Peer-Reviewed Journal Articles
- Effect of using a wearable device on clinical decision-making and motor symptoms in patients with Parkinson’s disease starting transdermal rotigotine patch: A pilot study
Isaacson S, Boroojerdi B, Waln O, McGraw M, Kreitzman D, Klos K, Revilla F, Heldman D, Phillips M, Terricabras D, Markowitz M, Woltering F, Carson S, Truong D
Parkinsonism & Related Disorders. 2019 (In Press) - App-Based Bradykinesia Tasks for Clinic and Home Assessment in Parkinson’s Disease: Reliability and Responsiveness
Heldman DA, Urrea-Mendoza E, Lovera LC, Schmerler DA, Garcia X, Mohammad ME, McFarlane MCU, Giuffrida JP, Espay AJ, Fernandez HH.
- Does Added Objective Tremor Monitoring Improve Clinical Outcomes in Essential Tremor Treatment?
Vittal P, Pulliam CL, Goetz CG, Ouyang B, Jankovic J, Ramirez-Castaneda JL, Heldman, DA.
- Telehealth Management of Parkinson’s Disease Using Wearable Sensors: An Exploratory Study
Dustin A. Heldman; Denzil A. Harris; Timothy Felong; Kelly L. Andrzejewski; E. Ray Dorsey; Joseph P. Giuffrida; Barry Goldberg; Michelle A. Burack.
- Continuous Assessment of Levodopa Response in Parkinson’s Disease Using Wearable Motion Sensors
Christopher L. Pulliam; Dustin A. Heldman; Elizabeth B. Brokaw; Thomas O. Mera; Zoltan K. Mari; Michelle A. Burack
- Effect of subthalamic stimulation on distal and proximal upper limb movements in Parkinson’s disease.
Tamás G, Kelemen A, Radics P, Valálik I, Heldman D, Klivényi P, Vécsei L, Hidasi E, Halász L, Kis D, Barsi P, Golopencza P, Erőss L.
Brain Res. 2016 Oct 1;1648(Pt A):438-44. doi: 10.1016/j.brainres.2016.08.019. Epub 2016 Aug 16.
- Wearable Sensors for Advanced Therapy Referral in Parkinson’s Disease
Heldman DA, Giuffrida JP, Cubo E
Journal of Parkinsons Disease. 2016 Jul 2. [Epub ahead of print]
- Prospective study on cost-effectiveness of home-based motor assessment in Parkinson’s disease
E Cubo, N Mariscal, B Solano, V Becerra, D Armesto, S Calvo, J Arribas, J Seco, A Martinez, L Zorrilla, and D Heldman
J Telemed Telecare 1357633X16638971, first published on March 21, 2016
- Randomized, Blinded Pilot Testing of Nonconventional Stimulation Patterns and Shapes in Parkinson’s Disease and Essential Tremor: Evidence for Further Evaluating Narrow and Biphasic Pulses
Umer Akbar MD, Robert S. Raike PhD, Nawaz Hack MD, Christopher W. Hess MD, Jared Skinner PhD, Daniel Martinez-Ramirez MD, Sol DeJesus MD, Michael S. Okun MD
Neuromodulation: Technology at the Neural Interface (onlinelibrary.wiley.com) DOI: 10.1111/ner.12397 First published: 22 March 2016
- Computer-Guided Deep Brain Stimulation Programming for Parkinson’s Disease
Heldman, D.A., Pulliam, C.L., Urrea Mendoza, E., Gartner, M., Giuffrida, J.P., Montgomery, E.B., Espay, A.J., and Revilla, F.J.
Neuromodulation: Technology at the Neural Interface, Dec 2015.
- Motion Sensor Strategies for Automated Optimization of Deep Brain Stimulation in Parkinson’s disease
Christopher L. Pulliam, Dustin A. Heldman, Tseganesh H. Orcutt, Thomas O. Mera, Joseph P. Giuffrida, Jerrold L. Vitek
- Development of a Clinician Worn Device for the Evaluation of Abnormal Muscle Tone
E. Brokaw, D. Heldman, R. Plott, E. Rapp, E. Montgomery, J. Giuffrida
Conf Proc IEEE Eng Med Biol Soc. 2014. - Motion Sensor Dyskinesia Assessment During Activities of Daily Living
C. Pulliam, M. Burack, D Heldman, J Giuffrida, T Mera
Journal of Parkinson’s Disease 2014Abstract
Background
Dyskinesia throughout the levodopa dose cycle has been previously measured in patients with Parkinson’s disease (PD) using a wrist-worn motion sensor during the stationary tasks of arms resting and extended. Quantifying dyskinesia during unconstrained activities poses a unique challenge since these involuntary movements are kinematically similar to voluntary movement.
Objective
To determine the feasibility of using motion sensors to measure dyskinesia during activities of daily living.
Methods
Fifteen PD subjects performed scripted activities of daily living while wearing motion sensors on bilateral hands, thighs, and ankles over the course of a levodopa dose cycle. Videos were scored by clinicians using the modified Abnormal Involuntary Movement Scale to rate dyskinesia severity in separate body regions, with the total score used as an overall measure. Kinematic features were extracted from the motion data and algorithms were generated to output severity scores.
Results
Movements when subjects were experiencing dyskinesia were less smooth than when they were not experiencing dyskinesia. Dyskinesia scores predicted by the model using all sensors were highly correlated with clinician scores, with a correlation coefficient of 0.86 and normalized root-mean-square-error of 7.4%. Accurate predictions were maintained when two sensors on the most affected side of the body (one on the upper extremity and one on the lower extremity) were used.
Conclusions
A system with motion sensors may provide an accurate measure of overall dyskinesia that can be used to monitor patients as they complete typical activities, and thus provide insight on symptom fluctuation in the context of daily life.
- Clinician Versus Machine: Reliability and Responsiveness of Motor Endpoints in Parkinson’s Disease
D. Heldman, A. Espay, P. Lewitt, and J. Giuffrida
Parkinsonism Relat Disord. 2014;20(6):590–5.Abstract
Background
Enhancing the reliability and responsiveness of motor assessments required to demonstrate therapeutic efficacy is a priority for Parkinson’s disease (PD) clinical trials. The objective of this study is to determine the reliability and responsiveness of a portable kinematic system for quantifying PD motor deficits as compared to clinical ratings.
