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Open research questions in Intracranial Aneurysms: Treatment and Complications

36 unresolved questions extracted from the limitations and future-work sections of 223 Intracranial Aneurysms: Treatment and Complications papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The current investigation of postoperative patient experience was limited to the first postoperative week, the most difficult period for patients. Despite such limitations, we consider our data a useful addition to the extremely limited literature available on this topic of patient experience following a craniotomy.

    Postoperative patient experience following different minimally invasive surgical approaches for unruptured intracranial aneurysms: Superciliary approach versus trans-scalp lateral supraorbital approach · 2026 · DOI

  • Future research should prioritize multicenter prospective studies with larger sample sizes and independent external validation cohorts to assess the stability, calibration, and transportability of the proposed models. Prospective impact studies are also needed to determine whether nomogram-guided risk stratification improves clinical decision-making or patient outcomes. Advanced imaging techniques, such as cardiac magnetic resonance imaging (CMR), together with dynamic cardiac biomarkers and hemodynamic parameters, may further clarify the clinical significance of non-coronary myocardial injury after SAH. With advances in artificial intelligence and machine learning, multidimensional data-fusion models may eventually support precision risk assessment, but such tools should undergo clinical implementation.

    A novel clinical perspective on subarachnoid hemorrhage complicated by myocardial injury: independent predictors and short-term prognostic assessment · 2026 · DOI

  • Third, the fol- low-up duration was relatively short, which may have limited the com- plete assessment of aneurysm occlusion progression, and longer-term outcomes remain to be determined. Future multicenter studies with larger sample sizes and longer follow-up periods are warranted to fur- ther validate these findings.

    Comparison of lattice and pipeline flow diverters for the treatment of distal intracranial aneurysms: an inverse probability of treatment weighting analysis · 2026 · DOI

  • This report has several limitations. As a single case report, generalization of hemodynamic behavior and rupture risk is limited. Long-term follow-up data are not yet available to determine aneurysm growth dynamics. In addition, standard aneurysm rupture-risk prediction models such as the PHASES score may not be directly applicable in the setting of bilateral ICA agenesis and extreme posterior-circulation dependence.

    Bilateral ICA agenesis with giant basilar tip aneurysm: a case report and literature review · 2026 · DOI

  • This case report is limited by its single-patient design and therefore does not allow definitive causal inference. The presumed embolic mechanism remains indirect, as no thrombus or gas embolus was directly visualized. Although venous Doppler ultrasonography was negative, occult thrombosis cannot be fully excluded. Reperfusion after intravenous thrombolysis was not angiographically confirmed and is inferred from rapid clinical recovery and diffusion-negative MRI findings. cONcLUsION Ischemic stroke is a medical emergency associated with high disability and mortality rates. A multirEFErENcEs 1. GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. 2. Dimitrova M. Diagnostic and therapeutical approaches in cryptogenic stroke. Sofia: J.A.M.G. BOOKS, 2021. p. 68. 3. Buttinelli C, Beccia M, Argentino C. Stroke in a scuba diver with patent foramen ovale. Eur J Neurol. 2002 Jan;9(1):89-91. doi: 10.1046/j.1468- 1331.2002.00347.x. 4. Ries S, Knauth M, Kern R, Klingmann C, Daffertshofer M, Sartor K, Hennerici M. Arterial gas embolism after decompression: correlation with right-to-left shunting. Neurology. 1999 Jan 15;52(2):401-4. doi: 10.1212/wnl.52.2.401. 5. Schwerzmann M, Seiler C, Lipp E, Guzman R, Lövblad KO, Kraus M, Kucher N. Relation between directly detected patent foramen ovale and ischemic brain lesions in sport divers. Ann Intern Med. 2001 Jan 2;134(1):21-4. doi: 10.7326/0003-4819-134-1-200101020-00009. 6. Gerriets T, Tetzlaff K, Liceni T, Schäfer C, Rosengarten B, Kopiske G, et al. Arteriovenous bubbles following cold water sport dives: relation to right-todisciplinary approach is mandatory in order to identify the etiological causes of its occurrence in young individuals. In patients with neurological symptoms after diving, paradoxical embolism through a PFO should be strongly considered. Assessing the individual risk profile is essential for implementing an optimal, personalized secondary stroke prevention plan. Authors' contributions: Conceptualization, M.A., M.T.-M., and A.K.; clinical management of the patient, M.A., V.D.-K., M.T.-M., and A.K.; diagnostic evaluation and interpretation, M.A., V.D.-K., and A.K.; data collection and curation, M.A. and V.D.-K.; writing—original draft preparation, M.A. and M.T.-M.; writing—review and editing, M.A., V.D.-K., M.T.-M., and A.K.; supervision, M.T.-M. and A.K. All authors have read and agreed to the published version of the manuscript.

