Kadirvel, Ramanathan

Abstract Stroke thrombi are heterogeneous; their composition influences their mechanical properties, including stiffness, elasticity, and adhesiveness, which in turn affect their response to therapy. Systemic characterization of the thrombi components could help select therapeutic techniques and anticipate outcomes. We conducted a systematic review and meta-analysis to evaluate associations between thrombi composition and angiographic and functional outcomes in acute ischemic stroke (AIS). Up to May 2025, relevant studies were sourced from four databases: PubMed, Web of Science, Scopus, and Embase. We included cohort studies whose populations are patients with AIS in relation to thrombi composition. Thirty-six studies involving 5,462 patients matched our eligibility criteria. Angiographic success (Thrombolysis in Cerebral Infarction ≥ 2b/3) did not differ significantly between red blood cell (RBC)-rich and fibrin-rich thrombi (risk ratio [RR] 1.02, 95% confidence interval [CI] 0.85–1.22; p = 0.84; I 2 = 63.8%; very low certainty). However, thrombi from patients with good angiographic outcomes had a significantly higher RBC content compared to patients with poor outcomes (mean difference = 7.22%, 95% CI 3.31–11.13; p < 0.001; low certainty). No significant difference was observed between RBC-rich and fibrin-rich thrombi regarding functional independence at 90 days (modified Rankin Scale 0–2) (RR = 1.22, 95% CI 0.73–2.05; p = 0.31; low certainty). While RBC-rich thrombi are associated with more favorable angiographic performance, thrombus composition alone does not predict functional outcomes. Stroke outcomes remain multifactorial, dominated by time to reperfusion, collateral circulation, and baseline severity. Preinterventional assessment of clot composition via imaging or biomarkers may support individualized therapy but should complement, not replace, other prognostic determinants.

ABSTRACT Endoluminal flow diverters are increasingly used to treat cerebral aneurysms. Despite good aneurysm occlusion efficacy, delayed ischemic complications due to side branch or perforator occlusion remain a serious concern. However, the mechanisms leading to side branch occlusion are poorly understood. To investigate these mechanisms, a combination of animal and computational models was utilized. Flow diverters were deployed in four rabbit superior mesenteric artery (SMA) and studied with computational fluid dynamics (CFD) and a previously developed fibrin dynamics model. Subject‐specific vascular models were reconstructed from 3D rotational angiography images and flow conditions were derived from Doppler ultrasound velocity measurements. Flow diverting devices were virtually deployed within the vascular models under guidance from angiography images. Coupled flow and fibrin production, transport, and adhesion simulations were carried out and the effects of fibrin accumulation at the origin of jailed side branches after flow diverter implantation were analyzed. The results of the computational models suggest significant fibrin accumulation across the struts of all flow diverting devices jailing side branches. Larger accumulation was observed at the more distal branches. However, minor flow alterations were produced which were not detectable in angiography sequences. These results were in agreement with experimental observations. On the other hand, fibrin accumulation alone did not explain complete side branch occlusions, which are likely the result of the interaction between initial fibrin accumulation and subsequent cell migration from the peripheral parent artery.

Background: Pulsatile tinnitus (PT) is frequently caused by venous sinus stenosis and may be associated with idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) directly addresses venous outflow obstruction and has emerged as a therapeutic option; however, outcome data remain heterogeneous. We performed an updated systematic review and meta-analysis to evaluate the efficacy and durability of VSS for PT and to compare outcomes between IIH-associated and isolated PT. Methods: MEDLINE, Scopus, and Web of Science were searched from inception through December 2025 following PRISMA guidelines. Clinical studies reporting PT outcomes after VSS were included. Random-effects meta-analyses of proportions were conducted to estimate pooled rates of overall improvement, complete resolution, and recurrence. Prespecified subgroup analyses compared IIH versus isolated PT. Results: Thirty-two studies comprising 850 patients were included (641 with IIH; 209 with isolated PT). Venous sinus stenosis accounted for 90.3% of treated etiologies. The pooled rate of overall PT improvement was 89.8% (95% CI, 85.5-92.9). Complete resolution occurred in 87.1% (95% CI, 82.5-90.6). Recurrence at last follow-up was 10.9% (95% CI, 8.3-14.2). Improvement and complete resolution rates did not differ significantly between IIH and isolated PT. Recurrence was higher in IIH (12.0%) than in isolated PT (5.7%), without reaching statistical significance. Conclusions: VSS is associated with high rates of PT improvement and complete resolution with low recurrence. Recurrence trends appear higher in IIH, suggesting underlying pathophysiology may influence durability.

