Scale For Assessment And Rating Of Ataxia Research Articles

Effects of Non-Invasive Brain Stimulation for Degenerative Cerebellar Ataxia: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to assess the effectiveness of non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta-analysis was performed. Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = -2.49, [95% confidence interval: -3.34, -1.64]) and ICARS (-5.27 [-7.06, -3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. Non-invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high-quality RCTs are required.

Multimodal, Longitudinal Profiling of SCA1 Identifies Predictors of Disease Severity and Progression.

Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant neurodegenerative disease. Objective surrogate markers sensitive to detect changes in disease severity are needed to reduce sample sizes in interventional trials and identification of predictors of faster disease progression would facilitate patient selection, enrichment, or stratification in such trials. We performed a prospective 1-year longitudinal, multimodal study in 34 ataxic SCA1 individuals and 21 healthy controls. We collected clinical, patient-reported outcomes, biochemical and magnetic resonance (MR) biomarkers at baseline and after 1 year. We determined 1-year progression and evaluated the potential predictive value of several baseline markers on 1-year disease progression. At baseline, multiple structural and spectroscopic MR markers in pons and cerebellum differentiated SCA1 from healthy controls and correlated with disease severity. Plasma and cerebrospinal fluid (CSF) neurofilament light (NfL) chain and CSF glial fibrillary acidic protein (GFAP) were elevated in SCA1. In longitudinal analysis, total brainstem and pontine volume change, inventory of non-ataxia signs (INAS) count, and SCA functional index (SCAFI) showed larger responsiveness compared to the Scale for Assessment and Rating of Ataxia (SARA). Longer disease duration, longer non-expanded CAG repeat length, and higher disease burden were associated with faster SARA increase after 1-year in the SCA1 group. Similarly, lower baseline brainstem, pontine, and cerebellar volumes, as well as lower levels of N-acetylaspartate and glutamate in the cerebellar white matter, were also associated with faster SARA increase. Our results guide the selection of the most sensitive measures of disease progression in SCA1 and have identified features associated with accelerated progression that could inform the design of clinical trials. ANN NEUROL 2024.

Sensitivity of Advanced Magnetic Resonance Imaging to Progression over Six Months in Early Spinocerebellar Ataxia.

Clinical trials for upcoming disease-modifying therapies of spinocerebellar ataxias (SCA), a group of rare movement disorders, lack endpoints sensitive to early disease progression, when therapeutics will be most effective. In addition, regulatory agencies emphasize the importance of biological outcomes. READISCA, a transatlantic clinical trial readiness consortium, investigated whether advanced multimodal magnetic resonance imaging (MRI) detects pathology progression over 6 months in preataxic and early ataxic carriers of SCA mutations. A total of 44 participants (10 SCA1, 25 SCA3, and 9 controls) prospectively underwent 3-T MR scanning at baseline and a median [interquartile range] follow-up of 6.2 [5.9-6.7] months; 44% of SCA participants were preataxic. Blinded analyses of annual changes in structural, diffusion MRI, MR spectroscopy, and the Scale for Assessment and Rating of Ataxia (SARA) were compared between groups using nonparametric testing. Sample sizes were estimated for 6-month interventional trials with 50% to 100% treatment effect size, leveraging existing large cohort data (186 SCA1, 272 SCA3) for the SARA estimate. Rate of change in microstructural integrity (decrease in fractional anisotropy, increase in diffusivities) in the middle cerebellar peduncle, corona radiata, and superior longitudinal fasciculus significantly differed in SCAs from controls (P < 0.005), with high effect sizes (Cohen's d = 1-2) and moderate-to-high responsiveness (|standardized response mean| = 0.6-0.9) in SCAs. SARA scores did not change, and their rate of change did not differ between groups. Diffusion MRI is sensitive to disease progression at very early-stage SCA1 and SCA3 and may provide a >5-fold reduction in sample sizes relative to SARA as endpoint for 6-month-long trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

SARA captures disparate progression and responsiveness in spinocerebellar ataxias.

