Background:Recent findings suggest that a single gait assessment in a clinic may not reflect everyday mobility. Objective:We compared gait measures that best differentiated individuals with spinocerebellar ataxia (SCA) from age-matched healthy controls (HC) during a supervised gait test in the clinic vs. a week of unsupervised gait during daily life. Methods:Twenty-six individuals with SCA types 1, 2, 3, and 6, and 13 (HC) wore three Opal inertial sensors (on both feet and lower back) during a 2-minute walk in the clinic and for seven days in daily life. Seventeen gait measures were analyzed to investigate the group differences using Mann-Whitney U-tests and area under the curve (AUC). Results:Ten gait measures were significantly worse in SCA than HC for the clinic test (p < 0.003), but only 3 were worse in daily life (p < 0.003). Only a few gait measures consistently discriminated groups in both environments. Specifically, variability in Swing Time and Double Support Time had AUCs of 0.99 (p < 0.0001) and 0.96 (p < 0.0001) in the clinic, and 0.84 (p < 0.0003) and 0.80 (p < 0.002) in daily life, respectively. Clinical gait measures showed stronger correlations with clinical outcomes (ie, SARA and FARS-ADL; r = 0.50-0.77) than between daily life gait measures (r = 0.31-0.49). Gait activity in daily life was not statistically significant between the SCA and HC groups (p > 0.06). Conclusions:Digital gait measures discriminate SCA in both environments. In-clinic measures are more sensitive, while daily life measures provide ecological validity, highlighting a trade-off and offering complementary insights.

Introduction The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical rating scale in ataxia. Remote video assessments of SARA examinations are increasingly used to reduce variability through centralized ratings. Remote video assessments have a high agreement with in-person ratings, but the intra- and inter-rater reliability of remote video ratings has not been examined. In this study, we compared the performance of live versus video SARA ratings and evaluated intra- and inter-rater reliability of SARA ratings via video review in patients with spinocerebellar ataxia (SCA) type 1, 2, 3, and 6. Methods We calculated the Bland-Altman analysis for average measures to assess the agreement between live and video ratings and the Intraclass Correlation Coefficient (ICC) for intra- and inter-rater reliability of video ratings. Results In all 15 participants, we found high agreement between live and video for all SARA items, with less than 0.5 point overestimation of video compared to live SARA total score, and excellent intra- and inter-rater reliability for the SARA total score rated by video revision, with an ICC of 0.98 and 0.95, respectively. Conclusions Our study highlights the ability to adopt SARA video ratings in clinical practice and research.

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

SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) regressions were used to identify which early life factors are predictive of SCA6 AAO, severity, and progression. Multiple linear regression models were then used to assess the degree to which these determinants influence SCA6 health outcomes. A total of 105 participants with genetically confirmed SCA6 completed the assessments. SCA6 participants with maternal difficulty during pregnancy, active participation in school sports, and/or longer CAG repeats were determined to have earlier AAO. We found a 13.44-year earlier AAO for those with maternal difficulty in pregnancy than those without ( p = 0.008) and a 12.31-year earlier AAO for those active in school sports than those who were not ( p < 0.001). Higher education attainment was associated with decreased SCA6 severity and slower progression. Early life biological and social factors can have a strong influence on the SCA6 disease course, indicating that non-genetic factors can contribute significantly to SCA6 health outcomes.

BackgroundMaintaining balance is crucial for independence and quality of life. Loss of balance is a hallmark of spinocerebellar ataxia (SCA).ObjectiveThe 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.MethodsFifty-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 (x2). 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).ResultsMost 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).ConclusionInertial 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. (c) 2024 International Parkinson and Movement Disorder Society.

Background: Progressive loss of standing balance is a feature of Friedreich's ataxia (FRDA). Objectives: This study aimed to identify standing balance conditions and digital postural sway measures that best discriminate between FRDA and healthy controls (HC). We assessed test-retest reliability and correlations between sway measures and clinical scores. Methods: Twenty-eight subjects with FRDA and 20 HC completed six standing conditions: feet apart, feet together, and feet tandem, both with eyes opened (EO) and eyes closed. Sway was measured using a wearable sensor on the lumbar spine for 30 seconds. Test completion rate, test-retest reliability with intraclass correlation coefficients, and areas under the receiver operating characteristic curves (AUCs) for each measure were compared to identify distinguishable FRDA sway characteristics from HC. Pearson correlations were used to evaluate the relationships between discriminative measures and clinical scores. Results: Three of the six standing conditions had completion rates over 70%. Of these three conditions, natural stance and feet together with EO showed the greatest completion rates. All six of the sway measures' mean values were significantly different between FRDA and HC. Four of these six measures discriminated between groups with >0.9 AUC in all three conditions. The Friedreich Ataxia Rating Scale Upright Stability and Total scores correlated with sway measures with P-values <0.05 and r-values (0.63-0.86) and (0.65-0.81), respectively. Conclusion: Digital postural sway measures using wearable sensors are discriminative and reliable for assessing standing balance in individuals with FRDA. Natural stance and feet together stance with EO conditions suggest use in clinical trials for FRDA. (c) 2024 International Parkinson and Movement Disorder Society.

