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.

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

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

Application of the Scale for the Assessment and Rating of Ataxia (SARA) in pediatric oncology patients: A multicenter study.

Posterior cranial fossa (PCF) tumors in childhood are often associated with ataxia as well as other motor, neurobehavioral and linguistic impairment. The use of a reliable outcome measure is mandatory to evaluate the severity of impairment and monitor rehabilitation effectiveness. The aim of this work is to explore the validity of the Scale for the Assessment and Rating of Ataxia (SARA) in pediatric subjects with ataxia secondary to PCF tumor resection and evaluate the influence of age and comorbidities. Seventy eight patients (3-18 years) were recruited in 5 centers from 2016 to 2018. The age effect on SARA was analyzed by correlating total SARA scores and item scores with age and gradually excluding youngest subjects. The comorbidity effect was evaluated by comparing the ataxia-only group vs a group of subjects with ataxia + dysfunction of cranial nerves or cerebellar mutism (CM) and a group of patients with ataxia + hemiparesis. Several negative correlations between SARA scores and age were found under age 9. Differences between ataxia-only group and the other two groups were closely associated with specific comorbidities (e.g. speech disturbance in cranial nerves or CM group (p value < 0.001) and gait, stance, sitting and finger chase in the hemiparetic group (mean p value 0.022)).

Development of SaraHome: A novel, well-accepted, technology-based assessment tool for patients with ataxia.

BACKGROUND AND OBJECTIVE: Early onset ataxias (EOAs) are a heterogeneous group of neurological conditions, responsible for severe motor disability in paediatric age, which still lack reliable outcome measures. Available scales to assess ataxia, such as the Scale for Assessment and Rating of Ataxia (SARA), are based on subjective assessment of specific motor and language tasks by an examiner, and therefore is age dependent and lacks accuracy in detecting small variations in disease severity. In last years, novel technologies, including computer interfaces and videogames, have emerged for clinical applications and the advent of Internet of Medical Things and of Information Communication Technology have allowed the remote control of such technologies. This pilot study describes a newly developed tool (SaraHome) for the assessment at home of EOA evaluating its feasibility and acceptability on a small sample of children. METHODS: Ten EOA children and ten caregivers have been enrolled for a preliminary outpatient evaluation. The Microsoft Kinect 2.0 and Leap Motion Controller (LMC) connected to a personal computer with an ad hoc software have been set-up, for the acquisition of standardized motor tasks performed by the patients with the caregivers' assistance. Acceptance and practicability have been tested by QUEST 2.0 and IMI questionnaires in caregivers and patients respectively. RESULTS: The SaraHome software was developed, based on a collection of services provided by a complex architecture that consists of a Restful interface, which enables to access a series of plugins for the execution of different tasks. A graphical user interface allows the acquisition of the patient movements while performing a motor task. A protocol of standard tasks inspired by SARA was established, and a system of video-assisted instruction provided. The set-up for the optimal acquisition of such protocol by Kinect and LMC has been defined. Both patients and caregivers accomplished the SaraHome assessment with good feedback at the technology acceptance questionnaires. CONCLUSIONS: SaraHome represents a newly developed tool for the assessment of ataxia in patients, resulting from the integration of low-cost and easy-accessible technologies. This pilot application highlighted the feasibility and the acceptability of the system, suggesting the potential use in clinical practice.

Is Dyssynergic Defecation an Unrecognized Cause of Chronic Constipation in Patients Using Opioids?

OBJECTIVES: The impact of opioids on anorectal function is poorly understood but potentially relevant to the pathogenesis of opioid-induced constipation (OIC). To evaluate anorectal function testing (AFT) characteristics, symptom burden, and quality of life in chronically constipated patients prescribed an opioid (OIC) in comparison with constipated patients who are not on an opioid (NOIC). METHODS: Retrospective analysis of prospectively collected data on 3,452 (OIC = 588 and NOIC = 2,864) chronically constipated patients (Rome 3) who completed AFT. AFT variables included anal sphincter pressure and response during simulated defecation, balloon expulsion test (BET), and rectal sensation. Dyssynergic defecation (DD) was defined as an inability to relax the anal sphincter during simulated defecation and an abnormal BET. Patients completed Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. RESULTS: The mean age of the study cohort was 49 years. Most patients were women (82%) and whites (83%). Patients with OIC were older than NOIC patients (50.7 vs 48.3, P = 0.001). OIC patients were significantly more likely to have DD (28.6% vs 21.4%, P < 0.001), an abnormal simulated defecation response on anorectal manometry (59% vs 43.8%, P < 0.001), and an abnormal BET (48% vs 42.5%, P = 0.02) than NOIC patients. OIC patients reported more severe constipation symptoms (P < 0.02) and worse quality of life (P < 0.05) than NOIC patients. DISCUSSION: Chronically constipated patients who use opioids are more likely to have DD and more severe constipation symptoms than NOIC.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

An ontology-aware integration of clinical models, terminologies and guidelines: an exploratory study of the Scale for the Assessment and Rating of Ataxia (SARA).

