Background Knowledge gaps exist regarding the effect of time elapsed after stroke on the effectiveness of exercise training interventions, offering incomplete guidance to clinicians. Methods and Results To determine the associations between time after stroke and 6‐minute walk distance, 10‐meter walk time, cardiorespiratory fitness and balance (Berg Balance Scale score [BBS]) in exercise training interventions, relevant studies in post‐stroke populations were identified by systematic review. Time after stroke as continuous or dichotomized (≤3 months versus >3 months, and ≤6 months versus >6 months) variables and weighted mean differences in postintervention outcomes were examined in meta‐regression analyses adjusted for study baseline mean values (pre‐post comparisons) or baseline mean values and baseline control‐intervention differences (controlled comparisons). Secondary models were adjusted additionally for mean age, sex, and aerobic exercise intensity, dose, and modality. We included 148 studies. Earlier exercise training initiation was associated with larger pre‐post differences in mobility; studies initiated ≤3 months versus >3 months after stroke were associated with larger differences (weighted mean differences [95% confidence interval]) in 6‐minute walk distance (36.3 meters; 95% CI, 14.2–58.5), comfortable 10‐meter walk time (0.13 m/s; 95% CI, 0.06–0.19) and fast 10‐meter walk time (0.16 m/s; 95% CI, 0.03–0.3), in fully adjusted models. Initiation ≤3 months versus >3 months was not associated with cardiorespiratory fitness but was associated with a higher but not clinically important Berg Balance Scale score difference (2.9 points; 95% CI, 0.41–5.5). In exercise training versus control studies, initiation ≤3 months was associated with a greater difference in only postintervention 6‐minute walk distance (baseline‐adjusted 27.3 meters; 95% CI, 6.1–48.5; fully adjusted, 24.9 meters; 95% CI, 0.82–49.1; a similar association was seen for ≤6 months versus >6 months after stroke (fully adjusted, 26.6 meters; 95% CI, 2.6–50.6). Conclusions There may be a clinically meaningful benefit to mobility outcomes when exercise is initiated within 3 months and up to 6 months after stroke.

Purpose To determine the prevalence of choroidal abnormalities (CAs) and Lisch nodules (LNs) in children who met the clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis (MCD) of neurofibromatosis type 1 (NF1), and to ascertain any differences between the groups. Methods This was a cross-sectional observational study. All children who met the CDC and/or had MCD of NF1 and underwent eye examination were included. At least two CAs or LNs between the two eyes were set as a threshold to define the presence of either abnormality. Frequencies alongside 95% confidence intervals (CIs) were calculated. The relationship between patient age and the presence of LNs and/or CAs was estimated using logistic regression. Results The study cohort included 94 patients; CAs (64%) were more prevalent than LNs (41%) (0.22; 95% CI, 0.08–0.36; P = 0.0023). The probability of the presence of LNs was lower than that of CAs across all ages (odds ratio = 0.37; 95% CI, 0.20–0.69; P = 0.00173). CAs were exclusively found in 37% of patients and LNs in 16%; 80% had either CAs or LNs, or both. In the CDC group ( n = 41), the difference in prevalence (CAs = 68%, LNs = 51%) did not attain statistical significance (0.17; 95% CI, −0.06 to 0.40; P = 0.18). In the MCD group ( n = 53), the difference in prevalence (CAs = 60%, LNs = 34%) was significant (0.26; 95% CI, 0.006–0.47; P = 0.023). Conclusions CAs were more frequent than LNs in pediatric NF1 patients regardless of age and MCD status. Combining ophthalmological exams with near-infrared imaging will increase the diagnostic reach in pediatric NF1. Translational Relevance CAs detected on near-infrared imaging are objective biomarkers in NF1. They are more prevalent and detected earlier in the pediatric population compared with LNs. Hence, the presence of CAs should be routinely ascertained in children suspected with NF1.

Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a−/− mice by examining knockout (KO; Epm2a−/−) and control (WT) littermates at two time points (10 and 14 months, respectively). In vivo exams included electroretinogram (ERG) testing, optical coherence tomography (OCT) and retinal photography. Ex vivo retinal testing included Periodic acid Schiff Diastase (PASD) staining, followed by imaging to assess and quantify LB deposition. There was no significant difference in any dark-adapted or light-adapted ERG parameters between KO and WT mice. The total retinal thickness was cFigure mparable between the groups and the retinal appearance was normal in both groups. On PASD staining, LBs were observed in KO mice within the inner and outer plexiform layers and in the inner nuclear layer. The average number of LBs within the inner plexiform layer in KO mice were 1743 ± 533 and 2615 ± 915 per mm2, at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an Epm2a−/− mouse model, demonstrating significant LB deposition in the bipolar cell nuclear layer and its synapses. This finding may be used to monitor the efficacy of experimental treatments in mouse models.