Abstract Brain arteriovenous malformations (AVMs) result from abnormal growth of vascular structures. AVMs pose a significant rupture risk, and its treatment is challenging due to the complex hemodynamics within the tangled nidus. Currently, investigating AVM hemodynamics remains a challenge due to the low resolution of clinical imaging modalities. In this study, a high-fidelity Computational Fluid Dynamics (CFD) simulation of a brain AVM from a KRAS-mutated mouse model is developed from micro-CT images. Brain AVMs were induced in mice through systemic delivery of AAV-BR1-CAG vector encoding KRASG12V-GFP transgene to cerebral endothelial cells. High-resolution microCT imaging at 6.551 𝜇𝑚 pixel size captured the complex vascular anatomy. The cerebral arteries were reconstructed using the 3D Slicer and Blender software. The curvilinear immersed boundary (CURVIB) method was employed with approximately 65 million grid points and spatial resolution of 0.7−2.3 𝜇𝑚. Our preliminary results reveal heterogeneous flow distribution through the nidus, with blood channeling through two primary pathways. The extremely low Reynolds number (0.038) indicates viscous-dominated flow characteristic of microcirculation. Our work presents the first high-resolution CFD simulation of brain AVM in the literature, providing a foundation for investigating flow-mediated vascular remodeling, rupture risk assessment, and therapeutic intervention planning in future.

ABSTRACT Incomplete aneurysm occlusion after flow disruption treatment strongly depends on the persistence of strong flow into the aneurysm, which in turn depends on the aneurysm and parent artery geometry as well as the device placement. However, at the time of treatment it remains challenging to predict future outcomes (complete or incomplete occlusion). This paper describes a strategy to evaluate the local hemodynamic environment created immediately after flow‐modifying device deployment to treat cerebral aneurysms and connect it to the subsequent long‐term outcomes. The approach is based on the concept of angiographic signatures that can be extracted from DSA sequences or computational models and represented as images that can be used to compare different aneurysmal environments. The methodology is demonstrated on two small series of four experimental rabbit aneurysms each, treated with either intrasaccular flow disruptors or endoluminal flow diverters. Noticeable differences in the angiographic signatures of completely and incompletely occluded aneurysms at follow‐up were observed. Specifically, larger values of mean transit times and longer time‐to‐peaks were observed deeper into the aneurysms that remained incompletely occluded in both series. The findings suggest that angiographic signatures can be used to assess the underlying hemodynamic environment immediately after device implantation and prognosticate the likelihood of future complete or incomplete occlusion.

Background The middle meningeal artery (MMA) has emerged as an endovascular route for treating chronic subdural hematoma (CSDH), meningioma, and refractory headaches. The third ARISE roundtable convened experts from neurology, neurosurgery, neuroradiology, industry, and regulatory agencies to develop consensus guidance on current evidence for MMA-based therapies Methods Over 50 experts participated in a multi-stakeholder discussion. Evidence from randomized and observational studies, early-phase interventional series, and preclinical work was reviewed. Breakout groups focused on four domains: (1) MMA embolization (MMAE) for CSDH, (2) preoperative embolization of meningiomas, (3) MMA-targeted therapies for headache, and (4) transvascular access for endovascular drainage of subdural hematomas. Consensus recommendations were developed by a writing committee Results Randomized trials support MMAE as an adjunct to surgery or medical management for selected patients with non-acute, symptomatic CSDH to reduce recurrence, progression, and reoperation. Evidence remains insufficient to support MMAE for acute or asymptomatic subdural hematomas. For meningioma, observational data suggest that preoperative embolization in experienced centers can reduce blood loss and operative time and may delay recurrence in large, hypervascular tumors with predominant dural or external carotid supply; primary embolization and intra-arterial oncologic therapies remain investigational. Early series of MMA-directed lidocaine infusion for refractory migraine, status migrainosus, and post-subarachnoid hemorrhage headache show short-term benefit, highlighting the need for controlled trials. Preclinical and first-in-human studies of combined MMAE and transvascular drainage for CSDH demonstrate high technical success, rapid radiographic and clinical improvement, and no early recurrences Conclusion The MMA represents a vascular pathway for an expanding spectrum of neurointerventional therapies.

