Motor Assessment Research Articles

Apolipoprotein C3-rich low-density lipoprotein (AC3RL) exacerbates cerebral ischaemic stroke injury by increasing BBB leakage via LOX-1

Abstract Background Ischaemic stroke causes the abrupt reduction or cessation of blood flow to the brain results in a cascade of events that can compromise blood-brain barrier (BBB) integrity. We revealed that an increase in apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (AC3RL) is associated with endothelial cell apoptosis and inflammatory responses, indicating that AC3RL is one of the risk factors for cardiovascular events. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) triggers a cascade of events within endothelial cells that leads to endothelial dysfunction. Purpose We aimed to investigate whether AC3RL affects BBB permeability via the LOX-1, and thus increases brain damage. Methods We collected the whole blood from normal and patients with ischaemic events and separated them by centrifugation. AC3RL were collected using FPLC. We performed middle cerebral artery occlusion (MCAO) surgery to induce ischaemic stroke using B6 (C57BL/6) and LOX-1-/- mice injected with AC3RL. Triphenyl tetrazolium chloride (TTC) and Evans blue stains were accessed to confirm brain injury and BBB permeability. Results FPLC results showed that patients with ischaemic events presented higher levels of AC3RL compared to normal people. TTC stain showed the increased area of ischaemic penumbra damage in B6 mice with AC3RL injection, and LOX-1-/- mice with AC3RL injection were significantly protected. Evans blue dye leakage was observed in the brain tissues of B6 mice with AC3RL injection. LOX-1-/- mice with AC3RL injection revealed a decrease in BBB permeability. The modified neurological severity score (mNSS) method revealed a significant rise in B6 mice with AC3RL injection, which suggested a decline in motor and nervous function. LOX-1-/- mice with AC3RL injection significantly improved in motor and neurological functioning. Conclusions We demonstrate that AC3RL, through its effects on LOX-1, is associated with an increased risk of BBB damage after stroke. Therefore, pharmacological inhibition of AC3RL-LOX-1 interaction will be the main strategy to reduce severe brain damage. Figure 1: (A) AC3RL percentage (%) in individuals. Normal: healthy people, Ischemic event: patients who have experienced an ischemic event. **p < 0.001 vs. Normal group. (B, C) TTC stain of brain tissue after euthanasia to pinpoint the site of brain damage. The white portion of the mice brains indicated the site of the injury. (D, E) Evans blue dye leakage study in mice brains exhibited BBB permeability changes. (F) Assessment of mice's motor and neurological performance using the mNSS. Data are expressed as the mean ± SEM. **p < 0.001, ****p < 0.0001 vs. sham group, ##p < 0.001 vs. B6 I.V. AC3RL group.Graphical abstractFigure 1.

Refractive and ocular motor status in autistic adults without learning disabilities: an exploratory study

ABSTRACT Clinical relevance Refractive and ocular motor anomalies may be more prevalent among autistic adults without learning disabilities, compared to a non-autistic clinical population. In line with current guidance, optometrists should exclude these anomalies prior to prescribing tinted lenses. Background Autistic adults report various visual experiences with largely negative consequences on daily living. Some of these overlap with symptoms of refractive and ocular motor anomalies. Therefore, this study investigated refractive and ocular motor status, and pattern glare, in autistic adults without learning disabilities. The impact of appropriate treatment on visual experiences was explored. Methods Twenty four autistic adults, aged 19–67 years, underwent an eye examination involving refraction, ocular motor and pattern glare assessments. Based on pre-determined criteria, anomalies were treated with spectacles, orthoptic exercises, or tinted lenses. Participants completed three questionnaires (Glasgow Sensory Questionnaire, Visual Function Index and Convergence Insufficiency Symptoms Survey) at the start and end of the study to assess the impact of treatment. Results Relative to population norms, a notable proportion of participants had: a significant change in refractive correction (83.3%); accommodative infacility (72.7%); convergence insufficiency (37.5%); uncompensated distance dissociated heterophoria (33.3%); significant accommodative inaccuracy (27.2%); and positive pattern glare (25%). All participants required treatment. 16.7% were given orthoptic exercises only. New spectacles were dispensed to 79.2%, followed by 16.7% requiring orthoptic exercises and 4.2% dispensed tinted lenses. Questionnaire scores did not significantly change post-treatment. Conclusion This exploratory study suggests autistic adults may be more likely to present with refractive, ocular motor and pattern glare issues. Impacts on autistic visual sensory experiences, vision-related quality of life and visual function remain unclear. Pattern Glare Test scores of autistic adults appear to be reduced by appropriate refractive and/or ocular motor management. Therefore, optometrists should take a conservative approach, managing refraction and ocular motor status of autistic patients prior to considering tinted lenses.