Methods
Eighteen PD patients with subthalamic nucleus deep-brain stimulation (DBS) performed three tasks for evaluating resting tremor, postural tremor, and finger-tapping speed, amplitude, and rhythm while wearing a wireless motion-sensor unit (Kinesia) on the more-affected index finger. These tasks were repeated three times with DBS turned off and at each of 10 different stimulation amplitudes chosen to yield small changes in treatment response. Each task performance was video-recorded for subsequent clinician rating in blinded, randomized order. Test-retest reliability was calculated as intraclass correlation (ICC) and sensitivity was calculated as minimal detectable change (MDC) for each DBS amplitude.
Results
ICCs for Kinesia were significantly higher than those for clinician ratings of finger-tapping speed (p < 0.0001), amplitude (p < 0.0001), and rhythm (p < 0.05), but were not significantly different for evaluations of resting or postural tremor. Similarly, Kinesia scores yielded a lower MDC as compared with clinician scores across all finger-tapping subscores (p < 0.0001), but did not differ significantly for resting and postural tremor.
Conclusions
The Kinesia portable kinematic system can provide greater test-retest reliability and sensitivity to change than conventional clinical ratings for measuring bradykinesia, hypokinesia, and dysrhythmia in PD patients.
- Tremor retrainment as therapeutic strategy in psychogenic (functional) tremor
A. Espay, M. Edwards, G. Oggioni, N. Phielipp, B. Cox, H. Gonzalez-Usigli, C. Pecina, D. Heldman, J. Mishra, A. Lang
Parkinsonism Relat Disord. 2014;20(6):647–50.Abstract
Background
Entrainment, the change or elimination of tremor as patients perform a voluntary rhythmical movement by the unaffected limb, is a key diagnostic hallmark of psychogenic tremor.
Objective
To evaluate the feasibility of using entrainment as a bedside therapeutic strategy (‘retrainment’) in patients with psychogenic tremor.
Methods
Ten patients with psychogenic tremor (5 women, mean age, 53.6 ± 12.8 years; mean disease duration 4.3 ± 2.7 years) were asked to participate in a pilot proof-of-concept study aimed at “retraining” their tremor frequency. Retrainment was facilitated by tactile and auditory external cueing and real-time visual feedback on a computer screen. The primary outcome measure was the Tremor subscale of the Rating Scale for Psychogenic Movement Disorders.
Results
Tremor improved from 22.2 ± 13.39 to 4.3 ± 5.51 (p = 0.0019) at the end of retrainment. The benefits were maintained for at least 1 week and up to 6 months in 6 patients, with relapses occurring in 4 patients between 2 weeks and 6 months. Three subjects achieved tremor freedom.
Conclusions
Tremor retrainment may be an effective short-term treatment strategy in psychogenic tremor. Although blinded evaluations are not feasible, future studies should examine the long-term benefits of tremor retrainment as adjunctive to psychotherapy or specialized physical therapy.
- Continuous In-Home Monitoring Of Essential Tremor
C. Pulliam, S. Eichenseer, C. Goetz, O. Waln, C. Hunter, J. Jankovic, D. Vaillancourt, J. Giuffrida, And D. Heldman
Parkinsonism Relat Disord. 2014 Jan;20(1):37-40.Abstract
Background
Essential tremor (ET) is typically measured in the clinic with subjective tremor rating scales which require the presence of a clinician for scoring and are not appropriate for measuring severity throughout the day. Motion sensors can accurately rate tremor severity during a set of predefined tasks in a laboratory.
Methods
We evaluated the ability of motion sensors to quantify tremor during unconstrained activities at home. 20 ET subjects wore a wireless sensor continuously for up to 10 h daily on two days and completed hourly standardized tremor assessments involving pre-defined tasks. Mathematical models were used to predict tremor rating scores from the sensor data.
Results
At home tremor scores from hourly standardized assessments correlated with at home tremor scores estimated during unconstrained activities immediately following the standardized assessments. The hourly standardized assessments did not significantly fluctuate throughout the day, while fluctuations in the continuous assessments tended to follow changes in voluntary activity level. Both types of tremor ratings (standardized and continuous) showed high day-to-day test-retest reliability with intraclass correlation coefficients ranging from 0.67 to 0.90 for continuous ratings and 0.77 to 0.95 for standardized ratings.
Conclusions
Results demonstrate the feasibility of continuous monitoring of tremor severity at home, which should provide clinicians with a measure of the temporal pattern of tremor in the context of daily life and serve as a useful tool for the evaluation of novel anti-tremor medications in clinical trials.
- Objective Motion Sensor Assessment Highly Correlated with Scores of Global Levodopa-Induced Dyskinesia in Parkinson’s Disease
T. Mera, M. Burack, J. Giuffrida
J Parkinsons Dis. 2013 Jan 1;3(3):399-407.Abstract
Background
Chronic use of medication for treating Parkinson’s disease (PD) can give rise to peak-dose dyskinesia. Adjustments in medication often sacrifice control of motor symptoms, and thus balancing this trade-off poses a significant challenge for disease management.
Objective
To determine whether a wrist-worn motion sensor unit could be used to ascertain global dyskinesia severity over a levodopa dose cycle and to develop a severity scoring algorithm highly correlated with clinician ratings.
Methods
Fifteen individuals with PD were instrumented with a wrist-worn motion sensor unit, and data were collected with arms in resting and extended positions once every hour for three hours after taking a levodopa dose. Two neurologists blinded to treatment status viewed subject videos and rated global and upper extremity dyskinesia severity based on the modified Abnormal Involuntary Movement Scale (mAIMS). Linear regression models were developed using kinematic features extracted from motion sensor data and extremity, global, or combined (average of extremity and global) mAIMS scores.
Results
Dyskinesia occurring during a levodopa dose cycle was successfully measured using a wrist-worn sensor. The logarithm of the power spectrum area between 0.3-3 Hz and the combined clinician scores resulted in the best model performance, with a correlation coefficient between clinician and model scores of 0.81 and root mean square error of 0.55, both averaged across the arms resting and extended postures
Conclusions
One sensor unit worn on either hand can effectively predict global dyskinesia severity during the arms resting or extended positions.
