Management of tiny unruptured intracranial aneurysms: A comparative effectiveness analysis

© 2017 American Medical Association. All rights reserved. Importance: Unruptured intracranial aneurysms (UIAs) are relatively common in the general population and are being increasingly diagnosed; a significant proportion are tiny (≤3 mm) aneurysms. There is significant heterogeneity in practice and lack of clear guidelines on the management of incidental, tiny UIAs. It is important to quantify the implications of different management strategies in terms of health benefits to patients. Objective: To evaluate the effectiveness of routine treatment (aneurysm coiling) vs 3 strategies for imaging surveillance compared with no preventive treatment or routine follow-up of tiny UIAs. Design, Setting, and Participants: A decision-analytic model-based comparative effectiveness analysis was conducted from May 1 to June 30, 2017, using inputs from the medical literature. PubMed searches were performed to identify relevant literature for all key model inputs, each of which was derived from the clinical study with the most robust data and greatest applicability. Analysis included 10 000 iterations simulating adult patients with incidental detections of UIAs 3 mm or smaller and no history of subarachnoid hemorrhage. Interventions: The following 5 management strategies for tiny UIAs were evaluated: annual magnetic resonance angiography (MRA) screening, biennial MRA screening, MRA screening every 5 years, aneurysm coiling and follow-up, and no treatment or preventive follow-up. Main Outcomes and Measures: A Markov decision model for lifetime rupture was constructed from a societal perspective per 10 000 patients with incidental, tiny UIAs. Outcomes were assessed in terms of quality-adjusted life-years. Probabilistic, 1-way, and 2-way sensitivity analyses were performed. Results: In this analysis of 10000 iterations simulating adult patients with a mean age of 50 years, the base-case calculation shows that the management strategy of no treatment or preventive follow-up has the highest health benefit (mean [SD] quality-adjusted life-years, 19.40[0.31]). Among the management strategies that incorporate follow-up imaging, MRA every 5 years is the best strategy with the next highest effectiveness (mean [SD] quality-adjusted life-years, 18.05 [0.62]). The conclusion remains robust in probabilistic and 1-way sensitivity analyses. Noroutine follow-up remains the optimal strategy when the annual growth rate and risk of rupture of growing aneurysms are varied. When the annual risk of rupture of nongrowing UIAs is less than 1.7%(0.23% in base case scenario), no follow-up is the optimal strategy. If annual risk of rupture is more than 1.7%, coiling should be performed directly. Conclusions and Relevance: Given the current literature, no preventive treatment or imaging follow-up is the most effective strategy in patients with aneurysms that are 3mm or smaller, resulting in better health outcomes. More aggressive imaging surveillance for aneurysm growth or preventive treatment should be reserved for patients with a high risk of rupture. Given these findings, it is important to critically evaluate the appropriateness of current clinical practices, and potentially determine specific guidelines to reflect the most effective management strategy for patients with incidental, tiny UIAs

Woven Endobridge (WEB) Device as a Re-treatment Strategy after Unsuccessful Surgical Clipping

BACKGROUND: Surgical clipping of intracranial aneurysms is typically robust and durable. However, residual aneurysmal components may be seen after clipping. Furthermore, there may be occasional aneurysmal recurrence. These factors are both clinically relevant because subarachnoid hemorrhage after clipping is a rare but important event. The rationale for any treatment is to substantially decrease the future risk of hemorrhage. Small series have shown coiling as a retreatment strategy after unsuccessful clipping, but none has explored the feasibility of Woven Endobridge (WEB) implantation. CASE DESCRIPTION: We examined the feasibility of WEB implantation as second-line treatment for wide-necked residual aneurysms after unsuccessful clipping. We also recorded the safety and efficacy in this small series of 6 patients. To determine safety, we measured the modified Rankin Scale score before and after the procedure, and at 2 later time points (mean follow-up, 5 months and 15 months). To determine efficacy, we obtained radiographic aneurysm occlusion outcomes (including WEB Occlusion Scale) at these 2 time points. Four middle cerebral artery and 2 anterior communicating artery complex aneurysms were treated with WEB implantation, showing feasibility in 6/6 cases (100%). Follow-up at 15 months showed no change from preprocedural modified Rankin Scale score and there were no other complications. There was adequate occlusion in 5/6 cases (83%). CONCLUSIONS: WEB implantation provided a feasible option in this challenging retreatment scenario. This is a small series and prospective data are required to make outcome inferences for this population. Nonetheless, we observed no complications and high adequate occlusion rates