Impact of Bell's palsy in facial emotion recognition: a prospective observational study of 60 patients.

Patients with Bell's palsy suffer from functional deficits and cannot convey their emotions through the face as well as they used to. According to embodied cognition, automatic mimicry and facial feedback modulate emotion perception. The aim of our study was to determine the impact of Bell's palsy on facial emotion perception. Facial motor skills, the use of botulinum toxin injections, and anxiety were studied. 60 patients completed Emotest-VA, an assessment tool of facial emotion perception, facial motor assessment and affective questionnaires. Facial perception scores of patients were compared to the normative data provided by Emotest-VA. Relationships between facial motor skills, anxiety and perceptual abilities were carried out with Pearson's correlations. Perception accuracy scores were abnormal in 12% of patients. Patients were more ambiguous than normative population to perceive emotion (t(23) = 4.14, p < .001). Happiness arousal was negatively correlated to smile asymmetry (n = 60, r=-.294 p = .022). Patients who received botulinum toxin were more accurate to perceive disgust (Z = 3.60, p < .001). State anxiety decreased when patients could improve their horizontal smile (r = - 440, p < .001). Bell's palsy impaired sensorimotor simulation, thereby reducing emotional contagion. Smile measures could indicate patients' recovery and patients' anxiety. It could also predict patient's perceptual abilities. These results provide new directions in the management of Bell's palsy. Additionally to physical therapy, it is relevant to improve emotional contagion both in its productive and perceptive aspects through facial feedback.

Commercial devices for monitoring symptoms in Parkinson's disease: benefits, limitations and trends

Parkinson's disease (PD) is a neurodegenerative disorder that significantly affects patients' quality of life. Treatment of PD requires accurate assessment of motor and non-motor symptoms, which is often complicated by subjectivity in reporting symptoms, and the limited availability of neurologists. Commercial wearable devices, which monitor PD symptoms continuously and outside the clinical setting, have appeared to address these challenges. These devices include PKG™, Kinesia 360™, Kinesia U™, PDMonitor™ and STAT-ON™. These devices use advanced technologies, including accelerometers, gyroscopes and specific algorithms to provide objective data on motor symptoms, such as tremor, dyskinesia and bradykinesia. Despite their potential, the adoption of these devices has been limited, due to concerns about their accuracy, complexity of use and the lack of independent validation. The correlation between the measurements obtained from these devices and traditional clinical observations varies, and their usability and patient adherence are critical areas for improvement. Validation and usability studies with a sufficient number of patients, standardised protocols and integration with hospitals' IT systems are essential to optimise their usefulness and improve patient outcomes.

LOCATE-SM PROTOCOL: LOCATION ORIENTED CORTICAL AND SUB-CORTICAL ASSESSMENT FOR THERAPEUTIC EVALUATION- SENSORY-MOTOR TESTING IN AWAKE CRANIOTOMY

Abstract AIMS Awake craniotomy is a well-established surgical procedure to debulk intracranial tumours in eloquent areas (‘functional hubs’). Intraoperative mapping facilitates maximal safe debulking. Review of current sensory motor assessment tools highlighted the absence of a comprehensive ‘location to function’ protocol. We aimed to develop a new protocol that enables ‘location to function’ sensory-motor task selection in preparation for, and during, awake craniotomy. METHOD A literature review demonstrated multiple different intraoperative strategies exist for the preservation of sensory-motor function in awake craniotomy. Incorporating these with functional neuroanatomy, and consensus agreement in the Tessa Jowell Academy Physiotherapy Awake Craniotomy Working Group and the National Brain Mapping MDT, led to the development of testing strategies aligned with ‘location to function’ task selection. Testing strategies were peer-reviewed by three specialist Neuro-Oncology physiotherapists. RESULTS A protocol (LOCATE-SM) has been developed at Leeds to identify critical cortical and subcortical sensory-motor functions that are aligned with anatomo-functional models. Physiotherapists have used this to select individualised pre-, intra- and postoperative tests depending on tumour location and sensory-motor impairment. Additionally, this facilitates intraoperative mapping of eloquent functional regions that are variably located. Cases using LOCATE-SM are presented. CONCLUSION LOCATE-SM is a new awake sensory-motor testing protocol developed by specialised Neuro-Oncology physiotherapists at a Tessa Jowell Centre of Excellence (Leeds). Current cases demonstrate that it leads to greater consistency between physiotherapists and specificity in ‘location to function’ sensory-motor task selection. Future work will systematically analyse the outcomes (onco-functional balance) of using this protocol, and validation in other centres.

