Steven A. Gunzler

Automated motion sensor quantification of gait and lower extremity bradykinesia

The objective was to develop and evaluate algorithms for quantifying gait and lower extremity bradykinesia in patients with Parkinsons 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 Parkinsons 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 Parkinsons disease motor symptoms.

Quantitative analysis of gait and balance response to deep brain stimulation in Parkinson's disease

Gait and balance disturbances in Parkinsons 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 Parkinsons 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.

Apomorphine in the treatment of Parkinson disease and other movement disorders.

Background: Apomorphine, a medication that has been studied intensively over the years, is available in the US as intermittent subcutaneous injections for treatment of ‘off’ motor states in Parkinson disease. Objective: The clinical literature is summarized with particular focus on randomized controlled studies of apomorphine in the treatment of Parkinson disease. Methods: After reviewing the pharmacologic properties of apomorphine, the English language literature is summarized with particular attention on articles resulting from a Medline search of apomorphine and Parkinson disease limited to randomized controlled studies. Other formulations and indications for treatment of movement disorders are also discussed. Results/conclusion: Subcutaneous apomorphine is well tolerated when co-administered with trimethobenzamide or domperidone premedication. It has a unique efficacy as a ‘rescue’ medication owing to its rapid onset of action. Subcutaneous infusion, although not an approved route of administration in the US, provides more continuous dopaminergic stimulation and, therefore, ameliorates dyskinesia and motor fluctuations.

Foot-tapping rate as an objective outcome measure for Parkinson disease clinical trials.

Objectives:To explore foot-tapping rate as a reliable and a valid measure of motor function in Parkinson disease (PD). Methods:We present data from a randomized, single-blind, outpatient study and a randomized, double-blind, placebo-controlled, crossover, inpatient study. Fifty PD subjects completed the outpatient study. A Unified Parkinson Disease Rating Scale motor score was determined for each subject. Subsequently, finger tapping, alternate (between 2 pedals) and repetitive (on 1 pedal) foot-tapping rates, and gait were measured. Thirteen PD subjects completed the inpatient study. Each subject received a daily infusion of high-dose apomorphine (APO), low-dose APO, and placebo in random order over 3 days. In this subanalysis, we compared variance and reliability of the finger- and the foot-tapping techniques during the placebo day and compared the validity of these outcome measures to detect improvement in parkinsonism during high-dose APO infusion. Results:Alternate foot tapping was reliable (interclass correlation on the placebo inpatient day, 84%). Only foot tapping detected improvement in parkinsonism with high-dose APO treatment (a measure of validity). In the outpatient study, there was a significant correlation between alternate and repetitive tapping with finger tapping (R2 = 0.28 and 0.23, respectively) and Unified Parkinson Disease Rating Scale motor score (R2 = 0.09 and 0.08), but only alternate tapping correlated with gait (R2 = 0.16). Conclusions:Alternate foot tapping was equally reliable but more valid than finger tapping. Alternate foot tapping correlated better did existing PD outcome measures than did repetitive foot tapping. Foot tapping may be a useful outcome measure for determination of dopaminergic medication effect in PD clinical trials.

A randomized trial of individual versus group-format exercise and self-management in individuals with Parkinson’s disease and comorbid depression

Background Depression is common in people with Parkinson’s disease (PD), and exercise is known to improve depression and PD. However, lack of motivation and low self-efficacy can make exercise difficult for people with PD and comorbid depression (PD-Dep). A combined group exercise and chronic disease self-management (CDSM) program may improve the likeli-hood that individuals will engage in exercise and will show a reduction in depression symptoms. The purpose of this study was to compare changes in depression in PD-Dep between individual versus group exercise plus CDSM and to examine participant adherence and perception of the interventions. Methods Participants (N=30) were randomized to either Enhanced EXerCisE thErapy for PD (EXCEED; group CDSM and exercise) or self-guided CDSM plus exercise. Outcomes were change in depression assessed with the Montgomery–Asberg Depression Rating Scale (MADRS), cognition, apathy, anxiety, sleep, quality of life, motor function, self-efficacy, and patient satisfaction. Results Both groups showed significant improvement in MADRS (P<0.001) with no significant group difference. Individuals in EXCEED group enjoyed the group dynamics but noted difficulty with the fixed-time sessions. Conclusion Both group CDSM plus exercise and self-guided CDSM plus exercise can improve depression in PD-Dep. These findings suggest that development of a remotely delivered group-based CDSM format plus manualized exercise program could be useful for this population.

