Daniel S. Peterson

Objective: To determine whether continuous, regression-based measures of balance discordance refine prediction of prospective, recurrent falls after subacute stroke relative to a previously published threshold-based classification in the same cohort, and to characterize how a purely data-driven, dimensionality-reduction-based composite expresses the same underlying measures. Design: Secondary, observational analysis of a randomized controlled trial. Recurrent falls were modeled using Andersen-Gill Cox proportional hazards regression with robust standard errors clustered by participant. Setting: Five-site, National Institutes of Health/National Institute of Neurological Disorders and Stroke funded multicenter trial (Locomotor Experience Applied Post-Stroke, LEAPS). Participants: 384 adults with subacute stroke (of 408 randomized in the parent trial) with valid baseline balance confidence, walking, and balance scores and at least one recorded follow-up interval (2,357 person-intervals, 179 fall events). Main Outcome Measures: Prospective, recurrent falls over 12 months, ascertained via self-report falls diary. Balance discordance was computed as the residual from regressing balance confidence on objective walking distance, Berg Balance Scale performance, or both jointly (multivariable discordance); threshold-based classification used established cut-points on the same measures and principal component analysis served as secondary comparators. Results: Single-variable discordance was associated with lower fall hazard (hazard ratio [HR] = 0.79, 95% CI 0.63-0.99, p = .037), and multivariable discordance was associated with higher fall hazard (HR = 1.27, 95% CI 1.03-1.58, p = .026). None of three threshold-based classification indicators reached significance. Multivariable discordance and a three-component principal-component composite showed comparable model fit (concordance 0.616 vs. 0.618) and were substantially correlated (Rsquared = .49). Conclusions: Continuous, regression-based balance discordance predicted prospective, recurrent falls where a previously published threshold-based classification did not. The divergent direction of single- and multivariable findings suggests overconfidence relative to combined objective function, rather than confidence broadly, may be the more specific marker of fall risk.

Objective: Cognitive and balance impairments are common in multiple sclerosis (MS). Practice effects may reflect neuroplasticity and predict rehabilitation responsiveness. This study examined cognitive practice effects and their relationship to reactive balance adaptation in MS. Methods: Twenty-seven people with MS and 17 neurotypical adults completed 2 baseline cognitive assessments over 2 weeks, followed by a 2-week perturbation-based balance training program over 6 progressive sessions. Verbal learning and processing speed were assessed using the California Verbal Learning Test-II (CVLT-II) and the Symbol Digit Modalities Test. Reactive balance was evaluated using backward margin of stability, step latency, and step length, pre-, post-, and 2 months after training. Results: People with MS improved on verbal learning (CVLT-II Total Recall: F (1, 42) = 83.11, p < .001, η2p = 0.66) and processing speed (F(1, 42) = 4.68, p = .036, η2p = 0.10). The magnitude of improvement did not differ significantly between groups; however, standardized regression-based scores indicated the MS group’s gains were smaller than normatively expected (t(26) = −2.60, p = .015, d = −0.50). Only delayed recall predicted immediate improvements in backward margin of stability (β = 0.71, p = .033, η2p = 0.22) and, with some sensitivity to influential observations, retained improvements at two-month follow-up (β = 1.12, p = .015, η2p = 0.29). Conclusions: Cognitive practice effects in MS are largely preserved. Delayed verbal recall was selectively associated with reactive balance adaptation, suggesting a possible role for consolidation-dependent memory in balance rehabilitation, though this association requires confirmatory replication.

Freezing of gait (FOG) is a common and enigmatic feature of Parkinson's disease (PD) because of its episodic and unpredictable nature. It is now clear that FOG is not a monolithic phenomenon but instead exhibits substantial heterogeneity across patients, suggesting the existence of subtypes. Among the heterogeneous features are levodopa response patterns and nonmotor features, cognitive impairment and anxiety/depression. It remains an open question as to whether these phenotypes are the result of different pathophysiology. In this paper, we develop the hypothesis that levodopa response patterns may identify FOG subpopulations tied to nonmotor symptoms and alterations in different neurotransmitter systems. Here, we review the levodopa response patterns of FOG seen in PD based on a rigorous levodopa challenge paradigm using a 40% higher dose of levodopa and blood levodopa levels to demonstrate that the majority of patients are either levodopa responsive (OFF‐FOG) or unresponsive (ONOFF‐FOG). The literature demonstrates that executive and affective changes are not universal in FOG and actually relate closely to levodopa response patterns, OFF‐FOG is associated with affective disorders, and ONOFF‐FOG is related to cognitive decline. In turn, OFF‐FOG and affective disorders appear to be associated with brain noradrenergic degeneration, whereas ONOFF‐FOG and cognitive decline are associated with cholinergic loss. These observations suggest different therapeutic targets by subtype. We suggest that levodopa challenge testing may help stratify FOG patients in trials and mechanistic studies.

