The relationship between corticospinal excitability and structural integrity in stroke patients.

BACKGROUND: Evaluation of the structural integrity and functional excitability of the corticospinal tract (CST) is likely to be important in predicting motor recovery after stroke. Previous reports are inconsistent regarding a possible link between CST structure and CST function in this setting. This study aims to investigate the structure‒function relationship of the CST at the acute phase of stroke (<7 days). METHODS: We enrolled 70 patients who had an acute ischaemic stroke with unilateral upper extremity (UE) weakness. They underwent a multimodal assessment including clinical severity (UE Fugl Meyer at day 7 and 3 months), MRI to evaluate the CST lesion load and transcranial magnetic stimulation to measure the maximum amplitude of motor evoked potential (MEP). RESULTS: A cross-sectional lesion load above 87% predicted the absence of MEPs with an accuracy of 80.4%. In MEP-positive patients, the CST structure/function relationship was bimodal with a switch from a linear relationship (rho=-0.600, 95% CI -0.873; -0.039, p<0.03) for small MEP amplitudes (<0.703 mV) to a non-linear relationship for higher MEP amplitudes (p=0.72). In MEP-positive patients, recovery correlated with initial severity. In patients with a positive MEP <0.703 mV but not in patients with an MEP ≥0.703 mV, MEP amplitude was an additional independent predictor of recovery. In MEP-negative patients, we failed to identify any factor predicting recovery. CONCLUSION: This large multimodal study on the structure/function of the CST and stroke recovery proposes a paradigm change for the MEP-positive patients phenotypes and refines the nature of the link between structural integrity and neurophysiological function, with implications for study design and prognostic information.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT04288128.

Prediction of Upper Limb Motor Recovery by the PREP2 Algorithm in a Nonselected Population: External Validation and Influence of Cognitive Syndromes.

BACKGROUND: Early prediction of poststroke motor recovery is challenging in clinical settings. The Prediction recovery potential (PREP2) algorithm is the most accurate approach for prediction of Upper Limb function available to date but lacks external validation. OBJECTIVES: (i) To externally validate the PREP2 algorithm in a prospective cohort, (ii) to study the characteristics of patients misclassified by the algorithm, and (iii) to compare the performance according to the presence of cognitive syndromes (aphasia, neglect, cognitive disorders). METHODS: We enrolled 143 patients with stroke and upper extremity weakness persistent at Day 3. Evaluation to predict the recovery status according to the PREP2 algorithm included age, SAFE and NIHSS scores at Day 3 and transcranial magnetic stimulation to determine the presence of the motor-evoked potential before day seven. Actual recovery (excellent, good, limited, or poor) was defined based on the Action Research Arm test score at 3 months. Accuracy was computed by comparing the predictions of the PREP2 and the actual category of the patient. Additionally, to investigate misclassifications and the impact of cognitive syndromes, we recorded SAFE and NIHSS scores at Day 7, the Montreal Cognitive Assessment (MoCA) score, the presence of aphasia and neglect and Magnetic Resonance Imaging was used to evaluate the corticospinal tract lesion load. RESULTS: The PREP2 algorithm showed a very good predictive value with 78% accuracy [95% CI: 71.2%-86.1%], especially for the extreme categories of recovery (EXCELLENT 87.5% [95% CI: 78.9%-96.2%] and POOR 94.9% [95% CI: 87.9%-100%]), and only 46.5% [95% CI: 19.05%-73.25%] for the GOOD category and even worse than chance for the LIMITED category 0%. Pessimistic predictions (false-negative cases) had a drastic improvement in the SAFE score acutely compared to that of well-predicted patients with unfavorable recovery (P < 001). The predictive value of PREP2 decreased significantly when patients had cognitive disorders (MoCA score <24) versus not (69.4% [95% CI: 52.8%-86.1%] vs 93.1% [95% CI: 83.9%-100%], P = .01). CONCLUSION: Our study provides an external validation of the PREP2 algorithm in a prospective population and underlines the importance of taking into account cognitive syndromes in motor recovery prediction.