    Acute ischemic stroke after scuba diving in a patient with patent foramen ovale: a case of paradoxical embolism · 2026 · DOI

  • The PHASES score has not been validated in our population; however, due to the lack of locally validated tools and considering the clinical context, its use was deemed appropriate [20,23]. Additionally, values for the UIATS score were adapted using MRA due to the unavailability of conventional angiography [14]. Another important limitation is that the patient opted for homeopathic treatment against medical recommendation, which limits the generalizability of the therapeutic approach presented in this case. Furthermore, the follow-up period remains limited, with no long-term imaging studies or extended clinical outcomes available, as the patient declined further invasive evaluations or surgical intervention in favor of conservative management.

    Multiple Saccular Aneurysms of the Posterior Cerebral Artery With Mass Effect: A Case Report · 2026 · DOI

  • Future works using in vivo lineage-tracing approaches are warranted to confirm the cellular origins of POSTN+ perivascular fibroblasts and the time-course of their appearance in brain aneurysms87–90.

    Cerebrovascular vulnerability and fibrosis in human brain aneurysms · 2026 · DOI

  • While ventriculostomy-associated hemorrhages are well-documented in spontaneous subarachnoid hemorrhage (SAH), the impact of external ventricular drainage (EVD) placement accuracy on puncture channel bleeding (PCB) remains underexplored.

    Influence of the correct placement of external ventricular drainage on puncture channel bleeding in patients with aneurysmal subarachnoid hemorrhage · 2026 · DOI

  • This study has several limitations that should be considered when interpreting the results. First, as an observational study, although we applied IPTW and E-value analyses to minimize confounding by indication and assessed the potential impact of unmeasured variables, residual confounding could not be com- pletely excluded and may have influenced our findings. Second, in clinical practice, clinicians may be more inclined to choose CM for lesions with more complex anatomical locations (e.g., involvement of the basilar artery), more challenging morpholo- gies (e.g., Types III–IV), or a perceived higher procedural risk. Consequently, the CM group may represent a cohort with an intrinsically poorer prognosis, which could lead to overestima- tion of the absolute benefit of FD. Third, the generalizability of our findings is limited. As demonstrated in the subgroup analy- ses, evidence supporting the benefit of FD remains limited for the most challenging subtypes, such as basilar artery or verte- brobasilar aneurysms, particularly Types III–IV VBFAs. This un- derscores the need for highly individualized clinical decision- making and caution against overgeneralizing our conclusions to high-risk subgroups. Fourth, due to the technical complexity and inherent risks of surgical intervention near the brainstem, patients treated with microsurgical approaches for VBFAs were not included in this study. Overall, well-designed randomized clinical trials are required to further evaluate the benefits of endovascular treatment for unruptured VBFAs.

    Treatment Modalities and Long-Term Outcomes in Unruptured Vertebrobasilar Fusiform Aneurysms: A Nationwide Observational Cohort Study · 2026 · DOI

