Scale For Assessment And Rating Of Ataxia Scores Research Articles

NCOG-11. FACTORS PREDICTING SPEECH AND GAIT RECOVERY IN CHILDREN WITH POST-OPERATIVE POSTERIOR FOSSA SYNDROME (PFS)

Abstract Posterior fossa syndrome/cerebellar mutism syndrome is a surgical complication of posterior fossa tumor resection, especially midline tumors. Initially thought to involve complete mutism, PFS is now recognized as a complex syndrome involving loss of language (complete [PFS1] and incomplete [PFS2]). Additional symptoms include apraxia, movement disorder, motor and coordination deficits, and emotional lability. The aim of this study was to identify factors that influence delayed speech and independent gait recovery in children with PFS. We prospectively studied 73 children ≥3 years of age with medulloblastoma who developed PFS (SJMB12, NCT01878617). Enrolled children received standardized neurologic examinations and serial imaging before, during and up to five years after completion of therapy. Neurological examinations included scale for assessment and rating of ataxia (SARA), CTCAE grading of neurologic deficits, and severity of injury to the superior cerebellar peduncles (SCP) on post-operative MRI. Median time to speech recovery was 1.4 months (range 0.3-14.3); 81% had return of speech at 3 months and 97% at 12 months. On multivariable Cox regression analysis, complete mutism (HR 0.17, p<0.0001) and inability to sit (HR 0.40, p=0.001) were associated with delayed speech return. Independent ambulation was regained by 80.8% at a median of 2.3 (range 0.3-71.3) months. 70% had a return of ambulation at 12 months and 77% at 24 months. On multivariable Cox regression analysis, complete mutism (HR 0.32, p=0.016), inability to sit (HR 0.30, p=0.002), SARA score (HR 0.94, p=0.002), and right SCP injury (HR 0.47, p=0.014) were significantly associated with delayed return of ambulation. Presence of mutism, inability to sit unassisted, higher SARA score, and right SCP injury at the time of PFS diagnosis are associated with time to recovery of speech/language and ambulation. Our findings have prognostic implications for families and to help identify children in need of more intensive interventions.

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.

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

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.

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.

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.

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.

Altered cerebral blood flow in patients with spinocerebellar degeneration.

ObjectivesSpinocerebellar degeneration (SCD) comprises a multitude of disorders with sporadic and hereditary forms, including spinocerebellar ataxia (SCA). Except for progressive cerebellar ataxia and structural atrophy, hemodynamic changes have also been observed in SCD. This study aimed to explore the whole-brain patterns of altered cerebral blood flow (CBF) and its correlations with disease severity and psychological abnormalities in SCD via arterial spin labeling (ASL).MethodsThirty SCD patients and 30 age- and sex-matched healthy controls (HC) were prospectively recruited and underwent ASL examination on a 3.0T MR scanner. The Scale for Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS) scores were used to evaluate the disease severity in SCD patients. Additionally, the status of anxiety, depression and sleep among all patients were, respectively, evaluated by the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Self-Rating Scale of Sleep (SRSS). We compared the whole-brain CBF value between SCD group and HC group at the voxel level. Then, the correlation analyses between CBF and disease severity, and psychological abnormalities were performed on SCD group.ResultsCompared with HC, SCD patients demonstrated decreased CBF value in two clusters (FWE corrected P < 0.05), covering bilateral dentate and fastigial nuclei, bilateral cerebellar lobules I-IV, V and IX, left lobule VI, right lobule VIIIb, lobules IX and X of the vermis in the cerebellar Cluster 1 and the dorsal part of raphe nucleus in the midbrain Cluster 2. The CBF of cerebellar Cluster 1 was negatively correlated with SARA scores (Spearman’s rho = –0.374, P = 0.042) and SDS standard scores (Spearman’s rho = –0.388, P = 0.034), respectively. And, the CBF of midbrain Cluster 2 also had negative correlations with SARA scores (Spearman’s rho = –0.370, P = 0.044) and ICARS scores (Pearson r = –0.464, P = 0.010).ConclusionThe SCD-related whole-brain CBF changes mainly involved in the cerebellum and the midbrain of brainstem, which are partially overlapped with the related function cerebellar areas of hand, foot and tongue movement. Decreased CBF was related to disease severity and depression status in SCD. Therefore, CBF may be a promising neuroimaging biomarker to reflect the severity of SCD and suggest mental changes.