BACKGROUND: Electronic rating scales represent an important resource for standardized data collection. However, the ability to exploit reasoning on rating scale data is still limited. The objective of this work is to facilitate the integration of the semantics required to automatically interpret collections of standardized clinical data. We developed an electronic prototype for the Scale of the Assessment and Rating of Ataxia (SARA), broadly used in neurology. In order to address the modeling challenges of the SARA, we propose to combine the best performances from OpenEHR clinical archetypes, guidelines and ontologies. METHODS: A scaled-down version of the Human Phenotype Ontology (HPO) was built, extracting the terms that describe the SARA tests from free-text sources. This version of the HPO was then used as backbone to normalize the content of the SARA through clinical archetypes. The knowledge required to exploit reasoning on the SARA data was modeled as separate information-processing units interconnected via the defined archetypes. Each unit used the most appropriate technology to formally represent the required knowledge. RESULTS: Based on this approach, we implemented a prototype named SARA Management System, to be used for both the assessment of cerebellar syndrome and the production of a clinical synopsis. For validation purposes, we used recorded SARA data from 28 anonymous subjects affected by Spinocerebellar Ataxia Type 36 (SCA36). When comparing the performance of our prototype with that of two independent experts, weighted kappa scores ranged from 0.62 to 0.86. CONCLUSIONS: The combination of archetypes, phenotype ontologies and electronic information-processing rules can be used to automate the extraction of relevant clinical knowledge from plain scores of rating scales. Our results reveal a substantial degree of agreement between the results achieved by an ontology-aware system and the human experts.

Assessment of Obstructive Defecation by High-Resolution Anorectal Manometry Compared With Magnetic Resonance Defecography.

BACKGROUND & AIMS: Patients with obstructive defecation have abnormalities of anorectal function and/or structure. Conventional anorectal manometry (ARM) can identify abnormal function and behavior (dyssynergia); however, agreement between manometry and defecography is only fair. High-resolution (HR)-ARM may improve diagnostic agreement by differentiating pressure effects caused by dyssynergia and obstruction. We compared HR-ARM findings with magnetic resonance (MR) defecography in the clinical assessment of patients with symptoms of obstructive defecation defined by Rome III criteria. METHODS: HR-ARM (Manoscan AR 360; Given Imaging, Yoqeam, Israel) assessed anal sphincter function and pressure during simulated defecation. Abnormal manometric findings were classified according to the Rao system and compared with MR defecography as the reference standard. RESULTS: A total of 188 consecutive patients (155 women; age, 19-93 y) with obstructive defecation underwent a full investigation. Compared with patients with dyssynergia on MR imaging (n = 66), patients with structural pathology (n = 87) had lower resting (P < .003) and squeeze pressures (P < .011), but a higher rectoanal pressure gradient (P < .0001) on HR-ARM. High intrarectal pressure with a steep, positive pressure gradient consistent with outlet obstruction on HR-ARM was present in 24 patients with intra-anal intussusception on MR imaging. This pattern was not observed in other patients. Interobserver agreement was substantial for HR-ARM diagnoses (κ = 0.67; 95% confidence interval, 0.559-0.779). Diagnostic accuracy for dyssynergia was 82% compared with MR imaging (sensitivity, 77% [51 of 66]; specificity, 85% [104 of 122]). CONCLUSIONS: The diagnostic agreement between anorectal HR-ARM and MR defecography is high and pressure measurements accurately identify recto-anal dyssynergia and intra-anal outlet obstruction by structural pathology as causes of obstructive defecation.

The Virtual Peg Insertion Test as an assessment of upper limb coordination in ARSACS patients: a pilot study.

OBJECTIVE: This paper introduces a novel assessment tool to provide clinicians with quantitative and more objective measures of upper limb coordination in patients suffering from Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS). The Virtual Peg Insertion Test (VPIT) involves manipulating an instrumented handle in order to move nine pegs into nine holes displayed in a virtual environment. The main outcome measures were the number of zero-crossings of the hand acceleration vector, as a measure of movement coordination and the total time required to complete the insertion of the nine pegs, as a measure of overall upper limb performance. RESULTS: 8\9 patients with ARSACS were able to complete five repetitions with the VPIT. Patients were found to be significantly less coordinated and slower than age-matched healthy subjects (p<0.01). Performance of ARSACS patients was positively correlated with the Nine-Hole Peg Test (r=0.85, p<0.01) and with age (r=0.93, p<0.01), indicative of the degenerative nature of the disease. CONCLUSION(S): This study presents preliminary results on the use of a robotics and virtual reality assessment tool with ARSACS patients. Results highlight its potential to assess impaired coordination and monitor its progression over time.

