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Menno R. Germans, Blessing N. R. Jaja, Airton Leonardo de Oliviera Manoel, Ashley H. Cohen and R. Loch Macdonald

OBJECTIVE

In this study the authors sought to investigate the sex differences in the risk of delayed cerebral ischemia (DCI), delayed cerebral infarction, and the role of hormonal status.

METHODS

Ten studies included in the SAHIT (SAH International Trialists) repository were analyzed using a fitting logistic regression model. Heterogeneity between the studies was tested using I2 statistics, and the results were pooled using a random-effects model. Multivariable analysis was adjusted for the effects of neurological status and fixed effect of study. An additional model was examined in which women and men were split into groups according to an age cut point of 55 years, as a surrogate to define hormonal status.

RESULTS

A pooled cohort of 6713 patients was analyzed. The risk of DCI was statistically significantly higher in women than in men (OR 1.29, 95% CI 1.12–1.48); no difference was found with respect to cerebral infarction (OR 1.17, 95% CI 0.98–1.40). No difference was found in the risk of DCI when comparing women ≤ 55 and > 55 years (OR 0.87, 95% CI 0.74–1.02; p = 0.08) or when comparing men ≤ 55 and > 55 years (p = 0.38). Independent predictors of DCI were World Federation of Neurosurgical Societies (WFNS) grade, Fisher grade, age, and sex. Independent predictors of infarction included WFNS grade, Fisher grade, and aneurysm size.

CONCLUSIONS

Female sex is associated with a higher risk of DCI. Sex differences may play a role in the pathogenesis of DCI but are not associated with menopausal status. The predictors of DCI and cerebral infarction were identified in a very large cohort and reflect experience from multiple institutions.

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Matthew E. Eagles, Michael K. Tso and R. Loch Macdonald

OBJECTIVE

Fluctuations in patient serum sodium levels are common after aneurysmal subarachnoid hemorrhage (aSAH), but their effect on patient outcome is not well described in the literature. The goal of this work was to better characterize the relationship between fluctuations in serum sodium levels, outcome, and the development of delayed cerebral ischemia (DCI) after aSAH.

METHODS

The authors performed a post hoc analysis of data from the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. Patients had their serum sodium values recorded daily for 14 days post-aSAH. Average and average absolute daily differences in sodium levels were calculated for each patient based on 3 reference points: admission sodium levels, a normal sodium level (defined as 140 mmol/L), and the previous day’s sodium level. These variables were also calculated for the classic “vasospasm window” (days 3–12) post-aSAH. A stepwise logistic regression model, locally weighted scatterplot smoothing curves, and receiver operator characteristic curve analysis were used to evaluate the relationship between alterations in serum sodium levels and clinical outcome or the development of DCI after aSAH. Poor outcome was defined as a modified Rankin Scale (mRS) score of > 2 at 3 months.

RESULTS

The average daily difference in sodium values from baseline (p < 0.001), average daily difference from a normal sodium level (p < 0.001), average absolute daily difference from a normal sodium level (p = 0.015), and average absolute daily difference from the previous day’s sodium level (p = 0.017) were significant predictors of poor outcome in a stepwise multivariate regression model. There was a trend toward significance for average absolute daily difference from admission sodium levels during the vasospasm window as an independent predictor of DCI (p = 0.052). There was no difference in the predictive capacity for DCI when sodium fluctuations from post-aSAH days 1–14 were compared with those from the classic vasospasm window (days 3–12).

CONCLUSIONS

Fluctuations in serum sodium levels may play a role in clinical outcome and the development of DCI after aSAH. The timing of these fluctuations appears to have no significant effect on the development of DCI.

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Tim E. Darsaut, Robert Fahed, R. Loch Macdonald, Adam S. Arthur, M. Yashar S. Kalani, Fuat Arikan, Daniel Roy, Alain Weill, Alain Bilocq, Jeremy L. Rempel, Michael M. Chow, Robert A. Ashforth, J. Max Findlay, Luis H. Castro-Afonso, Miguel Chagnon, Guylaine Gevry and Jean Raymond

OBJECTIVE

Ruptured intracranial aneurysms (RIAs) can be managed surgically or endovascularly. In this study, the authors aimed to measure the interobserver agreement in selecting the best management option for various patients with an RIA.

METHODS

The authors constructed an electronic portfolio of 42 cases of RIA in which an angiographic image along with a brief clinical vignette for each patient were displayed. Undisclosed to the responders was that the RIAs had been categorized as International Subarachnoid Aneurysm Trial (ISAT) (small, anterior-circulation, non–middle cerebral artery location, n = 18) and non-ISAT (n = 22) aneurysms; the non-ISAT group also included 2 basilar apex aneurysms for which a high number of endovascular choices was expected. The portfolio was sent to 132 clinicians who manage patients with RIAs and circulated to members of an American surgical association. Judges were asked to choose between surgical and endovascular management, to indicate their level of confidence in the choice of treatment on a quantitative 0–10 scale, and to determine whether they would include the patient in a randomized trial in which both treatments are compared. Eleven clinicians were asked to respond twice at least 1 month apart. Responses were analyzed using kappa statistics.

RESULTS

Eighty-five clinicians (58 cerebrovascular surgeons, 21 interventional neuroradiologists, and 6 interventional neurologists) answered the questionnaire. Overall, endovascular management was chosen more frequently (n = 2136 [59.8%] of 3570 answers). The proportions of decisions to clip were significantly higher for non-ISAT (50.8%) than for ISAT (26.2%) aneurysms (p = 0.0003). Interjudge agreement was only fair (kappa 0.210, 95% CI 0.158–0.276) for all cases and judges, despite high confidence levels (mean score > 8 for all cases). Agreement was no better within subgroups of clinicians with the same specialty, years of experience, or location of practice or across capability groups (ability to clip or coil, or both). When agreement was defined as > 80% of responders choosing the same option, agreement occurred for only 7 of 40 cases, all of which were ISAT aneurysms, for which coiling was preferred.

CONCLUSIONS

Agreement between clinicians regarding the best management option was infrequent but centered around coiling for some ISAT aneurysms. Surgical clipping was chosen more frequently for non-ISAT aneurysms than for ISAT aneurysms. Patients with such an aneurysm might be candidates for inclusion in randomized trials.

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Naif M. Alotaibi, Ghassan Awad Elkarim, Nardin Samuel, Oliver G. S. Ayling, Daipayan Guha, Aria Fallah, Abdulrahman Aldakkan, Blessing N. R. Jaja, Airton Leonardo de Oliveira Manoel, George M. Ibrahim and R. Loch Macdonald

OBJECTIVE

Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to assess the impact of DC on functional outcome and death in patients after poor-grade aSAH.

METHODS

A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified through the Ovid Medline, Embase, Web of Science, and Cochrane Library databases from inception to October 2015. Only studies dedicated to patients with poor-grade aSAH were included. Primary outcomes were death and functional outcome assessed at any time period. Patients were grouped as having a favorable outcome (modified Rankin Scale [mRS] Scores 1–3, Glasgow Outcome Scale [GOS] Scores 4 and 5, extended Glasgow Outcome Scale [GOSE] Scores 5–8) or unfavorable outcome (mRS Scores 4–6, GOS Scores 1–3, GOSE Scores 1–4). Pooled estimates of event rates and odds ratios with 95% confidence intervals were calculated using the random-effects model.

RESULTS

Fifteen studies encompassing 407 patients were included in the meta-analysis (all observational cohorts). The pooled event rate for poor outcome across all studies was 61.2% (95% CI 52%–69%) and for death was 27.8% (95% CI 21%–35%) at a median of 12 months after aSAH. Primary (or early) DC resulted in a lower overall event rate for unfavorable outcome than secondary (or delayed) DC (47.5% [95% CI 31%–64%] vs 74.4% [95% CI 43%–91%], respectively). Among studies with comparison groups, there was a trend toward a reduced mortality rate 1–3 months after discharge among patients who did not undergo DC (OR 0.58 [95% CI 0.27–1.25]; p = 0.168). However, this trend was not sustained at the 1-year follow-up (OR 1.09 [95% CI 0.55–2.13]; p = 0.79).

CONCLUSIONS

Results of this study summarize the best evidence available in the literature for DC in patients with poor-grade aSAH. DC is associated with high rates of unfavorable outcome and death. Because of the lack of robust control groups in a majority of the studies, the effect of DC on functional outcomes versus that of other interventions for refractory intracranial hypertension is still unknown. A randomized trial is needed.

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Naif M. Alotaibi, Daipayan Guha, Christopher S. Ahuja, Julian Spears, Paul J. Muller, William S. Tucker, Alan R. Hudson and R. Loch Macdonald

In this paper, the authors describe the history of neurosurgery at St. Michael's Hospital, University of Toronto. St. Michael's has long been regarded as one of the top teaching and research hospitals in Canada. A detailed literature review of published and unpublished works was performed to formulate a succinct but in-depth review of its development, successes, and challenges. This fascinating 125-year history serves as a reminder of the importance of their institution's origins, and the authors hope that it will be a useful guide for developing programs around the world.

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Naif M. Alotaibi, Justin Z. Wang, Christopher R. Pasarikovski, Daipayan Guha, Fawaz Al-Mufti, Muhammad Mamdani, Gustavo Saposnik, Tom A. Schweizer and R. Loch Macdonald

Elevated intracranial pressure (ICP) is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Despite significant advances in clinical research into aSAH, there are no consensus guidelines devoted specifically to the management of elevated ICP in the setting of aSAH. To treat high ICP in aSAH, most centers extrapolate their treatment algorithms from studies and published guidelines for traumatic brain injury. Herein, the authors review the current management strategies for treating raised ICP within the aSAH population, emphasize key differences from the traumatic brain injury population, and highlight potential directions for future research in this controversial topic.

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Anthony Wan, Blessing N. R. Jaja, Tom A. Schweizer and R. Loch Macdonald

OBJECTIVE

Intracerebral hematoma (ICH) with subarachnoid hemorrhage (SAH) indicates a unique feature of intracranial aneurysm rupture since the aneurysm is in the subarachnoid space and separated from the brain by pia mater. Broad consensus is lacking regarding the concept that ultra-early treatment improves outcome. The aim of this study is to determine the associative factors for ICH, ascertain the prognostic value of ICH, and investigate how the timing of treatment relates to the outcome of SAH with concurrent ICH.

METHODS

The study data were pooled from the SAH International Trialists repository. Logistic regression was applied to study the associations of clinical and aneurysm characteristics with ICH. Proportional odds models and dominance analysis were applied to study the effect of ICH on 3-month outcome (Glasgow Outcome Scale) and investigate the effect of time from ictus to treatment on outcome.

RESULTS

Of the 5362 SAH patients analyzed, 1120 (21%) had concurrent ICH. In order of importance, neurological status, aneurysm location, aneurysm size, and patient ethnicity were significantly associated with ICH. Patients with ICH experienced poorer outcome than those without ICH (OR 1.58; 95% CI 1.37–1.82). Treatment within 6 hours of SAH was associated with poorer outcome than treatment thereafter (adjusted OR 1.67; 95% CI 1.04–2.69). Subgroup analysis with adjustment for ICH volume, location, and midline shift resulted in no association between time from ictus to treatment and outcome (OR 0.99; 95% CI 0.94–1.07).

CONCLUSIONS

The most important associative factor for ICH is neurological status on admission. The finding regarding the value of ultra-early treatment suggests the need to more robustly reevaluate the concept that hematoma evacuation of an ICH and repair of a ruptured aneurysm within 6 hours of ictus is the most optimal treatment path.

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Blessing N. R. Jaja, Hester Lingsma, Ewout W. Steyerberg, Tom A. Schweizer, Kevin E. Thorpe and R. Loch Macdonald

OBJECT

Neuroimaging characteristics of ruptured aneurysms are important to guide treatment selection, and they have been studied for their value as outcome predictors following aneurysmal subarachnoid hemorrhage (SAH). Despite multiple studies, the prognostic value of aneurysm diameter, location, and extravasated SAH clot on computed tomography scan remains debatable. The authors aimed to more precisely ascertain the relation of these factors to outcome.

METHODS

The data sets of studies included in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository were analyzed including data on ruptured aneurysm location and diameter (7 studies, n = 9125) and on subarachnoid clot graded on the Fisher scale (8 studies; n = 9452) for the relation to outcome on the Glasgow Outcome Scale (GOS) at 3 months. Prognostic strength was quantified by fitting proportional odds logistic regression models. Univariable odds ratios (ORs) were pooled across studies using random effects models. Multivariable analyses were adjusted for fixed effect of study, age, neurological status on admission, other neuroimaging factors, and treatment modality. The neuroimaging predictors were assessed for their added incremental predictive value measured as partial R2.

RESULTS

Spline plots indicated outcomes were worse at extremes of aneurysm size, i.e., less than 4 or greater than 9 mm. In between, aneurysm size had no effect on outcome (OR 1.03, 95% CI 0.98–1.09 for 9 mm vs 4 mm, i.e., 75th vs 25th percentile), except in those who were treated conservatively (OR 1.17, 95% CI 1.02–1.35). Compared with anterior cerebral artery aneurysms, posterior circulation aneurysms tended to result in slightly poorer outcome in patients who underwent endovascular coil embolization (OR 1.13, 95% CI 0.82–1.57) or surgical clipping (OR 1.32, 95% CI 1.10–1.57); the relation was statistically significant only in the latter. Fisher CT subarachnoid clot burden was related to outcome in a gradient manner. Each of the studied predictors accounted for less than 1% of the explained variance in outcome.

CONCLUSIONS

This study, which is based on the largest cohort of patients so far analyzed, has more precisely determined the prognostic value of the studied neuroimaging factors. Treatment choice has strong influence on the prognostic effect of aneurysm size and location. These findings should guide the development of reliable prognostic models and inform the design and analysis of future prospective studies, including clinical trials.

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Tim E. Darsaut and Jean Raymond