Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers

The Cerebellum, Год журнала: 2023, Номер 23(4), С. 1566 - 1592

Опубликована: Ноя. 13, 2023

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait balance disturbances most often present as first signs of cerebellar ataxia reported disabling features in disease progression. Thus, gait constitute promising relevant performance outcomes trials.This narrative review with embedded consensus will describe evidence sensitivity evaluating severity progression, propose a protocol establishing metrics natural history studies trials, discuss issues their use outcomes.

Язык: Английский

---

Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

Annals of Neurology, Год журнала: 2023, Номер 94(3), С. 470 - 485

Опубликована: Май 27, 2023

The Scale for the Assessment and Rating of Ataxia (SARA) is most widely applied clinical outcome assessment (COA) genetic ataxias, but presents metrological regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity patient-focused outcomes) across a large number provide first natural history data several them.Subitem-level correlation distribution-based analysis 1,637 SARA assessments in 884 patients with autosomal recessive/early onset (370 2-8 longitudinal assessments) were complemented by linear mixed effects modeling estimate progression sample sizes.Although subitem varied between severities, gait/stance showed robust granular scaling broadest range (SARA < 25). Responsiveness was diminished incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), fluctuating decreases/increases. All subitems except nose-finger moderate-to-strong correlations activities daily living, indicating that metric properties-not content validity-limit responsiveness. captured mild-to-moderate many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, oculomotor apraxia type 2: 1.14 POLG-ataxia: 1.56 points/yr), no change others (autosomal recessive spastic Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity optimal mild 10), it substantially deteriorated advanced > 25; 2.7-fold size). Use novel rank-optimized without finger-chase reduces sizes 20 25%.This study comprehensively characterizes COA properties annualized changes within ataxias. It suggests specific approaches optimizing might qualification design. ANN NEUROL 2023;94:470-485.

Язык: Английский

---

Smartphone applications for Movement Disorders: Towards collaboration and re-use

Parkinsonism & Related Disorders, Год журнала: 2024, Номер unknown, С. 105988 - 105988

Опубликована: Янв. 1, 2024

Numerous smartphone and tablet applications (apps) are available to monitor movement disorders, but an overview of their purpose stage development is missing.

Язык: Английский

---

Digital Gait Measures Capture 1‐Year Progression in Early‐Stage Spinocerebellar Ataxia Type 2

Movement Disorders, Год журнала: 2024, Номер 39(5), С. 788 - 797

Опубликована: Фев. 28, 2024

Abstract Background With disease‐modifying drugs in reach for cerebellar ataxias, fine‐grained digital health measures are highly warranted to complement clinical and patient‐reported outcome upcoming treatment trials monitoring. These need demonstrate sensitivity capture change, particular the early stages of disease. Objective Our aim is unravel gait sensitive longitudinal change the—particularly trial‐relevant—early stage spinocerebellar ataxia type 2 (SCA2). Methods We performed a multicenter study with combined cross‐sectional 1‐year interval analysis early‐stage SCA2 participants (n = 23, including nine pre‐ataxic expansion carriers; median, ATXN2 CAG repeat 38 ± 2; Scale Assessment Rating Ataxia [SARA] score 4.8 4.3). Gait was assessed using three wearable motion sensors during 2‐minute walk, analyses focused on spatio‐temporal variability that have shown severity (eg, lateral step deviation). Results found significant changes between baseline follow‐up large effect sizes (lateral deviation P 0.0001, size r prb 0.78), whereas SARA showed no ( 0.67). Sample estimation indicates required cohort n 43 detect 50% reduction natural progression. Test–retest reliability minimal detectable confirm accuracy detecting identified change. Conclusions by can progression within just 1 year—in contrast outcome. Lateral represents promising measure interventional trials, particularly ataxia. © 2024 The Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Язык: Английский

---

Validation and application of computer vision algorithms for video-based tremor analysis

npj Digital Medicine, Год журнала: 2024, Номер 7(1)

Опубликована: Июнь 21, 2024

Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for granular phenotyping. Instrumented neurophysiological analyses have proven useful, but are highly resource-intensive lack broad accessibility. In contrast, bedside scores simple to administer, granularity capture subtle relevant tremor features. We utilise open-source computer vision pose tracking algorithm Mediapipe track hands in video recordings use resulting time series compute canonical This approach compared marker-based 3D motion capture, wrist-worn accelerometry, scoring a second, specifically trained tremor-specific two independent cohorts. These cohorts consisted 66 patients diagnosed with essential tremor, assessed different task conditions states deep brain stimulation therapy. find that Mediapipe-derived metrics exhibit high convergent validity (Spearman's ρ = 0.55-0.86, p≤ .01) as well an accuracy up 2.60 mm (95% CI [-3.13, 8.23]) ≤0.21 Hz [-0.05, 0.46]) amplitude frequency measurements, matching gold-standard equipment. Mediapipe, not disease-specific algorithm, was capable analysing videos involving complex configurational changes hands. Moreover, it enabled extraction features diagnostic prognostic relevance, dimension which conventional were unable provide. Collectively, this demonstrates current algorithms can be transformed into accurate accessible tool video-based analysis, yielding comparable results gold standard recordings.

