Multifeature quantitative motor assessment of upper limb ataxia including drawing and reaching.

OBJECTIVE: Voluntary upper limb movements are an ecologically important yet insufficiently explored digital-motor outcome domain for trials in degenerative ataxia. We extended and validated the trial-ready quantitative motor assessment battery "Q-Motor" for upper limb movements with clinician-reported, patient-focused, and performance outcomes of ataxia. METHODS: Exploratory single-center cross-sectional assessment in 94 subjects (46 cross-genotype ataxia patients; 48 matched controls), comprising five tasks measured by force transducer and/or position field: Finger Tapping, diadochokinesia, grip-lift, and-as novel implementations-Spiral Drawing, and Target Reaching. Digital-motor measures were selected if they discriminated from controls (AUC >0.7) and correlated-with at least one strong correlation (rho ≥0.6)-to the Scale for the Assessment and Rating of Ataxia (SARA), activities of daily living (FARS-ADL), and the Nine-Hole Peg Test (9HPT). RESULTS: Six movement features with 69 measures met selection criteria, including speed and variability in all tasks, stability in grip-lift, and efficiency in Target Reaching. The novel drawing/reaching tasks best captured impairment in dexterity (|rho9HPT| ≤0.81) and FARS-ADL upper limb items (|rhoADLul| ≤0.64), particularly by kinematic analysis of smoothness (SPARC). Target hit rate, a composite of speed and endpoint precision, almost perfectly discriminated ataxia and controls (AUC: 0.97). Selected measures in all tasks discriminated between mild, moderate, and severe impairment (SARA upper limb composite: 0-2/>2-4/>4-6) and correlated with severity in the trial-relevant mild ataxia stage (SARA ≤10, n = 20). INTERPRETATION: Q-Motor assessment captures multiple features of impaired upper limb movements in degenerative ataxia. Validation with key clinical outcome domains provides the basis for evaluation in longitudinal studies and clinical trial settings.

Fast-tracking action on the Sustainable Development Goals by enhancing national institutional arrangements.

Six years remain to achieve the Sustainable Development Goals (SDGs). Despite some progress, institutional effectiveness for SDG achievement has not been delivered at a national level. Identification and establishment of an institutional framework to operationalise the 2030 Agenda within national plans, giving science-based coordination of SDG implementation a central role, is urgently required to accelerate progress. This paper tackles this challenge. Drawing on literature analysis, it asks: 1) What are the deficiencies in institutional national arrangements that hinder SDG implementation? 2) How can existing institutional deficiencies in SDG implementation be addressed? and 3) How can institutional changes support fast-tracking of SDG implementation processes at national level? Findings show that country-specific horizontal institutional arrangements are usually advanced. However, national visions to improve mainstreaming across decision-making at different levels to enable whole-of-government and whole-of-society approaches to SDG implementation are commonly under-developed. Deficiencies are due to poor systematic engagement of scientific and technical expertise in operational day-to-day communication, as well as in the design, validation, implementation, monitoring and reporting of domestic SDG-related multi-stakeholder actions. Vertical institutional arrangements are complex, and risk resource-consuming, uncoordinated implementation. Our analyses suggest countries may benefit from establishing a national, centralised independent scientific and technical coordinating body for SDG implementation at national level, within existing science-based institutional arrangements. Such a body would not be led by governmental processes but would provide technical support to government agencies. We argue that scientific and technical skills in data and information management and quality control are central to coordinated and evidence-informed support, and could help to accelerate national SDG implementation. Such a supporting body would also enable a more joined-up approach between stakeholders working in the areas of science and technology, government and practice, improving orchestrated science-based actions and their auditing across sectors and stakeholder communities at national and sub-national levels. It would further guide actions to reduce trade-offs within national sustainable development aspirations, and would facilitate consideration of diverse values in advancing towards a durable and just transformative future. Such efforts are vital given the rapidly closing window of time for SDG achievement.

Are we really addressing the roadblocks to adoption of renewable and sustainable energy technologies? Total interpretive structural modeling approach.