The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale to assess cerebellar ataxia but faces some criticisms about the relevancy of all its items. To prepare for future clinical trials, we analyzed the progression of SARA and its items in several polyQ spinocerebellar ataxias (SCA) from various cohorts. We included data from patients with SCA1, SCA2, SCA3, and SCA6 from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) for a total of 850 carriers and 3431 observations. Longitudinal progression of the SARA and its items was measured. Cohort, stage and genetic effects were tested. We looked at the respective contribution of each item to the total scale. Sensitivity to change of the scale and the impact of item removal was evaluated by calculating sample sizes needed in various scenarios. Longitudinal progression was significantly different between cohorts in SCA1, SCA2 and SCA3, the EUROSCA cohort having the fastest progression. Advanced-stage patients were progressing slower in SCA2 and SCA6. Items were not contributing equally to the full scale through ataxia severity: gait, stance, hand movement, and heel-shin contributed the most in the early stage, and finger-chase, nose-finger, and sitting in later stages. Few items drove the sensitivity to the change of SARA, but changes in the scale structure could not improve its sensitivity in all populations. SARA and its item's progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately.

Prediction of Individual Disease Progression Including Parameter Uncertainty in Rare Neurodegenerative Diseases: The Example of Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS)

The aim of this study was to develop a model to predict individual subject disease trajectories including parameter uncertainty and accounting for missing data in rare neurological diseases, showcased by the ultra-rare disease Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS). We modelled the change in SARA (Scale for Assessment and Rating of Ataxia) score versus Time Since Onset of symptoms using non-linear mixed effect models for a population of 173 patients with ARSACS included in the prospective real-world multicenter Autosomal Recessive Cerebellar Ataxia (ARCA) registry. We used the Multivariate Imputation Chained Equation (MICE) algorithm to impute missing covariates, and a covariate selection procedure with a pooled p-value to account for the multiply imputed data sets. We then investigated the impact of covariates and population parameter uncertainty on the prediction of the individual trajectories up to 5 years after their last visit. A four-parameter logistic function was selected. Men were estimated to have a 25% lower SARA score at disease onset and a moderately higher maximum SARA score, and time to progression (T50) was estimated to be 35% lower in patients with age of onset over 15 years. The population disease progression rate started slowly at 0.1 points per year peaking to a maximum of 0.8 points per year (at 36.8 years since onset of symptoms). The prediction intervals for SARA scores 5 years after the last visit were large (median 7.4 points, Q1-Q3: 6.4–8.5); their size was mostly driven by individual parameter uncertainty and individual disease progression rate at that time.Graphical

Efficacy and safety of N-acetyl-L-leucine in patients with ataxia telangiectasia: A randomized, double-blind, placebo-controlled, crossover clinical trial

BackgroundAtaxia telangiectasia (AT) is an autosomal recessive multisystem disorder. Most patients have progressive cerebellar ataxia, oculocutaneous telangiectasia, frequent pulmonary infection, and an increased risk of malignancies. Although N-acetyl-dl-leucine (ADLL) has shown some efficacy in patients with AT, its more pharmacologically active enantiomer, N-acetyl-l-leucine (NALL), has just recently been investigated in ataxic individuals. The current study assessed the efficacy of NALL in patients with AT. MethodsThis 2 × 2 crossover, double-blind, randomized clinical trial was conducted on 20 patients with AT. After excluding four patients, 16 subjects (eight females, eight males; mean age 9.8 ± 3.5 years) with a definitive genetic diagnosis of AT were randomly assigned to one of two study groups, with one group receiving 1–4 g/day NALL or a placebo for six weeks. Subjects then had a 4-week washout before crossing over to the other treatment for an additional six weeks. The Spinocerebellar Ataxia Functional Index (SCAFI) and the Scale for Assessment and Rating of Ataxia (SARA) score assessed patients' motor function. Quality of life (QOL) was evaluated by a specialist using the PedsQL questionnaire. Fasting blood samples were taken from all subjects before and after each intervention to determine potential side effects. ResultsAlthough patients' nausea and constipation were improved, the results failed to reveal any significant benefits of NALL treatment on ataxia symptoms. NALL treatment had no significant effects on SARA, SCAFI-9HPT (9-hole peg test) nondominant, SCAFI-9HPT dominant, or SCAFI-8WMT (8 m walking time) (p > 0.05). Our patient's Physical Health score in Child self-report and Parent proxy-report did not significantly change in the treatment group compared to the placebo (p > 0.05). Furthermore, there were no significant changes in energy and macronutrient intake after NALL treatment. None of the volunteers reported serious or moderate side effects. ConclusionsTo the best of our knowledge, this was the first placebo-controlled, randomized clinical trial exploring NALL's potential effects for treating AT. Despite improvements in some symptomss, NALL intervention failed to improve motor function significantly. However, patients' nausea and constipation were improved by NALL, which can be a relevant benefit clinically.