Digital Gait Measures Capture 1-Year Progression in Early-Stage Spinocerebellar Ataxia Type 2.

BACKGROUND: With disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. OBJECTIVE: Our aim is to unravel gait measures sensitive to longitudinal change in the-particularly trial-relevant-early stage of spinocerebellar ataxia type 2 (SCA2). METHODS: We performed a multicenter longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n = 23, including nine pre-ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focused on gait measures of spatio-temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). RESULTS: We found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation P = 0.0001, effect size rprb = 0.78), whereas the SARA score showed no change (P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test-retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1-year change. CONCLUSIONS: Gait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just 1 year-in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association between superior longitudinal fasciculus, motor recovery, and motor outcome after stroke: a cohort study.

Introduction: Parieto-frontal interactions are mediated by the superior longitudinal fasciculus (SLF) and are crucial to integrate visuomotor information and mediate fine motor control. In this study, we aimed to characterize the relation of white matter integrity of both parts of the SLF (SLF I and SLF II) to both motor outcome and recovery and its evolution over time in stroke patients with upper limb motor deficits. Materials and methods: Fractional anisotropy (FA) values over the SLF I, SLF II, and corticospinal tract (CST) and upper limb motor performance evaluated by both the upper limb Fugl-Meyer Assessment score and maximum grip strength were measured for 16 patients at 3 weeks, 6 weeks, and 12 weeks poststroke. FA changes were assessed over time using repeated-measures Friedman ANOVA, and correlations between motor recovery, motor outcome at 12 weeks, and FA values in the CST, SLF I, and SLF II at 3 weeks were performed using Spearman's rank-order correlation. Results: FA values in the affected hemisphere's SLF I and SLF II at 3 weeks correlated with motor recovery at 12 weeks when assessed by the Fugl-Meyer Assessment for upper limb extremity (rho: 0.502, p: 0.04 and rho: 0.510, p: 0.04, respectively) but not when assessed by grip strength. FA values in the SLF I and SLF II were not correlated with motor outcomes. FA values in the SLF II in the affected hemisphere changed significantly over time (p: 0.016). Conclusion: Both SLF I and SLF II appeared to participate in poststroke motor recovery of complex movements but not in the motor outcome. These results argue that visually/spatially oriented motor tasks as well as more complex motor tasks using parietal associative areas should be used for poststroke rehabilitation strategies.

Evaluation of a shortened version of the Action Research Arm Test (ARAT) for upper extremity function after stroke: The Mini-ARAT.

OBJECTIVES: (i) to create a shortened version of the Action Research Arm Test scale, (ii) to investigate its psychometric properties compared to the original scale and (iii) to externally validate it within an independent cohort. DESIGN: Prospective longitudinal cohort study. SETTINGS: Two University Hospitals (France, Switzerland). PARTICIPANTS: 47 patients with poststroke motor deficits of the upper limb coming from two different sites were included and divided into two cohorts (n = 22 for the construction cohort; n = 25 for the validation cohort). MAIN MEASURES: We used the first cohort to build the Mini-ARAT by shortening the Action Research Arm Test scale on the basis of ceiling/floor effects and collinearity of the subscales. We studied its reliability, validity, and responsiveness and performed an external validation with the second cohort. RESULTS: The Mini-ARAT consisted of 2 subscales from the original Action Research Arm Test scale (Grip and Pinch). Internal consistency (α = 87) and inter-rater reliability (0.99, 95% CI: 0.98-0.99, p < 0.01) were good and similar to those of the Action Research Arm Test scale. The Minimal Clinically Important Difference of the Mini-ARAT was 9 points. The predictive validity in the construction and validation cohorts showed good correlation between the Mini-ARAT at baseline and the Fugl Meyer at 3 months (rho, 95% CI: 0.77, 0.49-0.90, p < 0.01, and 0.58, 0.19-0.96, p < 0.01). CONCLUSION: The Mini-ARAT is a time-effective tool able to capture the dynamics of motor deficits with high reliability and consistency, providing excellent information about residual motor functions, which is critically important for clinical and research purposes.