Ataxia Rating Scales Reveal Increased Scores in Very Preterm Born 5–6-Year-Old Preschool Children and Young Adults

The aim of this study is to investigate whether scores in ataxia rating scales (ARS) are different in very preterm (VP) preschool and adult participants compared to term controls. This is a case–control study. Sixty VP children (years: 5.5–6.5; gestational age: 23.9–31.7 weeks) and 56 VP adults (years: 17.8–27.9; gestational age: 23.3–32.0 weeks) without major cerebral lesions participated in the study; 60-age and sex-matched term children and 64 term adults for comparison were used in the study intervened with the assessment with International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA). Main outcome measures are primary outcome: total icars and sara scores in preterm (vp) participants versus controls. Results showed that VP children showed significantly higher total ICARS (M 15.98, SD 6.29, range 4.0–32.0; p < .001) and SARA scores (M 6.5, SD 2.53, range 1.0–15.0; p < .001) than controls (ICARS: M 9.17, SD 3.88, range 2.0–20.0; SARA: M 3.51, SD 1.54, range 1.0–8.0). VP adults also showed significantly higher total ICARS (M 1.0, SD 1.99, range 0.0–11.0; p < .001) and SARA scores (M 0.54, SD 1.08, range 0.0–6.0; p < .001) than controls (ICARS: M 0.11, SD 0.44, range 0.0–2.0; SARA: M 0.04, SD 0.18, range 0.0–1.0). In conclusion, VP children showed significantly higher scores in ARS than controls. These differences were also present in VP adults, suggesting that deficits likely prevail until adulthood. ARS are a time and cost-effective method to screen for difficulties in coordination and balance in a patient group at risk.

The association between educational attainment and SCA 3 age of onset and disease course

BackgroundThe number of trinucleotide CAG repeats is inversely correlated with the age at onset (AAO) of motor symptoms in individuals with Spinocerebellar Ataxia type 3 (SCA 3) and may be responsible for 50%–60% of the variability in AAO. Drawing from a social determinants of health model, we sought to determine if educational attainment further contributes to the AAO and motor symptom progression of SCA 3. MethodsWe performed a retrospective chart review in which twenty individuals met criteria for inclusion and had been seen by an ataxia specialist at our hospital between January 2005 and July 2019. AAO of motor symptoms and Scale for Assessment and Rating of Ataxia (SARA) scores were used as primary outcome measures. ResultsUsing a linear regression, we found that having greater CAG repeat length and greater than 16 years of education results in an earlier AAO. The importance of the CAG repeat length on AAO, however, is greater amongst individuals with lower education. Using a linear mixed model evaluating SARA score over time with AAO, we found that less than 16 years of education is associated with faster progression of the disease. ConclusionIn our group of SCA 3 patients, level of education correlated with both the AAO and SARA scores. Though our findings need to be confirmed with a larger cohort, our study suggests that level of education can have a strong influence on health outcomes in SCA 3 and possibly other groups of patients with ataxia.

Functionality and disease severity in spinocerebellar ataxias.

Spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterized by deterioration of balance and functionality that tends to follow disease progression. There is no established link between formal clinical markers for severity and functional/balance scores that could guide rehabilitation teams. To evaluate the relationship between functional scales and ataxia severity in order to identify cutoff landmarks for functional loss and estimate the mean SARA (Scale for Assessment and Rating of Ataxia) score for the risk ratings for falls on the BBS (Berg Balance Scale). Consecutive patients with a molecular diagnosis of SCA (total 89: 31 with SCA2 and 58 with SCA3) were assessed for functionality FIM-ADL (Functional Independence Measure-activities of daily living and Lawton-IADL (instrumental activities of daily living), balance (BBS) and disease severity (SARA). The main disability cutoff landmarks were that the need for supervision for FIM-ADL starts with 12 points on SARA and the need for supervision for Lawton-IADL starts with 14 points on SARA. The first items to require assistance were "expression" and "shopping", respectively. At 20 points on SARA, patients were dependent on all FIM and Lawton items. The item with the greatest impact on distinguishing dependents from independents was "means of transport" in Lawton-IADL and the domain "locomotion" in FIM-ADL. The mean SARA score for patients classified as low risk in the BBS was 9.9 points, and it was 17.4 for medium risk and 25.2 for high risk. Analysis on the correlation between the severity of ataxia and functional scales can form an important guide for understanding the progression of functional dependence among individuals with SCAs.