A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials

The trial on endovascular management of unruptured intracranial aneurysms (TEAM), a prospective randomized trial comparing coiling and conservative management, initiated in September 2006, was stopped in June 2009 because of poor recruitment (80 patients). Aspects of the trial design that may have contributed to this failure are reviewed in the hope of identifying better ways to successfully complete this special type of pragmatic trial which seeks to test two strategies that are in routine clinical use. Cultural, conceptual and bureaucratic hurdles and difficulties obstruct all trials. These obstacles are however particularly misplaced when the trial aims to identify what a good medical practice should be. A clean separation between research and practice, with diverging ethical and scientific requirements, has been enforced for decades, but it cannot work when care needs to be provided in the presence of pervasive uncertainty. Hence valid and robust scientific methods need to be legitimately re-integrated into clinical practice when reliable knowledge is in want

Endovascular Treatment of Brain Aneurysms

Topic: Chapter discussing the indications for treatment of brain aneurysms, endovascular techniques, tips and tricks. 1. Pathophysiology of aneurysms: Discuss the formation of aneurysms, current thinking of aneurysm development 2. Prevalence/Incidence of aneurysms: Discussion of current state of aneurysm prevalence and how it differs in different populations 3. Unruptured Aneurysms: Diagnosis, Management and Treatment: Imaging paradigms of brain aneurysms, current thoughts on how to follow aneurysms which are being observed, different treatment options for unruptured aneurysms, including clipping, coiling, stent assisted coiling, flow diverter stent, flow disruptors, including the medical management of stent placement 4. Ruptured Aneurysms: Diagnosis, Management and Treatment: Imaging paradigms of ruptured aneurysms, management options for co-morbidities associated with aneurysm rupture, treatment options including coiling, clipping, flow diverter stents, flow disruptors 5. Complication Avoidance: Tips and tricks to avoid complications in the treatment of brain aneurysms

Aneurysmal Subarachnoid Haemorrhage: An investigation of the utility of MRI as a non-invasive diagnostic tool and its acceptability as an alternative to lumbar puncture

Background Aneurysmal subarachnoid haemorrhage (SAH) is a potentially devastating but treatable condition, the seriousness of which is not always immediately apparent. An invasive test: the lumbar puncture (LP), is considered a mandatory part of the diagnostic pathway according to guidelines but is frequently omitted in clinical practice. Aims 1. To establish the extent to which current clinical practice diverges from recommendations. 2. To investigate the beliefs that inform clinician behaviour and establish if the demands required of a diagnostic test for SAH are best achieved by MRI or lumbar puncture. 3. To establish whether MRI has the potential to improve detection of spontaneous SAH compared to CT. Method 1. The use of LP in cases of suspected SAH was audited at three major teaching hospitals in London. 2. A survey was conducted at major neuroscience centres in London to investigate clinicians’ experiences of SAH investigation and their expectations of diagnostic test performance. 3. A prospective imaging study compared the relative locational sensitivities of CT and MRI to detect subarachnoid haemorrhage in a group of clinically well patients. Results LP was performed in a minority of patients undergoing CT as an investigation for suspected acute SAH (33%). Clinicians demonstrate wide-ranging opinions about the risks and benefits of SAH investigation strategies, with Emergency Medicine clinicians reporting significantly higher risk tolerances compared to Neuroscience clinicians. Blood-sensitive MRI sequences detected more regions of SAH compared to CT in a cohort of neurologically intact, treatment naïve, spontaneous SAH. Conclusion Low adherence to the recommended diagnostic pathway exists in UK practice. This may reflect different risk-tolerances of clinicians and legitimate concerns about the utility of LP. Future guidelines should consider patient and doctor risk-tolerances when making recommendations. MRI has potential value as an alternative non-invasive test and could reduce time, cost and patient discomfort

Clinical and genetic studies on the causes and prognosis of intracranial haemorrhage

