Middle Cerebral Artery Aneurysm Trial (MCAAT): A Randomized Care Trial Comparing Surgical and Endovascular Management of MCA Aneurysm Patients.

BACKGROUND: Whether the best management of middle cerebral artery (MCA) aneurysm patients is surgical or endovascular remains uncertain, with little evidence to guide decision-making. A randomized care trial offering MCA aneurysm patients a 50% chance of surgical and a 50% chance of endovascular management may optimize outcomes in the presence of uncertainty. METHODS: The Middle Cerebral Artery Aneurysm Trial (MCAAT) is an investigator-initiated, multicenter, parallel group, prospective, 1:1 randomized controlled clinical trial. All adult patients with MCA aneurysms, ruptured or unruptured, amenable to surgical and endovascular treatment can be included. The composite primary outcome is "Treatment Success": (i) occlusion or exclusion of the aneurysm using the allocated treatment modality; (ii) no intracranial hemorrhage during follow-up; (iii) no retreatment of the target aneurysm during follow-up, (iv) no residual aneurysm on angiographic follow-up; and (v) independence (mRS <3) at 1 year. The trial tests 2 versions of the same hypothesis (one for ruptured and one for unruptured MCA aneurysm patients): Surgical management will lead to a 15% absolute increase in the proportion of patients reaching Treatment Success from 55% to 70% (ruptured) or from 75% to 90% (unruptured aneurysm patients) compared with endovascular treatment (any method). In this pragmatic trial, outcome evaluations are by treating physicians, except for 1-year angiographic results which will be core lab assessed. The trial will be monitored by an independent data safety monitoring committee to assure safety of participants. MCAAT is registered at clinicaltrials.gov: NCT05161377. CONCLUSIONS: Patients with MCA aneurysms can be optimally managed within a care trial protocol.

Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison.

OBJECTIVE: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. METHODS: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. RESULTS: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling. CONCLUSIONS: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Comprehensive Aneurysm Management (CAM): An All-Inclusive Care Trial for Unruptured Intracranial Aneurysms.

BACKGROUND: In the absence of randomized evidence, the optimal management of patients with unruptured intracranial aneurysms (UIA) remains uncertain. METHODS: Comprehensive Aneurysm Management (CAM) is an all-inclusive care trial combined with a registry. Any patient with a UIA (no history of intracranial hemorrhage within the previous 30 days) can be recruited, and treatment allocation will follow an algorithm combining clinical judgment and randomization. Patients eligible for at least 2 management options will be randomly allocated 1:1 to conservative or curative treatment. Minimization will be used to balance risk factors, using aneurysm size (≥7 mm), location (anterior or posterior circulation), and age <60 years. RESULTS: The CAM primary outcome is survival without neurologic dependency (modified Rankin Scale [mRS] score <3) at 10 years. Secondary outcome measures include the incidence of subarachnoid hemorrhage during follow-up and related morbidity and mortality; morbidity and mortality related to endovascular treatment or surgical treatment of the UIA at 1 year; overall morbidity and mortality at 1, 5, and 10 years; when relevant, duration of hospitalization; and, when relevant, discharge to a location other than home. The primary hypothesis for patients randomly allocated to at least 2 options, 1 of which is conservative management, is that active UIA treatment will reduce the 10-year combined neurologic morbidity and mortality (mRS score >2) from 24% to 16%. At least 961 patients recruited from at least 20 centers over 4 years will be needed for the randomized portion of the study. CONCLUSIONS: Patients with unruptured intracranial aneurysms can be comprehensively managed within the context of an all-inclusive care trial.

Gliosarcoma in a Young Filipino Woman: A Case Report and Review of the Literature.

