Stroke

Background and Purpose-The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods-A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results-Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (β=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (β=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions-NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery. © 2020 Lippincott Williams and Wilkins. All rights reserved.Translational Research and Advanced Imaging Laborator

Radiology

Background: A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose: To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods: In this secondary analysis, two prospectively collected independent stroke data sets (2012–2015 and 2017–2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1–3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion–related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results: Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58–80 years]; 207 men) and 173 (median age, 74 years [IQR, 65–82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P =.02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P =.004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P =.20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P =.01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P =.03). Conclusion: Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. © RSNA, 2022.Translational Research and Advanced Imaging Laborator

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Association between neurological outcome and poststroke comorbid mood and anxiety disorders: A real‐life experience

Abstract Introduction Poststroke depression (PSD) and anxiety (PSA) are prevalent and have a strong impact on functional outcome. Beside stroke severity, little is known on their clinical determinants. This study investigated the association between stroke mechanism, neurological poststroke complications and remaining vascular risk factors and the presence of comorbid PSD and PSA, termed poststroke emotional distress (PSED). Methods This was a retrospective analysis of a prospectively compiled medical records database of consecutive patients evaluated during a follow‐up visit 3‐ to 4‐month poststroke. HAD scale was used to define PSED category (PSD+PSA vs. NoPSD+NoPSA). Stroke mechanism and poststroke complications were identified clinically or using appropriate scales. Their association with PSED was tested using a multivariate logistic regression model. Results The sample included 2,300 patients (male: 64.8%); 19% had a PSED and 56.39% were free of any depression or anxiety. The most frequent poststroke complications were fatigue/fatigability (58.4%), sleep problems (26.7%), and pain (20.4%). While no association was observed between PSED and stroke mechanism, higher functional disability (OR:1.572), lower cognitive abilities (OR:0.953), sleep problems (OR:2.334), pain (OR:1.478), fatigue/fatigability (OR:2.331), and abnormal movements (OR:2.380) were all independent risk factors. Persisting tobacco consumption (OR:1.360) was the only vascular significant risk factor. Conclusions The frequency of comorbid PSED remains high (1/5 patient) despite improved awareness of these conditions. The association between poststroke complications and the presence of PSED emphasizes the need for standardized neurological and psychological evaluations at follow‐up. These results foster the need to improve the management of addictive behaviors to reduce the burden of PSED

Gait Change Is Associated with Cognitive Outcome after an Acute Ischemic Stroke

Background: Cognition and gait have often been studied separately after stroke whereas it has been suggested that these two domains could interact through a cognitive-motor interference.Objective: To evaluate the influence of gait changes on cognitive outcome after an ischemic stroke (IS).Methods: We conducted a prospective and monocentric study including patients admitted for an acute supratentorial IS with a National Institute of Health Stroke Score ≤ 15. Cognition, gait and motor disability were evaluated at baseline, 3 months and 1 year post-stroke, using the Montreal Cognitive Assessment (MoCA), the 10-m walking test (10-MWT) and the Fugl-Meyer motor assessment (FMMA). The effect of changes in 10-MWT over the year of follow-up on MoCA changes was estimated using a generalized linear mixed model with FMMA, age and gender as covariates.Results: Two hundred and Twelve patients were included (71% male, age 64 ± 13 years old). 10-MWT improved from baseline to 1 year (p < 0.001), as did MoCA (p < 0.001) and FMMA (p < 0.001) scores. Ninety-nine patients (47%) had a MoCA <26 at 1 year. Changes in 10-MWT were independently associated with changes in MoCA (β = −0.2, 95% CI −0.24 to −0.07, Bonferroni-corrected p-value = 0.002). Analyses of MoCA sub-scores suggested that changes in gait performance was associated with changes in executive functions and recall.Conclusion: Gait performance is associated with cognitive outcome after a mild to moderate IS, suggesting that they should be managed together to improve post-stroke independence

Early Fiber Number Ratio Is a Surrogate of Corticospinal Tract Integrity and Predicts Motor Recovery After Stroke

International audienceBackground and purpose: The contribution of imaging metrics to predict post-stroke motor recovery needs to be clarified. We tested the added value of early diffusion tensor imaging (DTI) of the corticospinal-tract (CST) towards predicting long-term motor recovery. Methods: 117 patients were prospectively assessed at 24h-72h and 1 year after ischemic stroke with DTI and motor scores (Fugl-Meyer). The initial and final fiber number ratios (iFNr and fFNr) were computed as the number of streamlines along the affected CST normalized to the unaffected side and were compared to each other. The prediction of motor recovery (ΔFugl-Meyer) was first modeled using initial Fugl-Meyer and iFNr. Multivariate ordinal logistic regression models were also used to study the association of iFNr, initial Fugl- Meyer, age and stroke volume with Fugl-Meyer at 1 year.Results: The iFNr correlated with the fFNr at 1 year (r=0.70, p<0.0001). The initial Fugl- Meyer strongly predicted motor recovery (~73% of initial impairment) for all patients except those with initial severe stroke (Fugl-Meyer<50). For these severe patients (n=26), initial Fugl-Meyer was not correlated to motor recovery (R2=0.13, p=ns), while iFNr showed strong correlation (R2=0.56, p<0.0001). In multivariate analysis the iFNr was an independent predictor of motor outcome (β=2.601, 95%CI=0.304-5.110, p=0.031), improving prediction compared to using only initial Fugl-Meyer, age and stroke volume (p=0.026).Conclusion: Early measurement of FNr at 24h-72h post-stroke is a surrogate marker of CST integrity and provides independent prediction of motor outcome at 1 year especially for patients with severe initial impairment

Cerebrovasc Dis.

Objective: The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). Methods: We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo’s cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. Results: A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (β = −0.16, p = 0.02) and the number of errors to ZCT (β = 0.19, p = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (β = 0.14, p = 0.01) and number of errors (β = 0.17, p = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. Conclusion: The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment

Early multidisciplinary prevention program of post-stroke shoulder pain: A randomized clinical trial

OBJECTIVE: To evaluate if positioning the upper-limb promoting abduction, external rotation and flexion of the shoulder reduces the intensity of post-stroke shoulder pain at day-7 compared to usual clinical practice. DESIGN & SETTING: Prospective single-center randomized clinical trial using a superiority design comparing two preventive strategies of post-stroke shoulder pain in a stroke unit. SUBJECTS: Patients were included within 2 days from a first symptomatic ischemic stroke affecting shoulder motor function. INTERVENTIONS: Intervention group included specific positioning of the shoulder in abduction, external rotation and flexion in bed, chair and during mobilization. Control group referred to usual practice i.e. positioning using a standard support scarf. MAIN MEASURES: Primary outcome was the intensity of shoulder pain assessed by the visual analog scale (VAS) (0-100) at day-7 post-stroke. Other outcomes measured at day-7 and 2 months post-stroke were the VAS, motor function, spasticity, depression, functional independence and rates of complex regional Pain syndrome (CRPS). RESULTS: 76 patients (49 males; mean age = 68.3) were randomized. The shoulder pain at day-7 was not different between the control group (16.1, SD = 27.4) and the intervention group (10.3, SD = 21.5, p = 0.18) as well as at 2 months (p = 0.12). A lower rate of depression was observed in the intervention group at 2 months 36.7% (CI95% 19.9;56.1) vs 52.9% (CI95% 35.1;70.2). No between-group difference in other outcomes was observed at 2 months. CONCLUSIONS: This study failed to demonstrate the benefit of a specific positioning tool in reducing the intensity of post-stroke shoulder pain which was lower than previously reported in the literature