Connolly, E. Sander

BACKGROUND AND OBJECTIVES: Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs. METHODS: The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literature related to the clinical care of CM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and imaging standards, (4) neurosurgical considerations, and (5) neurological considerations. Building on prior evidence-based recommendations reflecting literature review through October 2014, the group conducted a systematic review of the more recent literature, identified references for mandatory citation, rated evidence, developed recommendations, and established consensus according to a prespecified protocol. Finally, the writing group outlined remaining knowledge gaps and controversies to guide future research. RESULTS: From 2672 publications published between October 1, 2014, and March 15, 2023, and meeting key word criteria, 234 were selected based on prearticulated criteria for mandatory consideration in evidence-based recommendations. Topic authors used these and other supporting references to summarize current knowledge and arrive at 53 management recommendations, with unanimous consensus based on a Delphi process. These were rated by class (strength of recommendation) and level (quality of evidence) per the American Heart Association/American Stroke Association criteria. Eighteen recommendations were class 1 (34%), class 2 in 31 (58%), and class 3 in 4 (8%). Three were level A (6%), 19 (36%) were level B, and 31 (58%) were level C. CONCLUSION: Current evidence supports prior and new recommendations for the management of CMs, but many reflect moderate classes and low levels, mandating further research to better inform clinical practice.

Objective: We previously derived the Unruptured Intracranial Aneurysm Treatment Score (UIATS), designed using a multidisciplinary consensus approach among neurovascular specialists from diverse geographic and practice backgrounds. Here, we report on the development and validation of the final version of UIATS. Method: An international, multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 (39 panel members and 30 blinded external reviewers) specialists in the research and treatment of UIAs was convened. A web survey-based Delphi consensus process consisting of 7 rounds was utilized to rate numerous features of potential relevance in the assessment and treatment of UIAs and to develop the UIATS. Mean ratings were repeatedly used to determine statistical weight for each factor and then transformed into corresponding scores for every item to create the UIATS. For internal and blinded external validation, 30 representative cases of patients with UIAs were used to test the level of agreement (5 point Likert Scale) with treatment recommendations based on the UIATS. Results: The final UIATS system was designed in three domains (patient-, aneurysm - and treatment-related), comprising 13 different categories and 29 different features (Figure 1). Mean agreement based on Likert scores (5 indicating strong agreement and 1 indicating strong disagreement) was 4·2 for both reviewer cohorts, whereas mean agreement per case was 4·2 (panel members) and 4·5 (external reviewers) (p=0·017, Mann-Whitney-U Test). Conclusion: The final version of UIATS system was internally and externally validated by a large multidisciplinary group of neurovascular specialists, which suggests that the UIATS reflects contemporary decision-making regarding management of a patient with an UIA. The UIATS may aid clinicians in deciding on the appropriate management for an UIA.

OBJECTIVE Indication for surgery in brainstem cavernous malformations (BSCMs) is based on many case series, few comparative studies, and no randomized controlled trials. The objective of this study was to seek consensus about surgical management aspects of BSCM. METHODS A total of 29 experts were invited to participate in a multistep Delphi consensus process on the surgical treatment of BSCM. RESULTS Twenty-two (76%) of 29 experts participated in the consensus. Qualitative analysis (content analysis) of an initial open-ended question survey resulted in 99 statements regarding surgical treatment of BSCM. By using a multistep survey with 100% participation in each round, consensus was reached on 52 (53%) of 99 statements. These were grouped into 4 categories: 1) definitions and reporting standards (7/14, 50%); 2) general and patient-related aspects (11/16, 69%); 3) anatomical-, timing of surgery–, and BSCM-related aspects (22/37, 59%); and 4) clinical situation–based decision-making (12/32, 38%). Among other things, a consensus was reached for surgical timing, handling of associated developmental venous anomalies, handling of postoperative BSCM remnants, assessment of specific anatomical BSCM localizations, and treatment decisions in typical clinical BSCM scenarios. CONCLUSIONS A summary of typical clinical scenarios and a catalog of various BSCM- and patient-related aspects that influence the surgical treatment decision have been defined, rated, and interpreted.

Background: Perfusion weighted imaging on MRI (MRP) and computerized tomography perfusion (CTP) are increasingly required to manage large vessel disease. Computerized algorithms can quantify perfusion data, but the programs are expensive and not widely used outside acute stroke evaluation. We aimed to determine how well human observers can identify asymmetries in cerebral perfusion images compared with an automated computer algorithm. Methods: Ten clinicians experienced in treating carotid artery disease (4 vascular neurologists, 3 neuroradiologists, 1 vascular surgeon, 1 neurosurgeon, 1 interventional radiologist) were given 28 post-processed, color-coded, axial-slice MRP scans from patients in the Carotid Revascularization Endovascular versus Stenting Trial - Hemodynamics (CREST-H) study. All patients had >70%, unilateral, asymptomatic carotid artery stenosis and had varying degrees of time-to-peak (TTP) delay on the side of stenosis, ranging from 0 to 2 secs, quantified by a semi-automated system that computes quantitative perfusion maps, using deconvolution of tissue and arterial signals (Olea, Cambridge, MA). A minimum volume of 10cc was required for a given TTP delay. Clinicians were asked to determine asymmetry (y/n) and side of occlusion for each case. Number of correct responses that matched the computer output were tallied. Results: We averaged correct responses by the 10 clinicians for cases at each increment of TTP delay; (Figure). At TTP delays ≥1.5 seconds, accuracy was ≥80%. At 1.25 sec accuracy fell to 60%, and at ≤ 1 sec, accuracy was ≤50%. For TTP=0 (no asymmetry), accuracy was 71%. Conclusions: Visual impression of hemodynamic asymmetry among experienced clinicians was reasonably accurate for TTP delays ≥1.5 seconds, but declined with more subtle asymmetries. Depending on the clinical impact of TTP delays (for CREST-H: correlation with cognitive decline), experienced clinicians may perform as well as an automated algorithm.