Background Large vessel occlusion (LVO) stroke is associated with a high risk of permanent disability. There are no reliable tools providing periprocedural information on clot characteristics, such as composition and length, that may impact first pass effect, which has been shown to improve functional outcomes. In the first study of a novel technology, we evaluated whether the Clotild Smart Guidewire System (Clotild), an impedance-based device, can provide in situ information on clot characteristics during a mechanical thrombectomy procedure. Methods This is the first-in-human, international, multicentric, single-arm trial involving LVO stroke patients. Of 45 enrolled subjects, 41 constituted the safety population; 39 was the per protocol population, of which 26 subjects with complete impedance data comprised the performance population. The latter was divided into development (11 subjects) and validation (15 subjects) populations for prediction model development and assessment. The safety endpoint assessed Clotild-related intracranial vessel perforation/dissection. Performance endpoints evaluated Clotild’s ability to perform classification of impedance measurements distinguishing substantial versus negligible local content in red blood cells (RBCs) and platelets, to detect the arterial wall and the distal end of the clot. Results The safety endpoint was met in all subjects. Performance analysis comparing the agreement between Clotild’s output and impedance experts’ readings showed an area under the receiver operating characteristic curve (AUC) of 0.97 (95% CI 0.93 to 0.99) for RBC, and 0.94 (95% CI 0.89 to 0.98) for platelet clot composition. Regarding detection, Clotild’s performance showed an AUC of 0.69 (95% CI 0.59 to 0.77) for the arterial wall, and 0.83 (95% CI 0.59 to 1.00) for the distal end of the clot. Conclusions Clotild was proven safe to acquire impedance data and to provide information on in situ clot characteristics in large vessel occlusions.

Background Ischemic stroke is an important cause of morbidity and mortality in children, yet no clinical trials have evaluated mechanical thrombectomy (MT) in this population. Consequently, in contrast to adults, pediatric MT remains an off-label intervention. This meta-analysis aimed to assess its safety and efficacy and compare outcomes with medical management (MM). Methods MEDLINE, Scopus, and Web of Science were searched to identify original studies reporting outcomes of MT, with or without intravenous thrombolysis (IVT) in pediatric ischemic stroke. In studies that concurrently reported MT±IVT and MM±IVT within the same study, outcomes from the MM arms were also extracted for comparative analysis. Results Eighteen studies encompassing 612 pediatric patients were included. The pooled successful recanalization rate (thrombolysis in cerebral infarction (TICI) 2b–3) after mechanical thrombectomy was 88.9% (95% confidence interval (CI) 85.65 to 92.06), and 43.9% (95% CI, 38.67 to 49.09) achieved complete recanalization (TICI 3). Favorable functional outcomes (modified Rankin Scale (mRS) 0–2) occurred in 78.6% (95% CI, 69.58 to 87.61) of patients, with mortality and symptomatic intracranial hemorrhage (sICH) rates of 3.9% (95% CI, 1.88 to 5.92) and 1.3% (95% CI, 1.07 to 2.58), respectively. Shift analysis demonstrated a significant overall improvement in functional outcomes with MT±IVT compared with MM±IVT (common (OR), 0.43; 95% CI, 0.30 to 0.63; P<0.001). Conclusion Our findings suggest that MT has a favorable safety and efficacy profile, resulting in a more favorable mRS shift compared with MM in pediatric ischemic stroke. Further research is needed to identify the pediatric stroke patients who are likely to benefit from MT.