Etiology and course of cerebellar ataxia: A study from eastern India

Objective: The course of various cerebellar ataxia disorders in our population is relatively unexplored, especially beyond the hereditary spinocerebellar ataxias (SCA). This study was conducted to objectively assess the severity and progression of various disorders causing the cerebellar ataxia. Materials and Methods: This longitudinal prospective study evaluated the etiologies and the corresponding severity and progression of the cerebellar ataxia. Clinical examination and the relevant investigations were performed. The severity of ataxia was assessed using the Scale for Assessment and Rating of Ataxia (SARA) - at initial presentation and another at 6 months of follow-up, and the change in SARA scores were calculated to find the disease progression. Results: Out of 145 patients studied, SCA predominated followed by Autoimmune/paraneoplastic disorders, Multiple System Atrophy-Cerebellar (MSA-C), Wilson's disease, and Multiple sclerosis. On follow-up, human immunodeficiency virus (HIV) associated progressive multifocal leukoencephalopathy was the most rapidly advancing disease, followed by MSA-C, Friedreich's ataxia, and Huntington's disease, all of which progressed faster than SCA. SCA 3 emerged as the most progressive SCA followed by SCA 1, SCA 6, SCA 2, and SCA 12. The autoimmune etiologies showed favorable response to treatment, although with some variability across the different disorders. In the paraneoplastic category, anti Tr associated ataxia improved better than other disorders. Multiple sclerosis and other treatable disorders also responded to treatment. Conclusion: Cerebellar ataxia is the predominant clinical feature in a wide variety of disorders. While some are progressive, others are responsive to treatment, the extent of which differed according to the etiology.

Reducing Ataxic Side Effects from Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation Implantation in Essential Tremor: Potential Advantages of Directional Stimulation

Objective: The aim of the study was to retrospectively evaluate the effect of directional deep brain stimulation (DBS) on ataxia in an essential tremor patient population. Materials and Methods: A retrospective chart review of documented Scale for Assessment and Rating of Ataxia (SARA) scores were analyzed using a case-control design. All subjects we evaluated were treated at a single, tertiary care academic center. We reviewed 14 patients who underwent bilateral ventral intermediate nucleus of the thalamus (VIM) implantation with microelectrode recording, with electrodeposition and segmented contact orientation confirmed via postoperative computed tomography. The main outcome was to determine change in ataxia scores between directional versus monopolar circumferential stimulation. Results: Fourteen patients (9 males, median age at implantation 69 [range 63–82]) underwent surgery between October 2017 and July 2020 at the UNC Movement Disorders Center. SARA scores between directional stimulation and monopolar circumferential stimulation demonstrated a significant reduction in total scores with best possible segmented stimulation (n = 13, p < 0.0001, 95% confidence interval [CI] −3.496 to −6.789). This difference remained statistically significant even after removing the SARA tremor subscore (n = 13, p < 0.0001, 95% CI −3.155 to −6.274). In line with prior reports, SARA score changes from the preoperative state were generally worsened when applying monopolar circumferential stimulation bilaterally (n = 13, p = 0.655; 95% CI −2.836 to 4.359), but improved with directional stimulation (n = 13, p = 0.010; 95% CI −1.216 to −7.547). Conclusion: This retrospective analysis appears to show evidence for improved outcomes through directional stimulation in bilateral VIM DBS implantation with reduction of ataxic side effects that have traditionally plagued postoperative results, all while providing optimized tremor reduction via stimulation.