Urban areas serve as a vital contribution to the global structural change towards renewable and sustainable energy technologies which also influence climate change. The aim of this paper is to identify the adoption roadblocks to renewable and sustainable urban energy technologies. This research has three parts: a mini-systematic literature study was conducted to identify the most prevalent roadblocks. Using total interpretive structural modeling (ISM), the relationships between the roadblocks and the source of causation were then examined. The roadblocks are classified based on their dependence and driving powers using MICMAC analysis in the third part of this research. The principal results and major conclusions demonstrate that all roadblocks are necessary for renewable and sustainable urban energy technologies. The roadblocks at level I are insufficient infrastructure, lack of coordination among authorities, lack of quality and reliable data and information, and competition with non-renewable technologies; roadblocks in level II are lack of skilled and trained personnel, limited public participation, awareness, and consumer interest, and lack of standardized technology; roadblock in level III is high initial investment cost; and lastly, roadblocks in level IV are lack of subsidies and financial support programs and absence of coherent related policies. Furthermore, as a result of the MICMAC analysis, none of the aforementioned roadblocks are classified as autonomous variables, implying that they are all required. The dependent roadblocks to renewable and sustainable energy technologies are defined as lack of coordination among authorities, lack of information, and competition with non-renewable technologies. Moreover, linkage roadblocks have high dependence and driving powers which are insufficient infrastructure, limited awareness and consumer interest, and lack of standardized technology. Lastly, high initial investment costs, lack of subsidies and financial support programs, absence of coherent related policies, and lack of skilled and trained personnel are the driving roadblocks with high driving power however not dependent.

Quantitative Oculomotor Assessment in Hereditary Ataxia: Discriminatory Power, Correlation with Severity Measures, and Recommended Parameters for Specific Genotypes.

Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 (n = 268), SCA6 (n = 117), other SCAs (n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia (n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression (n = 2; SCA2) or treatment response (n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores (n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification (n = 9), and imaging measures of atrophy (n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.

[Scale for the assessment and rating of ataxia (SARA): translation and cultural adaptation to German-speaking areas]. / Scale for the assessment and rating of ataxia (SARA): Übersetzung und kulturelle Anpassung an den deutschsprachigen Raum.

BACKGROUND/OBJECTIVE: The scale for the assessment and rating of ataxia (SARA) is a feasible assessment for the classification and evaluation of therapeutic interventions. In order to provide access to the SARA in German, the aim of this work was to translate the SARA into German and to adapt it according to international guidelines for German-speaking countries. METHOD: The process involved six steps. The comprehensibility of the scale was assessed using interviews with potential users. RESULTS: A total of nine physiotherapists and six physicians working in various clinical settings were interviewed, seven of them worked in Germany and four each in Austria and Switzerland. The interviews led to a refined version of the translation. The comprehensibility testing revealed no country-specific differences. CONCLUSION: A German version of the SARA authorized by the co-author of the original publication, is now available. The results provide methodological insights into the translation process of observation-based standardized assessments.

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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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. IMPACT: Our study shows that the SARA can be used in the telehealth setting for patients with ataxia.

Neurological gait assessment.

Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues to a myriad of causes. Understanding how to examine gait is not only essential for neurological diagnosis but also for treatment and prognosis. Here, we review aspects of the clinical history and examination of neurological gait to help guide gait disorder assessment. We focus particularly on how to differentiate between common gait abnormalities and highlight the characteristic features of the more prevalent neurological gait patterns such as ataxia, waddling, steppage, spastic gait, Parkinson's disease and functional gait disorders. We also offer diagnostic clues for some unusual gait presentations, such as dystonic, stiff-person and choreiform gait, along with red flags that help differentiate atypical parkinsonism from Parkinson's disease.

Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey.

BACKGROUND: Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one. RESULTS: Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-significant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients (P = 0.59). In Italy these figures were €2126 and €1971, respectively (P = 0.84). In Germany they were €2431 and €4087, respectively (P = 0.19). Inpatient stays made the largest contribution to total costs. CONCLUSIONS: Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.

Modified Recurrence Quantification Analysis for Objective Assessment of Cerebellar Ataxia.

Cerebellar Ataxia (CA) is a neurological condition that affects coordination, balance and speech. Assessing its severity is important for developing effective treatment and rehabilitation plans. Traditional assessment methods involve a clinician instructing a person with ataxia to perform tests and assigning a severity score based on their performance. However, this approach is subjective as it relies on the clinician's experience, and can vary between clinicians. To address this subjectivity, some researchers have developed automated assessment methods using signal processing and data-driven approaches, such as supervised machine learning. These methods still rely on subjective ground truth and can perform poorly in real-world scenarios. This research proposed an alternative approach that uses signal processing to modify recurrence plots and compare the severity of ataxia in a person with CA to a control cohort. The highest correlation score obtained was 0.782 on the back sensor with the feet-apart and eyes-open test. The contributions of the research include modifying the recurrence plot as a measurement tool for assessing CA severity, proposing a new approach to assess severity by comparing kinematic data between people with CA and a control reference group, and identifying the best subtest and sensor position for practical use in CA assessments.

Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients.

OBJECTIVE: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. METHODS: Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2-8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes. RESULTS: Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), and fluctuating decreases/increases. All subitems except nose-finger showed moderate-to-strong correlations to activities of daily living, indicating that metric properties-not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG-ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%. INTERPRETATION: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470-485.

Ataxia-telangiectasia: una revisión desde la etiopatogenia al manejo actual con descripción de casos reportados en Perú / Ataxia telangiectasia: A review from etiopathogenesis to current management with a description of reported cases in Peru

La Ataxia-Telangiectasia (AT) es una rara enfermedad de herencia autosómica recesiva y de afección multisistémica, caracterizada por ataxia progresiva, inmunodeficiencia variable con infecciones recurrentes, riesgo incrementado de neoplasias con o sin telangiectasias óculo-cutáneas. La AT es causada por variantes patogénicas bialélicas en el gen ATM. Su diagnóstico se basa en la sospecha de un cuadro clínico compatible, niveles elevados de alfafetoproteína, atrofia cerebelosa y estudios genéticos. No existe tratamiento curativo de AT y su manejo se basa en medidas de soporte y prevención de complicaciones y asesoramiento genético. En esta revisión, actualizamos la epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de AT incluyendo una búsqueda de casos publicados en el Perú.

Ataxia-Telangiectasia (AT) is a rare autosomal recessive disease with multisystemic involvement, characterized by slowly progressive ataxia, variable immunodeficiency with recurrent infections, increased risk of neoplasms with or without oculocutaneous telangiectasias. AT is caused by biallelic pathogenic variants within the ATM gene. Its diagnosis is based on suspicion of a compatible clinical symptomatology, increased levels of alpha-fetoprotein, cerebellar atrophy, and genetic testing. There is no curative treatment for AT and its management is based on supportive and preventive measures of eventual complications and genetic counseling. This review updates the epidemiology, clinical manifestations, diagnosis, and treatment of AT, including a search for cases published in Peru.

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

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients.

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD. METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review. RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at the time of data collection was 9.0 years (interquartile range = 5.3-15.9 years, range = fetal to 31.8 years). A total of 24 different TANGO2 alleles were observed. Patients showed normal development in early infancy, with progressive delay in developmental milestones thereafter. Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years. A total of 46/71 (65%) patients suffered metabolic crises, and of those, 30 (65%) developed cardiac crises. Metabolic crises were significantly decreased after the initiation of B-complex or multivitamin supplementation. CONCLUSION: We provide the most comprehensive review of natural history of TDD and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.

Coordination of health and rehabilitation services for person with disabilities in Sierra Leone - a stakeholders' perspective.

PURPOSE: To explore stakeholders' perceptions of the coordination of health and rehabilitation services for persons with disabilities in Sierra Leone. MATERIALS AND METHODS: A qualitative study including seven focus group discussions with health, rehabilitation, and disability organisations stakeholders in Sierra Leone. Content analysis was used for data analysis. RESULTS: One theme emerged; poor governance in implementing disability policies, healthcare, and rehabilitation services, which included seven subthemes: insufficient implementation of healthcare policies for persons with disabilities; changes, lack of coordination and communication between ministries governing disability policies and rehabilitation services; need for accurate disability data and clinical record keeping; absence of funds and poor political priority to healthcare and rehabilitation services; continuous support for non-governmental organisations (NGOs) to provide healthcare and rehabilitation service delivery; lack of coordination between different healthcare and rehabilitation service providers and calling for increasing persons with disabilities capacity for greater inclusion in society. CONCLUSIONS: Increasing governmental prioritisation, and ensuring coordination and trust between donors, NGOs, and governmental programmes were keys for sustainable health and rehabilitation services. Stakeholders need to ensure national coverage and equally distributed health and rehabilitation services. Including rehabilitation services and assistive technology in the Free Healthcare Initiative would contribute to implementing the Disability Act. Implications for rehabilitationPolitical prioritisation of persons with disability (PWD) need to increase to provide national coverage and equally distributed health and rehabilitation services for PWD.To ensure access to rehabilitation services and access to basic assistive technology for PWD, the government of Sierra Leone could agree on basic rehabilitation services and a priority list of assistive devices to be distributed through rehabilitation centres and funded by the Free Health Care Initiative programme or the Sierra Leone health insurance scheme.To increase access to health services for PWD, the government of Sierra Leone could ensure inclusion of PWD in the Free Health Care Initiative programme.The government, donors, and organisations providing or funding health and rehabilitation services for PWD need to mobilise and coordinate resources better and be mutually held accountable to maximise the benefits of PWD resources.

