The past decade has seen a transformation in our understanding of the genetics of stroke. However, a commonly asked question is how do these advances impact the practicing clinician now, and what are their implications for clinical care in the future? This review outlines the major recent advances in stroke genetics and addresses 4 questions most relevant to the clinician: What do we now know about the genetic architecture of stroke? When and how should genetic testing be used to identify monogenic stroke? How can genetic information be applied to risk stratification and prevention? And what therapeutic implications are emerging from genetic discoveries? It highlights the success of genome-wide association studies in stroke and how these have transformed how we understand the genetic architecture of stroke. An increasing number of monogenic forms of cerebral small vessel disease are being identified, and guidance on when and how to test for them is covered. Polygenic risk scores are gaining increasing attention. How these can be applied, and the challenges in their use are discussed. Lastly, the impact of genomics on stroke therapeutics, whether by identifying new targets, assessing causality using techniques such as Mendelian randomization, or pharmacogenomics, is discussed.
BACKGROUND Stroke recovery is highly heterogeneous, and predictive neurophysiological markers of motor outcome are still needed. Although transcranial magnetic stimulation-derived motor evoked potentials (MEPs) are widely used to assess corticospinal integrity, their trial-to-trial variability remains poorly explored and has largely been interpreted as noise rather than a source of clinically relevant information. METHODS In this prospective longitudinal observational study, we investigated MEP peak-to-peak amplitude and amplitude variability in 77 patients with subacute stroke assessed at baseline (T0, early subacute phase) and after a 2-month high-intensity daily rehabilitation program (T1), alongside 10 age- and sex-matched healthy controls. MEPs were recorded from both hemispheres at rest. Clinical outcomes were evaluated using the Fugl-Meyer Upper Extremity scale and a Motor Recovery Index. RESULTS Seventy-seven patients with subacute stroke (mean age, 68.5±12.7 years; 41.6% women) and 10 age- and sex-matched healthy controls (mean age, 73.9±4.3 years; 40.0% women) were included. At T0, MEP amplitude was lower in the affected than in the unaffected hemisphere (0.16±0.02 versus 0.38±0.01 mV; P=5.42×10-10), as was MEP variance (0.013±0.002 versus 0.038±0.003 mV2; P=8.43×10-12). Regarding T1, MEP amplitude increased over time in the affected hemisphere (0.21±0.02 mV; P=0.01), whereas MEP variance remained unchanged (P=0.55). Importantly, baseline MEP amplitude was strongly associated with motor status at follow-up (Fugl-Meyer Upper Extremity scale at T1; P=9.52×10-9), but not with the degree of recovery. In contrast, baseline MEP variability was significantly associated with both motor outcome (Fugl-Meyer Upper Extremity scale at T1; P=2.76×10-7) and the Motor Recovery Index (P=0.009), indicating a specific link with recovery potential. CONCLUSIONS These findings reveal a dissociation between MEP amplitude and variability, suggesting that they capture complementary aspects of corticospinal function. Although amplitude reflects the current functional state of motor pathways, variability appears to index network flexibility and adaptive capacity. MEP variability may, therefore, represent a novel neurophysiological biomarker for predicting motor recovery and guiding personalized rehabilitation strategies after stroke.
BACKGROUND Vascular geometry may impede catheter navigation during mechanical thrombectomy. We evaluated whether cervical curvature predicts recanalization success. METHODS This is a retrospective single-center cohort of 160 anterior large vessel occlusion patients treated with mechanical thrombectomy at a comprehensive stroke center (Barnes-Jewish Hospital/Washington University School of Medicine, St. Louis, MO) from May 2019 to February 2021. Cervical curvature was computed using 3-dimensional vessel centerlines derived from preprocedural computed tomography angiography. Primary outcomes were successful recanalization (final modified Thrombolysis in Cerebral Infarction score ≥2b) and intracranial access time (puncture→first pass). Associations were evaluated with multivariable linear or logistic regression, adjusting for age, National Institutes of Health Stroke Scale, first-line device, and access route. Random Forest and Gradient Boosting models with Gini Importance and Shapley Additive Explanation explained feature importance. RESULTS Mean age was 67±15 years; median National Institutes of Health Stroke Scale 16; mean total curvature was 9.80±2.85. Median intracranial access time was 24 minutes (interquartile range, 17-32), with no correlation to cervical curvature (ρ=0.054; adjusted β=0.20 min/unit [95% CI, -0.75, 1.15]; P=0.676). Successful recanalization occurred in 86% and varied across curvature tertiles (low 91%, mid 93%, high 75%; P=0.017). Per-unit curvature increase was associated with recanalization failure (adjusted odds ratio, 1.21 [95% CI, 1.02-1.43]; P=0.028). Receiver operating characteristic-derived curvature threshold (>11.54) identified a high-risk group (adjusted odds ratio, 5.10 [95% CI, 1.88-13.84]; P=0.001). Machine learning confirmed cervical curvature as the dominant predictor, with a Shapley Additive Explanation peak effect at 11.65. CONCLUSIONS Cervical curvature independently predicts mechanical thrombectomy recanalization failure, with a threshold effect near 11.6 units. Preprocedural curvature assessment derived from routine computed tomography angiography may improve risk stratification and inform mechanical thrombectomy strategy.
BACKGROUND: Identifying the intensity and frequency of physical activity associated with early independent walking in nonambulatory patients with subacute stroke may inform daily physical activity promotion during hospitalization, which was the aim of the present study. METHODS: This multicenter prospective cohort study was conducted at 11 facilities. Baseline was defined as admission to a subacute rehabilitation ward, with subacute referring to the phase after completion of acute stroke treatment. Patients with subacute stroke and a Functional Ambulation Category of 1 to 2 at admission were included. Physical activity was measured using an accelerometer for 1 week at baseline. The outcome was achievement of independent walking at 1 month from baseline (Functional Ambulation Category ≥4). To examine the intensity of physical activity associated with the outcome, modified Poisson regression was used to evaluate time spent in low -intensity physical activity (LPA; low-LPA, 1.6–1.9 metabolic equivalents [METs]), high-LPA (2.0–2.9 METs), and moderate-to-vigorous intensity physical activity (≥3.0 METs). Furthermore, to assess frequency associated with activity intensity, bouts of physical activity at or above the intensity level (≥1.6, ≥2.0, or ≥3.0 METs) were calculated as short-bouts (≥5 to <10 minutes) and long-bouts (≥10 minutes), and their associations with the outcome were examined. RESULTS: Of 389 participants (mean age, 68.1 years; 45.0% female), 113 achieved independent walking during follow-up. Time spent in high-LPA was associated with independent walking when expressed per 5 min/d (risk ratio, 1.067 [95% CI, 1.010–1.131]), whereas low-LPA and moderate-to-vigorous intensity physical activity were not. The number of short-bouts at ≥2.0 METs was associated with independent walking (risk ratio, 1.208 [95% CI, 1.060–1.375]), whereas long-bouts were not relevant. CONCLUSIONS: Accumulation of high-LPA and short-bouts at ≥2.0 METs was associated with early independent walking. These findings may help characterize activity intensity and bout frequency associated with walking independence in nonambulatory patients with subacute stroke during inpatient rehabilitation. REGISTRATION: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000058526.
