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Background Multiple randomized trials could not establish the noninferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large‐vessel occlusion stroke. The role of prior IVT in posterior circulation large‐vessel occlusion remains controversial. Methods In this multicenter, retrospective study, patients with stroke with large‐vessel occlusion in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry between 2013 and 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale≤3 at 90 days) and safety were investigated using multivariable logistic and linear regression models. Results Of the 588 included patients, 67% (n = 394) were treated with EVT alone and 29% (n = 170) with EVT after IVT, and 4% (n = 24) have missing values on this variable. Controlling for multiple confounding factors, IVT was not associated with a higher likelihood of favorable functional outcome at 90 days (odds ratio, 1.04 [95% CI, 0.52–2.09; P = 0.901). Thrombectomy alone did not show any safety advantages compared with those receiving IVT. Conclusion Similar functional outcomes and complication rates were seen in patients with posterior circulation large‐vessel occlusion treated with EVT alone versus EVT after IVT. Further prospective studies are required to determine the utility of IVT in posterior circulation stroke, especially in patients being directly admitted to thrombectomy centers.

Chiari Malformation type 1 (CM-I) is a neurological disorder characterized by morphological defects including excessive cerebellar tonsillar ectopia and associated manifestations. We used 3D amplified MRI on a cohort of healthy and CM-I subjects to investigate the brain’s intrinsic motion, its association with the morphology and patient’s symptomatology, and surgical outcomes. We observed that the regional brain motion in CM-I was significantly higher than that of the healthy subjects, with anterior-posterior (AP) and superior-inferior (SI) displacements in cerebellar tonsils and medulla having the highest differences between the healthy and CM-I (∼45%–∼73% increased motion in the CM-I group). Interestingly, we found the ratio of neural tissue in the foramen magnum to be directly correlated with the SI tonsillar motion (r=0.58). Tonsillar herniation was directly correlated with the AP motion of the tonsils (r=0.61), and AP and medial-lateral (ML) motions of the medulla (r=0.66, and r=0.57). Subjects with higher tonsillar ML motion prior to surgery showed improved outcome (p=0.03, and AUC=0.95). Although we did not observe a significant correlation between the brains motion and morphometrics on the CM-I symptoms (perhaps due to our small sample size), illustrative cases increase our hope for the development of a future tool based on brain biomechanics.

Background and Purpose Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2–5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT. Methods This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT for internal carotid artery or middle cerebral artery (M1) stroke. Results Of the 10,229 patients who underwent MT, 234 met the inclusion criteria. Of those, 98 (41.9%) achieved mTICI 2b, and 136 (58.1%) achieved mTICI 2c/3. There were no significant differences in baseline characteristics between the two groups. The 90-day favorable outcome (modified Rankin Scale score: 0–3) was significantly better in the mTICI 2c/3 group than in the mTICI 2b group (adjusted odds ratio 2.35; 95% confidence interval [CI] 1.18–4.81; P=0.02). Binomial logistic regression revealed that achieving mTICI 2c/3 was significantly associated with higher odds of a favorable 90-day outcome (odds ratio 2.14; 95% CI 1.07–4.41; P=0.04). Conclusion In patients with low ASPECTS, achieving an mTICI 2c/3 score after MT is associated with a more favorable 90-day outcome. These findings suggest that mTICI 2c/3 is a better target for MT than mTICI 2b in patients with low ASPECTS.

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the

Background: The pathophysiology of Idiopathic Intracranial Hypertension (IIH) is poorly understood, making the disease difficult to properly diagnose and treat. Endovascular venous stenting has emerged as an effective non-invasive treatment option for a select cohort of IIH patients with venous sinus stenosis and elevated venous sinus pressure gradient. Unfortunately, current methods of determining patient eligibility for stenting treatment depend on highly invasive and insufficient measurement methods such as venous manometry, which can only measure pressure gradients and not other components of the complex 3D hemodynamic environment. Thus, there is a need for a non-invasive methodology for determining the 3D flow environment of the dural venous sinuses. Objective: To develop a novel method of non-invasive, patient-specific computational fluid dynamic (CFD) simulation of venous sinus hemodynamics for evaluating stenting eligibility. Method: A patient with IIH and elevated sinus pressure gradient underwent MR venography, phase-contrast MR venography, and venous manometry. Patient-specific dural venous anatomy was segmented from the MR venography to construct 3D models of the venous sinuses. 3D transient patient-specific computational fluid dynamic simulations were conducted using flow velocities measured with phase-contrast MR venography as boundary conditions. Results: Successful computational simulations were completed, allowing for the calculation of the spatio-temporal evolution of blood flow through the dural venous sinuses, and the quantitative examination of pressure gradients. Calculated pressure gradients from CFD were validated against venous manometry with an error of only ∼5%. Conclusions: We have successfully developed time-resolved, patient-specific 3D computational simulations of the dural venous sinuses without assumptions at the boundary conditions for the first time. The methodology can accurately and non-invasively measure venous pressure gradients. This preliminary study serves as a proof of concept for our method to be used as a diagnostic tool for determining venous stenting eligibility, as well as a tool for advancing the general understanding of IIH pathophysiology. Statement of Significance: The pathophysiology of Idiopathic Intracranial Hypertension (IIH) is poorly understood making the disease difficult to properly diagnose and treat. Endovascular venous stenting has emerged as an effective non-invasive treatment option for a select cohort of IIH patients with venous sinus stenosis and elevated venous sinus pressure gradient. Our work provides a method for noninvasively determining eligibility for venous sinus stenting, avoiding costly and invasive venous manometry.

