Brent R. Bluett

All Publications

• The virtual reality of Parkinson's disease freezing of gait: A systematic review PARKINSONISM & RELATED DISORDERS Bluett, B., Bayram, E., Litvan, I. 2019; 61: 26?33

  View details for DOI 10.1016/j.parkreldis.2018.11.013

  View details for Web of Science ID 000468719900006

• Neural correlates of distinct cognitive phenotypes in early Parkinson's disease. Journal of the neurological sciences Bayram, E., Bluett, B., Zhuang, X., Cordes, D., LaBelle, D. R., Banks, S. J. 2019; 399: 22?29

  Abstract

  OBJECTIVE: Cognitive decline is common in Parkinson's disease (PD), but changes can occur in a variety of cognitive domains. The lack of a single cognitive phenotype complicates diagnosis and tracking. In an earlier study we used a data-driven approach to identify distinct cognitive phenotypes of early PD. Here we identify the morphometric brain differences between those different phenotypes compared with cognitively normal PD participants.METHODS: Six different cognitive classes were included (Weak, Typical, Weak-Visuospatial/Strong-Memory, Weak-Visuospatial, Amnestic, Strong). Structural differences between each class and the Typical class were assessed by deformation-based morphometry.RESULTS: The different groups evidenced different patterns of atrophy. Weak class had frontotemporal and insular atrophy; Weak-Visuospatial/Strong-Memory class had frontotemporal, insular, parietal, and putamen atrophy; Weak-Visuospatial class had Rolandic operculum; Amnestic class had left frontotemporal, occipital, parietal and insular atrophy when compared to the Typical class. The Strong class did not have any atrophy but had significant differences in left temporal cortex in comparison to the Typical class.CONCLUSIONS: Structural neuroimaging differences are evident in PD patients with distinct cognitive phenotypes even very early in the disease process prior to the emergence of frank cognitive impairment. Future studies will elucidate whether these have prognostic value in identifying trajectories toward dementia, or if they represent groups sensitive to different treatments.

  View details for PubMedID 30743154

• Non-motor predictors of freezing of gait in Parkinson's disease. Gait & posture Banks, S. J., Bayram, E., Shan, G., LaBelle, D. R., Bluett, B. 2018; 68: 311?16

  Abstract

  BACKGROUND: The etiology of freezing of gait in Parkinson's disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.RESEARCH QUESTION: We aimed to determine the predictive value of non-motor features in freezing of gait development.METHODS: Data were obtained from the Parkinson's Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.RESULTS: Patients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.SIGNIFICANCE: Our findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.

  View details for PubMedID 30553992

• The virtual reality of Parkinson's disease freezing of gait: A systematic review. Parkinsonism & related disorders Bluett, B., Bayram, E., Litvan, I. 2018

  Abstract

  INTRODUCTION: Freezing of gait is an episodic inability to move the feet forward despite the intention to walk. It is a common cause of falls and subsequent morbidity and mortality in Parkinson's disease. Virtual reality paradigms provide an opportunity to safely evaluate freezing of gait, in order to better understand the underlying pathophysiology. This article focuses on the methodology, threshold used to define freezing of gait, results, limitations of studies using virtual reality paradigms, and proposes future directions of research. Summarizing these articles improves our understanding of freezing of gait in Parkinson's disease, and critical evaluation provides an opportunity for future studies to improve upon these efforts.METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, of studies using VR paradigms to elucidate the underlying pathophysiology of PD-FOG.RESULTS: This review initially identified 57 articles, but after exclusion of duplicates, abstracts, and studies not focused on the underlying pathophysiology of this disorder, 12 peer-reviewed articles using virtual reality paradigms to evaluate freezing of gait in Parkinson's disease were found.CONCLUSION: Virtual reality paradigms are able to reproduce freezing of gait. Studies using MRI compatible virtual reality to evaluate freezing of gait found dysfunctional connectivity between cortical and subcortical structures during episodes. However, several important limitations of these studies should caution our interpretation of these results. Future studies which improve the design and methodology are needed to ultimately identify the cause and subsequent treatments for freezing of gait in Parkinson's disease.

  View details for PubMedID 30470656

• Neuroimaging and neuropsychological assessment of freezing of gait in Parkinson's disease. Alzheimer's & dementia (New York, N. Y.) Bluett, B., Banks, S., Cordes, D., Bayram, E., Mishra, V., Cummings, J., Litvan, I. 2018; 4: 387?94

  Abstract

  Freezing of gait (FOG) is a disabling phenomenon characterized by a brief, episodic absence or reduction of forward progression of the feet despite the intention to walk. It is a common cause of falls and mortality in cases with Parkinson's disease (PD). This article reviews neuropsychological and neuroimaging studies to date and introduces a new study of multimodal imaging and cognition in PD-FOG.A comprehensive literature search identified studies using neuropsychological evaluation and/or neuroimaging to evaluate PD-FOG.Several studies have evaluated PD-FOG, but few have combined neuropsychological and comprehensive neuroimaging and none longitudinally.A study using a combined approach longitudinally evaluating cognitive dysfunction and underlying neural networks in FOG is needed. We introduce the framework of a study which demonstrates the use of establishing an infrastructure for studying neurodegenerative disorders using the National Institutes of Health/National Institute of General Medical Science Center of Biomedical Research Excellence grant mechanism.

