Angela Roberts

Effectiveness of BoNT A in Parkinson's disease upper limb tremor management.

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 Parkinsons 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.

Differential impairments of upper and lower limb movements influence action verb processing in Parkinson disease

Theories of grounded cognition emphasize the role of the motor system in the processing of action concepts. The present study investigated whether persons with Parkinson disease (PD) who have greater upper versus greater lower limb motor impairments show different patterns of performance when processing action verbs. PD patients and controls made action decisions on upper-limb (reach), lower-limb (kick), and psych verbs (think). The primary result was an interaction between PD motor dominance (PD upper vs lower limb motor impairments) and verb type (upper- vs lower-limb verbs). PD patients with greater upper limb impairments took longer to respond to upper-limb than to lower-limb verbs, whereas those with greater lower limb impairments performed similarly on the two verb types. Our results add to recent studies and theories that highlight the complexity of verb impairments in PD, semantic task effects, effector-specific sensorimotor cortex engagement, and fine-grained semantic features and their possible interactions with effector-specific impairments.

Patterns and predictors of freezing of gait improvement following rasagiline therapy: A pilot study

OBJECTIVES Freezing of gait (FoG) is a challenging clinical symptom in Parkinsons 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-R2=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.

Information Content and Efficiency in the Spoken Discourse of Individuals With Parkinson's Disease

Purpose This study compared the information content and information efficiency of spoken language in individuals with Parkinsons disease (PD) to a healthy comparator group. Method Nineteen participants with PD and 19 healthy older adults completed the prospective, cross-sectional study. In the primary analysis, 2 language samples elicited by standardized protocols were analyzed for group differences using standard discourse informativeness measures including main events (MEs; Wright, Capilouto, Wagovich, Cranfill, & Davis, 2005) analyzed as %MEs and correct information units (CIUs; Nicholas & Brookshire, 1993) analyzed as %CIUs and CIUs/min. In exploratory analyses, the following were examined: (a) associations among conceptual (%MEs) and lexical (%CIUs and CIUs/min) measures and (b) associations among informativeness measures and age, education, disease severity/duration, global cognition, speech intelligibility, and a verb confrontation naming measure. Results In the primary analysis, the PD group differed significantly from the control group on conceptual (%MEs) and lexical measures of content (%CIUs) and efficiency (CIUs/min). In exploratory analyses, for the control group %MEs were significantly correlated with CIUs/min. Significant associations among conceptual and lexical measures of informativeness were not found in the PD group. For controls, there were no significant correlations between informativeness measures and any of the demographic or speech/cognitive/language variables. In the PD group, there was a significant and positive association between CIUs/min and Dementia Rating Scale-Second Edition scores (Mattis, 2001). A significant but negative correlation was found between CIUs/min and motor severity scores. However, %MEs and verb naming were significantly and positively correlated. Conclusions Individuals with PD without dementia demonstrated reduced discourse informativeness that reflects disruptions to both conceptual and lexical discourse processes. In exploratory analyses, reduced efficiency of information content was associated with global cognition and motor severity. Clinical and research implications are discussed within a Cognitivist framework of discourse production (Sheratt, 2007).

Altered resting-state functional connectivity of the putamen and internal globus pallidus is related to speech impairment in Parkinson's disease

Speech impairment in Parkinsons disease (PD) is pervasive, with life‐impacting consequences. Yet, little is known about how functional connections between the basal ganglia and cortex relate to PD speech impairment (PDSI). Whole‐brain resting‐state connectivity analyses of basal ganglia nuclei can expand the understanding of PDSI pathophysiology.

Non-Alzheimer Dementias

Dementias, not attributable to Alzheimer’s disease, include a varied group of neurodegenerative disorders with myriad and diverse neuropathology and clinical features. Collectively, these disorders are often referred to as ‘non-Alzheimer’s dementias’ (non-AD dementias). Language impairments, at the single word and discourse levels, are becoming well documented in non-AD dementias and are recognized as having great impact on the use of language for social purposes. However, an emerging body of literature suggests that in addition to impairments in language form and content, social cognition deficits may manifest downstream as pragmatic language impairments. Moreover, socially inappropriate and disinhibited behaviours that are core to several subtypes of non-AD dementias may contribute significantly to pragmatic communication impairments. Given the importance of social communication and language use to quality of life for persons with non-AD dementias, their families, and carers, increasing our understanding of how discrete impairments in cognition, language, and behaviour affect pragmatic communication abilities is of paramount importance for both clinicians and researchers in fields of communication and dementia. This chapter undertakes a wide-ranging examination of the pragmatic communication abilities of persons with non-AD dementias, which is informed by research evidence and clinical experience.