- Quantitative Analysis Of Gait And Balance Response To Deep Brain Stimulation In Parkinson’s Disease
T. Mera, D. Filipkowski, D. Riley, C. Whitney, B. Walter, S. Gunzler, J. Giuffrida
Gait & Posture. 2013 May;38(1):109-14Abstract
Gait and balance disturbances in Parkinson’s disease (PD) can be debilitating and may lead to increased fall risk. Deep brain stimulation (DBS) is a treatment option once therapeutic benefits from medication are limited due to motor fluctuations and dyskinesia. Optimizing DBS parameters for gait and balance can be significantly more challenging than for other PD motor symptoms. Furthermore, inter-rater reliability of the standard clinical PD assessment scale, Unified Parkinson’s Disease Rating Scale (UPDRS), may introduce bias and washout important features of gait and balance that may respond differently to PD therapies. Study objectives were to evaluate clinician UPDRS gait and balance scoring inter-rater reliability, UPDRS sensitivity to different aspects of gait and balance, and how kinematic features extracted from motion sensor data respond to stimulation. Forty-two subjects diagnosed with PD were recruited with varying degrees of gait and balance impairment. All subjects had been prescribed dopaminergic medication, and 20 subjects had previously undergone DBS surgery. Subjects performed seven items of the gait and balance subset of the UPDRS while wearing motion sensors on the sternum and each heel and thigh. Inter-rater reliability varied by UPDRS item. Correlation coefficients between at least one kinematic feature and corresponding UPDRS scores were greater than 0.75 for six of the seven items. Kinematic features improved (p<0.05) from DBS-OFF to DBS-ON for three UPDRS items. Despite achieving high correlations with the UPDRS, evaluating individual kinematic features may help address inter-rater reliability issues and rater bias associated with focusing on different aspects of a motor task.
- Active-Assisted Cycling Improves Tremor and Bradykinesia in Parkinson’s Disease
A. Ridgel, C. Peacock, E. Fickes, C. Kim
Arch Phys Med Rehabil. 2012 Nov;93(11):2049-54Abstract
Objective
To develop a rapid cadence cycling intervention (active-assisted cycling [AAC]) using a motorized bike and to examine physiological perimeters during these sessions in individuals with Parkinson’s disease (PD). A secondary goal was to examine whether a single session of AAC at a high cadence would promote improvements in tremor and bradykinesia similar to the on medication state.
Design
Before-after pilot trial with cross-over.
Setting
University research laboratory.
Participants
Individuals with idiopathic PD (N=10, age 45-74y) in Hoehn and Yahr stages 1 to 3.
Intervention
Forty minutes of AAC.
Main Outcome Measures
Heart rate, pedaling power, and rating of perceived exertion were recorded before, during, and after a bout of AAC. Functional assessments included tremor score during resting, postural, and kinetic tremor.
Results
This AAC paradigm was well tolerated by individuals with PD without excessive fatigue, and most participants showed improvements in tremor and bradykinesia immediately after a single bout of cycling.
Conclusions
This paradigm could be used to examine changes in motor function in individuals with PD after bouts of high-intensity exercise.
- Quantitative assessment of levodopa-induced dyskinesia using automated motion sensing technology
T. Mera, M. Burack, J. Giuffrida
Conf Proc IEEE Eng Med Biol Soc. 2012.Abstract
The objective was to capture levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease (PD) using body-worn motion sensors. Dopaminergic treatment in PD can induce abnormal involuntary movements, including choreatic dyskinesia (brief, rapid, irregular movements). Adjustments in medication to reduce LID often sacrifice control of motor symptoms, and balancing this tradeoff poses a significant challenge for management of advanced PD. Fifteen PD subjects with known LID were recruited and instructed to perform two stationary motor tasks while wearing a compact wireless motion sensor unit positioned on each hand over the course of a levodopa dose cycle. Videos of subjects performing the motor tasks were later scored by expert clinicians to assess global dyskinesia using the modified Abnormal Involuntary Rating Scale (m-AIMS). Kinematic features were extracted from motion data in different frequency bands (1-3Hz and 3-8Hz) to quantify LID severity and to distinguish between LID and PD tremor. Receiver operator characteristic analysis was used to determine thresholds for individual features to detect the presence of LID. A sensitivity of 0.73 and specificity of 1.00 were achieved. A neural network was also trained to output dyskinesia severity on a 0 to 4 scale, similar to the m-AIMS. The model generalized well to new data (coefficient of determination= 0.85 and mean squared error= 0.3). This study demonstrated that hand-worn motion sensors can be used to assess global dyskinesia severity independent of PD tremor over the levodopa dose cycle.
- Automated motion sensor quantification of gait and lower extremity bradykinesia
D. Heldman, D. Filipkowski, R. Riley, C. Whitney, B. Walter, S. Gunzler, T. Mera
Conf Proc IEEE Eng Med Biol Soc. 2012.Abstract
The objective was to develop and evaluate algorithms for quantifying gait and lower extremity bradykinesia in patients with Parkinson’s disease using kinematic data recorded on a heel-worn motion sensor unit. Subjects were evaluated by three movement disorder neurologists on four domains taken from the Movement Disorders Society Unified Parkinson’s Disease Rating Scale while wearing the motion sensor unit. Multiple linear regression models were developed based on the recorded kinematic data and clinician scores and produced outputs highly correlated to clinician scores with an average correlation coefficient of 0.86. The newly developed models have been integrated into a home-based system for monitoring Parkinson’s disease motor symptoms.
- Amplitude fluctuations in essential tremor
G. Mostile, R. Fekete, J. Giuffrida, T. Yaltho, A. Davidson, A. Nicoletti, M. Zappia, J. Jankovic
Parkinsonism Relat Disord. 2012 Aug;18(7):859-63Abstract
Objective
To assess temporal amplitude variability in patients with essential tremor (ET).
Methods
Patients who satisfied the diagnostic criteria for probable or definite ET were enrolled in the study. Each enrolled patient was first rated using the essential tremor rating assessment scale (TETRAS). Postural and kinetic tremors of the arms were then measured using a quantitative motor assessment system (QMAS) starting at 8:00 AM (T0-baseline) every 2 h for 6 h. Subjects were videotaped performing the tasks. Single subjects consecutively performed each assessment twice during every time-interval. At the end of the study, videos were randomized and blindly rated using TETRAS.
Results
Twelve ET subjects were enrolled. QMAS and video scores were directly correlated with high test-retest reliability for each time-interval. Furthermore, the QMAS scores at T0 significantly correlated with in-person rated TETRAS scores as well as with subsequent time-intervals instrumental scores. No significant differences were detected between time-intervals QMAS average measurements using ANOVA. There was a maximal 23% absolute variation in tremor amplitude from baseline as determined by the QMAS. Test for equality of variance showed high measurement variability for subjects with high QMAS scores at T0 and throughout the 6 h of assessment.
