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Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. Accordingly, the myelin observed in neocortical gray matter is thought to mostly ensheath excitatory axons connecting to subcortical regions and distant cortical areas. Using independent analyses of light and electron microscopy data from mouse neocortex, we show that a surprisingly large fraction of cortical myelin (half the myelin in layer 2/3 and a quarter in layer 4) ensheathes axons of inhibitory neurons, specifically of parvalbumin-positive basket cells. This myelin differs significantly from that of excitatory axons in distribution and protein composition. Myelin on inhibitory axons is unlikely to meaningfully hasten the arrival of spikes at their pre-synaptic terminals, due to the patchy distribution and short path-lengths observed. Our results thus highlight the need for exploring alternative roles for myelin in neocortical circuits. The brain is far away from the muscles that it controls. In humans, for example, the brain must be able to trigger the contraction of muscles that are more than a meter away. This task falls to specialized motor neurons that stretch from the brain to the spinal cord, and from the spinal cord to the muscles. Neurons transmit information (in the form of electrical nerve impulses) along their length through cable-like structures called axons. The axons of the motor neurons are so long that, if they were ‘naked’, it would take at least a second for nerve impulses to travel their entire length. Such a long delay between thoughts and actions would make rapid movement impossible. Nerve impulses are able to travel from the brain to the muscles much more quickly, because they are wrapped with a substance called myelin that acts like electrical insulation. Myelin helps the nerve impulses travel up to 100 times faster down the axon. Not surprisingly, diseases that damage myelin, such as multiple sclerosis, severely disrupt movement and sensation. Not all of the brain’s myelin is found around the long axons of motor neurons. The outer layer of the brain, known as the cerebral cortex, also contains myelin. However, most neurons within the cerebral cortex are only a few millimeters long. So what exactly is myelin doing there? Micheva et al. have now used electron microscopy and light microscopy to study the neurons in the cortex of the mouse brain. This revealed that up to half of the myelin in some layers of the cortex surrounds the axons of inhibitory neurons (which reduce the activity of the neurons they signal to). Moreover, one particular subtype of inhibitory neuron accounts for most of the myelinated inhibitory axons, namely inhibitory neurons that contain a protein called parvalbumin. Exactly why parvalbumin-containing neurons are myelinated remains a mystery. Myelin covers only short segments of the axons of these neurons, so it would speed up the transmission of signals by less than a millisecond – probably not enough to make a meaningful difference. Parvalbumin-containing neurons often signal frequently, and thus require large amounts of energy. One possibility therefore is that myelin helps to meet these energy requirements or to reduce energy consumption. Further research will be needed to test this and other ideas.

Background and Objective Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts ≥ 80 mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a < 80 mL ischemic core who do not achieve complete reperfusion. Methods We reviewed our institutional stroke registry and included patients who achieved unsuccessful revascularization, mTICI 0-2a, after ET and whose baseline imaging was notable for a core infarct < 80 mL, a T max  > 6 s volume ≥ 80 mL, and a mismatch ratio ≥ 1.8. MCE was defined as ≥ 5 mm of midline shift on follow-up imaging, obtained 6–48 h after the pre-ET perfusion scan. Results Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p  < 0.02). In multivariate logistic regression analysis, age, HIR, and core infarct volume were independent predictors of MCE. The optimal HIR threshold to predict MCE was ≥ 0.54 (OR 14.7, 95% CI 2.4–78.0, p  = 0.003). HIR was also associated with 3-month mRS (HIR ≥ 0.54 for mRS of 3–6: OR 10.8, 95% CI 1.9–44.0, p  = 0.02). Conclusions Younger age, larger core infarct volume, and higher HIR are predictive of MCE in patients with anterior circulation LVO, moderate-to-large tissue at risk, and suboptimal revascularization. HIR is correlated with three-month functional outcomes.

Dual-energy CT (DECT) material decomposition techniques may better detect edema within cerebral infarcts than conventional non-contrast CT (NCCT). This study compared if Virtual Ischemia Maps (VIM) derived from non-contrast DECT of patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are superior to NCCT for ischemic core estimation, compared against reference-standard DWI-MRI. Only patients whose baseline ischemic core was most likely to remain stable on follow-up MRI were included, defined as those with excellent post-thrombectomy revascularization or no perfusion mismatch. Twenty-four consecutive AIS-LVO patients with baseline non-contrast DECT, CT perfusion (CTP), and DWI-MRI were analyzed. The primary outcome measure was agreement between volumetric manually segmented VIM, NCCT, and automatically segmented CTP estimates of the ischemic core relative to manually segmented DWI volumes. Volume agreement was assessed using Bland–Altman plots and comparison of CT to DWI volume ratios. DWI volumes were better approximated by VIM than NCCT (VIM/DWI ratio 0.68 ± 0.35 vs. NCCT/DWI ratio 0.34 ± 0.35; P < 0.001) or CTP (CTP/DWI ratio 0.45 ± 0.67; P < 0.001), and VIM best correlated with DWI (r VIM  = 0.90; r NCCT  = 0.75; r CTP  = 0.77; P < 0.001). Bland–Altman analyses indicated significantly greater agreement between DWI and VIM than NCCT core volumes (mean bias 0.60 [95%AI 0.39–0.82] vs. 0.20 [95%AI 0.11–0.30]). We conclude that DECT VIM estimates the ischemic core in AIS-LVO patients more accurately than NCCT.