Quantitative Evaluation of Stance as a Sensitive Biomarker of Postural Ataxia Development in Preclinical SCA1 Mutation Carriers.

The aim of this study was to determine the time between the first detection of postural control impairments and the evident manifestation of ataxia in preclinical SCA1 individuals. Twenty five preclinical SCA1 mutation carriers: 13 with estimated disease onset ≤ 6years (SCA1 +) aged 27.8 ± 8.1years; 12 with expected disease onset > 6years (SCA1-) aged 26.6 ± 3.1years and 26 age and sex matched healthy controls (HCs) underwent static posturography during 5years of observation. The movements of the centre of feet pressure (COP) during quiet standing with eyes open (EO) and closed (EC) were quantified by calculating the mean radius (R), developed surface area (A) and mean COP movement velocity (V). Ataxia was evaluated by use of the Scale for Assessment and Rating of Ataxia (SARA).SCA1 + exhibited significantly worse quality of stance with EC vs. SCA1- (p < 0.05 for V) and HCs (p < 0.001) even 5 to 6years before estimated disease onset. There were no statistically significant differences between SCA1- and HCs. A slow increase in Cohen's d effect size was observed for VEO up to the clinical manifestation of ataxia. VEO and AEC recorded in preclinical SCA1 individuals correlated slightly but statistically significantly with SARA (r = 0.47).The study confirms that static posturography detects COP sway changes in SCA1 preclinical gene carriers even 5 to 6years before estimated disease onset. The quantitative evaluation of stance in preclinical SCA is a sensitive biomarker for the monitoring of the disease progression and may be useful in clinical trials.

Digital Measures of Postural Sway Quantify Balance Deficits in Spinocerebellar Ataxia.

Maintaining balance is crucial for independence and quality of life. Loss of balance is a hallmark of spinocerebellar ataxia (SCA). The aim of this study was to identify which standing balance conditions and digital measures of body sway were most discriminative, reliable, and valid for quantifying balance in SCA. Fifty-three people with SCA (13 SCA1, 13 SCA2, 14 SCA3, and 13 SCA6) and Scale for Assessment and Rating of Ataxia (SARA) scores 9.28 ± 4.36 and 31 healthy controls were recruited. Subjects stood in six test conditions (natural stance, feet together and tandem, each with eyes open [EO] and eyes closed [EC]) with an inertial sensor on their lower back for 30 seconds (×2). We compared test completion rate, test-retest reliability, and areas under the receiver operating characteristic curve (AUC) for seven digital sway measures. Pearson's correlations related sway with the SARA and the Patient-Reported Outcome Measure of Ataxia (PROM ataxia). Most individuals with SCA (85%-100%) could stand for 30 seconds with natural stance EO or EC, and with feet together EO. The most discriminative digital sway measures (path length, range, area, and root mean square) from the two most reliable and discriminative conditions (natural stance EC and feet together EO) showed intraclass correlation coefficients from 0.70 to 0.91 and AUCs from 0.83 to 0.93. Correlations of sway with SARA were significant (maximum r = 0.65 and 0.73). Correlations with PROM ataxia were mild to moderate (maximum r = 0.56 and 0.34). Inertial sensor measures of extent of postural sway in conditions of natural stance EC and feet together stance EO were discriminative, reliable, and valid for monitoring SCA. © 2024 International Parkinson and Movement Disorder Society.