Conclusions
Baseline measures are predictive of tremor amplitude at subsequent assessments during the day. High amplitude tremor is associated with high intra-assessment variability.
- Objective Measure of Upper Extremity Motor Impairment in Parkinsons Disease with Inertial Sensors
J. Hoffman, J. McNames
Conf Proc IEEE Eng Med Biol Soc. 2011;2011:4378-81Abstract
Functional motor impairment caused by Parkinson’s disease and other movement disorders is currently measured with rating scales such as the Unified Parkinson’s Disease Rating Scale (UPDRS). These are typically comprised of a series of simple tasks that are visually scored by a trained rater. We developed a method to objectively quantify three upper extremity motor tasks directly with a wearable inertial sensor. Specifically, we used triaxial gyroscopes and adaptive filters to quantify how predictable and regular the signals were. We found that simply using the normalized mean squared error (NMSE) as a test statistic permitted us to distinguish between subjects with and without Parkinson’s disease who were matched for age, height, and weight. A forward linear predictor based on the Kalman filter was able to attain areas under the curve (AUC) in receiver operator characteristic (ROC) curves in the range of 0.76 to 0.83. Further studies and development are warranted. This technology has the potential to more accurately measure the motor signs of Parkinson’s disease. This may reduce statistical bias and variability of rating scales, which could lead to trials with fewer subjects, less cost, and shorter duration.
- Feasibility of Home-Based Automated Parkinson’s Disease Motor Assessment
T. Mera, D. Heldman, A. Espay, M. Payne, J. Giuffrida
J Neurosci Methods. 2012 Jan 15;203(1):152-6Abstract
Patients with Parkinson’s disease (PD) receive therapies aimed at addressing a diverse range of motor symptoms. Motor complications in the form of symptom fluctuations and dyskinesias that commonly occur with chronic PD medication use may not be effectively captured by Unified Parkinson’s Disease Rating Scale (UPDRS) assessments performed in the clinic. Therefore, home monitoring may be a viable adjunct tool to provide insight into PD motor symptom response to treatment. In this pilot study, we sought to evaluate the feasibility of capturing PD motor symptoms at home using a computer-based assessment system. Ten subjects diagnosed with idiopathic PD used the system at home and ten non-PD control subjects used the system in a laboratory. The Kinesia system consists of a wireless finger-worn motion sensor and a laptop computer with software for automated tremor and bradykinesia severity score assessments. Data from control subjects were used to develop compliance algorithms for rejecting motor tasks performed incorrectly. These algorithms were then applied to data collected from the PD subjects who used the Kinesia system at home to complete motor exams 3-6 times per day over 3-6 days. Motor tasks not rejected by the compliance algorithms were further processed for symptom severity. PD subjects successfully completed motor assessments at home, with approximately 97% of all motor task data files (1222/1260) accepted. These findings suggest that objective home monitoring of PD motor fluctuations is feasible.
- Differential Response of Speed, Amplitude, and Rhythm to Dopaminergic Medications in Parkinson’s Disease
A. Espay, J. Giuffrida, R. Chen, M. Payne, F. Mazzella, E. Dunn, J. Vaughan, A. Duker, A. Sahay, S. Kim, F. Revilla, D. Heldman
Mov Disord. 2011 Dec;26(14):2504-8Abstract
Although movement impairment in Parkinson’s disease includes slowness (bradykinesia), decreased amplitude (hypokinesia), and dysrhythmia, clinicians are instructed to rate them in a combined 0-4 severity scale using the Unified Parkinson’s Disease Rating Scale motor subscale. The objective was to evaluate whether bradykinesia, hypokinesia, and dysrhythmia are associated with differential motor impairment and response to dopaminergic medications in patients with Parkinson’s disease. Eighty five Parkinson’s disease patients performed finger-tapping (item 23), hand-grasping (item 24), and pronation-supination (item 25) tasks OFF and ON medication while wearing motion sensors on the most affected hand. Speed, amplitude, and rhythm were rated using the Modified Bradykinesia Rating Scale. Quantitative variables representing speed (root mean square angular velocity), amplitude (excursion angle), and rhythm (coefficient of variation) were extracted from kinematic data. Fatigue was measured as decrements in speed and amplitude during the last 5 seconds compared with the first 5 seconds of movement. Amplitude impairments were worse and more prevalent than speed or rhythm impairments across all tasks (P < .001); however, in the ON state, speed scores improved exclusively by clinical (P < 10(-6) ) and predominantly by quantitative (P < .05) measures. Motor scores from OFF to ON improved in subjects who were strictly bradykinetic (P < .01) and both bradykinetic and hypokinetic (P < 10(-6) ), but not in those strictly hypokinetic. Fatigue in speed and amplitude was not improved by medication. Hypokinesia is more prevalent than bradykinesia, but dopaminergic medications predominantly improve the latter. Parkinson’s disease patients may show different degrees of impairment in these movement components, which deserve separate measurement in research studies.
- Acute effects of passive leg cycling on upper extremity tremor and bradykinesia in Parkinson’s disease
A. Ridgel, M. Muller, C. Kim, E. Fickes, T. Mera
Phys Sportsmed. 2011 Sep;39(3):83-93Abstract
Background
Previous studies have shown that single bouts of high-rate active cycling (> 80 rpm) improve upper extremity motor function in individuals with Parkinson’s disease (PD). It is unknown if passive leg cycling produces a similar effect on upper extremity function. This article examines whether passive leg cycling can promote immediate changes in upper tremor and bradykinesia in PD and if pedaling rates have variable effects.
Methods
Twenty individuals with mild-to-moderate idiopathic PD completed 4 sessions, with each session taking place 1 week apart. In the second to fourth sessions, a motorized bicycle was set to passively rotate the subjects’ legs at rates of 60, 70, or 80 rpm for 30 minutes. Quantitative upper extremity motor assessments were completed immediately before and after each session.
Results
Passive leg cycling was shown to reduce tremor and bradykinesia in PD. However, the rate of passive cycling did not affect the degree of improvement in bradykinesia or tremor.
Conclusions
These findings suggest that lower extremity passive cycling can promote changes in upper extremity motor function in individuals with PD.