Effectiveness of Mirror Therapy, Electrical Stimulation, and CIMT in Restoring Upper Extremity Function after Stroke

Objective: This study aimed to compare the effectiveness of mirror therapy (MT), electrical stimulation (EMS) combined with MT, and Constraint-Induced Movement Therapy (CIMT) in improving upper extremity function among stroke survivors. Methodology: A randomized controlled trial was conducted involving n=45 stroke patients undergoing rehabilitation at Wah International Hospital. The inclusion criteria for the study required participants to be above 45 years of age, to have survived either an ischemic or haemorrhagic stroke, and to have at least 10° wrist extension. Participants were excluded if they had an implanted electrical device such as an artificial pacemaker, paresis instead of paralysis, hemiplegia due to causes other than ischemic or haemorrhagic stroke (such as trauma, tumor, or coordination problems), or impaired sensory integration. Participants were divided into three groups: EMS combined with MT, CIMT alone, and Mirror therapy alone. Treatment sessions were administered four times a week for three months. Outcome measures included the Fugl-Meyer Assessment Scale (FMA) and Motor Assessment Scale (MAS). Results: Analysis revealed significant improvements in upper extremity function across all groups. However, the CIMT group exhibited the most substantial enhancement, with a mean difference of -68.5 (p &lt; 0.05) on the FMA and -24.1 (p &lt; 0.05) on the MAS compared to the other groups. Conclusion: The findings highlight the superior efficacy of CIMT in improving upper extremity function among stroke survivors. Incorporating CIMT into rehabilitation protocols is crucial for optimizing outcomes in this patient population. Further research is warranted to explore the long-term benefits and optimal implementation strategies of CIMT in diverse rehabilitation settings

Cognition Assessment in Virtual Reality (CAVIR): Associations with neuropsychological performance and activities of daily living in patients with mood or psychosis spectrum disorders

BackgroundMore ecologically valid tools are needed to better capture daily-life cognitive impairments in patients with mood or psychosis spectrum disorders in clinical settings and cognitive treatment trials. We developed the Cognition Assessment in Virtual Reality (CAVIR) test, which assesses daily-life cognitive skills in an immersive virtual reality kitchen scenario. This study investigated the validity and sensitivity of CAVIR, including its association with activities of daily living (ADL) ability. Methods70 symptomatically stable patients with mood or psychosis spectrum disorders and 70 healthy controls completed CAVIR and standard neuropsychological tests and were rated for clinical symptoms, functional capacity, and subjective cognition. In addition, patients' ADL ability was evaluated with the Assessment of Motor and Process Skills (AMPS). ResultsHigher global CAVIR performance correlated moderately with better global neuropsychological test scores (rs(138) = 0.60, p < 0.001) and showed a weak to moderate association with better ADL process ability in patients (r(45) = 0.40, p < 0.01), also after adjusting for sex and age (ps ≤ 0.03). In comparison, neuropsychological performance, interviewer- and performance-based functional capacity, and subjective cognition were not significantly associated with ADL process ability (ps ≥ 0.09). Further, CAVIR was sensitive to cognitive impairments in patients and was able to differentiate between patients with and without the ability to undertake regular employment. LimitationsThe modest sample size and concomitant medication. ConclusionOur results indicate that CAVIR is a sensitive measure of daily-life cognitive skills in patients with mood or psychosis spectrum disorders.