Assessing Cerebellar Disorders with Wearable Inertial Sensor Data Using Time-Frequency and Autoregressive Hidden Markov Model Approaches.

Wearable sensor data is relatively easily collected and provides direct measurements of movement that can be used to develop useful behavioral biomarkers. Sensitive and specific behavioral biomarkers for neurodegenerative diseases are critical to supporting early detection, drug development efforts, and targeted treatments. In this paper, we use autoregressive hidden Markov models and a time-frequency approach to create meaningful quantitative descriptions of behavioral characteristics of cerebellar ataxias from wearable inertial sensor data gathered during movement. We create a flexible and descriptive set of features derived from accelerometer and gyroscope data collected from wearable sensors worn while participants perform clinical assessment tasks, and use these data to estimate disease status and severity. A short period of data collection (<5 min) yields enough information to effectively separate patients with ataxia from healthy controls with very high accuracy, to separate ataxia from other neurodegenerative diseases such as Parkinson's disease, and to provide estimates of disease severity.

Objective Assessment of Upper-Extremity Motor Functions in Spinocerebellar Ataxia Using Wearable Sensors.

The study presents a novel approach to objectively assessing the upper-extremity motor symptoms in spinocerebellar ataxia (SCA) using data collected via a wearable sensor worn on the patient's wrist during upper-extremity tasks associated with the Assessment and Rating of Ataxia (SARA). First, we developed an algorithm for detecting/extracting the cycles of the finger-to-nose test (FNT). We extracted multiple features from the detected cycles and identified features and parameters correlated with the SARA scores. Additionally, we developed models to predict the severity of symptoms based on the FNT. The proposed technique was validated on a dataset comprising the seventeen (n = 17) participants' assessments. The cycle detection technique showed an accuracy of 97.6% in a Bland-Altman analysis and a 94% accuracy (F1-score of 0.93) in predicting the severity of the FNT. Furthermore, the dependency of the upper-extremity tests was investigated through statistical analysis, and the results confirm dependency and potential redundancies in the upper-extremity SARA assessments. Our findings pave the way to enhance the utility of objective measures of SCA assessments. The proposed wearable-based platform has the potential to eliminate subjectivity and inter-rater variabilities in assessing ataxia.

Application of the Scale for Assessment and Rating of Ataxia in toddlers.

INTRODUCTION: In young children with early onset ataxia (EOA), quantitative rating of ataxia by the Scale for Assessment and Rating of Ataxia (SARA) is longitudinally influenced by the physiological age effect on motor coordination. To enable longitudinal quantitative interpretation of ataxia by SARA in children with EOA, the EPNS ataxia working group has previously determined SARA-scores in typically developing children (4-16 years of age). In toddlers, this information is still lacking. We therefore aimed to investigate the feasibility and reliability of SARA-scores in typically developing toddlers. METHODS: In 57 typically developing toddlers (2-4 years), we aimed to determine the: 1. feasibility of SARA-scores, 2. age-related pre-requisites to obtain SARA-scores in toddlers over all domains, 3. SARA-score reliability, 4. mathematical age connection of SARA-scores in toddlers and older children. RESULTS: In typically developing toddlers, the feasibility of SARA is strongly age-dependent (p < .000). After computing compensations for two age-related, unfeasible and therefore un-assessable kinetic subtasks and after allowing the videotaping of non-kinetic SARA sub-task performances at home, the SARA was fully reliably assessable in all (n = 57) toddlers (ICC = 0.732). From two to 16 years of age, SARA-scores were mathematically represented by one continuous, exponentially decreasing trend line approaching the adult-optimum at 16 years of age. CONCLUSION: In toddlers, SARA-scores are reliably assessable, by using two age-compensations and allowing the videotaping of SARA-performances partly at home. In children with EOA, these data enable longitudinal quantification and interpretation of quantitative ataxia-scores by SARA from 2 years of age throughout childhood.