- The Modified Bradykinesia Rating Scale for Parkinson’s disease: Reliability and Comparison with Kinematic Measures
D. Heldman, J. Giuffrida, R. Chen, M. Payne, F. Mazzella, A. Duker, A. Sahay, S. Kim, F. Revilla, A. Espay.
Mov Disord. 2011 Aug 15;26(10):1859-63Abstract
Bradykinesia encompasses slowness, decreased movement amplitude, and dysrhythmia. Unified Parkinson’s Disease Rating Scale-based bradykinesia-related items require that clinicians condense abnormalities in speed, amplitude, fatiguing, hesitations, and arrests into a single score. The objective of this study was to evaluate the reliability of a modified bradykinesia rating scale, which separately assesses speed, amplitude, and rhythm and its correlation with kinematic measures from motion sensors. Fifty patients with Parkinson’s disease performed Unified Parkinson’s Disease Rating Scale-directed finger tapping, hand grasping, and pronation-supination while wearing motion sensors. Videos were rated blindly and independently by 4 clinicians. The modified bradykinesia rating scale and Unified Parkinson’s Disease Rating Scale demonstrated similar inter- and intrarater reliability. Raters placed greater weight on amplitude than on speed or rhythm when assigning a Unified Parkinson’s Disease Rating Scale score. Modified bradykinesia rating scale scores for speed, amplitude, and rhythm correlated highly with quantitative kinematic variables. The modified bradykinesia rating scale separately captures bradykinesia components with interrater and intrarater reliability similar to that of the Unified Parkinson’s Disease Rating Scale. Kinematic sensors can accurately quantify speed, amplitude, and rhythm to aid in the development and evaluation of novel therapies in Parkinson’s disease.
- Essential Tremor Quantification During Activities of Daily Living
D. Heldman, J. Jankovic, D. Vaillancourt, J. Prodoehl, R. Elble, J. Giuffrida
Parkinsonism Relat Disord. 2011 Aug;17(7):537-42Abstract
Background
Essential tremor (ET), characterized primarily by postural and kinetic tremor, is typically measured in the clinic with subjective tremor rating scales. These ratings are often used to adjust medications and assess efficacy in clinical trials. However, tremor ratings require the presence of a clinician and do not necessarily capture tremor fluctuations throughout the day during activities of daily living (ADL).
Objective
To evaluate the ability of motion sensors to discriminate tremor from voluntary posture and motion, classify tremor as postural or kinetic, and rate tremor severity during standardized tasks and non-standardized activities of daily living.
Methods
Ten subjects with ET wore motion sensors on the index finger and performed standardized motor tasks from the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) tremor rating scale (wTRS) and non-standardized ADL tasks. Four movement disorder specialists independently rated video segments of the standardized tasks but not the ADL tasks. Quantitative features were extracted from the motion sensors and used to develop mathematical models for predicting rating scores from kinematic data.
Results
The quantitative motion features were highly correlated with wTRS ratings for postural (r = 0.90) and kinetic (r = 0.80) tremors. Mathematical models produced tremor ratings that correlated strongly with clinician ratings of the wTRS tasks (mean r = 0.80) and also produced ADL task ratings that correlated well with the most recent clinician wTRS ratings (mean r = 0.72).
Conclusions
Recordings from motion sensors can be used to classify tremor as postural or kinetic and quantify tremor severity during both standardized and non-standardized activities.
- Kinematic Optimization of Deep Brain Stimulation Across Multiple Motor Symptoms in Parkinson’s Disease
T. Mera, J. Vitek, J. Alberts, J. Giuffrida
J Neurosci Methods. 2011 Jun 15;198(2):280-6Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms including tremor and bradykinesia (slowness of movement). Drug treatment, although capable of controlling these symptoms over a number of years, becomes less effective as the disease progresses and leads to motor complications such as drug-induced dyskinesia (involuntary abnormal movements). Deep brain stimulation (DBS) provides an alternative means of controlling motor symptoms in these patients, and while DBS has been effective in improving motor symptoms, these improvements are largely based on accurate placement of the lead and the ability of medical personnel to adequately program the DBS device following implantation. While guidelines exist for DBS programming, selection of stimulation parameters and patient outcome is greatly dependent on subjective clinical assessments and the experience of the medical personnel performing the programming. The aim of this project was to assess the feasibility of using a quantitative and objective approach to programming. Two subjects underwent standard procedures for DBS programming while wearing a small, compact motion sensor. Kinematic data were collected from subjects as they completed motor tasks to evaluate DBS efficacy. Quantitative variables characterizing tremor and bradykinesia were related to stimulation parameters. Results indicated different stimulation settings might be required for optimal improvement of different motor symptoms. A standardized method of programming DBS parameters utilizing motion analysis may provide an objective method of assessment that the programmer can use to better identify stimulation parameters to achieve optimal improvement across multiple motor symptoms.
- Correlation between Kinesia system assessments and clinical tremor scores in patients with essential tremor
M. Giovanni, J. Giuffrida, O. Adam, A. Davidson, J. Jankovic
Mov Disord. 2010 Sep 15;25(12):1938-43Abstract
The primary aim of this study was to determine whether scores on The Essential Tremor Rating Assessment Scale (TETRAS) correlate with quantitative assessments using the Kinesia™ (CleveMed) system in patients with essential tremor (ET). Patients sequentially evaluated and diagnosed with ET at the Parkinson’s Disease Center and Movement Disorders Clinic, Baylor College of Medicine were enrolled in the study. The Kinesia portable device was attached to the wrist and subjects were instructed to hold their arms in an outstretched position and then touch their nose while data were wirelessly transmitted to a computer. Subjects were rated on the arm where the system was placed using specific TETRAS items. A linear regression model was constructed for each task using the logarithmic values of both clinical scores and objective motion data parameters to compute a Kinesia score. Twenty subjects underwent complete clinical TETRAS and Kinesia quantitative assessments. TETRAS clinical scores significantly correlated with predicted Kinesia quantitative variables for postural (r = 0.738; P < 0.001) and kinetic (r = 0.57; P = 0.009) tremor. We conclude that the Kinesia system may, therefore, have a utility in quantitative assessments of ET when combined with standard clinical assessment.