Abstract TP84: Characteristics of Cerebellar Cognitive Affective Syndrome in Patients With Acute Cerebellar Stroke and Its Impact on Outcome

Background: Recently, cerebellar cognitive affective syndrome-scale (CCAS-S) was developed to assess CCAS in which cognitive impairment is caused by cerebellar lesions. However, very few studies have been conducted regarding CCAS in patients with stroke, and its impact on outcomes is unclear. This study aimed to evaluate CCAS in patients with acute cerebellar stroke and examine its association with outcome. Methods: Patients who experienced acute cerebellar stroke for the first time and were admitted to Steel Memorial Yawata Hospital, Japan within seven days of stroke onset between April 2021 and April 2023 were included in this observational study. CCAS-S, Mini-Mental State Examination (MMSE), and Scale for Assessment and Rating of Ataxia (SARA) scores were measured one week after stroke onset, and Functional Independence measure (FIM)/ Barthel Index (BI) at discharge, physical function, activities of daily living, length of hospital stay, and outcome (discharge destination) were evaluated. The Mann-Whitney U test was used to compare CCAS-S scores and other variables between patients with acute cerebellar stroke and healthy controls. Additionally, we compared these variables between patients discharged home and those discharged to a rehabilitation hospital. A significance level of less than 5%. Results: Thirteen consecutive patients with acute cerebellar stroke (9 women) and age-and sex-matched healthy controls (7 women) were included. The MMSE score was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, interquartile range [IQR] 66-80) and a higher number of failed tests (median 4, IQR 3-5) than healthy controls. Significant deficits were observed in semantic fluency (p=0.008), category switching (p=0001), and similarity (p=009). Possible, probable, and definite CCAS were diagnosed in 2, 1, and 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI scores but similar CCAS-S scores compared to those discharged to rehabilitation hospitals. Conclusion: CCAS along with impaired executive and language functions is frequently observed in patients with acute cerebellar stroke; however, impaired motor function, and not CCAS, influenced the outcome.

The Scale for Assessment and Rating of Ataxia Is Reliable and Valid in the Telehealth Setting for Patients With Cerebellar Ataxia.

Health care has increasingly expanded into a hybrid in-person/telehealth model. Patients with a variety of health conditions, including cerebellar ataxia, have received virtual health evaluations; however, it remains unknown whether some outcome measures that clinicians utilize in the telehealth setting are reliable and valid. The goal of this project is to evaluate the psychometric properties of the Scale for Assessment and Rating of Ataxia (SARA) for patients with cerebellar ataxia in the telehealth setting. Nineteen individuals with cerebellar impairments were recruited on a voluntary basis. Participants completed 2 30-minute testing sessions during which a clinical examination and the SARA were performed. One session was performed in person, and the other session was assessed remotely. Outcome measure performance was video recorded in both environments and independently scored by 4 additional raters with varying levels of clinical experience (ranging from 6 months to 29 years). Concurrent validity was assessed with the Spearman rank order correlation coefficient (α < .05), comparing the virtual SARA scores to their gold standard in-person scores. Interrater reliability was evaluated with the intraclass correlation coefficient (ICC) (2,4) (α < .05). Fourteen of the 19 participants completed both in-person and telehealth SARA evaluations. We found that the in-person SARA and the telehealth SARA have large concurrent validity (Spearman rho significant at the 2-tailed α of .01 = 0.90; n = 14). Additionally, raters of varying years of experience had excellent interrater reliability for both the in-person SARA (ICC [2,4] = 0.97; n = 19) and the telehealth SARA (ICC [2,4] = 0.98; n = 14). Our results show that the telehealth SARA is comparable to the in-person SARA. Additionally, raters of varying years of clinical experience were found to have excellent interrater reliability scores for both remote and in-person SARA evaluations. Our study shows that the SARA can be used in the telehealth setting for patients with ataxia.

