Consensus Recommendations for Clinical Outcome Assessments and Registry Development in Ataxias: Ataxia Global Initiative (AGI) Working Group Expert Guidance.

To accelerate and facilitate clinical trials, the Ataxia Global Initiative (AGI) was established as a worldwide research platform for trial readiness in ataxias. One of AGI's major goals is the harmonization and standardization of outcome assessments. Clinical outcome assessments (COAs) that describe or reflect how a patient feels or functions are indispensable for clinical trials, but similarly important for observational studies and in routine patient care. The AGI working group on COAs has defined a set of data including a graded catalog of COAs that are recommended as a standard for future assessment and sharing of clinical data and joint clinical studies. Two datasets were defined: a mandatory dataset (minimal dataset) that can ideally be obtained during a routine clinical consultation and a more demanding extended dataset that is useful for research purposes. In the future, the currently most widely used clinician-reported outcome measure (ClinRO) in ataxia, the scale for the assessment and rating of ataxia (SARA), should be developed into a generally accepted instrument that can be used in upcoming clinical trials. Furthermore, there is an urgent need (i) to obtain more data on ataxia-specific, patient-reported outcome measures (PROs), (ii) to demonstrate and optimize sensitivity to change of many COAs, and (iii) to establish methods and evidence of anchoring change in COAs in patient meaningfulness, e.g., by determining patient-derived minimally meaningful thresholds of change.

Predictive Validity of the Scale for the Assessment and Rating of Ataxia for Medium-Term Functional Status in Acute Ataxic Stroke.

OBJECTIVES: This study examines the prognostic validity of the Scale for the Assessment and Rating of Ataxia for patients with acute stroke. MATERIALS AND METHODS: We enrolled 120 patients with posterior circulation stroke having ischemic or hemorrhagic lesions with ataxia who had physical therapy. We recorded the clinical stroke features and obtained the scale for the assessment and rating of ataxia and National Institutes of Health Stroke Scale scores 7 days after admission and at discharge. Predictive factors for a 3-month modified Rankin Scale score of <3 were investigated. RESULTS: During hospitalization, the Scale for the Assessment and Rating of Ataxia score decreased from 7.5 (interquartile range, 4.5-12.5) to 4.0 (interquartile range, 1.5-8.0) points, whereas the National Institutes of Health Stroke Scale score changed from 1 (interquartile range, 0-3) to 1 (interquartile range, 0-2) point. A significant correlation between functional outcome and the Scale for the Assessment and Rating of Ataxia scores 7 days after onset was observed. The cutoff value for the assessment and rating of ataxia for predicting favorable outcome (modified Rankin scale, 0-2) at 3 months post-onset was 14 points (0-40) at 7 days after onset. CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia scores showed good responsiveness to neurological changes in patients with acute ataxic stroke, could predict functional outcomes 3 months after onset on day 7, and could be a useful and reliable marker for patients with ataxic stroke.

Anti-glutamate Dehydrogenase Antibody Positive Cerebellar Ataxia and Stiff Person Syndrome Responding to Dual Treatment with Steroids and Intravenous Immunoglobulin: A Case Presentation and Literature Review.

Anti-glutamic acid decarboxylase (anti-GAD) antibody syndrome (aGAS) has various presentations including cerebellar ataxia (CA) and stiff person syndrome (SPS). This is a treatable cause of CA and SPS. We present a case of a 49-year-old man who developed blurred vision, slurred speech, difficulty walking, unsteady gait, and clumsiness which had progressed over four months. The patient was found to have anti-GAD ab (+) CA and SPS and experienced significant symptomatic improvements after treatment with intravenous (IV) steroids followed by intravenous immunoglobulin (IVIG). The patient's improvement persisted when he was reevaluated at follow up one month later. Since anti-GAD ab related diseases, including anti-GAD CA and SPS, are rarely diagnosed, there is limited data regarding the treatment of this condition. As there are only a few cases in the literature similar to this one, highlighting the successful treatment of anti-GAD ab cerebellar ataxia and SPS with dual therapy (steroids followed by IVIG) is important.

Comparable progression of spinocerebellar ataxias between Caucasians and Chinese.

