Sofia Guedes

Introduction The development and progression of Parkinson’s disease (PD) is associated with increased resistance of the joints to passive movement, termed rigidity. The severity of rigidity is thought to be different between people with PD depending upon the expression and level of abnormal muscle activity during rapid eye movement (REM) sleep (Postuma et al., 2019; Schenck et al., 2013). It has been shown that forearm rigidity is elevated in people with early-stage PD and REM sleep without atonia (RSWA; elevated muscle tone) and more symmetric between limbs compared to people with PD without RSWA (Linn-Evans et al., 2020). However, it is not known if rigidity progresses more quickly in people with PD and RSWA (PD-RSWA+) compared to PD without RSWA (PD-RSWA-). This project aimed to test if, over a 3-year period, (1) the rate of progression of rigidity is faster in people with PD and RSWA in relation to people with PD without RSWA, and age-matched controls, and (2) if rigidity would become more symmetrical between arms in people with PD without RSWA. We hypothesized that quantitative measures of rigidity would progress more rapidly in the PD-RSWA+ group compared to those without RSWA and that rigidity would become increasingly more symmetric over the course of 3 years. Methods Thirty-one people with PD and 16 sex-matched healthy older adults completed baseline and follow-up testing. The PD-RSWA groups were assigned based on the percentage of REM sleep with phasic or tonic muscle activity recorded during an overnight sleep study at the Sleep Center at the University of Minnesota at baseline. All testing was conducted after overnight withdrawal from Parkinson’s disease medications. A robotic manipulandum was used to quantitatively measure rigidity in the forearm by imposing sinusoidal movements of ±40° about the pronation-supination axis in the forearm at 1.5Hz for 45 seconds. A single trial was collected on each arm, with and without an activation maneuver, which involved tapping the contralateral hand on the leg. Data was processed in MATLAB to derive measures of rigidity including: peak negative power, angular impulse, and negative work. The relationship of RSWA symptoms to the progression of rigidity was tested with a linear mixed model in the R software (R Core Team, 2021) to assess the factors of group (PD-RSWA+, PDRSW-, controls) and repeated measures factors of visit (baseline, year 3), side (more, MA, or less affected, LA arm) and activation maneuver (active vs passive), and covariates of age of enrollment, time to follow up, and sex. Post-hoc assessments were conducted using Tukey’s Honest Significant Difference test. Significance was set at p < 0.05. Results Forty-seven people completed baseline and follow-up testing (16 controls, 17 PD-RSWA+, 14 PD-RSWA-). The average age of enrollment of the control, PD-RSWA-, and PD-RSWA+ groups were, respectively, 62.3 ± 8.48, 63.4 ± 8.37, and 65.1 ± 5.19 years. All three rigidity measures (peak negative power, angular impulse, and negative work) showed main effects of arm (MA arm higher than LA arm), and activation maneuver (higher during active vs. passive), while negative work also showed an effect of visit (baseline higher than visit 2). All three measures had significant Group x Activation maneuver interactions (p < 0.007) such that the active task had higher rigidity values than the passive task in the PD groups, but not controls. Similarly, all measures had significant Group x Arm interactions. Post hoc assessments showed that the MA arm had higher peak negative power scores than the LA arm in for both PD groups (p < 0.004), while for angular impulse and negative work, only the PD-RSWA- group had higher scores in the MA arm compared to the LA arm (p < 0.0002). Angular impulse and negative work showed a significant interaction of Group x Visit x Arm (p ≤ 0.0003), identifying an asymmetric relationship in the PD-RSWA- group between arms (MA higher than LA) at visit 1, with no difference between arms at visit 2, implying a more symmetric relationship between arms at the time of the 3 year follow-up. Conclusion Contrary to our primary hypothesis, most measures of rigidity did not show significant worsening over the course of 3 years in the participants with PD, including the PD-RSWA+ group. In fact, some measures of rigidity (negative work) were improved at follow-up in the PD-RSWA- group. This unexpected finding may reflect changes in medication status at the time of follow-up and an insufficient wash-out at the time of testing. However, significant differences in rigidity between arms observed at baseline for the PD-RSWA- group were no longer present at visit 2, indicating that rigidity had become more symmetric between sides. These results provide evidence that rigidity does not progress more rapidly over the course of 3 years in people with PD and RSWA compared to those without RSWA and that rigidity becomes more symmetric over time in people with PD without RSWA. These findings can be used to predict the course of rigidity in people who are newly diagnosed with PD.