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

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.

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.

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.

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.