- Gender differences in onset timing and activation of the muscles of the dominant knee during stair climbing
P. Sung, D. Lee
Knee. 2009 Oct;16(5):375-80Abstract
An electromyographical analysis (EMG) of knee muscle activation patterns and time delays has rarely been discussed in the literature. The purpose of this study was to compare the activation time and EMG amplitude of the dominant vastus medialis and medial hamstring muscles during stair climbing. Fifteen male and 18 female subjects participated in this study. The subjects were asked to ascend and descend 14 steps, five times. There was a significant time delay difference between genders during stair climbing (F=8.37, p=0.008). The female subjects demonstrated longer time delays while descending the steps. In addition, the female subjects demonstrated significantly lower normalized EMG amplitude during down stair climbing (F=5.77, p=0.025) while the male subjects demonstrated higher normalized EMG amplitude for the vastus medialis muscle while descending the steps. These results suggest that female subjects possess an increased risk factor for knee injuries during down stair climbing due to muscle activation delays with decreased vastus medialis muscle activity.
- Clinically Deployable Kinesia Technology for Automated Tremor Assessment
J. Giuffrida, D. Riley, B. Maddux, D. Heldman
Mov Disord. 2009 Apr 15;24(5):723-30Abstract
The objective was to design, build, and assess Kinesia, a wireless system for automated assessment of Parkinson’s disease (PD) tremor. The current standard in evaluating PD is the Unified Parkinson’s Disease Rating Scale (UPDRS), a qualitative ranking system typically completed during an office visit. Kinesia integrates accelerometers and gyroscopes in a compact patient-worn unit to capture kinematic movement disorder features. Objectively quantifying PD manifestations with increased time resolution should aid in evaluating efficacy of treatment protocols and improve patient management. In this study, PD subjects performed the tremor subset of the UPDRS motor section while wearing Kinesia. Quantitative kinematic features were processed and highly correlated to clinician scores for rest tremor (r(2) = 0.89), postural tremor (r(2) = 0.90), and kinetic tremor (r(2) = 0.69). The quantitative features were used to develop a mathematical model that predicted tremor severity scores for new data with low errors. Finally, PD subjects indicated high clinical acceptance.
- Upper-extremity stroke therapy task discrimination using motion sensors and electromyography
J. Giuffrida, A. Lerner, R. Steiner, J. Daly
IEEE Trans Neural Syst Rehabil Eng. 2008 Feb;16(1):82-90Abstract
Brain injury resulting from stroke often causes upper-extremity motor deficits that limit activities of daily living. Several therapies being developed for motor rehabilitation after stroke focus on increasing time spent using the extremity to promote motor relearning. Providing a novel system for user-worn therapy may increase the amount and rate of functional motor recovery. A user-worn system comprising accelerometers, gyroscopes, and electromyography amplifiers was used to wirelessly transmit motion and muscle activity from normal and stroke subjects to a computer as they completed five upper-extremity rehabilitation tasks. An algorithm was developed to automatically detect the therapy task a subject performed based on the gyroscope and electromyography data. The system classified which task a subject was attempting to perform with greater than 80% accuracy despite the fact that those with severe impairment produced movements that did not resemble the goal tasks and were visually indistinguishable from different tasks. This developed system could potentially be used for home-therapy compliance monitoring, real-time patient feedback and to control therapy interventions.
Book Chapters
- Healthcare Sensor Networks: Challenges Toward Practical Implementation
Chapter 10: Ambulatory and Remote Monitoring Of Parkinson’s Disease Motor Symptoms
J. Giuffrida, E. Rapp
Presentations and Posters
- The impact of a wearable device on Parkinson’s disease motor symptom management in patients starting rotigotine transdermal patch
S. Isaacson, B. Boroojerdi, K. Klos, S. Carson, M. Markowitz, D. Heldman, M. Phillips, D. Terricabras, F. Woltering, D. Truong.
Movement Disorders Society Annual Meeting, 2018, Hong Kong. - Using Objective Measurement Via Wearable Sensors To Evaluate Real-world Effectiveness Of Carbidopa/Levodopa Enteral Suspension For Managing Motor Fluctuations: PROviDE Study Design And Baseline Characteristics
R. Pahwa, R. Dorsey, I. Pan, S. van Norman, T. Marshall, D. Heldman, Y. Jalundhwala.
70th Annual Meeting of the American Academy of Neurology, Los Angeles, CA, 2018 - Wearable Motion Quantification and Electronic Diaries for Long-Term Monitoring of Parkinson’s Disease
A. Hadley, E. Urrea-Mendoza, N. Mennucci, C. Zimmerman, J. Giuffrida, Z. Mari, M. Burack, I. Itin, F. Revilla, D. Heldman.
70th Annual Meeting of the American Academy of Neurology, Los Angeles, CA, 2018 - Reliability of Continuous Parkinson’s Assessment Using Wearables
Dustin Heldman, Enrique Urrea Mendoza, Nicola Mennucci , Carol Zimmerman, Joseph Giuffrida, Zoltan Mari, Michelle Burack, Fredy J. Revilla
69th Annual Meeting of the American Academy of Neurology, Boston, MA, 2017
- Telehealth Management of Parkinson’s Disease Using Wearable Sensors: An Exploratory Study
Dustin Heldman, Denzil Harris, Timothy Felong, Kelly Andrzejewski, E. Ray Dorsey, Joseph Giuffrida, Barry Goldberg, Michelle Burack
69th Annual Meeting of the American Academy of Neurology, Boston, MA, 2017
- Reliability and responsiveness of in-clinic and at-home app-based bradykinesia assessment.
Heldman, D.A., Urrea Mendoza, E, Lovera, L.C., Schmerler, D.A., Giuffrida, J.P., Espay, A. J., Garcia, J.X.O., Mohammad, M.E., McFarlane, M.C.U., Fernandez, H.H.
Movement Disorders Society Annual Meeting, 2016, Berlin, Germany.
- Wearable sensors and decision algorithms for advanced therapy referral in Parkinson’s disease.
Heldman, D.A., Giuffrida, J.P., Cubo, E.
Movement Disorders Society Annual Meeting, 2016, Berlin, Germany.
- Advanced Therapy Referral in Parkinson’s Disease Using Wearable Sensors
Heldman, DA., Giuffrida, J.P., Cubo, E.