An acceptability and feasibility investigation of a community-based motor program for autistic children with moderate and high support needs

BackgroundGeneral motor impairments are ubiquitous in Autism and are positively correlated with autism symptom severity. This study assessed the feasibility and acceptability of a 13-week community-based motor program for autistic children with moderate and high support needs (MHS). MethodIn this exploratory single arm within-subject study, 10 autistic children with MHS, ages 4–10 years, completed a community-based motor program delivered in a one-on-one format by therapists. Feasibility was determined through recruitment, retention, attendance, enjoyment, engagement and useability of motor, physical activity (PA), and behavioural assessment tools. Thematic analysis evaluated post-intervention semi-structured parent interviews. ResultsHigh program attendance and retention were demonstrated, and therapists reported child engagement and enjoyment were high. Identified themes revealed parents perceived unexpected substantial positive impacts including improvements in social, motor, and behavioural outcomes. They highly valued both the program and the therapeutic relationships fostered within it. Although parents of the children with the higher support needs reported the most substantial improvements, these children were unable to score on motor assessments due to difficulties following instructions and off-task behaviours. Additionally, only four participants wore an accelerometer-based PA monitor. ConclusionsThis community-based motor program was considered feasible and acceptable by the children’s parents, and qualitative findings provided valuable insights into clinical practice for children with MHS. However, recruitment challenges and assessment tools being unfeasible for children with higher support needs led to low participant numbers. Future evaluations should explore alternative assessment measures and study designs, given the challenges associated with studying such a heterogenous and complex group.

Oral Feeding Readiness Assessment Tools for Preterm Infants

Due to their underdeveloped physiological maturity, preterm infants often face challenges related to sucking, breathing, and swallowing coordination during initial feeding. This lack of coordination may lead to episodes of apnea and choking, resulting in unstable vital signs. Preterm infants with this issue must gradually learn oral feeding skills appropriate to their developmental stage. Registered nurses play a critical role in assessing the right time to transition from tube to oral feeding and in providing a safe and positive oral feeding experience. In this article, three validated assessment tools for feeding premature infants are introduced, accompanied by clinical research data demonstrating their use in clinical practice. These three tools include: (1) the Neonatal Oral Motor Assessment Scale, which is applied to evaluate oral motor skills using observations of nonnutritive sucking and the sucking state during the two minutes before feeding; (2) the Premature Oral Feeding Readiness Assessment Scale, which is used to assess readiness for oral feeding in preterm infants; and (3) the Early Feeding Skills assessment, which is used to evaluate the oral feeding skills of preterm infants. These tools aid nurses in helping preterm infants achieve independent oral feeding, facilitating earlier discharge and return to home. The clinical implications and effectiveness of these tools are also discussed to provide to nurses the means and confidence necessary to apply them appropriately in clinical settings.

Quality Of Care In Parkinson's Disease: Lessons From A National Audit

Abstract Background It is recommended that people with Parkinson’s disease (PD) are treated within specialised services. As part of a research project mapping and evaluating PD services nationally, the first audit of PD services in the Republic of Ireland was conducted. Methods A de novo audit tool was developed by an expert group, based on a rigorous review of existing international standards, guidelines and audit tools, with extensive stakeholder input (including people with PD). All 14 specialist PD services in the Republic of Ireland were eligible; up to 30 case-notes were randomly selected per service in 2022/2023, looking at the most recent 2 visits (new patient) or 3 visits (established patient). Results In total, 261 case-notes were included, from 11 specialist PD services, led by a geriatrician (n=5) or neurologist (n=6). Overall, 16.8% of patients were seen less often than annually. Motor and mobility assessments were well performed (&amp;gt;75%); but cognition (70%) and pain assessments (64%), saliva management (50%), and bone density determination (18%) were inadequate. Access to PD nurses (65%), physiotherapy (69%), speech and language therapy (53%), and occupational therapy (50%) was inadequate; PD nurses were mainly in Dublin. However, specialist nurse and MDT access was better than reported by people attending generic services for PD care (1). Providing written information following diagnosis (24%), and communication with the carer were infrequently documented (financial support discussion: 12%; availability of support locally: 26%). Gerontology-led services more often screened for malnutrition (99% v 78%) or orthostatic hypotension (94% v 52%). Conclusion PD care relating to assessment, multidisciplinary involvement, and information sharing was sub-optimal in some areas, with the caveat that documentation may not reflect actual practice. Reference 1. O’Shea E, et al. Experiences of Health Service Access and Use for People Living with Parkinson’s Disease in Ireland: A National Survey. Health &amp; Social Care in the Community. 2023 Aug 9;2023.

