Search

Objectives: Freezing of gait (FoG) is a challenging clinical symptom in Parkinson's disease with variable improvements in FoG with rasagiline. In this prospective, uncontrolled, pre-/post- treatment pilot study, we explore the clinical variables that contribute to this variability and those that predict improvement., Patients and Methods: Frequency and duration of FoG, along with other standardized scales, were evaluated in 18 optimally medicated PD participants with intractable FoG, prior to and after completion of a 90-day course of 1mg daily rasagiline. Gait tasks were video-recorded and analyzed by two independent reviewers. After evaluating the simple main effect, hierarchical cluster analysis was used to identify subgroups for treatment responsiveness. Bidirectional elimination stepwise regression analysis was conducted to identify which clinical variables predicted reduction in frequency of FoG events post-treatment., Results: There were no overall pre-/post- treatment improvements, a result driven by a heterogeneous response to treatment. Three subgroups were identified: improved (n=6) with a 136% and 162% reduction in FoG count and duration; worsened (n=5) with 154% and 141% increase in FoG count and duration; and no change (n=3). The final predictive model had good explanatory power (adjusted-R 2 =0.9898, p<0.01), explaining 99% of the variance between the improved and worsened groups. In this model, lower UPDRS gait scores, higher LEDD dose, lower anxiety scores, lower FOG-Q scores, and higher UPDRS scores for lower extremity rigidity and rise from chair, predicted FoG-related rasagiline benefit., Conclusion: Using both objective and subjective measures for FoG, the current pilot study identified a set of clinical variables that may elucidate the heterogeneous FoG-responsiveness following rasagiline treatment and aid in predicting improvement., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: In Parkinson disease, tremor is a challenging symptom to manage, partly due to inadequate characterization. The current (classic) model of tremor is characterized by a resting tremor with a single strong peak in 3.5-6.5Hz range. The presence of action tremor, including postural, isometric, and kinetic tremors, has been disputed in the literature but not comprehensively evaluated. Analysis of hand tremor in action compared to rest, and possible subgrouping of tremor trends, may improve characterization., Methods: Twenty Parkinson patients and 14 controls were recruited. Tremor amplitude was measured across 9 sequentially loaded tasks, in off and on medication states. Tremor energy was separated into 2 frequency bands (B1, 3.5-6.5Hz; B2=physiological tremor, 7.5-16.5Hz) across all activity levels. Automatic classification was used for subgroup analysis., Findings: Automatic classification yielded 3 predominant tremor trends (G1, G2, and G3). These were significantly different from each other and from controls. G1 demonstrated closest resemblance to classical Parkinsonian tremor, with highest tremor energy at rest and with overall dominance in B1 for lower loads. G2-G3 did not show tremor energy dominance in either band. Medication reduced tremor energy only for G1 in both B1 and B2., Interpretation: Subgrouping the loading effect on tremor is a novel and viable method of rationalizing (non-classic) action tremor in Parkinson disease. Rest and action tremors appear not to be limited to 3.5-6.5Hz and may have considerable share of physiological tremor. Finding the contribution of each frequency band to total tremor energy and their trends with load may optimize therapy options., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Upper limb motor blocks (ULMB) (inability to initiate or sudden discontinue in voluntary movements) have been identified in both unimanual and bimanual tasks in individuals with Parkinson's disease (PD). In particular, ULMB have been observed during rhythmic bimanual coordination when switching between phase patterns which is required (e.g. between in-phase and anti-phase). While sensory-perceptual mechanisms have recently been suggested to be involved in lower limb freezing, there has been no consensus on the mechanism that evokes ULMB or whether motor blocks respond to dopamine replacement like other motor symptoms of PD. The current study investigated the occurrence of ULMB in PD participants without ('off') and with ('on') dopamine replacement using bimanual wrist flexion-extension with external auditory cues. In Experiment 1, coordination was performed in either in-phase (simultaneous flexion and extension) or anti-phase (asymmetrical flexion and extension between the limbs) in one of three sensory conditions: no vision, normal vision or augmented vision. Cycle frequency was increased within each trial across seven cycle frequencies (0.75-2 Hz). In Experiment 2, coordination was initiated in either phase pattern and participants were cued to make an intentional switch between phases in the middle of trials. Trials were performed at one of two cycle frequencies (1 or 2 Hz) and one of two sensory conditions: no vision or normal vision. Healthy age-matched control participants were also investigated in both experiments for the occurrence of motor blocks that were measured using automated detection from a computer algorithm. The results from Experiment 1 indicated that increasing cycle frequency resulted in more ULMB in individuals with PD during continuous coordinated movement, regardless of dopaminergic status, phase pattern or sensory condition. Experiment 2 also confirmed an increased occurrence of ULMB with increased cycle frequency. Furthermore, a large amount of ULMB were observed when initiating anti-phase coordination at 2 Hz, as well as after both externally-cued switches and in 'catch trials' with distracting auditory cues when no switch was required. Dopamine replacement was not found to influence the frequency of ULMB in either experiment. Therefore, ULMB likely result from non-hypodopaminergic impairments associated with PD. Specifically, ULMB may be caused by an inability to shift attentional control under increased cognitive demand that could be associated with hypoactivation in motor and prefrontal areas.