People with Parkinson's disease and freezing of gait (PD+FOG) exhibit altered gait and turning compared to nonfreezing peers with PD (PD‐FOG). However, less work has examined the effects of FOG status on daily‐life mobility. Therefore, we compared daily‐life gait and turning across PD+FOG and PD‐FOG and related gait deficits to self‐reported FOG severity and health‐related quality of life (QOL). We collected daily‐life mobility data over 7 days from 119 people with PD (PD+FOG = 47). Inertial sensors on the feet and lower back assessed 33 gait and balance outcomes. One‐way ANCOVAs assessed the effect of FOG status on mobility. Five variables reflecting gait and turning quality were significantly worse in PD+FOG compared to PD‐FOG after Holm correction: smaller turn angles, smaller foot pitch at initial contact, and increased variability of double‐support time, stride length, and pitch at toe‐off. Of these outcomes, two (turn angle & stride length variability) were significantly correlated with freezing severity, and 4 (turn angle, stride length variability, pitch at initial contact and pitch at toe‐off variability) related to QOL. Turns per hour also related to QOL. In sum, PD+FOG exhibited worse daily‐life gait quality (small turn angle and foot angle at heel strike and increased gait variability) and these outcomes were related to QOL and FOG severity. Daily‐life gait quantity (number of turns, strides, and gait bouts per hour) was less affected by FOG. These results provide insight into daily‐life mobility of PD+FOG, and support interventions aimed at quality of gait and turning for PD+FOG.

Background and Purpose: Falls remain an important and undertreated outcome in people with multiple sclerosis (PwMS). Understanding the paths through which neurophysiological changes contribute to altered balance and falls can improve our understanding of and ability to treat falls in this group. The purpose of this analysis was to assess the relationship between specific aspects of balance (reactive balance and sway) in PwMS and to assess whether balance deficits mediate relationships between neurophysiological changes (cutaneous sensation at the foot) and falls. Methods: In this observational, cross-sectional study, cutaneous sensation, reactive balance, and standing sway data were collected in 121 PwMS and 48 controls. Correlation analyses assessed relationships between reactive and standing balance. Single and multiple mediator models determined the individual and joint mediating effect of sway and reactive stepping on the cutaneous sensation-falls relationship. Results: Significant correlations were observed between reactive step latency (but not length) and multiple standing sway outcomes in PwMS. Statistically significant relationships were not observed in controls. Mediation models showed a significant mediating effect of reactive step latency and sway on the cutaneous sensation-falls relationship in PwMS. Discussion and Conclusions: Results indicate that the latency (but not length) of reactive stepping is related to standing sway, cutaneous sensation, and (via previous analyses) falls. Further, mediation analyses suggest that poor sensation leads to greater sway and slower reactive steps, which lead to greater fall risk. Together, these results inform links between balance outcomes and quantitatively confirm previous hypotheses regarding possible pathways through which sensory deficits contribute to falls.

Background: Misalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD). Objective: Determine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition. Methods: Actual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes were quality of life and cognitive domains frequently altered in people with PD (global cognition & executive function). Secondary cognitive domains assessed were attention, memory, visuo-spatial, verbal function, and information processing. Linear and non-linear models assessed the relationship between discordance, quality of life, and cognition. Results: Discordance related to mobility-related quality of life, such that under-confidence was related to poorer quality of life. Non-linear (quadratic) models were shown to fit the discordance-Global cognition ( p = 0.02) data better than linear models such that over- and under-confidence related to poorer cognition. Secondary cognitive domains were not robustly related to discordance. Conclusions: In a clinical sample of people with PD, discordance was related to mobility-related quality of life and global cognition. Global cognition further exhibited a possible non-linear relationship to discordance indicating that over- or under-confidence may relate to poorer cognition. This work underscores the functional relevance of misalignment of actual and balance abilities.

Purpose: We assessed the relationship between prescription of medications (both individually and in combination) and consequential falls. Methods: Medication prescription and prospectively registered falls over 2.5 years were extracted from 441 participants within a Swedish National Quality Register. Conditional generalized estimating equations, considering dependence of longitudinal data as a cluster to correct confidence intervals, were used to relate medications (individual and in combination) and falls. Results: Regarding individual-medications, Angiotensin II receptor blockers and diuretics (C09DA) were significantly related to incidence of consequential falls ( p = 0.022). Six drug combinations significantly related to fall incidence. Most frequently, falls were observed when platelet aggregation inhibitors (B01AC) were prescribed with C09DA, opioids (N02AA), or blood glucose lowering drugs (biguanides, A10BA). Discussion: Caution should be taken when prescribing cardiovascular medications. Further, prescription of platelet aggregation inhibitors could increase the incidence of a negative outcome of a fall when prescribed in people at risk for falls.