty, MD, is Assistant Professor, Center for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville. · Ramon L. Rodriguez, MD, is Director, Movement Disorders Clinic, Center for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville. · Michael S. Okun, MD, is Co-Director, Center for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville. · Nikolaus R. McFarland, MD, PhD, is Assistant Professor, Department of Neurology, University of Florida, Gainesville. ·Am J Occup Ther · Pubmed #24367958.

ABSTRACT: Age-related medical conditions such as Parkinson's disease (PD) compromise driver fitness. Results from studies are unclear on the specific driving errors that underlie passing or failing an on-road assessment. In this study, we determined the between-group differences and quantified the on-road driving errors that predicted pass or fail on-road outcomes in 101 drivers with PD (mean age = 69.38 ± 7.43) and 138 healthy control (HC) drivers (mean age = 71.76 ± 5.08). Participants with PD had minor differences in demographics and driving habits and history but made more and different driving errors than HC participants. Drivers with PD failed the on-road test to a greater extent than HC drivers (41% vs. 9%), χ²(1) = 35.54, HC N = 138, PD N = 99, p < .001. The driving errors predicting on-road pass or fail outcomes (95% confidence interval, Nagelkerke R² =.771) were made in visual scanning, signaling, vehicle positioning, speeding (mainly underspeeding, t(61) = 7.004, p < .001, and total errors. Although it is difficult to predict on-road outcomes, this study provides a foundation for doing so.

25 Article Postural/Gait and cognitive function as predictors of driving performance in Parkinson's disease. 2013

Crizzle, Alexander M / Classen, Sherrilene / Lanford, Desiree N / Malaty, Irene A / Okun, Michael S / Wang, Yanning / Wagle Shukla, Aparna / Rodriguez, Ramon L / McFarland, Nikolaus R. ·Department of Occupational Therapy, University of Florida, Gainesville, FL 32601-0164, USA. acrizzle@sympatico.ca ·J Parkinsons Dis · Pubmed #23938345.

ABSTRACT: BACKGROUND: The primary influence of motor symptoms on driving performance remains unclear due to the inconsistent use of various motor rating scales used in prior studies. OBJECTIVE: This study aimed to determine which of three measures utilized in PD, the Unified Parkinson's Disease Rating Scale (UPDRS) motor section; the Modified Hoehn and Yahr; and the Rapid Paced Walk Test would best predict pass/fail outcomes on a road test in a sample of PD drivers. METHODS: All participants (N = 55; 79% men) completed a road test. Receiver Operating Characteristics were then contrasted for all subjects based on assessments from all three disease severity indices. MMSE scores were then modelled with significant disease severity measures (if any) to determine if the predictive accuracy could be improved. RESULTS: The Rapid Paced Walk Test and the Modified Hoehn & Yahr both predicted pass/fail outcomes on the road test (Area under the curve of 0.73 and 0.82, respectively). UPDRS motor scores, however, did not predict safe driving. When optimal cut-off points on the Modified Hoehn & Yahr (≥ 2.5) and Rapid Paced Walk Test (>6.22 seconds) were modelled with MMSE scores indicative of mild cognitive impairment (<27), the model accurately classified 92% and 100% as failing the road test, respectively. CONCLUSION: Although the Rapid Paced Walk Test had a slight advantage in differentiating between pass/fail outcomes compared to the Modified Hoehn & Yahr, both tests alone cannot be used in isolation to predict driving safety. Predictive accuracy can be improved using both select cut-off points on the Modified Hoehn & Yahr and Rapid Paced Walk test with MMSE scores in PD drivers. Though these findings are useful, an on-road test is still the gold standard, and screening should always be followed by formal testing.

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