INTRODUCTION: The aim of this study is to reappraise the progression of the five most common spinocerebellar ataxias (SCAs) in the Chinese population and to establish a much-needed critical comparison with that in other ethnic groups. There are very few longitudinal cohort studies of SCAs in Asian populations. An intriguing finding in an earlier study demonstrated a faster progression of SCA among Chinese than that among Caucasians. METHODS: Patients with SCA1, SCA2, SCA3, SCA6 or SCA17 were consecutively assessed using the scale for the assessment and rating of ataxia (SARA) for five years. A linear mixed model was used to compare the annual progression rates measured using the SARA among patients with different SCA subtypes. Predictors of the progression rates were analyzed. RESULTS: A total of 199 patients with SCA (10 with SCA1, 37 with SCA2, 118 with SCA3, 25 with SCA6 and 9 with SCA17) were enrolled. The mean annual increase in SARA scores was 1.23 points for SCA1, 1.52 points for SCA2, 1.60 points for SCA3, 0.99 points for SCA6 and 3.26 points for SCA17. A larger CAG repeat length (≥74) was associated with faster progression in SCA3, whereas a lower total SARA score at the first visit (<12) was associated with faster clinical progression in SCA6. CONCLUSION: The results of this study confirm that the annual progression rates of SCA2 and SCA3 are comparable between Han Chinese and other ethnic populations. More studies are warranted to confirm the rapid progression of SCA17 observed in our cohort.

Validity and reliability of the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) in multiple sclerosis patients with ataxia.

BACKGROUND: Ataxia is an extremely common problem in multiple sclerosis (MS) patients. Thus, appropriate scales are required for detailed assessment of this issue. The aim of our study was to investigate the reliability and validity of the Turkish version of the International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxia (SARA), which are widely used in ataxia evaluation in the context of other cerebellar diseases. METHOD: This cross-sectional study included 80 MS patients with Kurtzke cerebellar functional system score (C-FSS) greater than zero and slight pyramidal involvement. The Expanded Disability Status Scale (EDSS), C-FSS, and Berg Balance Scale (BBS) were administered. SARA and ICARS were assessed on first admission by two physical therapists. Seven days later, second assessments were repeated in same way for reliability. RESULTS: Intra-rater and inter-rater reliability were found to be high for both ICARS and SARA (p< 0.001) The Cronbach's α coefficients were 0.922 and 0.921 for SARA (reviewer 1 and reviewer 2 respectively) and 0.952 and 0.952 for ICARS (reviewer 1 and reviewer 2, respectively). There were no floor or ceiling effects determined for either scale except for item 17 of ICARS (p= 0.055). The EDSS total score had significant correlations with both SARA and ICARS (rho: 0.557 and 0.707, respectively). C-FSS had moderate correlation with SARA and high correlation with ICARS (rho: 0.469 and 0.653, respectively). BBS had no significant correlation with SARA and ICARS. (rho: -0.048 and -0.008 respectively). According to the area under the curve (AUC) value, ICARS is the best scale to discriminate mild and moderate ataxia. (AUC: 0.875). Factor analyses of ICARS showed that the rating results were determined by five different factors that did not coincide with the ICARS sub-scales. CONCLUSION: Our study demonstrated that ICARS and SARA are both reliable in MS patients with ataxia. Although ICARS has some structural problems, it seems to be more valid given its high correlations with EDSS and C-FSS. SARA also can be preferred as a brief assessment.

Natural History of Spinocerebellar Ataxia Type 31: a 4-Year Prospective Study.

Spinocerebellar ataxia type 31 (SCA31) is known as a late-onset, relatively pure cerebellar form of ataxia, but a longitudinal prospective study on the natural history of SCA31 has not been done yet. In this prospective cohort study, we enrolled 44 patients (mean ± standard deviation 73.6 ± 8.5 years) with genetically confirmed SCA31 from 10 ataxia referral centers in the Nagano area, Japan. Patients were evaluated every year for 4 years using the Scale for the Assessment and Rating of Ataxia (SARA) and the Barthel Index (BI). Of the 176 follow-up visits (91.5%), 161 were completed in this study. Five patients (11.4%) died during the follow-up period, and two patients (4.5%) were lost to follow-up. The annual progression of the SARA score was 0.8 ± 0.1 points/year and that of the BI was -2.3 ± 0.4 points/year (mean ± standard error). Shorter disease duration at baseline was associated with faster progression of the SARA score. Our study indicated the averaged clinical course of SCA31 as follows: the patients develop ataxic symptoms at 58.5 ± 10.3 years, become wheelchair bound at 79.4 ± 1.7 years, and died at 88.5 ± 0.7 years. Our prospective dataset provides important information for clinical trials of forthcoming disease-modifying therapies for cerebellar ataxia. It also represents a useful resource for SCA31 patients and their family members in genetic counseling sessions.

Quantitative evaluation of gait ataxia by accelerometers.

An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia.