Freeman, William D

The effect of induced hypertension (iHTN) on functional outcomes in noncardioembolic acute ischemic stroke (AIS) with early neurological deterioration remains unclear. We performed a systematic review and meta-analysis evaluating the safety and efficacy of iHTN vs medical management. A literature search of PubMed/MEDLINE, Web of Science, Ovid Embase, and Scopus from inception through November 6th, 2025. The protocol was registered in PROSPERO (CRD420261282211). Studies evaluating iHTN within 72 h of AIS onset and reporting 90-day functional independence (modified Rankin Scale [mRS] 0-2) were included. Safety outcome was hemorrhagic transformation. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects model based on Restricted Maximum-Likelihood (REML) methods. Three studies were included, comprising 366 patients (iHTN, n = 180; control, n = 186). Mean age was 65.8 ± 11.8 years, 60.9% were men, and the mean initial NIHSS was 5.4 ± 3.5. Target systolic blood pressure (SBP) was a 15-25% increase from baseline SBP using phenylephrine. Functional independence at 90-days occurred more often in the iHTN group than in controls (68.8% vs 50.5%; RR = 1.37; 95% CI, 1.09-1.73; P = 0.007). Hemorrhagic transformation was uncommon and did not differ significantly between groups (3.3% vs 0.5%; RR = 2.08; 95% CI, 0.05-88.07; P = 0.70). In our study, phenylephrine-induced hypertension was associated with greater 90-day functional independence in selected AIS subtypes,without a significant increase in hemorrhagic transformation. However, the limited studies, predominance of retrospective designs, exclusively Asian cohorts, and heterogeneity in treatment protocols and populations warrant cautious interpretation and underscore the need for larger multicenter RCTs.

BACKGROUND: Intraventricular hemorrhage and subarachnoid hemorrhage are associated with neuroinflammation and increased morbidity and mortality. Rapid clearance of blood from the cerebrospinal fluid space may mitigate neuroinflammatory cascades and improve clinical outcomes. This systematic review and meta-analysis aimed to compare the clinical effectiveness of active cerebrospinal fluid exchange, including neuroendoscopic lavage and IRRAflow systems, versus external ventricular drainage in patients with intraventricular hemorrhage or subarachnoid hemorrhage. METHODS: The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and thoroughly assessed databases, including PubMed, Embase, Scopus, Cochrane, and Web of Science, up to September 18, 2025. Statistical analysis, both fixed-effect and random-effect model analyses, was performed by the Comprehensive Meta-Analysis software. In addition, the Cochran Q test was conducted to determine the statistical heterogeneity. In terms of low heterogeneity, the fixed-effect model is reported. RESULTS: This review included 7 studies with a total sample size of 834. Our analysis showed that active cerebrospinal fluid exchange was associated with significantly higher hematoma clearance (odds ratio, 2.72 [95% CI, 1.22–6.08]; P =0.015), better functional outcomes (odds ratio, 1.66 [95% CI, 1.12–2.48]; P =0.012), lower shunt dependency (odds ratio, 0.22 [95% CI, 0.10–0.50]; P <0.001), and reduced infection rates (odds ratio, 0.22 [95% CI, 0.12–0.42]; P <0.001). Subgroup analysis showed that neuroendoscopic lavage was most effective for hematoma clearance, while IRRAflow reduced infection rates. Also, younger patients had better neurological recovery. CONCLUSIONS: Active cerebrospinal fluid exchange techniques demonstrated superior outcomes over external ventricular drainage in managing intraventricular hemorrhage and subarachnoid hemorrhage, particularly in clot resolution and neurological recovery. Large-scale trials are warranted.

ABSTARCT BACKGROUND: IRRAflow is a novel active cerebrospinal fluid (CSF) exchange system for the treatment of hemorrhagic strokes and intracranial infections. It is a closed system that irrigates various medications dissolved in irrigation solutions at a speed of up to 180 mL/h, expediting resolution. Disrupting this closed system to withdraw CSF samples or infuse medications is necessary in certain circumstances. We report our novel approach for maintaining the sterility of the closed IRRAflow system using a needleless extension and assess the compatibility and safety of this technology throughout treatment. METHODS: We used a needleless extension to withdraw CSF samples and deliver medications to 5 patients treated with the IRRAflow system. We used 1 stopcock with a 3-way valve, 2 neutral needleless connectors, and 2 antiseptic caps. The stopcock was connected between the irrigation and drainage ports of the catheter. The needleless connectors were mounted at the 12 o’clock position of the attached stopcock and the irrigation port with antiseptic caps covering the distal ends. To initiate fluid exchange, the 2 needleless connectors were separated. The extra stopcock valve was connected between the drainage arm, the cassette, and the irrigation arm. The needleless connectors remained mounted at the 12 o’clock position of the stopcock and irrigation port throughout treatment. RESULTS: The needleless connectors mounted on the 12 o’clock position of the stopcock and irrigation port on the drainage and irrigation arms, respectively, provided efficient management of fluid exchange, CSF fluid sampling, and medication delivery. Our needleless extension was compatible with the IRRAflow device and prevented secondary infections despite repeated CSF sampling and medication delivery. CONCLUSION: The needleless extension facilitated a simple and safe interaction with the closed IRRAflow system without compromising the sterile environment during CSF sampling and medication delivery.