Background Mechanical thrombectomy of middle cerebral artery M2 segment occlusion of the middle cerebral artery has reported safety and efficacy in recent post‐hoc and observational studies. However, there is no known benefit of mechanical thrombectomy for patients with M2 segment occlusions in the delayed time window (>6 hours). Methods The Stroke Thrombectomy and Aneurysm Registry (STAR) is a prospective, multicenter, nonrandomized observational study registry for acute ischemic stroke thrombectomy and aneurysm treatment. We analyzed all patients who underwent mechanical thrombectomy within the late time window (>6 hours from symptom onset) involving isolated M2 occlusions. We used propensity score matching to select a comparison group of patients who underwent mechanical thrombectomy for M1 occlusion in the same time window. Results Of 1083 consecutive patients analyzed, propensity matching yielded 180 well matched M1 and M2 pairs. Baseline demographics were well balanced between the groups (M1 and M2). Alberta stroke program early CT score (7.6±1.7 versus 8.3±1.5; P

Background Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion. Methods Using murine stroke models of middle cerebral artery occlusion, we sought to evaluate feasibility of delivery of viable mitochondria to ischemic brain parenchyma. We evaluated the effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood–brain barrier, on efficacy of delivery of mitochondria. Results Following intraarterial delivery, mitochondria distribute through the stroked hemisphere and integrate into neural and glial cells in the brain parenchyma. Consistent with functional integration in the ischemic tissue, the transplanted mitochondria elevate concentration of adenosine triphosphate in the stroked hemisphere, reduce infarct volume and increase cell viability. The addition of focused ultrasound leads to improved blood–brain barrier opening without hemorrhagic complications. Conclusion Our results have implications for the development of interventional strategies after ischemic stroke and suggest a novel potential modality of therapy after mechanical thrombectomy.

Background Mechanical thrombectomy has become the first‐line treatment strategy for patients with large‐vessel occlusion strokes. Often >1 thrombectomy maneuver is necessary to achieve reperfusion. A first‐pass (FP) effect with improved functional outcomes after mechanical thrombectomy has been described. Aim of the present study is to investigate the FP effect in a large, international, multicenter stroke database. Methods Patients who underwent mechanical thrombectomy for large‐vessel occlusion stroke in the anterior cerebral circulation between January 2014 and January 2021 and achieved complete reperfusion were identified from the STAR (Stroke Thrombectomy and Aneurysm Registry). We compared functional outcomes of patients with FP (defined as modified treatment in cerebral ischemia score 3 after a single thrombectomy maneuver) versus multiple‐pass complete reperfusion (defined as modified treatment in cerebral ischemia 3 after ≥1 thrombectomy maneuver). Results A total of 1481 patients with anterior circulation large‐vessel occlusion stroke and successful recanalization were included in the analysis. FP complete recanalization was achieved in 778 patients versus 703 patients with multiple‐pass complete reperfusion. Patients with FP complete recanalization had higher Alberta Stroke Programme Early CT [Computed Tomography] Score at baseline (9 [7–10] versus 8 [7–10]; P=0.002), were less likely to be men (47% versus 51%; P=0.078) and to have intracranial internal carotid artery occlusions (14% versus 27%), as well as more likely to have M1/M2 occlusions (86% versus 73%; P

ObjectiveThe pupillary light reflex (PLR) and the pupillary diameter over time (the PLR curve) is an important biomarker of neurological disease, especially in the diagnosis of traumatic brain injury (TBI). We investigated whether PLR curves generated by a novel smartphone pupillometer application could be easily and accurately interpreted to aid in the diagnosis of TBI.MethodsA total of 120 PLR curves from 42 healthy subjects and six patients with TBI were generated by PupilScreen. Eleven clinician raters, including one group of physicians and one group of neurocritical care nurses, classified 48 randomly selected normal and abnormal PLR curves without prior training or instruction. Rater accuracy, sensitivity, specificity, and interrater reliability were calculated.ResultsClinician raters demonstrated 93% accuracy, 94% sensitivity, 92% specificity, 92% positive predictive value, and 93% negative predictive value in identifying normal and abnormal PLR curves. There was high within-group reliability (k = 0.85) and high interrater reliability (K = 0.75).ConclusionThe PupilScreen smartphone application-based pupillometer produced PLR curves for clinical provider interpretation that led to accurate classification of normal and abnormal PLR data. Interrater reliability was greater than previous studies of manual pupillometry. This technology may be a good alternative to the use of subjective manual penlight pupillometry or digital pupillometry.

Abstract Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified in central nervous system disorders. Membrane leakage and electrolyte imbalances, pro-apoptotic pathway activation, and mitophagy are among the mechanisms implicated in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as ischemic stroke. In this review, we summarize mitochondrial pathways that contribute to disease progression. Further, we discuss pathological states that damaged mitochondria impose on normal nervous system processes and explore new therapeutic approaches to mitochondrial diseases.

Abstract Anatomic variability in the posterior circulation and small, fragile, or otherwise treacherous origins of vertebral arteries can create a challenge to acute endovascular intervention. We report a case of unsuccessful reperfusion due to inability to access the posterior circulation in a patient with acute basilar artery occlusion.

Abstract Not all complications from transradial access can be prevented, even with diligent patient selection and preprocedure planning. This brief visual report offers technical suggestions to reverse knots and kinks encountered during catheter manipulation for endovascular transradial cerebral procedures.

A Correction to this paper has been published: https://doi.org/10.1038/s41536-021-00125-3