BACKGROUND Gliosarcoma (GS) is a rare variant of glioblastoma (GBM), which is typically seen in patients age 40-60 years and located in the supratentorial region. We present an unusual case of GS in a young patient with an unusual presentation, which eventually led to the finding of this neoplasm. CASE REPORT Our patient was a 38-year-old woman originally from the Philippines who was transferred to our institution with an isolated left foot drop that developed over the course of several months. Subsequent neuroimaging revealed an extensive mixed cystic and solid mass in the posterior mesial right frontal lobe. Subtotal surgical resection revealed a multi-lobed tumor with a malignant glioma-like surface component overlying a smooth, well-encapsulated, avascular, sarcoma-like component. Neuropathologic examination of the resected tumor revealed a biphasic histologic pattern of predominantly sarcomatous components with fewer adjacent-area glial components. Post-operatively, the patient was left with a mild worsening of left leg segmental strength. She was referred to our neurooncologist colleagues for adjuvant treatment options. CONCLUSIONS Our case is unique in that it represents a rare neoplasm in a patient whose demographics are atypical for this type of tumor, as well as the unusual presentation of isolated foot drop.

A Systematic Review of Atypical Teratoid Rhabdoid Tumor in Adults.

Background: Atypical teratoid/rhabdoid tumor in adults is a relatively rare malignant neoplasm. It is characterized by the presence of rhabdoid cells in combination with loss of either the INI1 or BRG1protein from the tumor cells. Methods: A systematic review was conducted using MEDLINE using the terms "atypical teratoid rhabdoid tumor" AND "adult." The systematic review was supplemented with relevant articles from the references. Cases were included if the pathology was confirmed by loss of INI1 or BRG1. We included a case from our institution. The dataset was analyzed using descriptive statistics and log-rank test. Results: A total of 50 cases from 29 articles were included in this study. The average age at diagnosis was 36.7 years. The most common locations reported are the sellar region and cerebral hemispheres (without deep gray matter involvement). Of the 50 cases, 14 were reported to show evidence of dissemination. The average overall survival was 20 months. There was a significant difference in survival between the adjuvant therapy groups (p = < 0.0001). Conclusion: Atypical teratoid rhabdoid tumor of the central nervous system in adults is a rare neoplasm associated with a poor prognosis in a majority of patients. The treatment and clinical course are highly variable, and it remains unclear which factors impact prognosis.

Surgical or endovascular management of ruptured intracranial aneurysms: an agreement study.

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.

Vanishing cerebral vasculitis in a patient with Lewy pathology.

Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson's disease (PD, brainstem-predominant Lewy pathology), but the presentation of cerebral vasculitis with comorbid Lewy pathology has not yet been reported. Here we present a case of pathologically confirmed vasculitis in a 73-year-old male patient whose postmortem examination revealed Lewy pathology diagnostic of PD. This case study suggests a comorbidity of cerebral vasculitis and Lewy pathology, as well as potential pathogenic interactions between these two disorders with immune-mediated mechanisms.

Combined Stump Pressure and Oximetry for Shunt Use During Carotid Endarterectomy.

BACKGROUND: Cross-clamp ischemia during carotid endarterectomy can be prevented with carotid bypass shunts in vulnerable patients identified by cerebral monitoring for ischemia. We compared transcranial cerebral oximetry (TCO) with carotid stump pressure measurements for selective shunt use. METHODS: We prospectively collected data on 300 consecutive patients operated on under general anesthesia between 2009 and 2016. Shunts were inserted for a 10% or greater drop in cerebral saturations and/or a mean stump pressure less than 40 mmHg. RESULTS: Seventy-five patients, 25% of the study population, were shunted. The indication was a combined desaturation and stump pressure in 38 (50% of the shunted group), desaturation alone in 11 patients (15%), and a low stump pressure alone in 26 patients (35%). There were no significant differences in baseline characteristics between those patients who were or were not shunted, except angiographic collateral blood supply, which was more commonly identified in patients who were not shunted. A watershed infarct occurred in just one patient with borderline TCO and stump pressure measurements in whom a shunt was not used. CONCLUSIONS: There was poor concordance between TCO and stump pressures, but using both in determining the need for shunt use almost eliminated cross-clamp ischemia in this series of 300 carotid endarterectomy patients.