  • The condition (aneurysm rupture) and the setting (United Kingdom) are ideally suited to the methodology described and address the major limitations that exist in any other study trying to address this clinical problem. Aneurysm rupture is a binary event that would be expected to result in either hospital admission or death, with few exceptions. HES-APC and CRD provide universal coverage for these outcomes. Patients who die, are too frail or sick to be transferred to a neurosurgery unit, or have migrated around the country since the UIA diagnosis will therefore still be detected. It will also detect patients presenting late who will still more often than not eventually make contact with healthcare. Although, there are limitations to the coding, all patients and events are present in these databases. The Civil Registration Deaths database will allow identification of aSAH sudden deaths which occur in the pre-hospital setting and would otherwise be missed from hospital admission-based records. These solve the major problem in this field, in that patients who experience an aneurysm rupture do not necessarily present to the hospital managing their UIA. In fact, in this series half of rupture events were managed outside of the hospital managing the UIA (half managed in other hospitals and half suffering out of hospital death) and would be missed if local hospital records alone were used. This demonstrates the severe limitations to any series based only on clinically available follow-up. One limitation is that although we are confident of coverage of rupture events that occurred in Southampton, we had to make estimates of the number of cases missed by HES-APC that were managed in other centres based on the assumption of similar coding practices between hospitals. ROAR will also use hospital admission data from Patient Episode Database for Wales (PEDW) and Scottish Morbidity Records (SMR), and death data from National Records for Scotland (NRS)-Deaths for rupture events occurring in Wales and Scotland. It is not known how the high sensitivity in the current data will generalise to patients identified in other home nations. PLOS Digital Health | https://doi.org/10.1371/journal.pdig.0001388 May 18, 2026 10 / 13 Manual case note review served as our gold standard in this study. Although we believe this was thorough, and additionally imaging was reviewed for all cases of rupture by a neurosurgeon with 10 years’ experience in neurosurgery, there remain limitations to this methodology. A prospectively followed cohort would be ideal for this purpose. A further limitation is that there is no practical gold standard to estimate rates of missed out of hospital deaths, or patients with rupture events who survived without attending hospital. This is inherent in any study of UIA in the absence of post-mortem examinations for all out of hospital deaths.

    Use of UK national health databases for detecting intra-cranial aneurysm rupture in the Risk of Aneurysm Rupture (ROAR) study · 2026 · DOI

  • Author contributions First, despite a registry-based design, data were collected mainly from two centers, which may limit generalizability and introduce selection bias. Second, the model was only validated internally; external validation is needed to confirm clinical appli- cability. Third, TyG was measured only at postoperative day 3 and may be affected by perioperative stress, so it should be inter- preted as a prognostic marker rather than a causal factor. Fourth, detailed information regarding antiplatelet therapy timing and adherence was incomplete, representing a potential confounder. Fifth, as an observational study, residual confounding and treat- ment-selection bias could not be fully eliminated. Although ACS and cerebral infarction represent distinct clinical entities, the consistent directionality and robust predictive performance observed in component-specific analyses support the clinical validity of the composite ICCE endpoint for capturing overall post-treatment vascular vulnerability. YH: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing, Software. SC: Data curation, Investigation, Writing – review & editing. DL: Data curation, Investigation, Writing – review & editing. ZZ: Methodology, Validation, Writing – review & editing. YL: Methodology, Validation, Writing – review & editing. YW: Conceptualization, Funding acquisition, Project admin- istration, Supervision, Writing – review & editing.

    Machine learning-based prediction of ischemic cardio-cerebrovascular events after endovascular or microsurgical treatment of unruptured intracranial aneurysms and risk stratification by the early post-treatment triglyceride-glucose index · 2026 · DOI

  • Our study has several limitations. The evidence is weakened by the heterogeneity between included studies and the rarity of the disease. Due to the rarity of the disease and complications following FD placement, meta-regression was limited, missing some correlated factors. Many of the included studies did not provide a clear or standardized definition of BBAs. Variations in occlusion criteria restricted our analysis to complete occlusion. Short follow-up periods may have affected observed clinical safety and efficacy. The time between symptom onset and treat- ment varied significantly, influencing occlusion and complica- tion rates. Most studies were small and monocentric, potentially causing a small study effect. Some studies had overlapping patients but were included due to incomplete overlap and addi- tional data provided for these patients.

    Safety and efficacy of flow diversion for blood blister aneurysms: A comprehensive systematic review and meta-analysis · 2026 · DOI

  • The negative correlation observed between elevated CSF ApoC3 levels and poor prognosis may be related to inflammation, oxidative stress, and dysregulated lipid ratios.