The American Board of Neurological Surgery (ABNS) was incorporated in 1940 in recognition of the need for detailed training in and special qualifications for the practice of neurological surgery and for self-regulation of quality and safety in the field. The ABNS believes it is the duty of neurosurgeons to place a patient’s welfare and rights above all other considerations and to provide care with compassion, respect for human dignity, honesty, and integrity. At its inception, the ABNS was the 13th member board of the American Board of Medical Specialties (ABMS), which itself was founded in 1933. Today, the ABNS is one of the 24 member boards of the ABMS. To better serve public health and safety in a rapidly changing healthcare environment, the ABNS continues to evolve in order to elevate standards for the practice of neurological surgery. In connection with its activities, including initial certification, recognition of focused practice, and continuous certification, the ABNS actively seeks and incorporates input from the public and the physicians it serves. The ABNS board certification processes are designed to evaluate both real-life subspecialty neurosurgical practice and overall neurosurgical knowledge, since most neurosurgeons provide call coverage for hospitals and thus must be competent to care for the full spectrum of neurosurgery. The purpose of this report is to describe the history, current state, and anticipated future direction of ABNS certification in the US.

Rationale For patients with asymptomatic high-grade carotid stenosis, clinical investigations have focused on preventing cerebral infarction, yet stenosis that reduces cerebral blood flow may independently impair cognition. Whether revascularization of a hemodynamically significant carotid stenosis can alter the course of cognitive decline has never been investigated in the context of a randomized clinical trial. Hypothesis Among patients randomized in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST-2) trials, the magnitude of treatment differences (revascularization versus medical management alone) with regard to cognition will differ between those with flow impairment compared to those without flow impairment. Sample size We will enroll approximately 500 patients from CREST-2, of which we anticipate 100 will have hemodynamic impairment. We estimate 93% power to detect a clinically meaningful treatment difference of 0.5 SD. Methods and design We will use perfusion-weighted magnetic resonance imaging to stratify by hemodynamic status. Linear regression will compare treatment differences, controlling for baseline cognitive status, age, depression, prior cerebral infarcts, silent infarction, white matter hyperintensity volume, and cerebral microbleeds. Study outcomes The primary outcome is change in cognition at one year. Secondary outcomes include silent infarction, change in white matter hyperintensity volume, number of cerebral microbleeds, and cortical thickness over one year. Discussion If cognitive impairment can be shown to be reversible by revascularization, then we can redefine “symptomatic carotid stenosis” to include cognitive impairment and identify a new population of patients likely to benefit from revascularization. Trial Registration US National Institutes of Health (NIH) clinicaltrials.gov NCT03121209

Background and Purpose— To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. Methods— After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Results— Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Conclusions— Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Background and Purpose— Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. Methods— We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family’s proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. Results— There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04–2.27]; P =0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22–3.22]; P =0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05–8.24], P =0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34–2.46]; P <0.001). Conclusions— In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.

Background Higher mortality for patients with aneurysmal subarachnoid haemorrhage has been reported. Aims In families with intracranial aneurysms, we sought to determine whether mortality among subjects with intracranial aneurysm (affected) was higher and related to rupture, compared with unaffected family members. Methods Subjects enrolled in the Familial Intracranial Aneurysm protocol were contacted yearly and their status was obtained. If reported to be deceased, the cause of death was verified by available records. A Cox proportional hazards model was utilized to compare mortality rates. Results Of the 2794 subjects, 1073 were affected and 1721 were unaffected. There were 8525 person-years of follow-up (mean 3·05 ± 1·73 years) and 85 deaths. Age at study entry for the affected (58·4 ±11·9 years) was significantly older ( P < 0·0001) than for the unaffected (52·2 ± 16·1). After adjusting for age, the overall mortality rate for the affected subjects was not significantly different from that for the unaffected (Rate Ratio [RR] 1·26, 95% confidence interval 0·82–1·93, P = 0·292). There was a strong effect modification due to age. The mortality rate ratio of the affected to the unaffected who were ≤60 years of age was RR = 3·48 (95% confidence interval: 1·59–7·63, P = 0·002), the rate for the affected subjects who were ≥60 was less than the rate for the unaffected (RR = 0·69, 95% confidence interval: 0·404–1·19, P = 0·178). The affected who had ruptures had 2·62 times the mortality rate as those without ruptures (95% confidence interval 1·43–4·80, P = 0·002). Conclusion The overall mortality was similar for the affected and unaffected subjects in this cohort. Among the affected only, those with ruptured intracranial aneurysm had a higher mortality rate than those without ruptured.

Object Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry. Results Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p < 0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p = 0.016). Conclusions Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.