Surgical clipping or endovascular coiling for unruptured intracranial aneurysms: a pragmatic randomised trial.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed and are commonly treated using endovascular treatment or microsurgical clipping. The safety and efficacy of treatments have not been compared in a randomised trial. How to treat patients with UIAs suitable for both options remains unknown. METHODS: We randomly allocated clipping or coiling to patients with one or more 3-25 mm UIAs judged treatable both ways. The primary outcome was treatment failure, defined as: initial failure of aneurysm treatment, intracranial haemorrhage or residual aneurysm on 1-year imaging. Secondary outcomes included neurological deficits following treatment, hospitalisation >5 days, overall morbidity and mortality and angiographic results at 1 year. RESULTS: The trial was designed to include 260 patients. An analysis was performed for slow accrual: 136 patients were enrolled from 2010 through 2016 and 134 patients were treated. The 1-year primary outcome, available for 104 patients, was reached in 5/48 (10.4% (4.5%-22.2%)) patients allocated surgical clipping, and 10/56 (17.9% (10.0%-29.8%)) patients allocated endovascular coiling (OR: 0.54 (0.13-1.90), p=0.40). Morbidity and mortality (modified Rankin Scale>2) at 1 year occurred in 2/48 (4.2% (1.2%-14.0%)) and 2/56 (3.6% (1.0%-12.1%)) patients allocated clipping and coiling, respectively. New neurological deficits (15/65 vs 6/69; OR: 3.12 (1.05-10.57), p=0.031), and hospitalisations beyond 5 days (30/65 vs 6/69; OR: 8.85 (3.22-28.59), p=0.0001) were more frequent after clipping. CONCLUSION: Surgical clipping or endovascular coiling of UIAs did not show differences in morbidity at 1 year. Trial continuation and additional randomised evidence will be necessary to establish the supposed superior efficacy of clipping.

Cerebral Vasospasm: A Review.

Cerebral vasospasm is a prolonged but reversible narrowing of cerebral arteries beginning days after subarachnoid hemorrhage. Progression to cerebral ischemia is tied mostly to vasospasm severity, and its pathogenesis lies in artery encasement by blood clot, although the complex interactions between hematoma and surrounding structures are not fully understood. The delayed onset of vasospasm provides a potential opportunity for its prevention. It is disappointing that recent randomized, controlled trials did not demonstrate that the endothelin antagonist clazosentan, the cholesterol-lowering agent simvastatin, and the vasodilator magnesium sulfate improve patient outcome. Minimizing ischemia by avoiding inadequate blood volume and pressure, administering the calcium antagonist nimodipine, and intervention with balloon angioplasty, when necessary, constitutes current best management. Over the past two decades, our ability to manage vasospasm has led to a significant decline in patient morbidity and mortality from vasospasm, yet it still remains an important determinant of outcome after aneurysm rupture.

Predicting recurrence after chronic subdural haematoma drainage.

BACKGROUND: Recurrence of chronic subdural haematomas (CSDHs) after surgical drainage is a significant problem with rates up to 20%. This study focuses on determining factors predictive of haematoma recurrence and presents a scoring system stratifying recurrence risk for individual patients. METHODS: Between the years 2005 and 2009, 331 consecutive patients with CSDHs treated with surgery were included in this study. Univariate and multivariate analyses were performed searching for risk factors of increased post-operative haematoma volume and haematoma recurrence requiring repeat drainage. RESULTS: We found a 12% reoperation rate. CSDH septation (seen on computed tomogram scan) was found to be an independent risk factor for recurrence requiring reoperation (p=0.04). Larger post-operative subdural haematoma volume was also significantly associated with requiring a second drainage procedure (p<0.001). Independent risk factors of larger post-operative haematoma volume included septations within a CSDH (p<0.01), increased pre-operative haematoma volume (p<0.01), and a greater amount of parenchymal atrophy (p=0.04). A simple scoring system for quantifying recurrence risk was created and validated based on patient age (< or ≥ 80 years), haematoma volume (< or ≥ 160 cc), and presence of septations within the subdural collection (yes or no). CONCLUSION: Septations within CSDHs are associated with larger post-operative residual haematoma collections requiring repeat drainage. When septations are clearly visible within a CSDH, craniotomy might be more suitable as a primary procedure as it allows greater access to a septated subdural collection. Our proposed scoring system combining haematoma volume, age, and presence of septations might be useful in identifying patients at higher risk for recurrence.