Objective: To assess the effect of early life conditions and events on age at onset (AAO), severity, and progression in SCA6 patients. Background: Caused by pathologically expanded CAG repeats in the CACNA1A gene, SCA6 AAO and clinical progression can vary significantly between individuals with the same size CAG repeat allele. Although this indicates that non-genetic factors can influence the disease course, the impact of these external factors is poorly understood. Design/Methods: We performed a survey of social factors in SCA6 patients enrolled at the University of Chicago through consecutive sampling. AAO of ataxia symptoms and Patient-Reported Outcome Measure (PROM) of Ataxia were used as primary outcome measures. Using least absolute shrinkage and selection operation (LASSO) regression, we identified which early life factors are predictive of SCA6 AAO, severity, and progression. We then created multiple linear regression models to assess the degree to which these determinants influence SCA6 health outcomes. Results: A total of 105 participants with SCA6 completed the assessments. Maternal difficulty during pregnancy and participation in school sports were found to be predictive of AAO in addition to pathological CAG repeat length. We found a 12.76 year earlier AAO for those with maternal difficulty in pregnancy than those who did not (p = 0.022), and a 16.36 year earlier AAO for those active in school sports than those who were not (p <0.001). Higher education attainment was found to be associated with decreased SCA6 severity and slower progression. Compared to those with only primary education, those receiving post-secondary education were determined to have a 43.64 lower PROM-Ataxia score (p <0.001) and a slower rate of ataxia progression by 3.23 PROM-Ataxia score per year (p <0.001). Conclusions: Early life biological, behavioral, and social factors can have a strong influence on the SCA6 disease course and may contribute to the disease course of other monogenetic disorders. Disclosure: Tiffany Chen has nothing to disclose. Ms. Casey has nothing to disclose. Dr. Lin has a non-compensated relationship as a Secretary with Broadway for Ataxia Foundation (a 501 (c) (3) non-profit organization) that is relevant to AAN interests or activities. An immediate family member of Dr. Boyle has stock in Ionis Pharmaceuticals. The institution of Dr. Boyle has received research support from Bristol Myers Squibb. Dr. Schmahmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medavante. Dr. Schmahmann has stock in Cadent. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has received stock or an ownership interest from biohaven pharmaceuticals. Dr. Kuo has nothing to disclose. Dr. Gomez has nothing to disclose.

Background Quantitative assessment of severity of ataxia-specific gait impairments from wearable technology could provide sensitive performance outcome measures with high face validity to power clinical trials. Objectives The aim of this study was to identify a set of gait measures from body-worn inertial sensors that best discriminate between people with prodromal or manifest spinocerebellar ataxia (SCA) and age-matched, healthy control subjects (HC) and determine how these measures relate to disease severity. Methods One hundred and sixty-three people with SCA (subtypes 1, 2, 3, and 6), 42 people with prodromal SCA, and 96 HC wore 6 inertial sensors while performing a natural pace, 2-minute walk. Areas under the receiver operating characteristic curves (AUC) were compared for 25 gait measures, including standard deviations as variability, to discriminate between ataxic and normal gait. Pearson's correlation coefficient assessed the relationships between the gait measures and severity of ataxia. Results Increased gait variability was the most discriminative gait feature of SCA; toe-out angle variability (AUC = 0.936; sensitivity = 0.871; specificity = 0.896) and double-support time variability (AUC = 0.932; sensitivity = 0.834; specificity = 0.865) were the most sensitive and specific measures. These variability measures were also significantly correlated with the scale for the assessment and rating of ataxia (SARA) and disease duration. The same gait measures discriminated gait of people with prodromal SCA from the gait of HC (AUC = 0.610, and 0.670, respectively). Conclusions Wearable inertial sensors provide sensitive and specific measures of excessive gait variability in both manifest and prodromal SCAs that are reliable and related to the severity of the disease, suggesting they may be useful as clinical trial performance outcome measures. (c) 2021 International Parkinson and Movement Disorder Society

