Assessing balance is crucial in neurological rehabilitation, yet while wearable sensors enable real-world monitoring, identifying reliable digital biomarkers remains challenging. This study utilized a high-fidelity instrumented walkway to determine which gait parameters best predict balance impairment, providing robust targets for future wearable applications. We analyzed 49 steady-state gait metrics from 140 individuals with diverse neurological conditions. Using statistical analysis and machine learning, we evaluated these parameters against objective force plate sway scores and clinical fall-history labels. Group analysis identified 16 parameters significantly distinguishing fallers from non-fallers, and a neural network classified fallers with an area under the curve of 0.75. Across all analytical approaches, overall gait variability, e.g., Stride Width S.D. and the Gait Variability Index, emerged as a universal predictor of balance impairment and fall risk. Furthermore, while traditional linear models emphasized spatial postural control, machine learning classification uniquely identified inter-limb asymmetry as a premier driver of fall prediction. These findings indicate that instrumented gait analysis effectively identifies digital biomarkers for balance deficits. Isolating these specific metrics provides a clear blueprint for meaningful metrics required for continuous objective monitoring and future development of personalized, adaptive rehabilitation strategies.
White Matter Hyperintensity Association With Cognitive Impairment and Mortality in a Population-Based Cohort of Incident Parkinsonism
Juvenile Parkinson's disease (JPD) is a rare condition characterized by the onset of parkinsonian motor symptoms before the age of 21. Sixteen patients with JPD who presented to the Mayo Clinic between 1990-2020 were included. The median age of symptoms onset was 18.5 years, and six cases had pathogenic PRKN mutations. Resting tremor was the most frequent initial symptom (81.3%), and non-motor symptoms were notably common, including mild cognitive impairment (56.3%), anxiety (62.5%), and depression (56.3%). Levodopa responsiveness was suboptimal in 9 patients and 14 exhibited motor fluctuations. JPD demonstrates distinct clinical characteristics compared with early-onset and late-onset PD.
Familial Aggregation of Parkinson Disease and Essential Tremor in Early and Late Onset Parkinson Disease Cohorts
ABSTRACT Background Long‐term outcome data for stiff person spectrum disorder (SPSD) remain limited and sustained response to treatment varies. Methods In this retrospective cohort study, we included patients with probable or definite SPSD (Mayo Clinic criteria), evaluated at Mayo Clinic (12/1995‐07/2024) with ≥ 5 years of follow‐up after diagnosis. Primary outcome measures included the modified Rankin scale (mRS) and use of gait aids. Results Fifty‐four patients were included, 41 (76%) were female; median age at onset was 45 years (16–78). Most were antibody‐positive (51 [94%]), with high‐titer (serum, ≥ 20 nmol/L) GAD65‐IgG in 45 (83%). Nine patients had a stiff‐limb presentation (17%). The median interval from onset to diagnosis was 2 years (0–34), and median follow‐up was 9 years (5–26). Most patients (46 [85%]) received immune therapy; 37 (82%) reported improvement. All patients had significant impairment (mRS ≥ 2) at nadir, with 31 (57%) losing functional independence (mRS ≥ 3) and 40 (75%) requiring bilateral gait assistance. The median time from onset to nadir was 6 years (0–39). At last follow‐up, most (37 [69%]) were functionally independent (mRS ≤ 2), including 8 (15%) with minimal restrictions (mRS ≤ 1). Bilateral gait assistance was needed in 22 (41%). Among 40 patients with ≥ 10 years of follow‐up, 22 (56%) had an mRS ≤ 2 and 25 (63%) required a gait aid at last follow‐up. Poor outcome in this population was associated with bilateral gait assistance at nadir and older age ( p < 0.05). Conclusions Although over half of SPSD patients lose functional independence at disease nadir, many regain independence and achieve well‐controlled symptoms.