  View details for DOI 10.1016/j.trci.2018.04.010

  View details for PubMedID 30211293

  View details for PubMedCentralID PMC6131985

• Understanding falls in progressive supranuclear palsy PARKINSONISM & RELATED DISORDERS Bluett, B., Litvan, I., Cheng, S., Juncos, J., Riley, D. E., Standaert, D. G., Reich, S. G., Hall, D. A., Kluger, B., Shprecher, D., Marras, C., Jankovic, J., ENGENE PSP Study 2017; 35: 75?81

  Abstract

  Progressive supranuclear palsy (PSP) is characterized by frequent falls which worsen with disease progression, causing substantial morbidity and mortality. Few studies have investigated which factors contribute to falls in PSP, and all have involved few participants, thus lacking necessary statistical power. The aim of this study was to identify clinical parameters most significantly associated with increasing falls in PSP, using the largest sample of patients to date.Comprehensive clinical data were collected from 339 not demented PSP patients meeting the NINDS-SPSP criteria, who were divided into two groups - Infrequent Fallers (IF; n = 118) with rare falls, and Frequent Fallers (FF; n = 221) who fell occasionally to multiple times a day. Of 198 clinical parameters, we hypothesized 38 to be correlated with an increasing risk of falls. These 38 parameters were analyzed via univariate regression analysis to determine the strength of their association with fall frequency. Unit odds ratios identified the magnitude with which each parameter resulted in an increasing risk of falls.Twenty-five of 38 parameters analyzed were significantly associated with fall frequency based on univariate analysis. Symptom duration, clinical measures of disease severity, and several motoric and oculomotor clinical parameters were associated with FF. Examined cognitive parameters and slowing of vertical saccades were not.The clinical parameters identified as associated with increased frequency of falls improve our understanding of why they occur and may help identify not demented PSP patients at risk for increasing falls.

  View details for DOI 10.1016/j.parkreldis.2016.12.009

  View details for Web of Science ID 000394074100012

  View details for PubMedID 28007518

• Understanding, predicting, and preventing falls in progressive supranuclear palsy Bluett, B. R., Litvan, I., Cheng, S., Juncos, J., Bordelon, Y., Riley, D. E., Standaert, D., Reich, S. G., Hall, D. A., Kluger, B., Shprecher, D., Marras, C., Jankovic, J. WILEY-BLACKWELL. 2016: S82?S83

  View details for Web of Science ID 000382559800239

• Pathophysiology, genetics, clinical features, diagnosis and therapeutic trials in progressive supranuclear palsy EXPERT OPINION ON ORPHAN DRUGS Bluett, B., Litvan, I. 2015; 3 (3): 253?65

  View details for DOI 10.1517/21678707.2015.1018180

  View details for Web of Science ID 000350106400003

• Temperature Affects Thrombolytic Efficacy Using rt-PA and Eptifibatide, an In Vitro Study THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT Meunier, J. M., Chang, W. W., Bluett, B., Wenker, E., Lindsell, C. J., Shaw, G. J. 2012; 2 (3): 112?18

  Abstract

  The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf?), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5??g/mL) and Epf (0.63??g/mL) in human fresh-frozen plasma (rt-PA+Epf?), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf?treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents.

  View details for DOI 10.1089/ther.2012.0007

  View details for Web of Science ID 000209354800004

  View details for PubMedID 23667777

  View details for PubMedCentralID PMC3621317

• Appearance and impact of post-operative intracranial clips and coils on whole-brain CT angiography and perfusion EUROPEAN JOURNAL OF RADIOLOGY Roach, C. J., Russell, C. L., Hanson, E. H., Bluett, B., Orrison, W. W. 2012; 81 (5): 960?67

  Abstract

  To evaluate the effect of vascular clips and endovascular coils placed for intracranial aneurysms and arteriovenous malformations on whole-brain computed tomography (CT) angiography and perfusion.A 320-detector row dynamic volume CT system imaged 11 patients following surgical placement of vascular clips or endovascular coils. The extent of clip and coil subtraction by automated software was evaluated using CT digital subtraction angiography and CT perfusion. Impact on CT perfusion values by retained intracranial devices was compared to age- and gender-matched controls.Clip and coil subtraction on CT angiography was graded as good in 8 and moderate in 3 cases. A residual neck and additional aneurysm were noted in 1 of 11 patients. Post-procedural axial slice level CT perfusion values decreased in reliability with increasing proximity to the metallic devices secondary to beam hardening. However, the intracranial devices did not affect axial slice level CTP values of cerebral blood volume, cerebral blood flow and mean transit time outside of the level of the device. Time to peak values was globally decreased outside of the immediate vascular intervention region.Advances in CT technology have provided clinically useful subtraction of intracranial clips and coils. While CT perfusion values were altered in device subtraction areas and within beam hardening artifact areas; they can provide valuable postoperative information on whole-brain hemodynamics. In selected cases, the combination of CT angiography and whole-brain CT perfusion can offer an alternative to conventional angiography that is a more invasive option.

  View details for DOI 10.1016/j.ejrad.2011.01.118

  View details for Web of Science ID 000303108000041

  View details for PubMedID 21367552