Objective The manual extraction of valuable data from electronic medical records is cumbersome, error-prone, and inconsistent. By automating extraction in conjunction with standardized terminology, the quality and consistency of data utilized for research and clinical purposes would be substantially improved. Here, we set out to develop and validate a framework to extract pertinent clinical conditions for traumatic brain injury (TBI) from computed tomography (CT) reports. Materials and Methods We developed tbiExtractor, which extends pyConTextNLP, a regular expression algorithm using negation detection and contextual features, to create a framework for extracting TBI common data elements from radiology reports. The algorithm inputs radiology reports and outputs a structured summary containing 27 clinical findings with their respective annotations. Development and validation of the algorithm was completed using two physician annotators as the gold standard. Results tbiExtractor displayed high sensitivity (0.92-0.94) and specificity (0.99) when compared to the gold standard. The algorithm also demonstrated a high equivalence (94.6%) with the annotators. A majority of clinical findings (85%) had minimal errors (F1 Score ≥ 0.80). When compared to annotators, tbiExtractor extracted information in significantly less time (0.3 sec vs 1.7 min per report). Discussion and Conclusion tbiExtractor is a validated algorithm for extraction of TBI common data elements from radiology reports. This automation reduces the time spent to extract structured data and improves the consistency of data extracted. Lastly, tbiExtractor can be used to stratify subjects into groups based on visible damage by partitioning the annotations of the pertinent clinical conditions on a radiology report.

OBJECTIVE: Traumatic brain injuries (TBIs) are largely underdiagnosed and may have persistent refractory consequences. Current assessments for acute TBI are limited to physical examination and imaging. Biomarkers such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B) have shown predictive value as indicators of TBI and potential screening tools. METHODS: In total, 37 controls and 118 unique trauma subjects who received a clinically ordered head computed tomography (CT) in the emergency department of a level 1 trauma center were evaluated. Blood samples collected at 0-8 hours (initial) and 12-32 hours (delayed) postinjury were analyzed for GFAP, UCH-L1, and S100B concentrations. These were then compared in CT-negative and CT-positive subjects. RESULTS: Median GFAP, UCH-L1, and S100B concentrations were greater in CT-positive subjects at both timepoints compared with CT-negative subjects. In addition, median UCH-L1 and S100B concentrations were lower at the delayed timepoint, whereas median GFAP concentrations were increased. As predictors of a positive CT of the head, GFAP outperformed UCH-L1 and S100B at both timepoints (initial: 0.89 sensitivity, 0.62 specificity; delayed: 0.94 sensitivity, 0.67 specificity). GFAP alone also outperformed all possible combinations of biomarkers. CONCLUSIONS: GFAP, UCH-L1, and S100B demonstrated utility for rapid prediction of a CT-positive TBI within 0-8 hours of injury. GFAP exhibited the greatest predictive power at 12-32 hours. Furthermore, these results suggest that GFAP alone has greater utility for predicting a positive CT of the head than UCH-L1, S100B, or any combination of the 3.

Reporting of sports-related concussions (SRCs) has risen dramatically over the last decade, increasing awareness of the need for treatment and prevention of SRCs. To date most prevention studies have focused on equipment and rule changes to sports in order to reduce the risk of injury. However, increased neck strength has been shown to be a predictor of concussion rate. In the TRAIN study, student-athletes will follow a simple neck strengthening program over the course of three years in order to better understand the relationship between neck strength and SRCs. Neck strength of all subjects will be measured at baseline and biannually over the course of the study using a novel protocol. Concussion severity and duration in any subject who incurs an SRC will be evaluated using the Sports Concussion Assessment Tool 5th edition, a questionnaire based tool utilizing several tests that are commonly affected by concussion, and an automated eye tracking algorithm. Neck strength, and improvement of neck strength, will be compared between concussed and non-concussed athletes to determine if neck strength can indeed reduce risk of concussion. Neck strength will also be analyzed taking into account concussion severity and duration to find if a strengthening program can provide a protective factor to athletes. The study population will consist of student-athletes, ages 12-23, from local high schools and colleges. These athletes are involved in a range of both contact and non-contact sports.