Язык: Английский

---

4-Aminopyridine improves real-life gait performance in SCA27B on a single-subject level: a prospective n-of-1 treatment experience

Journal of Neurology, Год журнала: 2023, Номер 270(11), С. 5629 - 5634

Опубликована: Июль 13, 2023

Язык: Английский

---

Item performance of the scale for the assessment and rating of ataxia in rare and ultra‐rare genetic ataxias

CPT Pharmacometrics & Systems Pharmacology, Год журнала: 2024, Номер 13(8), С. 1327 - 1340

Опубликована: Май 21, 2024

Abstract The Scale for the Assessment and Rating of Ataxia (SARA) is widely used assessing severity progression genetic cerebellar ataxias. SARA now considered a primary end point in several ataxia treatment trials, but its underlying composite item measurement model has not yet been tested. This work aimed to evaluate properties items using response theory (IRT) demonstrate applicability across even ultra‐rare Leveraging subscores data from 1932 visits 990 patients Autosomal Recessive Cerebellar Ataxias (ARCA) registry, we assessed performance IRT methodology. characteristics were evaluated over range entire population as well assessment validity 115 ARCA subpopulations. A unidimensional was able describe data, indicating that captures one single latent variable. All had high discrimination values (1.5–2.9) effectiveness differentiating between subjects with different disease statuses. Each contributed 7% 28% total informativeness. There no evidence differences subpopulations applicability. These results show good ability all adding informational value. framework provides thorough description on level, facilitates utilization clinical outcome upcoming longitudinal natural history or large number ataxias, including ones.

Язык: Английский

---

Step Width Haptic Feedback for Gait Stability in Spinocerebellar Ataxia: Preliminary Results

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Background Wider step width and lower step‐to‐step variability are linked to improved gait stability reduced fall risk. It is unclear if patients with spinocerebellar ataxia (SCA) can learn adjust these aspects of reduce Objectives The aims were examine the possibility using wearable haptic biofeedback enhance risk in individuals SCA. Methods Thirteen people SCA type 3 performed training (single session) real‐time feedback. Results Step increased post‐training (19.3 cm, interquartile range [IQR] 16.3–20.2 cm) at retention (16.6 IQR 16.2–21.1 cm), compared baseline (11.0 5.2–15.2 cm; P < 0.001). decreased during (19.7%, 17.4%–26.2%) (22.3%, 18.6%–30.2%), (44.5%, 28.5%–71.2%; Crossover steps, another mark instability, after ( 0.031). Conclusions These pilot results suggest that use a novel, system improve their stability. © 2025 International Parkinson Movement Disorder Society.

Язык: Английский

---

Computer Vision in Clinical Neurology

JAMA Neurology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Importance Neurological examinations traditionally rely on visual analysis of physical clinical signs, such as tremor, ataxia, or nystagmus. Contemporary score-based assessments aim to standardize and quantify these observations, but tools suffer from clinimetric limitations often fail capture subtle yet important aspects human movement. This poses a significant roadblock more precise personalized neurological care, which increasingly focuses early stages disease. Computer vision, branch artificial intelligence, has the potential address challenges by providing objective measures signs based solely video footage. Observations Recent studies highlight computer vision measure disease severity, discover novel biomarkers, characterize therapeutic outcomes in neurology with high accuracy granularity. may enable sensitive detection movement patterns that escape eye, aligning an emerging research focus stages. However, accessibility, ethics, validation need be addressed for widespread adoption. In particular, improvements usability algorithmic robustness are key priorities future developments. Conclusions Relevance technologies have revolutionize practice objective, quantitative signs. These could enhance diagnostic accuracy, improve treatment monitoring, democratize specialized care. Clinicians should aware their complement traditional assessment methods. further focusing validation, ethical considerations, practical implementation is necessary fully realize neurology.

Язык: Английский

---

Smartphone Application for Spastic Ataxias Cross-Sectional Validation of a Newly Developed Smartphone App for Remote Monitoring in Spastic Ataxias

The Cerebellum, Год журнала: 2025, Номер 24(3)

Опубликована: Март 24, 2025

Abstract Effective trial-planning in Spastic ataxias (SPAX) is impeded by the absence of validated outcome measures for detecting longitudinal changes. Digital show promise, demonstrating sensitivity to disease severity changes ataxia and strong correlations with clinical scales. The objective this study was develop a smartphone application SPAX (SPAX-app) obtain valid digital use trials. app contains four tasks assessing gait, standing balance (stance), finger hand movements. We carried out validation 22 patients 10 controls. Subjects performed three times during one visit. In parallel, we Ambulatory Parkinson’s Disease Monitoring (APDM) sensor recordings, Q-motor upper limb assessment, Scale Assessment Rating Ataxia (SARA). Significant were found between SPAX-app APDM or step time ( r = 0.91), all stance 0.51–0.87) duration alternation 0.64). No significant variability (e.g. standard deviation time). All SPAX-app, except stance, can discriminate from controls moderate high test-retest reliability (ICC 0.67–0.97). SARA 0.70), inter-onset interval tapping 0.57), 0.65). task did not SARA. With present set potential Longitudinal studies are needed evaluate whether these track progression.

Язык: Английский

---