Analysis of oral sensory-motor function characteristics and influencing factors in children with functional dysarthria and their typically developing peers

The aim was to explore and analyze of oral sensory-motor function characteristics and influencing factors in children with functional dysarthria and their typically developing peers. Sixty children with functional dysarthria (the age range was 4.0 to 5.9 years old, with an average age of (4.29 ± 0.92) years, and 60 children with normal physical examination (the age range was 4.0 to 5.6 years old, with an average age of (4.11 ± 0.88) years were recruited. The Oral Motor Assessment Scale was used to collect data. The results of this study show that the total oral sensory-motor function scores of normal children gradually increase with age. Oral sensory scores for each age group are all 1.00, with no age or gender differences, indicating that normal children’s oral sensory functions have matured when they are four years old. Results indicate that there is a certain relationship between allergies and functional dysarthria. As shown, it can be concluded that allergy in children is an influencing factor in the onset of functional dysarthria.

Predictive utility of self-efficacy in early stroke rehabilitation

ABSTRACT Introduction A biopsychosocial approach entailing person-centered factors provides valuable insight to post-stroke rehabilitation potential. The consideration of an individual’s belief in their capabilities, known as self-efficacy, may prove especially informative in the inpatient rehabilitation setting where motor learning often occurs. Objective To assess the predictive utility of self-efficacy in functional independence status change during inpatient rehabilitation. Methods Individuals with stroke admitted to an inpatient rehabilitation facility (IRF) completed an assessment battery near IRF admission and discharge involving motor assessments, participant-reported self-efficacy (Stroke Self-Efficacy Questionnaire), and functional independence status evaluation (sum of self-care and mobility Quality Indicators (QI) from the IRF-Patient Assessment Instrument). Linear regression was performed to determine the predictive performance of self-efficacy on QI change during IRF stay while accounting for age, time post-stroke, and IRF length of stay. Regression procedures were repeated for separate subgroups based on initial motor impairment level. Results Thirty individuals with stroke (14 females, age = 67.0 ± 9.80 years, 10.4 ± 3.46 days post-stroke) were enrolled. Self-efficacy at IRF admission explained a significant percentage of variance in QI Change for the cohort (R2 = 30.7%, p = .001) and for the moderate to severe motor impairment subgroup (n = 12; R2 = 49.9%, p = .010). After accounting for confounders, self-efficacy remained a significant predictor for the cohort (n = 30) model. Discussion Findings generated from this work support the predictive utility of self-efficacy in early post-stroke motor recovery. The inclusion of self-efficacy in a multi-faceted evaluation framework may therefore optimize rehabilitation outcomes by providing therapists with additional knowledge to better tailor an individual’s care.

Psychiatric predictors of quality of life in Parkinson's disease: A three-year longitudinal study

IntroductionParkinson's disease (PD) is associated with worsened quality of life (QOL) over time. Few longitudinal studies exist investigating the relationship of psychiatric comorbidities with QOL in people with PD (PwP). We sought to determine specific psychiatric symptoms associated with decreasing QOL in PwP over time. MethodsWe recruited PwP without dementia from a movement disorders clinic at an academic medical center. Participants were evaluated annually with motor and neuropsychological assessments at each visit. QOL was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). We assessed psychiatric symptoms, including depression (Beck Depression Inventory II, BDI-II), anxiety (Beck Anxiety Index, BAI), and apathy (Apathy Scale). Psychosis and impulse control disorders (ICDs) were recorded as present or absent. Using random coefficient regression, we analyzed psychiatric features associated with worsened QOL in PwP over three years. ResultsFrom the 105 participants enrolled at baseline, 67 completed three years of follow up. Mean PDQ-39 scores increased from 16.0 at baseline to 19.8 at year three. In multivariate analysis, higher BDI-II scores, BAI scores, and apathy scores were uniquely associated with worsened QOL over time (p < 0.001 for all measures), while presence of ICDs (p = 0.18) or psychosis (p = 0.10) were not. Changes in the BAI score and the BDI-II score exerted similar effects on the overall PDQ-39 score. ConclusionDepression, anxiety, and apathy are all associated with worsening quality of life over time in PwP, while presence of ICDs and psychosis are not. Treatment of these symptoms may lead to improved QOL in PwP.