Purpose Early infarcts are hard to diagnose on non-contrast head CT. Dual-energy CT (DECT) may potentially increase infarct differentiation. The optimal DECT settings for differentiation were identified and evaluated. Methods One hundred and twenty-five consecutive patients who presented with suspected acute ischemic stroke (AIS) and underwent non-contrast DECT and subsequent DWI were retrospectively identified. The DWI was used as reference standard. First, virtual monochromatic images (VMI) of 25 patients were reconstructed from 40 to 140 keV and scored by two readers for acute infarct. Sensitivity, specificity, positive, and negative predictive values for infarct detection were compared and a subset of VMI energies were selected. Next, for a separate larger cohort of 100 suspected AIS patients, conventional non-contrast CT (NCT) and selected VMI were scored by two readers for the presence and location of infarct. The same statistics for infarct detection were calculated. Infarct location match was compared per vascular territory. Subgroup analyses were dichotomized by time from last-seen-well to CT imaging. Results A total of 80–90 keV VMI were marginally more sensitive (36.3–37.3%) than NCT (32.4%; p  > 0.680), with marginally higher specificity (92.2–94.4 vs 91.1%; p  > 0.509) for infarct detection. Location match was superior for VMI compared with NCT (28.7–27.4 vs 19.5%; p  < 0.010). Within 4.5 h from last-seen-well, 80 keV VMI more accurately detected infarct (58.0 vs 54.0%) and localized infarcts (27.1 vs 11.9%; p  = 0.004) than NCT, whereas after 4.5 h, 90 keV VMI was more accurate (69.3 vs 66.3%). Conclusion Non-contrast 80–90 keV VMI best differentiates normal from infarcted brain parenchyma.

BackgroundTransradial access (TRA) is increasingly common in cerebrovascular intervention, but its safety and efficacy in mechanical thrombectomy (MT) in acute ischemic stroke remain unclear.MethodsWe reviewed a prospectively maintained single-institution stroke database including consecutive cases between January 1, 2016 and December 31, 2023. Patients were categorized by initial access site, TRA or transfemoral access (TFA). Access site complications (ASCs) were tabulated and classified by Clavien-Dindo (CD) grade.Results1121 patients were included (862 TFA, 259 TRA). TRA was associated with a mean 7.7 (95% CI 5.9 to 9.6) additional minutes from puncture-to-first-pass, and 7.7 (95% CI 4.8 to 10.6) additional minutes from puncture-to-recanalization. Among anterior circulation occlusions, TRA was associated with a 47% increase in the puncture-to-first-pass interval and a 27% increase in puncture-to-recanalization interval (P<0.001). Among posterior circulation occlusions, procedural times were not significantly different between TFA and TRA approaches. There were no significant differences in mean number of passes (1.7 vs 1.8, P=0.58), first pass successful recanalization rates (42.4% vs 45.6%, P=0.37), and post-procedural successful recanalization rates (67.2% vs 68.2%, P=0.76). Crossover rates were higher among the TRA group (5.8% vs 2.6%, P=0.01); ASCs and ASCs of CD grade >1 presented less frequently in the TRA group (12 (4.8%) vs 53 (6.1%), P=0.36; 4 (1.5%) vs 30 (3.5%), P=0.11, respectively), though both failed the predetermined threshold of statistical significance.ConclusionTRA MT was associated with similar posterior circulation but longer anterior circulation procedural times, overall similar rates of Thrombolysis In Cerebral Infarction (TICI) 2c/3 reperfusion, and similar neurologic outcomes when compared against TFA procedures.

Collegiate football athletes are subject to repeated traumatic brain injuriesthat may cause brain injury. The hippocampus is composed of several distinct subfields with possible differential susceptibility to injury. The aim of this study is to determine whether there are longitudinal changes in hippocampal subfield volume in collegiate football. A prospective cohort study was conducted over a 5-year period tracking 63 football and 34 volleyball male collegiate athletes. Athletes underwent high-resolution structural magnetic resonance imaging, and automated segmentation provided hippocampal subfield volumes. At baseline, football (n = 59) athletes demonstrated a smaller subiculum volume than volleyball (n = 32) athletes (−67.77 mm3; p = 0.012). A regression analysis performed within football athletes similarly demonstrated a smaller subiculum volume among those at increased concussion risk based on athlete position (p = 0.001). For the longitudinal analysis, a linear mixed-effects model assessed the interaction between sport and time, revealing a significant decrease in cornu ammonis area 1 (CA1) volume in football (n = 36) athletes without an in-study concussion compared to volleyball (n = 23) athletes (volume difference per year = −35.22 mm3; p = 0.005). This decrease in CA1 volume over time was significant when football athletes were examined in isolation from volleyball athletes (p = 0.011). Thus, this prospective, longitudinal study showed a decrease in CA1 volume over time in football athletes, in addition to baseline differences that were identified in the downstream subiculum. Hippocampal changes may be important to study in high-contact sports.