The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial.

BACKGROUND AND PURPOSE: Acute blood pressure (BP) reduction aimed at attenuation of intracerebral hemorrhage (ICH) expansion might also compromise cerebral blood flow (CBF). We tested the hypothesis that CBF in acute ICH patients is unaffected by BP reduction. METHODS: Patients with spontaneous ICH <24 hours after onset and systolic BP > 150 mm Hg were randomly assigned to an intravenous antihypertensive treatment protocol targeting a systolic BP of <150 mm Hg (n=39) or <180 mm Hg (n=36). Patients underwent computed tomography perfusion imaging 2 hours postrandomization. The primary end point was perihematoma relative (relative CBF). RESULTS: Treatment groups were balanced with respect to baseline systolic BP: 182±20 mm Hg (<150 mm Hg target group) versus 184±25 mm Hg (<180 mm Hg target group; P=0.60), and for hematoma volume: 25.6±30.8 versus 26.9±25.2 mL (P=0.66). Mean systolic BP 2 hours after randomization was significantly lower in the <150 mm Hg target group (140±19 vs 162±12 mm Hg; P<0.001). Perihematoma CBF (38.7±11.9 mL/100 g per minute) was lower than in contralateral homologous regions (44.1±11.1 mL/100 g per minute; P<0.001) in all patients. The primary end point of perihematoma relative CBF in the <150 mm Hg target group (0.86±0.12) was not significantly lower than that in the <180 mm Hg group (0.89±0.09; P=0.19; absolute difference, 0.03; 95% confidence interval -0.018 to 0.078). There was no relationship between the magnitude of BP change and perihematoma relative CBF in the <150 mm Hg (R=0.00005; 95% confidence interval, -0.001 to 0.001) or <180 mm Hg target groups (R=0.000; 95% confidence interval, -0.001 to 0.001). CONCLUSIONS: Rapid BP lowering after a moderate volume of ICH does not reduce perihematoma CBF. These physiological data indicate that acute BP reduction does not precipitate cerebral ischemia in ICH patients. Clinical Trial Registration Information- URL:http://clinicaltrials.gov. Unique Identifier: NCT00963976.

Derivation of transcranial Doppler criteria for angiographically proven middle cerebral artery vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Transcranial Doppler (TCD) has been subjected to criticism for detecting vasospasm (VSP). Our study's aim is to derive criteria for middle cerebral artery (MCA) vasospasm (MCA-VSP) based on cerebral angiography (CA). METHODS: A prospective data of patients with aneurysmal subarachnoid hemorrhage (aSAH) from January 2004 to August 2009. TCD was performed daily from day 2 to 14 from symptom's onset. Follow-up CA was done at day 7-9. TCD mean flow velocities (MFV) of all vessels at baseline (b), middle (m) and before CA (preangio) were recorded. Several MCA MFV ratios were computed. Moderate to severe VSP on CA was defined as >1/3 luminal narrowing. Univariate and stepwise logistic regression analysis were performed. RESULTS: One hundred sixty-nine patients (338 MCA) with aSAH were included, mean age: 54.8 ± 13, women: 103 (62%). Twenty-nine patients (8.6%) had angiographic MCA-VSP. TCD scoring system of 3 points for MCA-VSP was computed based on (a) bMCA MFV ≥ 120 cm/s (sensitivity: 59.3%, specificity: 85%, PPV: 36.4%, NPV: 93.5%, P < .001) (1 point), Preangio MCA MFV ≥ 150 cm/s (79.3%, 89.9%, 39%, 97.3%, <.001) (1 point), and affected preangio MCA/bMCA MFV ratio ≥ 1.5 (84%, 63%, 25.6%, 96.3%, .001) (1 point). The score of 3 has 96% sensitivity and 96% specificity (OR: 300) whereas the score of 1 has 12% sensitivity and 58% specificity (OR: 4.3) for identifying MCA-VSP. CONCLUSION: TCD stringent criteria for moderate to severe MCA-VSP are feasible and applicable in aSAH population.