P-MD008. Differential effects of thyrotropin releasing hormone on motor performance and motor adaptation in patients with spinocerebellar degeneration

Introduction . The cerebellum is known to play an important role in motor adaptation, including prism adaptation. Thyrotropin releasing hormone (TRH) has been used as a treatment for cerebellar ataxia in Japan. However, effects of TRH on cerebellar adaptation function have not been studied. Herein, we studied effects of TRH treatment on the prism adaptation task. Methods . Eighteen patients with spinocerebellar degeneration (SCD), including MSA-C, SCA3, SCA6, SCA31, participated in this study. The participants received intravenous injection of 2 mg/day protirelin tartrate once a day for 14 days. In the prism adaptation task, the participants reached to the target on the screen wearing wedge prisms. We compared the Scale for Assessment and Rating of Ataxia (SARA), baseline errors and the after effect (AE) of the prism adaptation task between before and after TRH therapy. We also performed correlation analysis between improvement of baseline errors or AE in the adaptation task, and 1) improvement of the total SARA score, 2) improvement of upper limb ataxia score, and 3) improvement of axial ataxia score. Results . TRH therapy significantly improved SARA (p = 0.005). Multiple regression analysis revealed that improvement of SARA score was mainly due to improvement of “Stance” category score. TRH decreased baseline errors of the prism adaptation task (p = 0.021), while unaffected AEs (p = 0.25). Correlation analysis revealed no significant correlation between any factors. Conclusion . TRH differentially affected cerebellar ataxic symptoms including baseline reaching performance in the prism adaptation task, whereas TRH did not affect the learning process of prism adaptation. Different cerebellar functional aspects may underlie the learning process of motor adaptation and simple motor performance (classical ataxia).

\u201cHot cross bun\u201d is a potential imaging marker for the severity of cerebellar ataxia in MSA-C

To evaluate the correlation between “hot cross bun” sign (HCBs) and disease severity in multiple system atrophy (MSA). We recruited patients with probable and possible MSA with parkinsonism (MSA-P) or the cerebellar ataxia (MSA-C) subtypes. Clinical and imaging characteristics were collected and comparison was performed between MSA-C and MSA-P cases. Spearman test was used to evaluate the correlation between HCBs and other variables. Curve estimate and general linear regression was performed to evaluate the relationship between HCBs and the Scale for Assessment and Rating of Ataxia (SARA). Unified Multiple System Atrophy Rating Scale (UMSARS) IV was used to assess the severity of disease. Multinomial ordered logistic regression was used to confirm the increased likelihood of disability for the disease. Eighty-one MSA with HCBs comprising of 50 MSA-C and 31 MSA-P were recruited. We demonstrated that the severity of HCBs showed a positive linear correlation with SARA scores in MSA-C. Multinomial ordered logistic regression test revealed that the increase in the HCBs grade may be associated with an increased likelihood of disability for the disease severity in MSA, especially in those with cerebellar ataxia subtype. We demonstrated that HCBs is a potential imaging marker for the severity of cerebellar ataxia. The increase in the HCBs grade may be associated with an increased likelihood of disability in MSA-C, but not MSA-P cases, suggesting that it may be a useful imaging indicator for disease progression in Chinese patients with MSA-C.

Trehalose in Machado-Joseph Disease: Safety, Tolerability, and Efficacy.

Machado-Joseph disease (MJD) is relatively prevalent among the Yemenite Jewish subpopulation living in Israel. Currently, there is no treatment able to modify the disease progression. Trehalose is a disaccharide with protein-stabilizing and autophagy-enhancing properties. In animal models of MJD, trehalose showed reduction of cerebellar lesion size and improved motor function. This study was designed to be a proof-of-concept, phase 2 study lasting 6 to 12 months, to determine the safety, tolerability, and efficacy of weekly IV administration of 15 g or 30 g 10% trehalose solution in 14 MJD patients. Primary endpoints were safety and tolerability, which were assessed by various clinical and laboratory tests. Secondary endpoints were changes in the Scale for Assessment and Rating of Ataxia (SARA) score, Neurological Examination Score for Spinocerebellar Ataxia (NESSCA), time to do 9-hole peg test (9HPT), time to do 8-meter walk (8MW), and quality of life assessed by the World Health Organization Quality-of-Life Questionnaire-BREF (WHOQoL-BREF). Trehalose was well tolerated, and no serious drug-related adverse events were noted. The average SARA score, NESSCA, and time to do 9HPT and 8MW and the WHOQoL-BREF for all patients remained stable at 6 months. Six patients received treatment for as long as 12 months and continued to remain stable on all the above tests. IV trehalose seems to be safe in humans and probably effective to stabilize neurological impairment in MJD.