Objective Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS‐LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90‐day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS‐LVO patients who have undergone successful reperfusion. Methods We performed a retrospective analysis of prospectively collected data from consecutive adult AIS‐LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change. Results In 119 patients of median (IQR) age 71 (63–81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT− patients (17 [14–23.5] vs. 13 [9.5–19], p = 0.011, and 7.5 [4–12] vs. 3 [1–7], p < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (B = −0.163, 95%CI −0.326 to −0.001, p = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127–0.863, p = 0.024). Interpretation PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS‐LVO patients, highlighting the critical role of VO impairment in short‐term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS‐LVO.

To compare the effectiveness and safety of tenecteplase (TNK) versus alteplase (TPA) in patients with basilar artery occlusion prior to endovascular treatment (EVT). In this retrospective multicenter study (BAO-TNK), we analyzed consecutive BAO patients from 14 U.S. stroke systems who received TNK or TPA within 4.5 h of last known well and were referred for EVT (01/2020-08/2024). Multivariable logistic regression models were adjusted for age, sex, NIH Stroke Scale (NIHSS), posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS), last-known-well-to-door time, and stroke etiology. Outcomes included 90-day modified Rankin Scale (mRS), reperfusion rates, and intracranial hemorrhage (ICH) per Heidelberg classification. Of 163 BAO patients, 75 (46.0%) received TNK and 88 (54.0%) received TPA. Rates of 90-day good functional outcome (mRS 0-3) were comparable between groups (TNK: 61.8% vs. TPA: 48.8%, adjusted odds ratio [aOR] 1.372, 95% CI 0.616-3.054, p = 0.439). No significant differences were observed in rates of pre-thrombectomy early reperfusion (18.7% vs. 14.8%, aOR 0.933, 95% CI 0.369-2.359, p = 0.884), post-thrombectomy final reperfusion (97.3% vs. 92.0%, aOR 2.133, 95% CI 0.376-12.116, p = 0.393), 90-day mortality (32.4% vs. 39.5%, aOR 0.989, 95% CI 0.436-2.244, p = 0.979), or symptomatic ICH (4.0% vs. 4.5%, aOR 1.319, 95% CI 0.245-7.114, p = 0.747). Predictors of favorable outcome included younger age, lower NIHSS, higher pc-ASPECTS, shorter LKW-to-puncture time, and non-atherothrombotic stroke etiology. In BAO stroke, TNK and TPA administered within 4.5 h pre-EVT were associated with similar functional outcomes, reperfusion success and hemorrhage rates.

BackgroundAcute ischaemic stroke (AIS) is a leading cause of mortality and disability globally, with volume contracted state (VCS), as indicated by an elevated blood urea nitrogen to creatinine (BUN/Cr) ratio, potentially influencing outcomes. This study investigates the association between VCS and clinical outcomes in patients with AIS due to large vessel occlusion (LVO).MethodsA retrospective cohort study was conducted involving 298 patients with LVO-AIS from two comprehensive stroke centres. Patients were divided into two groups based on BUN/Cr ratio: ≤20 (n=205) and >20 (n=93). Primary outcomes included 90-day mortality and unfavourable functional outcomes, defined as a modified Rankin Scale score of 3–6. Secondary outcomes included the successful reperfusion, haemorrhagic transformation and National Institutes of Health Stroke Scale score at discharge.ResultsPatients with a BUN/Cr ratio >20 had significantly higher 90-day mortality (35% vs 13%, p<0.001) and this association remained significant after adjusting for confounding factors (OR 2.20; 95% CI 1.11 to 4.39; p=0.024). However, VCS was not significantly associated with unfavourable functional outcomes at 90 days (OR 1.28; 95% CI 0.67 to 2.51; p=0.46). Age and initial stroke severity were more strongly associated with long-term functional outcomes.ConclusionsVCS is associated with higher odds of 90-day mortality in patients with LVO-AIS but not with unfavourable functional outcomes. These findings suggest the need for further research into the role of hydration management in improving survival in patients with AIS, potentially informing future treatment protocols.

Background and purposeAcute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).Materials and methodsThis retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.ResultsTwo hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).ConclusionAIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.