68th Annual Meeting of the American Academy of Neurology, Vancouver, BC, 2016
- Computer-guided deep brain stimulation programming using automated motion sensor-based functional mapping
D.A. Heldman, C.L. Pulliam, E. Urrea Mendoza, M. Gartner, J.P. Giuffrida, E.B. Montgomery, F.J. Revilla
Movement Disorders Society Annual Meeting, 2015, San Diego, CA
- Wearable sensors for quantifying deep brain stimulation washout effects on gait in Parkinson’s disease
D.A. Heldman, E.B. Brokaw, A.J. Espay, F.J. Revilla, D.E. Riley, T.O. Mera, J.P. Giuffrida, B.L. Walter
Movement Disorders Society Annual Meeting, 2015, San Diego, CA
- Continuous motion sensor assessment of Parkinson’s disease during activities of daily living
C.L. Pulliam, D.A. Heldman, M.A. Burack, T.O. Mera
Movement Disorders Society Annual Meeting, 2015, San Diego, CA
- Pilot study to evaluate transcranial direct current stimulation (tDCS) during sleep for the treatment of Parkinson’s disease
D.A. Heldman, C.L. Pulliam, L.M. Blassucci, J.P. Giuffrida, C.L. Comella
Movement Disorders Society Annual Meeting, 2015, San Diego, CA
- Evaluation of a clinician worn device for the quantitative assessment of abnormal muscle tone type and severity
E Brokaw, I Itin, D Heldman, J Giuffrida, E Montgomery
67th Annual Meeting of the American Academy of Neurology, Washington, DC, 2015 - Prospective, comparative study on cost-effectiveness of home-based motor monitoring system and office-based medical assessment in advanced Parkinson´s disease
E Cubo Delgado, N Mariscal-Pérez, B Solano, V Becerra, J Arribas
67th Annual Meeting of the American Academy of Neurology, Washington, DC, 2015 - Continuous Motion Sensor Assessment of Parkinson’s Disease During Activities of Daily Living
C Pulliam, D Heldman, E Brokaw, M Burack, T Mera
67th Annual Meeting of the American Academy of Neurology, Washington, DC, 2015 - Motion Sensor Dyskinesia Assessment During Activities of Daily Living
C Pulliam, M Burack, J Giuffrida, T Mera
18th International Congress of Parkinson’s Disease and Movement Disorders, Stockholm, Sweden, 2014 - Automated Deep Brain Stimulation Programming Using Motion Sensors
C Pulliam, E Mendoza, M Gartner, T Orcutt, F Revilla, E Montgomery, J Vitek, J Giuffrida, T Mera, D Heldman
18th International Congress of Parkinson’s Disease and Movement Disorders, Stockholm, Sweden, 2014 - Methodology for a Symptomatic Impact Study Using a Portable Essential Tremor Monitor to Direct Therapeutic Interventions
P Vittal, C Pulliam, C Goetz, J Jankovic, J Ramirez-Castaneda, D Heldman
18th International Congress of Parkinson’s Disease and Movement Disorders, Stockholm, Sweden, 2014 - Quantifying Abnormal Muscle Tone Due To Neurological Impairment
E. Brokaw
Midwest American Society of Biomechanics Regional Meeting. Akron, Ohio. 2014 - Motion Sensor Dyskinesia Assessment During Activities of Daily Living
C. Pulliam, M. Burack, J. Giuffrida, T. Mera
66th Annual Meeting Of The American Academy Of Neurology, Philadelphia, PA, 2014
- Wearable sensors for quantifying deep brain stimulation washout effects on gait in Parkinson’s disease
E. Brokaw, T. Mera, D. Riley, B. Walter, A. Espay, F. J. Revilla, J. Giuffrida, D. Heldman
66th Annual Meeting of the American Academy of Neurology, Philadelphia, PA, 2014
- Bradykinesia and timed up and go are improved after dynamic cycling in Parkinson’s disease
R. Phillips, K. Wilson, B. Walter, A. Ridgel
3rd World Parkinson Congress. Montreal, Canada, 2013 - Tremor retrainment as therapeutic strategy for patients with psychogenic tremor: A proof-of-concept study
A. Espay, G. Oggioni, M. Edwards, N. Phielipp, H. Gonzalez-Usigli, C. Pecina, D. Heldman, J. Mishra, A. Lang
17th International Congress of Parkinson’s Disease and Movement Disorders. Sydney, Australia, 2013 - Deep brain stimulation programming in Parkinson’s disease using functional motor symptom response tuning maps
T. Mera, J. Vitek, J. Giuffrida
17th International Congress of Parkinson’s Disease and Movement Disorders. Sydney, Australia, 2013 - Effect of unilateral and bilateral STN stimulation and levodopa on distal and proximal alternating movement of the upper limb in Parkinson’s disease
Radics P, Erőss L, Takáts A, Heldman D, Giuffrida J, Entz L, Fabó D, Tamás G
International Conference on Deep Brain Stimulation. Dusseldorf, Germany, 2013 - Deep brain stimulation programming in PD using functional motor symptom response tuning maps
T. Mera, Vitek J, J. Giuffrida
International Conference on Deep Brain Stimulation. Dusseldorf, Germany, 2013 - Test-Retest Reliability of a Parkinson’s Disease Monitoring System
Dustin Heldman, Alberto Espay, Peter LeWitt, and J. Giuffrida
65th Annual Meeting of the American Academy of Neurology, San Diego, CA, 2013 - Continuous home monitoring of essential tremor using motion sensors
C. Pulliam, S. Eichenseer, C. Goetz, O. Waln, C. Hunter, J. Jankovic, D. Vaillancourt, J. Giuffrida, and D. Heldman
65th Annual Meeting of the American Academy of Neurology, San Diego, CA, 2013 - Deep brain stimulation programming in Parkinson’s disease using functional motor symptom response tuning maps
T. Mera, J. Vitek, J. Giuffrida
65th Annual Meeting of the American Academy of Neurology, San Diego, CA, 2013 - Quantitative Motor Assessment of Gait and Lower Extremity Bradykinesia Following the Discontinuation of Deep Brain Stimulation
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T. Mera, D. Riley, B. Walter, A. Espay, F. Revilla, J. Giuffrida
3rd World Parkinson Congress. Montreal, Canada, 2013 - Home-based Motion Sensor Monitoring for Parkinson’s Disease Clinical Trials