Differential effects of thyrotropin releasing hormone (TRH) on motor execution and motor adaptation process in patients with spinocerebellar degeneration

BackgroundThe cerebellum is known to play a crucial role in sensori-motor adaptation, which includes the prism adaptation. TRH has been widely used as a treatment for cerebellar ataxia in Japan, however effects of TRH on cerebellar adaptation process have not been studied. Here, we studied effects of TRH treatment on the prism adaptation task. MethodsEighteen spinocerebellar degeneration (SCD) patients participated in this study. The participants received intravenous injection of 2 mg/day protirelin tartrate once a day for 14 days. In the prism adaptation task, the participants reached to the target on the screen wearing wedge prisms. We compared the Scale for Assessment and Rating of Ataxia (SARA), baseline errors and the aftereffect (AE) of the prism adaptation task between before and after TRH therapy. ResultsTRH therapy improved SARA significantly (p = .005). Multiple regression analysis revealed that improvement of SARA score was mainly due to improvement of “Stance” category score. TRH decreased baseline errors of the prism adaptation task (p = .021), while unaffected AEs (p = .252). ConclusionTRH differentially affected clinical cerebellar ataxia including baseline reaching performance in the prism adaptation task, whereas TRH did not affect the learning process of prism adaptation. Different cerebellar functional aspects may underlie the learning process of sensori-motor adaptation and simple motor execution (clinically evaluated cerebellar ataxia).

O-06 Motor cortex excitability and conduction time of pyramidal tracts in preclinical SCA1 gene carriers

Background Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative, dominantly inherited disease caused by CAG repeat expansion. It manifests mainly as trunk and limbs ataxia, dysarthria, gaze palsy and peripheral neuropathy. We aimed to assess the functional alterations of corticospinal tracts in preclinical SCA1 gene carriers performed during 4-years follow-up. Methods Transcranial magnetic stimulation (TMS) was carried out in 26 SCA1 gene carries with age at study entry 25.6 ± 4.7, CAG repeat number 49.5 ± 4.8 and 30 age- and gender-matched healthy controls (HC). Presence of ataxia was assessed by the Scale for Assessment and Rating of Ataxia (SARA). TMS was performed every ± 12 months to evaluate motor threshold (MT), silent period (SP) from hypothenar and extensor digitorum brevis muscles, central motor conduction time (CMCT) and motor evoked potentials amplitude (MEPs). Results Baseline SARA score increased from 0.6 ± 0.7 to 4.9 ± 5.2 points across follow-up. In 43% SCA1 cases MT of lower limbs was elevated and MEPs were in 35% decreased. SP was longer (p Conclusions In the preclinical SCA1 gene carriers before the onset of overt clinical signs TMS revealed functional alterations of corticospinal pathways. TMS could serve as an objective measure of disease progression in SCA1 patients.

Age-related reference values for the pediatric Scale for Assessment and Rating of Ataxia: a multicentre study.

For reliable assessment of ataxia severity in children, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society aimed to validate the Scale for Assessment and Rating of Ataxia (SARA) according to age. Twenty-two pediatric ataxia experts from 15 international institutions scored videotaped SARA performances in 156 typically developing children (4-16y: m/f=1; 12 children per year of age; including nine different nationalities). We determined age-dependency and reliability of pediatric SARA scores by a mixed model. In typically developing children, age was the only variable that revealed a relationship with SARA scores (p<0.001). The youngest children revealed the highest scores and the highest variation in scores (<8y; p<0.001). After 11 years of age, pediatric scores approached adult outcomes. The interobserver agreement of total SARA scores was substantial with an intraclass correlation coefficient of 0.63 (95% confidence interval 0.56-0.69; p<0.001). In typically developing European children, both SARA scores and interobserver agreement are age-dependent. For reliable interpretation of pediatric SARA scores, consideration of the underlying test construct appears prudent. These data will hopefully contribute to a correct and uniform interpretation of longitudinal SARA scores from childhood to adulthood.