Background: Functional motor impairments including mobility are major reasons for clinical intervention and medication adjustment in symptomatic therapy for Parkinson's disease (PD). Outcome measures used to assess the impact of medication are mostly based on patients' memory or diaries which, considering the gaps between visits, are neither objective nor very reliable., Objective: Investigating the feasibility of using movement features extracted from ecological whole-body kinematics recordings to measure the quantitative and qualitative changes in multiple aspects of mobility after medication changes in PD., Methods: Eleven patients with PD (PwPD) performed mobility tasks in their own home, wearing a full body wireless inertial sensing based motion capture system. Three scripted walking tasks (walking, fast walking, and walk turns) were examined at baseline and two weeks after medication changes. Clinical scales, including investigator-rated clinical global impression of improvement (CGI-I), were collected at both visits., Results: Out of 59 recorded body joint variables, five were identified as pertinent. Changes were represented in vector space as a plot of mean versus peak amplitude. Regression analysis was used to predict clinical improvement or worsening based on these vector features. The predictors were able to explain (>98.5% of variance) patients' clinical global impression of improvement, thus correctly predicting 5 cases of improvement and 2 cases of worsening., Conclusions: This study provided a method of extracting clinically meaningful reports from ecological kinematic data showing changes after drug adjustments. The results are presented using a novel concept called change space that may be more understandable for clinical staff.

Objective: One the greatest challenges of BoNT A therapy for tremor lies in the complexity and variation of components involved in tremor movement, and the lack of objective measures to determine these components. This 3 month open-label single injection study aims to couple clinician best judgment with kinematics to improve effect of BoNT A (incobotulinumtoxinA) injection in 7 patients with upper limb Parkinson's disease (PD) tremor., Methods: Injection was guided with clinical and kinematic assessment of tremor using angular wrist position in 3 degrees of freedom: flexion/extension, pronation/supination, and radial/ulnar deviation. Overall tremor severity and change were measured by linear finger acceleration., Results: Kinematic data from static and functional tasks demonstrate no improvement at one month post-injection, but significant improvement at two and three months. Clinical scales across UPDRS Items 20 (1, 2, 3 months post) and 21 (2 months), and spiral drawings (3 months) showed significant improvement from baseline, while line drawings did not., Conclusions: This study suggests injection of BoNT A as a viable focal management option for upper limb PD tremor. In addition to clinical judgment, objective quantification of tremor dynamics by kinematics may be a feasible assessment and guidance tool which can be used to optimize injection conditions for focal tremor therapy. Kinematic analysis of tremor across a variety of joints in all degrees of movement may provide important insight into tremor dynamics, allowing optimized, targeted focal therapy.

Recent research has proposed that proprioceptive deficits may exist in Parkinson's disease (PD); however, proprioception has not been studied in those who experience freezing of gait (FOG). Proprioception was investigated through stimulation of proprioceptive receptors via patellar tendon vibration. In a force matching task to either 10% or 30% maximal voluntary contraction, response to vibration with and without vision of a force target was compared between 15 PD with FOG (PD-FOG), 16 PD without FOG (PD non-FOG), and 15 non-PD control participants (Controls). In a 15-s trial, vision of the target was provided for the first 10 s but in the last 5 s, four conditions were possible: (i) vision, no vibration; (ii) vision, vibration; (iii) no vision, no vibration; or (iv) no vision, vibration. The expected healthy response to vibration was an overshoot of the target. Controls and PD non-FOG did not perform significantly different with or without: vibration or vision. PD-FOG performed similarly to Controls and PD non-FOG in the baseline condition (i). Errors by PD-FOG on the other conditions (ii-iv) were significantly different from the baseline condition but were not significantly different from each other. The PD-FOG group significantly undershot the target when vibration was added [F((2,36))=4.8376, P<0.02] and when vision was removed [F((2,36))=4.8376, P<0.02]. It is suggested that any deviation from normal sensory availability contributes to severe deficits in PD-FOG., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

While many studies have reported on the use of kinematic analysis on well-controlled, in-laboratory mobility tasks, few studies have examined the challenges of recording dynamic mobility in home environments. This preliminary study evaluated whole body mobility in eleven patients with Parkinson disease (H&Y 2-4). Patients were recorded in their home environment during scripted and non-scripted mobility tasks while wearing a full-body kinematic recording system using 11 inertial motion sensors (IMU). Data were analyzed with principal component analysis (PCA) in order to identify kinematic variables which best represent mobility tasks. Results indicate that there was a large degree of variability within subjects for each task, across tasks for individual subjects, and between scripted and non-scripted tasks. This study underscores the potential benefit of whole body multi-sensor kinematic recordings in understanding the variability in task performance across patients during daily activity which may have a significant impact on rehabilitation assessment and intervention.

While the majority of tremor-afflicted Parkinso-nian (PD) patients suffer from rest tremors, which is not considered highly disabling, a portion of these PD patients also demonstrate action tremors that interfere with their daily lives. Two main considerations in designing an orthosis that aims at suppressing the tremor, are the frequency bands of the tremor and the joints tremor affects. Nine subjects, which included six healthy people, two PD patients with typical tremor afflictions, and a PD patient with severe tremor of not only in her fingers and wrist, but also in her elbow, participated in this study. The highly afflicted patient displayed the need for tremor suppression in action as well as when in rest. The study focuses on uncommon elbow tremors and demonstrates that, for typically afflicted patients, tremor amplitudes are comparable to healthy subjects, but the frequency distribution of the tremors are different at high levels of elbow torque. For the highly afflicted patient, both tremor amplitude and its frequency distribution are different at all levels of elbow torque. The study further investigates the tremors in two bands of frequency on both hands of the highly troubled patient before, and after medication. The two bands are those of classical Parkinsonian tremor (4-6 Hz) and physiological (or enhanced physiological) tremor (8-12 Hz). Power spectrum and tremor amplitude comparisons reveal that, for part of tremulous PD patients, both tremors coexist and, depending on the level of affliction, the designed orthosis needs to suppress tremors in both bands, even at more proximal joints, such as the elbow.