Cognitive-affective manifestations since premanifest phases of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease

BackgroundCognitive deficits were related to Spinocerebellar Ataxia type 3/Machado-Joseph Disease (SCA3/MJD), but the Cerebellar Cognitive Affective Syndrome (CCAS) needs further investigation in this disorder. We aimed to characterize cognitive-affective deficits in manifest and premanifest SCA3/MJD carriers. MethodsSubjects at 50% risk, manifest carriers and unrelated controls were evaluated in-person or in virtual settings with CCAS Scale (CCAS-S), Stroop Color-Word Test (SCWT), Trail-Making Test (TMT), and Reading the Mind in the Eyes Test (RMET). Scale for Assessment and Rating of Ataxia (SARA) >2.5 or Friedreich Ataxia Rating Scale/Activities of Daily Living (FARS-adl) >4 divided carriers into manifest and premanifest. Time after onset or time left to gait ataxia onset (TimeToAfterOnset) were estimated. Differences between groups and correlations with TimeToAfterOnset, SARA and FARS-adl were checked. ResultsAfter random selection to balance groups, 23 manifest and 35 premanifest carriers, and 58 controls were included. CCAS-S, semantic fluency, phonemic fluency, category switching, affect, SCWT, and RMET showed significant differences between manifest carriers and controls; premanifest carriers mostly displayed intermediate values between controls and manifest carriers. These variables correlated with TimeToAfterOnset and SARA scores of the carriers. Correlations with SARA were stronger in the pre-ataxic group. CCAS-S had the strongest correlations with time and SARA. DiscussionCognitive-affective deficits in SCA3/MJD involve executive function, language, affect, and social cognition, which seem to be altered prior to the ataxia onset, and correlate with markers of motor progression. CCAS-S was the most promising biomarker and should be evaluated in longitudinal studies.

Optimal Design of Galvanic Vestibular Stimulation for Patients with Vestibulopathy and Cerebellar Disorders.

Galvanic vestibular stimulation (GVS) has shown positive outcomes in various neurological and psychiatric disorders, such as enhancing postural balance and cognitive functions. In order to expedite the practical application of GVS in clinical settings, our objective was to determine the best GVS parameters for patients with vestibulopathy and cerebellar disorders using optimal design calculation. A total of 31 patients (26 males, mean age 57.03 ± 14.75 years, age range 22-82 years) with either unilateral or bilateral vestibulopathy (n = 18) or cerebellar ataxia (n = 13) were enrolled in the study. The GVS intervention included three parameters, waveform (sinusoidal, direct current [DC], and noisy), amplitude (0.4, 0.8, and 1.2 mA), and duration of stimulation (5 and 30 min), resulting in a total of 18 GVS intervention modes as input variables. To evaluate the effectiveness of GVS, clinical vertigo and gait assessments were conducted using the Dizziness Visual Analogue Scale (D-VAS), Activities-specific Balance Confidence Scale (ABC), and Scale for Assessment and Rating of Ataxia (SARA) as output variables. Optimal design and local sensitivity analysis were employed to determine the most optimal GVS modes. Patients with unilateral vestibulopathy experienced the most favorable results with either noisy or sinusoidal GVS at 0.4 mA amplitude for 30 min, followed by DC GVS at 0.8 mA amplitude for 5 min. Noisy GVS at 0.8 or 0.4 mA amplitude for 30 min demonstrated the most beneficial effects in patients with bilateral vestibulopathy. For patients with cerebellar ataxia, the optimal choices were noisy GVS with 0.8 or 0.4 mA amplitude for 5 or 30 min. This study is the first to utilize design optimization methods to identify the GVS stimulation parameters that are tailored to individual-specific characteristics of dizziness and imbalance. A sensitivity analysis was carried out along with the optimal design to offset the constraints of a limited sample size, resulting in the identification of the most efficient GVS modes for patients suffering from vestibular and cerebellar disorders.

Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset.