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D. Heldman, A. Espay, P. LeWitt, J. Giuffrida
3rd World Parkinson Congress. Montreal, Canada, 2013 - Patient Compliance with Parkinson’s Disease Home Monitoring System
Danielle Filipkowski, Dustin Heldman, Alberto Espay, Jaya Mishra, Thomas Mera, and J. Giuffrida
16th International Congress of Parkinson’s Disease and Movement Disorders, Dublin, Ireland 2012 - Capturing Choreatic Dyskinesia Over Levodopa Dose Cycle in Parkinson’s Disease
T. Mera, Michelle Burack, MD, PhD, Frank Bonsignore, MS, J. Giuffrida, PhD
16th International Congress of Parkinson’s Disease and Movement Disorders, Dublin, Ireland 2012 - Intra- and Multi-Day Home-Based Monitoring of Parkinson’s Disease Motor Symptoms
D. Heldman, D. Filipkowski, A. Espay, Jaya Mishra,J. Giuffrida
16th International Congress of Parkinson’s Disease and Movement Disorders, Dublin, Ireland 2012 - Patient Compliance with Parkinson’s Disease Home Monitoring System
Danielle Filipkowski, Dustin Heldman, Alberto Espay, Jaya Mishra, Thomas Mera, and J. Giuffrida
American Academy of Neurology 64th Annual Meeting, New Orleans, LA 2012 - Capturing Choreatic Dyskinesia Over Levodopa Dose Cycle in Parkinson’s Disease
T. Mera, Michelle Burack, MD, PhD, Frank Bonsignore, MS, J. Giuffrida, PhD
American Academy of Neurology 64th Annual Meeting, New Orleans, LA 2012 - Intra- and Multi-Day Home-Based Monitoring of Parkinson’s Disease Motor Symptoms
D. Heldman, D. Filipkowski, A. Espay, Jaya Mishra,J. Giuffrida
American Academy of Neurology 64th Annual Meeting, New Orleans, LA 2012 - Quantitative Home-Based Monitoring of Parkinson’s Disease Motor Symptoms
D. Heldman, T. Mera, A. Espay, Payne M, J. Giuffrida
International Congress of Parkinson’s Disease and Movement Disorders, Toronto, CA 2011 - Ergonomic and Human Interface Design Factors for Home-Based Medical devices in Movement Disorders
D. Filipkowski, T. Mera, D. Heldman, J. Giuffrida
International Congress of Parkinson’s Disease and Movement Disorders, Toronto, CA 2011 - Automated Parkinson’s Disease Gait and Balance Assessment for Optimization of Deep Brain Stimulation
T. Mera, D. Filipkowski, Riley R, Walter B, Gunzler S, J. Giuffrida
International Congress of Parkinson’s Disease and Movement Disorders, Toronto, CA 2011 - Amplitude Fluctuations in Essential Tremor: A Prospective Study
Mostile G, Fekete R, J. Giuffrida, Yaltho T, Davidson A, Nicoletti A, Zappia M, J. Jankovic
International Congress of Parkinson’s Disease and Movement Disorders, Toronto, CA 2011 - Logarithmic Relationship Between Head Tremor and 5-Point Tremor Rating
Rodger Elble, MD PhD, Helge Hellriegel, MD, Jan Raethjen, MD and Günther Deuschl, MD
International Congress Of Parkinson’s Disease And Movement Disorders, Toronto, CA 2011
- Automated Optimization of Deep Brain Stimulation Settings across Multiple Parkinson’s Disease Motor Symptoms
Joseph P. Giuffrida, Jay L. Alberts, Jerrold Vitek, T. Mera
Presented at the 2010 American Academy of Neurology Annual Meeting - Differential Response of Speed, Amplitude, and Rhythm to Dopaminergic Medications in Parkinson’s Disease
A. Espay, D. Heldman, Robert Chen, Sang-jin Kim, Jennifer E. Vaughan, Emily Dunn, Andrew P. Duker,J. Giuffrida
Presented at the 2010 American Academy of Neurology Annual Meeting - Differential Response of Bradykinesia and Hypokinesia to Levodopa in Parkinson’s Disease
A. Espay, J. Giuffrida, Robert Chen, Jennifer E. Vaughan, Andrew P. Duker, D. Heldman
Presented at the 2009 World Federation of Neurology World Congress on Parkinson’s Disease and Related Disorders - ParkinTune: Automated Parkinson’s Disease Motor Assessment for DBS Programming
T. Mera, MS, Jerrold Vitek, MD, PhD, Jay Alberts, PhD,J. Giuffrida
Presented by the 2009 World Federation of Neurology World Congress on Parkinson’s Disease and Related Disorders - Automated Parkinson’s Disease Motor Assessment for Clinical and Ambulatory Monitoring
D. Heldman, Ph.D., A. Espay, M.D., Peter LeWitt, M.D.,J. Giuffrida, Ph.D.
Presented by the 2009 World Federation of Neurology World Congress on Parkinson’s Disease and Related Disorders - Effects of Pedaling Rate on Upper Extremity Motor Improvements During Passive Leg Cycling in Parkinson’s Disease
A.L. Ridgel, M.D. Muller, C-H. Kim, E.J. Fickes, K. Wilson, T. Mera and J. L. Alberts
Presented at the 2009 Society for Neuroscience Annual Meeting - Correlation between Kinesia System Assessments and Clinical TETRAS Scores in Patients with Essential Tremor
Giovanni Mostile, MD,J. Giuffrida, PhD, Octavian R. Adam, MD, Anthony Davidson, BS, Joseph Jankovic, MD
Presented at the 2009 13th International Congress of Parkinson’s Disease and Movement Disorders - Correlation Between Clinical Rating of Parkinsonian and Essential Tremor and Quantitative Assessments
L. Giselle Aguilar, M.D.,J. Giuffrida, Ph.D., D. Heldman, Ph.D., Joseph Jankovic, M.D.
Presented at the 2008 12th International Congress of Parkinson’s Disease and Movement Disorders - Kinematic Akinesia Feature Extraction Using Kinesia
D. Heldman, Ph.D., David E. Riley, M.D., Brian N. Maddux, M.D., Ph.D.,J. Giuffrida, Ph.D.
Presented at the 2008 12th International Congress of Parkinson’s Disease and Movement Disorders - Comparison of Kinesia to the Unified Parkinson’s Disease Rating Scale: Tremor and Bradykinesia Results
D. Heldman, Ph.D., David E. Riley, M.D., Brian N. Maddux, M.D., Ph.D.,J. Giuffrida, Ph.D.
Presented at the 2008 American Academy of Neurology Annual Meeting