Quantitative assessment of interutterance stability: application to dysarthria.

PURPOSE: Following recent attempts to quantify articulatory impairment in speech, the present study evaluates the usefulness of a novel measure of motor stability to characterize dysarthria. METHOD: The study included 8 speakers with ataxic dysarthria (AD), 16 speakers with hypokinetic dysarthria (HD) as a result of Parkinson's disease, and 24 unimpaired control participants. Each participant performed a series of sentence repetitions under habitual, fast, and slow speaking rate conditions. An algorithm to measure utterance-to-utterance spectro-temporal variation (UUV; Cummins, 2009) was used. Speech rate and intelligibility were also measured. RESULTS: UUV scores were significantly correlated with perceptually based intelligibility scores. There were significant differences in UUV between control speakers and the AD but not the HD groups, presumably because of differences in intelligibility in the samples used and not because of differences in pathology. Habitual speaking rate did not correlate with UUV scores. All speaker groups had greater UUV levels in the slow conditions compared with habitual and fast speaking rates. CONCLUSIONS: UUV results were consistent with those of other variability indices and thus appear to capture motor control issues in a similar way. The results suggest that the UUV could be developed into an easy-to-use clinical tool that could function as a valid and reliable assessment and outcome measure.

Early recognition of pelvic floor dyssynergia and colorectal assessment in Parkinson's disease associated with bowel dysfunction.

AIM: Slow colonic transit time (CTT) and pelvic floor dyssynergia (PFD) are major contributors to constipation in patients with Parkinson's disease (PD). However, no symptom survey yet exists that effectively differentiates the contributing aetiologies. The significance of individual pelvic floor musculature behaviours and their relationship with colorectal dysmotility in constipated patients with PD are still controversial and need further clarification. We aimed to investigate how differentiated constipation-related symptoms of PD patients with constipation may identify constipation groupings and to register the pathophysiological features of the pelvic musculature. METHOD: Our subjects undertook CTT, defaecography and the Knowles-Eccersley-Scott Symptom questionnaire. The pathological aetiologies were categorized as group 1 (slow CTT) and/or group 2 (puborectalis syndrome) and/or group 3 (pubococcygeus syndrome), in accordance with the CTT and defaecography results. RESULTS: Constipation-related symptoms such as incomplete evacuation and defaecation difficulty yielded high post-test probabilities (81% and 88%, respectively) in groups 3 and 2, but a low post-test probability in group 1 (58%). Changes in the anorectal angle and perineum descent during straining were significantly correlated with CTT (r = 0.57 and r = 0.61, respectively) and with each other (r = 0.82). CONCLUSION: Our findings that neural control of the puborectalis and pubococcygeus, along with colorectal peristalsis, were in a similar state of degeneration is key information that should assist physicians to instigate more effective management for colonic dysmotility or PFD.

Reliability and validity of the scale for the assessment and rating of ataxia: a study in 64 ataxia patients.

The objective of this study was to test the reliability and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in ataxia patients not suffering from autosomal dominant spinocerebellar ataxia (SCA). To this end, 64 patients with various ataxia disorders or stable cerebellar lesions were rated independently by two investigators. In addition to SARA, the following assessment instruments were applied: ataxia disease stage, Barthel index and part IV (functional assessment) of the Unified Huntington's Disease Rating scale (UHDRS-IV). Eighteen patients were rated twice. Inter-rater and intrarater reliability were very high with ICCs of 0.98 and 0.99. Internal consistency was high indicated by Cronbach's alpha of 0.97. Factorial analysis revealed that the rating results were mainly determined by one major factor with an eigenvalue of 6.34 which explained 52.8% of the variance. SARA score increased with disease stage (P<0.0001) and was closely correlated with Barthel index (r=-0.63, P<0.0001) and UHDRS-IV (r=-0.62, P<0.0001), but only weakly correlated with disease duration (r=0.44, P<0.001). The results suggest that SARA is a reliable and valid measure of ataxia in non-SCA ataxia patients.

Standardized finger-nose test validity for coordination assessment in an ataxic disorder.