The Scale for Assessment and Rating of Ataxia (SARA) is widely used in different types of ataxias and has been chosen as the primary outcome measure in the European natural history study for Friedreich ataxia (FA). To assess distribution and longitudinal changes of SARA scores and its single items, we analyzed SARA scores of 502 patients with typical-onset FA (<25 years) participating in the 4-year prospective European FA Consortium for Translational Studies (EFACTS). Pattern of disease progression was determined using linear mixed-effects regression models. The chosen statistical model was re-fitted in order to estimate parameters and predict disease progression. Median time-to-change and rate of score progression were estimated using the Kaplan-Meier method and weighted linear regression models, respectively. SARA score at study enrollment and age at onset were the major predictive factors of total score progression during the 4-year follow-up. To a less extent, age at evaluation also influenced the speed of SARA progression, while disease duration did not improve the prediction of the statistical model. Temporal dynamics of total SARA and items showed a great variability in the speed of score increase during disease progression. Gait item had the highest annual progression rate, with median time for one-point score increase of 1 to 2 years. Analyses of statistical properties of SARA suggest a variable sensitivity of the scale at different disease stages, and provide important information for population selection and result interpretation in future clinical trials.

Comparison of Live and Remote Video Ratings of the Scale for Assessment and Rating of Ataxia.

Video recordings of neurological examinations are often used in clinical trials. The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale for ataxic patients. Despite several advantages of video ratings, correlation between live ratings and remote video-ratings has not been systematically investigated. To compare live and remote video assessment of SARA. Full SARA examinations of 69 patients with cerebellar ataxia were recorded on video. Live rating from site investigators were compared with remote video rating of three experienced ataxia clinicians using Bland-Altman analysis. Live and remote video ratings showed a high level of agreement for the complete score (bias = 0.09, with standard deviation = 2.00) and all single SARA items (bias <0.20 for all items). Remote video ratings of SARA are a reliable means to assess severity of ataxia.

Intensive Multimodal Treatment for A Young Adult with Friedreich Ataxia: A Case Report

Background: Friedreich’s ataxia (FRDA) is a progressive, neurodegenerative autosomal recessive disorder affecting multiple systems of the body. Physical therapy has been found to be beneficial for improving function and quality of life in individuals with FRDA. However, there is little evidence supporting specific interventions that would address functional concerns in these patients, and the most optimal rehabilitation strategy has yet to be determined. Case Presentation: The participant was a twenty-six-year-old female who had been diagnosed with FRDA ten years earlier. After discontinuing physical therapy for three years, she started using a wheelchair and her function declined. The primary outcome measures employed to assess FRDA were the scale for assessment and rating of ataxia (SARA) and the functional independence measure (FIM). Other measures included strength, range of motion and neurologic screening. At initial examination, the participant presented with muscle weakness, poor balance and coordination, and mobility restrictions. The patient received intensive physical therapy with five weekly sessions over a period of three months. Interventions focused on coordinative, balance, and strength training activities. Results: The patient demonstrated a 30-point increase in the FIM, a 9-point decrease in the SARA, and amelioration in manual muscle testing scores upon completion of the rehabilitation program. Conclusion: The FRDA patient displayed improvement in all outcome measures. Strength, ataxia severity and functional abilities were enhanced while a higher level of independence was gained. Our observations suggest that an intensive multimodal approach holds potential in the management of FRDA and call for further research. KEYWORDS: Friedreich’s ataxia, Rehabilitation outcomes, Physical therapy.

SARAspeech—Feasibility of automated assessment of ataxic speech disturbance

Ataxias are a group of movement disorders that are characterized by progressive loss of balance, impaired coordination and speech disturbance, which together lead to markedly reduced quality of life. Speech disturbance is clinically diagnosed, but methods for objective assessment of severity are lacking. Using 71 sets of speech recordings from ataxia patients, we developed an automated classification system. With a tolerance of ±1 point, this classification system correctly predicted experts’ ratings of speech disturbance according to item 4 of the Scale for Assessment and rating of ataxia (SARA) in 80% of cases. We thereby demonstrate feasibility of computer-assisted voice analysis for automated assessment of severity of speech disturbance.

Scale for the Assessment and Rating of Ataxia (SARA): Development of a Training Tool and Certification Program

Monitoring of disease severity is of great importance for treatment and management of clinical trials. The Scale for Assessment and Rating of Ataxia (SARA) is a frequently used, short and easily applicable clinical scale used to assess the severity of ataxia. The objective of our study was to develop a training and certification tool for the SARA. SARA scores were recorded according to a standardized protocol and rated by three clinical experts in consensus. Four hundred thirty-eight videos of 67 patients were included in the SARA training tool. The tutorial section demonstrates a complete SARA examination on a healthy control. In the training section, users can compare their ratings to consensus ratings and access a video library covering the complete SARA range. The tool also includes a section that allows optional certification. The SARA training tool provides comprehensive and standardized training material and certification to reduce variability in applying the SARA. Standardization aims to improve the quality of patient care and research in ataxia.