The design of the Canadian UnRuptured Endovascular versus Surgery (CURES) trial.

BACKGROUND: Once a decision has been made to treat an intact aneurysm, the best treatment remains uncertain. Both surgical and endovascular management strategies are commonly performed for these lesions. Surgical clipping, for years the standard treatment, is gradually becoming supplanted by endovascular treatment. However, there is no randomized data available to compare the results of surgery versus endovascular treatment of unruptured aneurysms (UIAs). METHODS: We report the design of the Canadian UnRuptured Endovascular versus Surgery (CURES) trial to compare angiographic and clinical outcomes following treatment of UIAs. RESULTS: The Canadian pilot phase will serve two purposes: i) to determine feasibility of the pivotal international study, and ii) to determine the incidence of treatment failure, a composite primary end-point comprising the occurrence of either: failure to accomplish aneurysm obliteration with the initial treatment modality, a major saccular aneurysm remnant or recurrence, or intracranial hemorrhage following treatment at one year. The pivotal international study will address which strategy leads to the best overall clinical outcomes in terms of mortality, morbidity, and clinical efficacy. CURES is designed to be a pragmatic management trial with loose inclusion criteria. The pilot study plans to enroll 260 patients, a size sufficient (at 80% power and 0.05 significance) to detect a decrease in the incidence of treatment failure from 13% to 4%. The formulation of specific hypotheses for the pivotal phase awaits the preliminary CURES morbidity and mortality results. CONCLUSIONS: The CURES trial intends to test surgical versus endovascular management strategies for the treatment of unruptured intracranial aneurysms.

Appropriateness of lumbar spine referrals to a neurosurgical service.

BACKGROUND: Patients with lumbar spine complaints are often referred for surgical assessment. Only those with clinical and radiological evidence of nerve root compression are potential candidates for surgery and appropriate for surgical assessment. This study examines the appropriateness of lumbar spine referrals made to neurosurgeons in Edmonton, Alberta. METHODS: Lumbar spine referrals to a group of ten neurosurgeons at the University of Alberta were reviewed over three two month intervals. Clinical criteria for "appropriateness" for surgical assessment were as follows: •"Appropriate" referrals were those that stated leg pain was the chief complaint, or those that described physical exam evidence of neurological deficit, and imaging reports (CT or MRI) were positive for nerve root compression. •"Uncertain" referrals were those that reported both back and leg pain without specifying which was greater, without mention of neurologic deficit, and when at least possible nerve root compression was reported on imaging. •"Inappropriate" referrals contained no mention of leg symptoms or signs of neurological deficit, and/or had no description of nerve root compression on imaging. RESULTS: Of the 303 referrals collected, 80 (26%) were appropriate, 92 (30%) were uncertain and 131 (44%) were inappropriate for surgical assessment. CONCLUSIONS: Physicians seeking specialist consultations for patients with lumbar spine complaints need to be better informed of the criteria which indicate an appropriate referral for surgical treatment, namely clinical and radiological evidence of nerve root compression. Avoiding inappropriate referrals could reduce wait-times for both surgical consultation and lumbar spine surgery for those patients requiring it.