Sensory Stimulation and Robot-Assisted Arm Training After Stroke: A Randomized Controlled Trial.

Functional recovery after stroke is often limited, despite various treatment methods such as robot-assisted therapy. Repetitive sensory stimulation (RSS) might be a promising add-on therapy that is thought to directly drive plasticity processes. First positive effects on sensorimotor function have been shown. However, clinical studies are scarce, and the effect of RSS combined with robot-assisted training has not been evaluated yet. Therefore, our objective was to investigate the feasibility and sensorimotor effects of RSS (compared to a control group receiving sham stimulation) followed by robot-assisted arm therapy. Forty participants in the subacute phase (4.4-23.9weeks) after stroke with a moderate to severe arm paresis were randomized to RSS or control group. Participants received 12 sessions of (sham-) stimulation within 3weeks. Stimulation of the fingertips and the robot-assisted therapy were each applied in 45-min sessions. Motor and sensory outcome assessments (e.g. Fugl-Meyer-Assessment, grip strength) were measured at baseline, post intervention and at a 3-week follow-up. Participants in both groups improved their sensorimotor function from baseline to post and follow-up measurements, as illustrated by most motor and sensory outcome assessments. However, no significant group effects were found for any measures at any time ( P >0.058). Stimulations were well accepted, no safety issues arose. Feasibility of robot-assisted therapy with preceding RSS in persons with moderate to severe paresis was demonstrated. However, RSS preceding robot-assisted training failed to show a preliminary effect compared to the control intervention. Participants might have been too severely affected to identify changes driven by the RSS, or these might have been diluted or more difficult to identify because of the additional robotic training and neurorehabilitation. for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A478 ).

Diagnostic accuracy of Ages and Stages Questionnaire, Third Edition to identify abnormal or delayed gross motor development in high-risk infants.

To investigate the diagnostic accuracy of parent-completed Ages and Stages Questionnaire, Third Edition (ASQ-3) to identify abnormal or delayed gross motor development in infants born less than 1000 g or less than 28 weeks gestation. Prospective cohort study of high-risk infants comparing ASQ-3 as the index test with concurrent score on Alberta Infant Motor Scale (AIMS) as the reference standard, at 4-, 8- and 12-month corrected (post-term) age. Reference standard positivity cut-offs were 'Abnormal motor development' (AIMS Clinical Range) and 'Motor delay' (AIMS score >1 SD below mean, not captured in Clinical Range). Participating infants (n = 191) had mean gestational age (95% confidence interval (CI)) 26.8 weeks (26.6-27.1) and mean birthweight (95% CI) 870 g (844-896). AIMS rated 51%, 31% and 23% of infants as having 'Abnormal motor development' and 12%, 28% and 13% with 'Motor delay', at 4, 8 and 12 months, respectively. Diagnostic accuracy of ASQ-3 to identify abnormal motor development was acceptable for older infants only if 'Monitor' cut-off was used: sensitivity (95% CI) 33% (23-44), 86% (73-95) and 80% (63-92) and specificity (95% CI) 84% (74-92), 76% (66-84), and 76% (67-83) at 4, 8 and 12 months, respectively. ASQ-3 sensitivity to identify motor delay was low. ASQ-3 has poor sensitivity to identify abnormal or delayed motor development at 4 months. Using the 'Monitor' cut-off improves the diagnostic accuracy of ASQ-3 for identification of older infants with abnormal motor development who are at high risk of motor disability. However, ASQ-3 has poor sensitivity to identify motor delay. Clinical motor assessment of high-risk infants is recommended, particularly in early infancy.

Longitudinal Changes of Clinical, Imaging, and Fluid Biomarkers in Preataxic and Early Ataxic Spinocerebellar Ataxia Type 2 and 7 Carriers.