    Elevated ApoC3 levels in cerebrospinal fluid predict poor outcomes in patients with aneurysmal subarachnoid hemorrhage · 2026 · DOI

  • In the 3D group, titanium implants predominated, with only a few PEEK implants, and as these materials differ in biomechanical and complication-related properties, this heterogeneity is a study limitation.

    Outcomes of cranioplasty with customized artificial bone flap made by 3D printing technique in patients with aneurysmal subarachnoid hemorrhage · 2026 · DOI

  • in one-third infarction stent-assisted approximately Notably, a prior case series involving 26 branch vesselinvolving aneurysms (BVA) treated with coiling showed that only 31% achieved near-complete occlusion (whereas 50% had a residual neck), and 23% recurred at follow-up (4). Beyond complicating durability, BVAs also carry higher procedural risk, with prior studies reporting branch vesselterritory of BVA coiling cases, despite overall technical success (5). techniques have Although balloon- and expanded the utility of endovascular coiling, BVAs have been shown to limit optimal results (4, 6, 7). Thus, the existing studies and fails to account for the role of various confounders on aneurysm occlusion, specifically in the context of BVAs. Packing density (PD) is the percentage of the aneurysm volume that is occupied by implanted coils and can act as a quantitative measure of and treatment success (8). Furthermore, the presence of small from branch vessels originating the aneurysm, which cannot be protected with the use of double-catheter techniques (such as balloon- or stent-assisted coiling), are compromise feature a potentially notable coiling durability. aneurysm occlusion comparative that may literature larger lacks critical endovascular To this end, we collected a cohort of IAs with and without branch vessel involvement and conducted a propensity score-matched analysis to evaluate the impact on postprocedural PD, Raymond-Roy Occlusion Classification (RROC), recurrence, and retreatment. Our study offers novel insights into a critically understudied but important morphological feature and seeks to inform both procedural planning in aneurysm management.

    Presence of small and large branch vessels from intracranial aneurysms increases the risk of post-treatment recurrence and retreatment following endovascular coiling: insights from a propensity score-matched cohort · 2026 · DOI

  • BackgroundAlthough calcium channel blockers (CCBs) are useful in stroke prevention, their specific role in preventing stroke in hypertensive patients with intracranial aneurysms undergoing endovascular stent placement remains unclear.

    Effects of calcium channel blockers on perioperative ischemic events in hypertensive patients with intracranial aneurysms undergoing neurointervention · 2024 · DOI

  • RONSD at admis- sion showed good predictive performance for myocardial injury, and the underlying explanation warrants further study.

    A novel clinical perspective on subarachnoid hemorrhage complicated by myocardial injury: independent predictors and short-term prognostic assessment · 2026 · DOI

  • Background: Giant thrombosed anterior communicating artery (AComA) aneurysms represent a significant neurosurgical challenge with no consensus regarding their optimal management.

    Clipping of a giant thrombosed anterior communicating artery aneurysm with A3–A3 bypass: A technical case report with 4K video · 2026 · DOI

  • All above observations are limited to these 2 individuals and cannot be generalized to all SAH patients without large independent cohort validation.

    Integrated analysis of scRNA-seq and TCR-seq on T cells in aneurysmal subarachnoid hemorrhage: A descriptive, hypothesis-generating case study · 2026 · DOI

  • While CTA-based vasospasm grading is frequently used, its relationship with actual cerebral perfusion remains incompletely understood.

    Beyond Binary Vasospasm: A Continuum Model Relating Severity and Distribution to Perfusion Deficits After Aneurysmal SAH · 2026 · DOI

  • The non-randomized selection of cranioplasty materials may have introduced selection bias, as patient or guardian choice rather than predetermined criteria determined implant use.

    Outcomes of cranioplasty with customized artificial bone flap made by 3D printing technique in patients with aneurysmal subarachnoid hemorrhage · 2026 · DOI

  • The interaction between VP shunt and cranioplasty outcomes, particularly in patients with aSAH, warrants further investigation.

    Outcomes of cranioplasty with customized artificial bone flap made by 3D printing technique in patients with aneurysmal subarachnoid hemorrhage · 2026 · DOI

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36 open questions have been extracted from the limitations and future-work passages of 223 Intracranial Aneurysms: Treatment and Complications papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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