Behnam Rezai Jahromi

Fourth ventricular hemorrhage is a devastating subtype of hemorrhagic stroke that can be primary or secondary to subarachnoid hemorrhage. In both cases, inflammatory reactions triggered by blood in...

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 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.

Brain aneurysms are a cerebrovascular disease that results in a severe type of stroke. The cell-specific molecular pathology underlying their formation and rupture is unknown. Here we profile 227,663 neurovascular cells, including 52,946 aneurysmal cells, from a total of 14 adult human brain aneurysms and 11 control vessels. Our atlas of human brain aneurysms, as well as cell-resolution spatial transcriptomics, revealed that pathological cerebrovascular remodeling occurs with the loss of structurally supportive smooth muscle cells and the emergence of activated perivascular fibroblasts, which re-populate the vascular wall and express multiple genes linked to aneurysm risk. Fibrotic changes coincide with fibroblast–myeloid cell signaling pathways and an influx of specialized macrophages that are rarely detected in non-aneurysmal cerebrovasculature and that express destabilizing vascular cell programs. Thus, we reveal an unrecognized interplay between cerebrovascular fibrosis and myeloid inflammation during disease progression, substantially advancing our understanding of the cellular drivers and mechanisms underlying this devastating cerebrovascular disease that will inform translational development.

Therapeutic hypothermia is neuroprotective after brain injury, reducing metabolic demand, inflammation, and secondary injury cascades. However, clinical application is limited by systemic side effects, and selective brain cooling without systemic hypothermia has not been demonstrated in large mammals. We aimed to demonstrate the feasibility of selective brain cooling using cerebrospinal fluid (CSF) exchange with cooled saline via a double-lumen external ventricular drain (EVD) system in a porcine model. Using 12 pigs under general anesthesia, we placed a double-lumen EVD in the lateral ventricle and a lumbar spinal drain to enhance CSF outflow. Cooled NaCl (13 °C) was infused at 120, 360, or 720 mL/h while maintaining intracranial pressure. After reperfusion, mean arterial pressure was increased to 140 mmHg. Brain temperatures were recorded bilaterally; core temperature was monitored. Ipsilateral brain temperature decreased by 7.5 °C, contralateral cooled by 3.1 °C. Core temperature remained stable. Target temperature was reached in 1.5 h at 120 mL/h, and within 10–15 min at 360–720 mL/h. Arrhythmias occurred with NaCl but not with Ringer’s acetate. We demonstrate that selective brain cooling is feasible in a large mammal model via CSF exchange without systemic hypothermia. This method may offer a safe, controllable approach for neuroprotection.

The IRRAflow Active Fluid Exchange System (IRRAS, San Diego, California, USA) is a novel medical device designed to manage intracranial pressure (ICP) and cerebrospinal fluid (CSF) in patients with neurological conditions such as subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH), and chronic subdural hematoma (cSDH). This study presents a series of evaluations assessing the system's performance across multiple technical aspects: catheter-bolt sealing, catheter liquid flow characterization with bolt fixation, torque limit evaluation of the metal bolt and plastic wing interface, fluid equilibrium, injection volume accuracy, 24-hour pressure drift evaluation of IRRAflow ICP sensor output, and pressure accuracy. The results are reported relative to predefined acceptance criteria for each test. The engineering and potential clinical implications of these findings are described in the context of intracranial fluid management.

OBJECTIVE: Dolichoectatic vertebrobasilar aneurysms (DVBAs) are expansions of arterial tissue leading to aneurysmal formations without an obvious neck. Their natural history is poorly understood; usually patients are admitted with thromboembolic complications and/or neurological symptoms from the mass effect. There have not been international collective data, and correct timing for highly risky treatments has been under discussion. The goal of this study was to define the natural history of DVBA by long-term follow-up in an international population of patients with DVBA. METHODS: The authors collected data in 382 patients with DVBAs from 11 centers in Europe, the US, and Japan. The patients were followed until new ischemic or hemorrhagic stroke, symptomatic compression of the brainstem or cranial nerves, decline in modified Rankin Scale score, or death. Treatment excluded patients from further analysis. Demographic and radiological characteristics of patients were collected and a new classification was created based on the radiological characteristics of the DVBA. In total 223 patients were treated conservatively in the first phase of treatment. The data required for natural history calculations were available for 221 patients, with a cumulative follow-up of 622.3 patient-years. Kaplan-Meier and Cox regression analyses were used to assess risk factors with an influence on patient outcomes. RESULTS: In total, 21.5% of patients were admitted due to the mass effect, and there were 67 (30%) patient deaths during follow-up, 45 (20.2%) of which were related to aneurysms. The annual mortality and morbidity were 10.8% and 1.6%, respectively. Most of the patients with DVBAs were male, although sex did not affect prognosis when compared to the radiological characteristics of the lesion. The natural history of DVBAs was also impacted by a new classification, in which an age 50 years and older predicted mortality. Furthermore, a DVBA’s maximum diameter was directly proportional to adverse events. CONCLUSIONS: This study verifies the malignancy of DVBAs and encourages invasive treatment in the early phase of disease progression based on radiological characteristics and patient age when a treatment option is considered suitable. This also stresses the need for continued investigations to develop new therapeutics with acceptable safety profiles.

Intracranial aneurysms (IAs) are a major cause of subarachnoidal hemorrhage (SAH) which can have a significant morbidity and mortality. The processes underlying the aneurysm development remains unclear. We performed whole exome sequencing of DNA derived from 20 saccular cerebral aneurysms of 20 patients, followed by somatic variant calling. Eleven (55%) of the 20 patients had detectable nonsynonymous somatic mutations and in total, 48 mutations were detected in the aneurysm samples. The mutations were highly enriched in cancer-related genes and 77% were predictably deleterious. A p.Tyr562Asp somatic mutation was detected in the PDGFRB gene; somatic mutations at the same codon have been reported in fusiform cerebral aneurysms. These results widen the concept on the role of somatic mutations in cerebral aneurysms, indicating their possible role in the more common saccular aneurysm, similarly to the rarer fusiform aneurysm.

Cerebral cavernous malformation (CCM) is a neurovascular disease with symptoms such as strokes, hemorrhages and neurological deficits. With surgery being the only treatment strategy, understanding the molecular mechanisms of CCM is crucial in finding alternative therapeutic options for CCM. Neutrophil extracellular traps (NETs) were recently reported in CCM, and NETs were shown to have positive or negative effects in different disease contexts. In this study, we investigated the roles of NETs in CCM by pharmacologically inhibiting NET formation using Cl-amidine (a peptidyl arginine deiminase inhibitor). We show here that Cl-amidine treatment reduced lesion burden, coagulation and endothelial-to-mesenchymal transition. Furthermore, NETs promoted the activation of microglia and fibroblasts, leading to increased neuroinflammation and a chronic wound microenvironment in CCM. The inhibition of NET formation caused endothelial quiescence and promoted a healthier microenvironment. Our study suggests the inhibition of NETs as a potential therapeutic strategy in CCM.