Brain MRI abnormalities and increases in neurofilament light chain (NfL) have mostly been observed in cross-sectional studies before ataxia onset in polyglutamine spinocerebellar ataxias. Our study aimed to identify longitudinal changes in biological, clinical, and/or imaging biomarkers in spinocerebellar ataxia (SCA) 2 and SCA7 carriers over 1 year. We studied SCA2 and SCA7 carriers and controls (expansion-negative relatives) at the Paris Brain Institute. Inclusion criteria included Scale for the Assessment and Rating of Ataxia (SARA) scores between 0 and 15. Assessments at baseline, 6 months, and 12 months comprised neurologic, quality of life, orofacial motor, neuropsychological, and ophthalmologic examinations, along with gait and oculomotor recordings, brain MRI, CSF, and blood sampling. The primary outcome was the longitudinal change in these assessments over 1 year. We included 15 SCA2 carriers, 15 SCA7 carriers, and 10 controls between May 2020 and April 2021. At baseline, the ages were similar (41 [37, 46] for SCA2, 38 [28.5, 39.8] for SCA7, and 39.5 [31, 54.5] for controls, p = 0.78), as well the sex (p = 0.61); SARA scores were low but different (4 [1.25, 6.5] in SCA2, 2 [0, 11.5] in SCA7, and 0 in controls, p < 0.01). Pons and medulla volumes were smaller in SCAs (p < 0.05) and cerebellum volume only in SCA2 (p = 0.01). Plasma NfL levels were higher in SCA participants (SCA2: 14.2 pg/mL [11.52, 15.89], SCA7: 15.53 [13.27, 23.23]) than in controls (4.88 [3.56, 6.17], p < 0.001). After 1-year follow-up, in SCA2, there was significant pons (-144 ± 60 mm3) and cerebellum (-1,508 ± 580 mm3) volume loss and a worsening of gait assessment; in SCA7, SARA score significantly increased (+1.3 ± 0.4) and outer retinal nuclear layer thickness decreased (-15.4 ± 1.6 μm); for both SCA groups, the orofacial motor assessment significantly worsened. For preataxic and early ataxic carriers, the strongest longitudinal deterioration on outcome measures was orofacial motility in SCA2 and retinal thickness in SCA7. Despite the limitation of the small sample size, we detected annual changes in preataxic and early ataxic SCA individuals across brain MRI imaging, clinical scores, gait parameters, and retinal thickness. These parameters could serve as potential end points for future therapeutic trials in the preataxic phase. ClinicalTrials.gov NCT04288128.

A Multicenter Cross-Sectional Study of the Swiss Cohort of LAMA2-Related Muscular Dystrophy.

LAMA2-related muscular dystrophy (LAMA2-RD) is an autosomal-recessive disorder and one of the most common congenital muscular dystrophies. Due to promising therapies in preclinical development, there is an increasing effort to better define the epidemiology and natural history of this disease. The present study aimed to describe a well-characterized baseline cohort of patients with LAMA2-RD in Switzerland. The study used data collected by the Swiss Registry for Neuromuscular Disorders (Swiss-Reg-NMD). Diagnostic findings were derived from genetics, muscle biopsy, creatine kinase-level and electrophysiological testing, as well as from brain MRIs. Further clinical information included motor assessments (CHOP INTEND, MFM20/32), joint contractures, scoliosis, ophthalmoplegia, weight gain, feeding difficulties, respiratory function, cardiac investigations, EEG findings, IQ and schooling. Eighteen patients with LAMA-RD were included in the Swiss-Reg-NMD as of May 2023 (age at inclusion into the registry: median age 8.7 years, range 1 month - 31 years F = 8, M = 10). Fourteen patients presented with the severe form of LAMA2-RD (were never able to walk; CMD), whereas four patients presented with the milder form (present or lost walking capability; LGMD). All patients classified as CMD had symptoms before 12 months of age and 11/14 before the age of six months. 15 carried homozygous or compound heterozygous pathogenic or likely pathogenic variants in LAMA2 and two were homozygous for a variant of unknown significance (one patient unknown). Brain MRI was available for 14 patients, 13 had white matter changes and 11 had additional structural abnormalities, including cobblestone malformations, pontine hypoplasia and an enlarged tegmento-vermial angle not reported before. This study describes the Swiss cohort of patients with LAMA2-RD and gives insights into measuring disease severity and disease progression, which is important for future clinical trials, as well as for a better clinical understanding and management of patients with LAMA2-RD.

Testing a Motor Score Based on PANSS Ratings: A Proxy for Comprehensive Motor Assessment.