Ataxia Rating Scales: Content Analysis by Linking to the International Classification of Functioning, Disability and Health.

Ataxia management is mainly based on rehabilitation, symptomatic management, and functional improvement. Therefore, it is important to comprehensively assess ataxic symptoms and their impact on function. Recently, the movement disorders society recommended four generic ataxia rating scales: scale for assessment and rating of ataxia (SARA), international cooperative ataxia rating scales, Friedreich's ataxia rating scale (FARS), and unified multiple system atrophy rating scale (UMSARS). The aim of the study was to analyze and compare the content of the recommended ataxia rating scales by linking them to the international classification of functioning, disability and health (ICF). A total of 125 meaningful concepts from 93 items of the four included scales were linked to 57 different ICF categories. The ICF categories were distributed in body structure (n = 8), body function (n = 26), activity and participation (n = 20), and environmental factors (n = 3) components. UMSARS and FARS were the only ones that have addressed the body structure or environmental factors component. The content analysis of ataxia rating scales would help clinicians and researchers select the most appropriate scale and understand ataxic symptoms and their impact on function. It seems that SARA is the optimal scale for rapid assessment of ataxia or in busy clinical settings. UMSARS or FARS are more appropriate for the investigating the impact of ataxia on overall health, and monitoring ataxia progression and disability.

Scale for Ocular motor Disorders in Ataxia (SODA)

Eye movements are fundamental diagnostic and progression markers of various neurological diseases, including those affecting the cerebellum. Despite the high prevalence of abnormal eye movements in patients with cerebellar disorders, the traditional rating scales do not focus on abnormal eye movements. We formed a consortium of neurologists focusing on cerebellar disorders. The consortium aimed to design and validate a novel Scale for Ocular motor Disorders in Ataxia (SODA). The primary purpose of the scale is to determine the extent of ocular motor deficits due to various phenomenologies. A higher score on the scale would suggest a broader range of eye movement deficits. The scale was designed such that it is easy to implement by non-specialized neurological care providers. The scale was not designed to measure each ocular motor dysfunction's severity objectively. Our validation studies revealed that the scale reliably measured the extent of saccade abnormalities and nystagmus. We found a lack of correlation between the total SODA score and the total International Cooperative Ataxia Rating Scale (ICARS), Scale for Assessment and Rating of Ataxia (SARA), or Brief Ataxia Rating Scale (BARS). One explanation is that conventionally reported scales are not dedicated to eye movement disorders; and when present, the measure of ocular motor function is only one subsection of the ataxia rating scales. It is also possible that the severity of ataxias does not correlate with eye movement abnormalities. Nevertheless, the SODA met the consortium's primary goal: to prepare a simple outcome measure that can identify ocular motor dysfunction in patients with cerebellar ataxia.

Scale for the assessment and rating of ataxia: Age-dependent performance of healthy adults.

The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale. The objective was to study the age dependence of SARA in healthy adults and to define age-specific cut-off values to differentiate healthy from ataxic individuals. Data from 390 healthy individuals and 119 spinocerebellar ataxia patients were analyzed. SARA scores were mapped on functional SARA (fSARA). Age-adjusted cut-off values were determined by receiver operating characteristic curve analysis. The cut-off value was 3 for SARA and 1.5 for fSARA. Older patients had higher SARA cut-off values (4.5 for 60-69 years and 6.5 for 70-79 years). Age-adjusted cut-off values for fSARA are 1 for 18-29, 30-39 and 50-59 years, 2 for 40-49 and 60-69 years and 3 for 70-79 years. Sensitivity and specificity were higher for SARA than for fSARA. In this study, age-dependent cut-off values were defined for SARA and fSARA. The results may be relevant for the design of future preventive trials in spinocerebellar ataxias that use conversion to ataxia as an outcome.