Background We automated subarachnoid hemorrhage volume (SAHV) calculation with artificial intelligence (SAHVAI) and created 3‐dimensional volumetric images (SAHVAI‐3D) using noncontrast head computed tomography data for patients with aneurysmal SAH. We also defined 4‐dimensional SAHVAI (SAHVAI‐4D), representing SAHV over time. We aimed to compare automated SAHVAI values and computational times to manual SAHV measurement methods, explore the potential of imaging biomarkers to identify at‐risk brain regions for delayed cerebral ischemia and explore potential insights in future neurotherapeutic interventions for patient recovery after SAH. Methods A training set of 10 consecutive patients with aneurysmal SAH was used to manually compute SAHV, SAHVAI‐3D, and SAHVAI‐4D, including 92 noncontrast computed tomography scans (182 slices each). The SAHVAI deep learning algorithm generated automated SAHV values in cubic centimeters. A 3‐dimensional SAH brain map was created for each patient for the SAHVAI and manual evaluations. Blood volumetric outputs were analyzed and compared to neurologic outcomes at discharge, including delayed cerebral ischemia events, symptomatic vasospasm, and areas with the thickest SAH blood concentration. Results SAHVAI quantified SAHV in a mean of 6.7 seconds per scan, significantly faster than the manual method, which took >60 minutes per scan (Fisher exact test, P <0.001). SAHVAI demonstrated an accuracy of 99.8%, Dice score of 0.701, false‐positive rate of 0.0005, and negative predictive value of 0.999. The mean absolute error between SAHVAI and manual methods was 5.67 mL. SAHVAI‐3D brain map and total SAHV at admission were inversely associated with Glasgow Coma Scale (R 2 = 0.23, P = 0.017) and directly associated with length of hospital stay (R 2 = 0.175, P = 0.004), especially in regions with dense blood concentration. Conclusion SAHVAI‐3D and SAHVAI‐4D brain mapping techniques represent innovative imaging biomarkers for SAH. These advancements enable rapid evaluation and targeted interventions, potentially improving patient care in SAH management.

With increased patient volumes and complexity, stroke occurrence in hospitalized patients has become relatively more common. The process of activating a code stroke in-hospital differs in many institutions. An emergency team-based response to inpatient acute code stroke is warranted, with many protocols modeled similarly to the cardiac arrest response. However, several studies have demonstrated delays in recognition and management of acute stroke in-hospital as compared to those arriving directly to the emergency department (ED). Furthermore, there are several shared challenges with code stroke resuscitation in the ED and the ward, which include the assembly of ad hoc teams and requirement of access to urgent imaging. Delays in activating in-hospital code stroke contributes to increased morbidity, mortality, prolonged hospitalization, and associated health care costs. In the following commentary, we discuss the current landscape of acute in-hospital code stroke protocols, review the differences in neurologic outcomes between inpatient vs ED/out-of-hospital code stroke patients, and propose future directions for in-hospital code stroke paradigms for improved patient outcomes and quality of care.

Background We developed a simplified ABC/2‐derived method to estimate total subarachnoid hemorrhage volume (SAHV) on noncontrast computed tomography in patients with aneurysmal SAH and compared the clinical and radiographic outcomes. Methods and Results In this retrospective observational cohort study, we analyzed 277 patients with SAH admitted to our Comprehensive Stroke Center between 2012 and 2022. We derived a mathematical model (model 1) by measuring SAH basal cisternal blood volume using an ABC/2‐derived ellipsoid formula (A=width/thickness, B=length, C=vertical extension) on head noncontrast computed tomography in 5 major SAH cisternal compartments. We compared model 1 against a manual segmentation method (model 2) on noncontrast computed tomography. Data were analyzed using logistic regression analysis, t test, receiver operator characteristic curves, and area under the curve analysis. There was no significant difference in cisternal SAHV analysis between the 2 models ( P =0.14). Mean SAHV by the simplified method was 7.0 mL (95% CI, 5.89–8.09) for good outcome and 16.6 mL (95% CI, 13.49–19.77) for poor outcome. Patients with delayed cerebral ischemia had higher SAHV, with a cutoff value of 10 mL. Conclusions Our simplified ABC/2‐derived method to estimate SAHV is comparable to manual segmentation and can be performed in low‐resource settings. Higher total SAHV was associated with worse outcomes and higher risk of delayed cerebral ischemia. A potential dose–response relationship was observed, with SAHV >10 mL predicting worse outcomes and higher risk of DCI.

Abstract Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct amyotrophic lateral sclerosis and frontotemporal dementia cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in silico tools. In addition, gene burden analyses in the 100 000 Genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls [odds ratio: 57.0847 (10.2−576.7); P = 4.02 ×10−7]. Taken together, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harbouring a predicted pathogenic TUBA4A missense mutation, including five confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from three patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organization and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes.

Susac Syndrome was first described as an inflammatory microangiopathy of the brain and retina. Since then, multiple articles have been published in attempts to improve the understanding of this rare disease. Clinically Susac Syndrome is known to present with triad of encephalopathy, sensorineural hearing loss and branch of retinal artery occlusion (BRAO), along with characteristic “snowball” or “spoke” appearing white matter lesions of the corpus callosum. It has been characterized by vast heterogeneity in terms of its presenting symptoms, severity, and clinical course. Although subset of patients present with severe forms of Susac Syndrome and can develop prominent residual neurologic deficits, it has been reported to be mostly non-life-threatening and only few fatal cases have been described in the literature. Based on the available case reports with fatal outcome, mortality has been related to the systemic complications either during acute disease flare or during chronic-progressive phase. We describe a case of fulminant Susac Syndrome complicated by the sudden and rapid progression of diffuse cerebral edema leading to brain herniation and ultimate brain death, in order to increase awareness of this rare and catastrophic complication.