OBJECTIVES: Evaluation of coordination with the Finger-Nose Test is an essential part of the neurological examination. This study explored the convergent and discriminant construct validity of the Standardized Finger-Nose Test (SFNT) in a neuromuscular disorder with ataxic features. METHOD: A cross-sectional study was carried out with 24 participants with recessive spastic ataxia of Charlevoix-Saguenay. Convergent construct validity was tested by correlating the SFNT with other upper extremity function tests, a functional independence measure and social participation. Upper extremity function tests included gross and fine dexterity (Box and Block Test and Purdue Pegboard), upper extremity strength (dynamometry) and global upper extremity performance (TEMPA). The Functional Independence Measure (FIM) and the Assessment of Life Habits scale (LIFE-H) measured functional independence and social participation respectively. Discriminant construct validity was explored by comparing performance on the SFNT between two age groups (< 40 years and > or = 40 years). RESULTS: Convergent validity of the SFNT was demonstrated by moderate to strong correlations with gross and fine finger dexterity (r = 0.82-0.84), global upper extremity performance (0.74-0.79), functional independence (r = 0.74) and social participation (r = 0.78). Upper extremity coordination of the older group was significantly lower than in the younger group, suggesting the ability of the SFNT to discriminate between different levels of function. CONCLUSION: This study demonstrated the convergent and discriminant construct validity of the SFNT in a neuromuscular disorder with ataxic features.

Response of avian embryonic brain to spatially segmented x-ray microbeams.

Duck embryo was studied as a model for assessing the effects of microbeam radiation therapy (MRT) on the human infant brain. Because of the high risk of radiation-induced disruption of the developmental process in the immature brain, conventional wide-beam radiotherapy of brain tumors is seldom carried out in infants under the age of three. Other types of treatment for pediatric brain tumors are frequently ineffective. Recent findings from studies in Grenoble on the brain of suckling rats indicate that MRT could be of benefit for the treatment of early childhood tumors. In our studies, duck embryos were irradiated at 3-4 days prior to hatching. Irradiation was carried out using a single exposure of synchrotron-generated X-rays, either in the form of parallel microplanar beams (microbeams), or as non-segmented broad beam. The individual microplanar beams had a width of 27 microm and height of 11 mm, and a center-to-center spacing of 100 microm. Doses to the exposed areas of embryo brain were 40, 80, 160 and 450 Gy (in-slice dose) for the microbeam, and 6, 12 and 18 Gy for the broad beam. The biological end point employed in the study was ataxia. This neurological symptom of radiation damage to the brain developed within 75 days of hatching. Histopathological analysis of brain tissue did not reveal any radiation induced lesions for microbeam doses of 40-160 Gy (in-slice), although some incidences of ataxia were observed in that dose group. However, severe brain lesions did occur in animals in the 450 Gy microbeam dose groups, and mild lesions in the 18 Gy broad beam dose group. These results indicate that embryonic duck brain has an appreciably higher tolerance to the microbeam modality, as compared to the broad beam modality. When the microbeam dose was normalized to the full volume of the irradiated tissue. i.e., the dose averaged over microbeams and the space between the microbeams, brain tolerance was estimated to be about three times higher to microbeam irradiation as compared with broad beam irradiation.

Behaviour management needs for the orthodontic treatment of children with disabilities.

A displeasing dental appearance may have a significant emotional impact on an individual's well being. Although malocclusions occur more often in physically and/or mentally handicapped children than in normal children, the most severely handicapped patients are those least likely to receive orthodontic treatment. This investigation studied the modes of behaviour management used in the orthodontic treatment of disabled children, and the preferred criteria. The files of 49 disabled children were retrospectively evaluated. Two classification systems, the Frankl Behaviour Rating Scale (FBRS), and that of Owen and Graber were found to be unsuitable for determining the appropriate treatment modality. Five specific factors, frequently seen in disabled children, gag reflex, drooling, uncontrollable movements, inability to remain still, and the need for additional procedures, were graded and a scoring system was devised to include these factors within the assessment. This scoring system may be used to evaluate new patients and to assist in the choice of the appropriate behavioural management mode.

Increased energy cost of walking in multiple sclerosis: effect of spasticity, ataxia, and weakness.

Multiple sclerosis patients with motor involvement of the lower extremities and the trunk often experience exertional dyspnea and generalized or leg fatigue on walking, and their walking performance is reduced. It has recently been suggested that a high energy cost of walking (Cw) may be an important contributing factor to the observed dyspnea and fatigue. The purpose of this study was to determine which factors influence Cw. Clinical tests were used to assess the major alterations of the motor system. Thirty-three patients (mean age 41 years, mean maximal speed 2.8 km/h, range 1.2 to 6.2 km/h) in a stable phase of their disease were examined. Cost of walking (mean +/- SE) at 1.8 km/h was 0.287 +/- 0.018 ml 02.kg-1.m-1 (normal value 0.163 +/- 0.007, p less than 0.001). A multivariate regression analysis showed that Cw was significantly related to spasticity of the lower extremities, whereas lower extremity and truncal weakness did not contribute to the observed high Cw.