Longitudinal Changes in Patient‐ and Clinical‐Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Abstract Background Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia‐specific, sensitive change, clinically relevant, and meaningful patients. Objectives To evaluate the longitudinal 1‐ 2‐year performances of different patient reported outcomes, including Patient Reported Outcome Measure Ataxia (PROM‐Ataxia), clinician FARS SARA, those with early manifest symptoms SCA 1, 2, 3, 6. Methods We studied 53 patients stage SCA1‐3 SCA6 from The Instrumented Data Exchange for Study 24 age‐matched healthy controls. Participants were seen every 6 months 2 years. Mixed models used estimate change over 12‐ 24‐months follow‐up. Changes on FARS‐FS PGI‐C as anchors changes. Results Among persons SCA, mean age was 48.7 years SARA score 9.3. Few measures showed statistically significant changes at 12 months. At 24‐months, FARS‐ADL, PROM‐Ataxia total, physical, ADL scores strongest associations change. Conclusions or derived outcome measures, such FARS‐ADL sub domain PROM‐Ataxia, can capture patients’ symptom experience a period its impact daily activities, even disease. More work is needed identify that reliably earlier.

Language: Английский

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Longitudinal description of health-related quality of life and depressive symptoms in polyQ spinocerebellar ataxia patients

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(5)

Published: April 9, 2025

Language: Английский

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FARS‐ADL across Ataxias: Construct Validity, Sensitivity to Change, and Minimal Important Change

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(6), P. 965 - 974

Published: March 20, 2024

Abstract Background Patient‐focused outcomes present a central need for trial‐readiness across all ataxias. The Activities of Daily Living part the Friedreich Ataxia Rating Scale (FARS‐ADL) captures functional impairment and longitudinal change but is only validated in Ataxia. Objective Validation FARS‐ADL regarding disease severity patient‐meaningful impairment, its sensitivity to genetic Methods Real‐world registry data 298 ataxia patients genotypes were analyzed, including (1) cross‐correlation with FARS‐stage, Assessment (SARA), Patient‐Reported Outcome Measure (PROM)‐ataxia, European Quality Life 5 Dimensions visual analogue scale (EQ5D‐VAS); (2) within trial‐relevant 1‐year median follow‐up, anchored Patient Global Impression Change (PGI‐C); (3) general linear modeling factors age, sex, depression (nine‐item Health Questionnaire [PHQ‐9]). Results correlated overall disability (rho FARS‐stage = 0.79), clinical SARA 0.80), patient‐reported PROM‐ataxia 0.69, rho EQ5D‐VAS –0.37), indicating comprehensive construct validity. Also at item level, genotype (SCA3, RFC1), corresponding effector domains; items quality life. was sensitive interval, progressing worsening PGI‐C. Minimal important 1.1. points based on intraindividual variability stable Depression captured using (+0.3 points/PHQ‐9 count) EQ5D‐VAS, not or SARA. Conclusion reflects both ataxias, timescales perceiving change. It thus presents promising patient‐focused outcome upcoming trials. © 2024 Authors. Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

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Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia

The Cerebellum, Journal Year: 2024, Volume and Issue: 23(5), P. 2012 - 2027

Published: May 7, 2024

Abstract The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, Speech. It was developed as a potentially clinically meaningful measure spinocerebellar ataxia (SCA) progression clinical trial use. Here, we evaluated content validity f-SARA. Qualitative interviews were conducted among individuals with SCA1 ( n = 1) SCA3 6) healthcare professionals (HCPs) SCA expertise (USA, 5; Europe, 3). Interviews symptoms signs relevance f-SARA concepts SCA. HCP cognitive debriefing conducted. recorded, transcribed, coded, analyzed by ATLAS.TI software. Individuals 3 reported 85 symptoms, signs, impacts All indicated difficulties walking, stance, balance, speech, fatigue, emotions, work. considered Speech relevant concepts; Sitting (42.9%). HCPs Gait relevant; 5 (62.5%) Stance relevant. late-stage disease indicator. Most suggested inclusion appendicular items would enhance relevance. Cognitive supported clarity comprehension Maintaining current abilities on 1 year most 3. changes stability in score over 1–2 years, 1–2-point change total score, deviation from natural history. These results support assessing trials.