2D Gait Skeleton Data Normalization for Quantitative Assessment of Movement Disorders from Freehand Single Camera Video Recordings.

Overlapping phenotypic features between Early Onset Ataxia (EOA) and Developmental Coordination Disorder (DCD) can complicate the clinical distinction of these disorders. Clinical rating scales are a common way to quantify movement disorders but in children these scales also rely on the observer's assessment and interpretation. Despite the introduction of inertial measurement units for objective and more precise evaluation, special hardware is still required, restricting their widespread application. Gait video recordings of movement disorder patients are frequently captured in routine clinical settings, but there is presently no suitable quantitative analysis method for these recordings. Owing to advancements in computer vision technology, deep learning pose estimation techniques may soon be ready for convenient and low-cost clinical usage. This study presents a framework based on 2D video recording in the coronal plane and pose estimation for the quantitative assessment of gait in movement disorders. To allow the calculation of distance-based features, seven different methods to normalize 2D skeleton keypoint data derived from pose estimation using deep neural networks applied to freehand video recording of gait were evaluated. In our experiments, 15 children (five EOA, five DCD and five healthy controls) were asked to walk naturally while being videotaped by a single camera in 1280 × 720 resolution at 25 frames per second. The high likelihood of the prediction of keypoint locations (mean = 0.889, standard deviation = 0.02) demonstrates the potential for distance-based features derived from routine video recordings to assist in the clinical evaluation of movement in EOA and DCD. By comparison of mean absolute angle error and mean variance of distance, the normalization methods using the Euclidean (2D) distance of left shoulder and right hip, or the average distance from left shoulder to right hip and from right shoulder to left hip were found to better perform for deriving distance-based features and further quantitative assessment of movement disorders.

Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann-Pick disease, type C1.

Identifying meaningful predictors of therapeutic efficacy from preclinical studies is challenging. However, clinical manifestations occurring in both patients and mammalian models offer significant translational value. Many neurological disorders, including inherited, metabolic Niemann-Pick disease, type C (NPC), exhibit ataxia. Both individuals with NPC and murine models manifest ataxia, and investigational therapies impacting this phenotype in mice have been reported to slow disease progression in patients (e.g. miglustat, intrathecal 2-hydroxypropyl-beta-cyclodextrin, and acetyl-L-leucine). Reproducible phenotypic scoring of animal models can facilitate comparisons between genotypes, sexes, disease course, and therapies. Previously, other groups have developed a composite phenotypic scoring system (CPSS), which was subsequently used to distinguish strain-dependent phenotypes and, with modifications, to evaluate potential therapies. However, high inter-rater reliability is paramount to widespread use. We have created a comprehensive, easy-to-follow phenotypic assessment based on the CPSS and have verified its reproducibility using murine models of NPC disease. Application of this scoring system is not limited to NPC disease and may be applicable to other models of neurodegeneration exhibiting motor incoordination, thereby increasing its utility in translational studies.

The cost of non-coordination in urban on-demand mobility.

Over the last 10 years, ride-hailing companies (such as Uber and Grab) have proliferated in cities around the world. While generally beneficial from an economic viewpoint, having a plurality of operators that serve a given demand for point-to-point trips might induce traffic inefficiencies due to the lack of coordination between operators when serving trips. In fact, the efficiency of vehicle fleet management depends, among other things, density of the demand in the city, and in this sense having multiple operators in the market can be seen as a disadvantage. There is thus a tension between having a plurality of operators in the market, and the overall traffic efficiency. To this date, there is no systematic analysis of this trade-off, which is fundamental to design the best future urban mobility landscape. In this paper, we present the first systematic, data-driven characterization of the cost of non-coordination in urban on-demand mobility markets by proposing a simple, yet realistic, model. This model uses trip density and average traffic speed in a city as its input, and provides an accurate estimate of the additional number of vehicles that should circulate due to the lack of coordination between operators-the cost of non-coordination. We plot such cost across different cities-Singapore, New York (limited to the borough of Manhattan in this work), San Francisco, Vienna and Curitiba-and show that due to non-coordination, each additional operator in the market can increase the total number of circulating vehicles by up to 67%. Our findings could support city policy makers to make data supported decisions when regulating urban on-demand mobility markets in their cities. At the same time, our results outline the need of a more proactive government participation and the need for new, innovative solutions that would enable a better coordination of on-demand mobility operators.