Abnormal psychomotor behavior is a core schizophrenia symptom. However, assessment of motor abnormalities with expert rating scales is challenging. The Positive and Negative Syndrome Scale (PANSS) includes 3 items broadly related to hypokinetic motor behavior. Here, we tested whether a sum score of the PANSS items mannerisms and posturing (G5), motor retardation (G7), and disturbance of volition (G13) corresponds to expert ratings, potentially qualifying as a proxy-marker of motor abnormalities. Combining baseline datasets (n = 196) of 2 clinical trials (OCoPS-P, BrAGG-SoS), we correlated PANSS motor score (PANSSmot) and 5 motor rating scales. In addition, we tested whether the cutoff set at ≥3 on each PANSS motor item, ie, "mild" on G05, G07, and G13 (in total ≥9 on PANSSmot) would differentiate the patients into groups with high vs low scores in motor scales. We further sought for replication in an independent trial (RESIS, n = 102), tested the longitudinal stability using week 3 data of OCoPS-P (n = 75), and evaluated the validity of PANSSmot with instrumental measures of physical activity (n = 113). PANSSmot correlated with all motor scales (Spearman-Rho-range 0.19-0.52, all P ≤ .007). Furthermore, the cutoff set at ≥3 on each PANSS motor item was able to distinguish patients with high vs low motor scores in all motor scales except using Abnormal Involuntary Movement Scale (Mann-Whitney-U-Tests: all U ≥ 580, P ≤ .017). Our findings suggest that PANSSmot could be a proxy measure for hypokinetic motor abnormalities. This might help to combine large datasets from clinical trials to explore whether some interventions may hold promise to alleviate hypokinetic motor abnormalities in psychosis.

Reliability and Validity of the Turkish Version of the Gross Motor Function Measurement (GMFM-88&66) in Children with Cerebral Palsy.

The gross motor function measurement is considered as the gold standard for the motor assessment of children with cerebral palsy. The aim was to carry out the cross-cultural adaptation and investigate psychometric properties. A total of 150 children with cerebral palsy aged 2-16 (mean 8.82 ± 3.78 years; 54.7% male) included. The Gross Motor Function Measurement was adapted into Turkish. Two physiotherapies independently administered the gross motor function measurement. Internal consistency and intra/inter-rater reliability were assessed using Cronbach's alpha, intraclass-correlation-coefficient. Standard-error-of-measurement, minimal-detectible-change calculated. The Bland-Altman method was applied to estimate the measurement bias in reliability analysis. Construct validity assessed with Spearman's correlation coefficient between the gross motor function measurement and the gross motor function classification system, pediatric-evaluation-of-disability-inventory-mobility; confirmatory-factor-analysis was carried. Internal-consistency (α: 0.997-1.00); reliability indices were excellent for total scale (intraclass-correlation-coefficient for intra-rater reliability 0.994-0.999, inter-rater reliability 0.997-0.999) and for each sub-dimension and total score. Standard-error-of-measurement was ranging 1.044-1.677, minimal-detectible-change was 2.435-5.520. Construct validity was supported by strong to excellent negative significant correlations (p < 0.05).

Adaptation and development of the instruction manual for a videoconference-based Motor Assessment Scale: validity, reliability and measurement error of Tele-MAS

Purpose To develop an instruction manual to administer the Motor Assessment Scale (MAS) via videoconferencing (Tele-MAS), investigate its validity, reliability and measurement error. Materials and methods In-person assessment, conducted at the participant’s home, was compared to remote assessment conducted by rater A. Then, within two days, the rater B, repeat the remote assessment (n = 41). Part of the sample (n = 10) was assessed again within seven days by rater A to determine test-retest reliability. Concurrent validity, agreement of alternate forms (in-person x remote) for total score and reliability of individual items were analyzed using respectively the Pearson correlation coefficient, Bland-Altman plots and weighted Kappa (Kw). Interrater and test-retest reliability were analyzed by Intraclass Correlation Coefficient (ICC). Standard Error of Measurement (SEM) and Minimal detectable changes (MDC) were computed. Results The Tele-MAS instruction manual was developed. In-person MAS and Tele-MAS present a high positive correlation (r = 0.97). Bland-Altman plots showed adequate agreement (MD=-0.0 point). Most Individual items showed excellent reliability (Kw > 0.70). Tele-MAS showed excellent interrater (ICC(2,1)=0.92) and test-retest (ICC(3,1)=0.98) reliability. Tele-MAS presents a SEM = 3% and MDC = 8%. Conclusion The Tele-MAS is a valid and reliable global motor assessment scale to be applied in individuals after stroke.