Influence of orbital eye position on vertical saccades in progressive supranuclear palsy

Disturbance of vertical saccades is a cardinal feature of progressive supranuclear palsy (PSP). We investigated whether the amplitude and peak velocity (PV) of saccades are affected by the orbital position from which movements start in PSP patients and age‐matched control subjects. Subjects made vertical saccades in response to ±5° vertical target jumps with their heads in one of three positions: head “center,” head pitched forward ∼15°, and head pitched back ∼15°. All patients showed some effect of starting eye position, whether beginning in the upward or downward field of gaze, on saccade amplitude, PV, and net range of movement. Generally, reduction of amplitude and PV were commensurate and bidirectional in the affected hemifield of gaze. Such findings are unlikely to be because of orbital factors and could be explained by varying degrees of involvement of rostral midbrain nuclei in the pathological process.

Effect of low concentrations of apomorphine on parkinsonism in a randomized, placebo-controlled, crossover study.

OBJECTIVE To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state. DESIGN Randomized, double-blind, placebo-controlled, crossover clinical trial. SETTING Academic movement disorders center. PATIENTS Patients with Parkinson disease and motor fluctuations. INTERVENTION Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (subthreshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 microg/kg/h every 2 hours and 25 microg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 microg/kg/h every 2 hours and 100 microg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days. MAIN OUTCOME MEASURES Finger and foot tapping rates. RESULTS There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P < .001) and trended toward increasing finger tapping compared with placebo infusions. CONCLUSIONS Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that presynaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease. Trial Registration clinicaltrials.gov Identifier: NCT00472355.

Motor and non-motor features of Parkinson's disease in LRRK2 G2019S carriers versus matched controls

INTRODUCTION LRRK2 G2019S mutation carriers with Parkinsons disease (PD) have been generally indistinguishable from those with idiopathic PD, with the exception of variable differences in some motor and non-motor domains, including cognition, gait, and balance. LRRK2 G2019S is amongst the most common genetic etiologies for PD, particularly in Ashkenazi Jewish (AJ) populations. METHODS This cross-sectional data collection study sought to clarify the phenotype of LRRK2 G2019S mutation carriers with PD. Primary endpoints were the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA). Other motor and non-motor data were also assessed. The Mann-Whitney U Test was utilized to compare LRRK2 G2019S carriers with PD (LRRK2+) with non-carrier PD controls who were matched for age, gender, education, and PD duration. Survival analyses and log rank tests were utilized to compare interval from onset of PD to development of motor and non-motor complications. RESULTS We screened 251 subjects and 231 completed the study, of whom 9 were LRRK2+, including 7 AJ subjects. 22.73% of AJ subjects with a family history of PD (FH) and 12.96% of AJ subjects without a FH were LRRK2+. There were no significant differences between the 9 LRRK2+ subjects and 19 matched PD controls in MDS-UPDRS, MoCA, or other motor and non-motor endpoints. CONCLUSION Prevalence of the LRRK2 G2019S mutation in AJ and non-AJ subjects in our study population in Cleveland, Ohio was comparable to other clinical studies. There were no significant motor or non-motor differences between LRRK2+ PD and matched PD controls.

Teaching Video NeuroImages: Essential palatal tremor Is it a peripherally triggered central movement disorder?

A 30-year-old woman had progressively severe audible clicks after endoscopic sinus surgery. These involuntary clicks increased with stress, disappeared during sleep, and correlated with palatal movements suggesting essential palatal tremor (EPT) (video on the Neurology ® Web site at [www.neurology.