Language: Английский

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Local Dynamic Stability of Trunk During Gait is Responsive to Rehabilitation in Subjects with Primary Degenerative Cerebellar Ataxia

The Cerebellum, Journal Year: 2024, Volume and Issue: 23(4), P. 1478 - 1489

Published: Jan. 27, 2024

This study aimed to assess the responsiveness rehabilitation of three trunk acceleration-derived gait indexes, namely harmonic ratio (HR), short-term longest Lyapunov's exponent (sLLE), and step-to-step coefficient variation (CV), in a sample subjects with primary degenerative cerebellar ataxia (swCA), investigate correlations between their improvements (∆), clinical characteristics, spatio-temporal kinematic features. The acceleration patterns antero-posterior (AP), medio-lateral (ML), vertical (V) directions during 21 swCA were recorded using magneto-inertial measurement unit placed at lower back before (T0) after (T1) period inpatient rehabilitation. For comparison, age- speed-matched healthy (HS

Language: Английский

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

CPT Pharmacometrics & Systems Pharmacology, Journal Year: 2024, Volume and Issue: 13(8), P. 1327 - 1340

Published: May 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.

Language: Английский

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Psychometric Validation of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) in Patients With Spinocerebellar Ataxia

The Cerebellum, Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

This study aimed to generate evidence support psychometric validity of the modified functional Scale for Assessment and Rating Ataxia (f-SARA) among patients with spinocerebellar ataxia (SCA). Psychometric measurement properties minimal change thresholds f-SARA were evaluated using data from a cohort SCA subjects (recruited at Massachusetts General Hospital [MGH]; n = 33) phase 3 trial troriluzole in adults (NCT03701399 [Study 206]; 217), including subset SCA3 genotype (n 89). item ceiling effects absent within MGH cohort, while floor present. Excellent internal consistency reliability was demonstrated (α

Language: Английский

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SARA captures disparate progression and responsiveness in spinocerebellar ataxias

Journal of Neurology, Journal Year: 2024, Volume and Issue: 271(7), P. 3743 - 3753

Published: June 1, 2024

Language: Английский

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Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study

European Journal of Neurology, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 1, 2025

Abstract Background Friedreich ataxia is a rare neurodegenerative disorder caused by frataxin deficiency. Both underweight and overweight occur in mitochondrial disorders, each with adverse health outcomes. We investigated the longitudinal evolution of anthropometric abnormalities hypothesis that both weight loss gain are associated faster disease progression. Methods Participants were drawn from European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). Age‐ sex‐specific BMI height scores calculated using KIGGS‐BMI percentiles children. Height correction was applied scoliosis. Longitudinal data analysed linear mixed effects models incremental standard deviation growth mixture identified subclasses varying trajectories. Results Five hundred forty‐three adults fifty‐nine children assessed up to 5 years. In children, severe (26%), (7%), short stature (16%) (23%) common. The corrected percentile stable although 48% had negative over 1 year 63% 3 years versus 10%/year normal reference cohort. Overweight common (19%), slight increase time. Longer GAA repeat size linked lower adults. Weight trajectory not progression Conclusion Significant identified, prevalent These findings highlight need regular nutritional monitoring interventions manage promote healthy

Language: Английский

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Movement Disorders in Hereditary Cerebellar Ataxia

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract Background Hereditary cerebellar ataxia (HCA) represents a complex group of disorders, with wide spectrum neurological symptoms. Among these, non‐ataxia movement disorders (MD) have been increasingly acknowledged, variable frequency across different forms. Objectives To characterize the type and MD in patients HCA. identify factors associated analyze their impact on disability. Methods We conducted prospective study starting 2017, annual visits according to structured protocol. Patients were selected from database clinical genetic features analyzed. Results The cohort comprised 193 symptomatic patients. Machado‐Joseph disease (MJD, also SCA3 or ATX‐ ATXN3 ) ataxia, neuropathy vestibular areflexia syndrome (ATX‐ RFC1 most common autosomal dominant (AD) recessive forms, 14.0% 15.0%, respectively. present 95 (54.4%), dystonia being (49.2%). Tremor was identified 10.9%, Parkinsonism 4.1% chorea 3.6% Myoclonus tics rare (2.6% 0.5%). presence AD inheritance . MD, regardless type, correlated higher SARA score at baseline, increased fall frequency, confinement wheelchair, earlier occurrence falls permanent use walking aid. Conclusions Movement particularly dystonia, our cohort. This highlights possible role cerebellum but extra‐cerebellar involvement some Presence significantly worsened motor disability, highlighting need for strategies early identification tailored management.

Language: Английский

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