Introduction: Intracranial haemorrhage occurs within the compartments of the intracranial vault (skull). Spontaneous (non-traumatic) intracerebral haemorrhage (ICH) and aneurysmal subarachnoid haemorrhage (aSAH) have a high mortality and morbidity rate, while convexity subarachnoid haemorrhage (cSAH) in older people is associated with a high risk of future intracranial bleeding. In this thesis I present several studies investigating factors associated with the development and prognosis of ICH, aSAH cSAH. Methods: I evaluated patients recruited to the Genetics and Observational Subarachnoid Haemorrhage (GOSH) study with aSAH or unruptured intracranial aneurysm as well as patients with ICH recruited to the Clinical Relevance Of Cerebral Microbleeds In Stroke (CROMIS-2) study, both multicentre observational studies recruiting patients from the UK. Individual patient data was also collected for meta-analysis of published studies. Main findings: 1) We found a different risk factor profile in patients with aSAH compared to patients with unruptured intracranial aneurysms and continued our research by validating a prediction model for the prediction of long-term functional outcome after aSAH; 2) in our cohort of patients with convexity SAH we found that it is associated with a higher rate of symptomatic ICH in patients with probable cerebral amyloid angiopathy (CAA); 3) our genetic association analysis showed that Haptoglobin might be associated with mortality after ICH. Additionally, Apolipoprotein E is associated with novel neuroimaging markers of CAA. In our genome-wide association analysis we found new loci (rs4675692) associated with ICH status in a genome-wide association study (but did not find a repeat expansion for C9orf72) and finally found previously reported and novel genetic variants in familial aSAH. Conclusion: These findings, in diverse cohorts, confirm the importance of clinical, radiological and genetic factors for disease expression and prognosis in different forms of intracranial haemorrhage

New Insight into Cerebrovascular Diseases

“Brain circulation is a true road map that consists of large extended navigation territories and a number of unimagined and undiscovered routes.” Dr. Patricia Bozzetto Ambrosi This book combines an update on the review of cerebrovascular diseases in the form of textbook chapters, which has been carefully reviewed by Dr. Patricia Bozzetto Ambrosi, Drs. Rufai Ahmad and Auwal Abdullahi and Dr. Amit Agrawal, high-performance academic editors with extensive experience in neurodisciplines, including neurology, neurosurgery, neuroscience, and neuroradiology, covering the best standards of neurological practice involving basic and clinical aspects of cerebrovascular diseases. Each topic was carefully revised and prepared using smooth, structured vocabulary, plus superb graphics and scientific illustrations. In emphasizing the most common aspects of cerebrovascular diseases: stroke burden, pathophysiology, hemodynamics, diagnosis, management, repair, and healing, the book is comprehensive but concise and should become the standard reference guide for this neurological approach

Genetic and Observational Subarachnoid Haemorrhage (GOSH) Study - A UK-wide clinical and genetic cohort study of aneurysmal subarachnoid haemorrhage

Introduction: Intracranial aneurysms affect 2-5% of the general population.1 A tiny proportion of these rupture leading to aneurysmal subarachnoid haemorrhage (SAH), which can be fatal instantly or lead to life-changing neurological morbidity in a young group of stroke survivors. Understanding the pathophysiological mechanisms underlying intracranial aneurysms, and being able to predict which patients have a higher risk of rupture has led to intensive research efforts, via epidemiological, molecular and genetic studies. Our aim was to determine the association of candidate genes with intracranial aneurysms in a large UK Caucasian population. Methods: We performed a case-control genetic association study of single nucleotide polymorphisms (SNPs) in over 1600 patients with intracranial aneurysms from a UK-wide Genetic and Observational Subarachnoid Haemorrhage (GOSH) study and 1500 controls from the Wellcome cohort,2 utilising a candidate-gene approach. We conducted a literature review and performed a meta-analysis of the existing candidate gene studies to better determine which genes would be suitable for analysis in our cohort. We also performed a new meta-analysis using our data for each SNP examined to determine if our genetic associations with intracranial aneurysms were robust. Results: We examined 22 SNPs related to vascular endothelial integrity, the extracellular matrix, and inflammation. Two SNPs showed associations with intracranial aneurysms in our UK cohort: the D allele of ACE Insertion/Deletion SNP (associated with vascular endothelial function; OR 1.14 [1.02-1.28], p=0.02) and the MMP-2 C>T rs243865 SNP (associated with extracellular matrix integrity; OR 1.18 [1.04 – 1.33], p=0.012). Conclusions: We found associations with intracranial aneurysms for the D allele of the ACE I/D SNP, and a potentially functionally significant MMP-2 SNP. Both genes have plausible connections to IA pathophysiology (endothelial function and extracellular matrix integrity, respectively), and could potentially predispose patient to aneurysm rupture as demonstrated by sub-group analysis