Nonaneurysmal perimesencephalic subarachnoid hemorrhage on noncontrast head CT: An accuracy, inter-rater, and intra-rater reliability study.

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.

Angiographic results of surgical or endovascular treatment of intracranial aneurysms: a systematic review and inter-observer reliability study.

PURPOSE: Results of surgical or endovascular treatment of intracranial aneurysms are often assessed using angiography. A reliable method to report results irrespective of treatment modality is needed to enable comparisons. Our goals were to systematically review existing classification systems, and to propose a 3-point classification applicable to both treatments and assess its reliability. METHODS: We conducted two systematic reviews on classification systems of angiographic results after clipping or coiling to select a simple 3-category scale that could apply to both treatments. We then circulated an electronic portfolio of angiograms of clipped (n=30) or coiled (n=30) aneurysms, and asked raters to evaluate the degree of occlusion using this scale. Raters were also asked to choose an appropriate follow-up management for each patient based on the degree of occlusion. Agreement was assessed using Krippendorff's α statistics (αK), and relationship between occlusion grade and clinical management was analyzed using Fisher's exact and Cramer's V tests. RESULTS: The systematic reviews found 70 different grading scales with heterogeneous reliability (kappa values from 0.12 to 1.00). The 60-patient portfolio was independently evaluated by 19 raters of diverse backgrounds (neurosurgery, radiology, and neurology) and experience. There was substantial agreement (αK=0.76, 95%CI, 0.67-0.83) between raters, regardless of background, experience, or treatment used. Intra-rater agreement ranged from moderate to almost perfect. A strong relationship was found between angiographic grades and management decisions (Cramer's V: 0.80±0.12). CONCLUSION: A simple 3-point scale demonstrated sufficient reliability to be used in reporting aneurysm treatments or in evaluating treatment results in comparative randomized trials.

How I do it: lateral supra-cerebellar infra-tentorial approach for P2-P3 junction cerebral aneurysms.

BACKGROUND: P2-P3 junction aneurysms are challenging to treat surgically because of their frequent complex morphology and their location deep in close proximity to the midbrain. The sub-temporal route requires significant retraction of the temporal lobe in addition to potential injury to the vein of Labbe. We describe the technique for treating such aneurysms via a lateral supra-cerebellar infra-tentorial (LSCIT) approach, which eliminates manipulation of the temporal lobe. METHOD: Cadaveric dissection provided comprehensive understanding of relevant anatomy. Intraoperative video shows clipping of the aneurysm using a LSCIT approach. CONCLUSION: LSCIT approach allows safe clipping of P2-P3 aneurysms with minimal brain manipulation.

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.

The Treatment of Brain Arteriovenous Malformation Study (TOBAS): A preliminary inter- and intra-rater agreement study on patient management.

OBJECT: The best management of brain arteriovenous malformation (bAVM) patients remains unknown. Randomized allocation may be more readily accepted when there is uncertainty and disagreement regarding the management of potential participants. In planning for a trial, we aimed to assess variability and agreement among physicians managing bAVM patients. METHODS: A portfolio composed of 35 patients was sent to 47 clinicians of various specialties managing bAVM patients. For each patient, physicians were asked their best management decision (surgery/embolization/radiosurgery/conservative), their confidence level, and whether they would include the patient in a randomized trial comparing conservative and curative management. Seven physicians, who had access to all images of each patient, independently responded twice, to assess inter and intra-rater agreement using kappa statistics. RESULTS: The inter-rater agreement (30 raters, including 16 neuroradiologists) for best management decision was only "fair" (κ [95%CI]=0.210[0.157; 0.295]). Agreement remained below 'substantial' (κ<.6) between physicians of the same specialty, and when no distinctions were made between various treatments (when responses were dichotomized as conservative versus curative). With access to all images the inter-rater agreement remained fair. The intra-rater agreement reached "substantial" only for the dichotomized decisions. Responding clinicians were willing to include 54.4% of patients (mainly unruptured bAVMs) in a randomized trial. CONCLUSION: There is a lack of agreement among clinicians involved in the management of bAVM patients. In this study a substantial proportion of clinicians were willing to offer randomized allocation of management options to a substantial number of patients.

Anatomy of the craniocervical junction - A review.

An in-depth understanding of the anatomy of the craniocervical junction (CCJ) is indispensable in skull base neurosurgery. In this paper, we discuss the osteology of the occipital bone, the atlas (C1) and axis (C2), the ligaments and the muscle anatomy of the CCJ region and their relationships with the vertebral artery. We will also discuss the trajectory of the vertebral artery and review the anatomy of the jugular foramen and lower cranial nerves (IX to XII). The most important surgical approaches to the CCJ, including the far lateral approach, the anterolateral approach of Bernard George and the endoscopic endonasal approach, will be discussed to review the surgical anatomy.

Spontaneous intracranial vertebral artery dissections presenting with subarachnoid hemorrhage.

BACKGROUND: Vertebral artery dissection (VAD) is an infrequent source of subarachnoid hemorrhage (SAH), with a high mortality rate, primarily due to the risk of rebleeding both before and after medical intervention. This paper provides a comprehensive analysis of the anatomy, pathophysiology, clinical presentation, treatment strategies, and outcomes of intracranial vertebral artery dissections that result in subarachnoid hemorrhage. METHODS: Comprehensive five-year literature review (2018-2022) and a retrospective analysis of patient records from our institution between 2016 and 2022. We included studies with a minimum of 5 patients. RESULTS: The study incorporated ten series from the literature and 22 cases from CHUM. Key anatomical factors increasing the risk of VAD include the vertebral artery's origin from the aortic arch, asymmetry of the vertebral artery, and its tortuosity. Patients may display specific collagen and genetic abnormalities. The occurrence of VAD appears to be more prevalent in men. Those with a ruptured intracranial VAD typically show prodromal symptoms and present with severe SAH. Rebleeding within the first 24 h is frequent. While standard imaging methods are usually adequate for VAD diagnosis, they may not provide detailed information about the perforator anatomy. Treatment approaches include both deconstructive and reconstructive methods. CONCLUSION: Ruptured VAD is a critical, life-threatening condition. Many patients have a poor neurological status at presentation, and rebleeding prior to treatment is a significant concern. Deconstructive techniques are most effective in preventing rebleeding, whereas the efficacy of reconstructive techniques needs more investigation.

Hemodynamic factors of spontaneous vertebral artery dissecting aneurysms assessed with numerical and deep learning algorithms: Role of blood pressure and asymmetry.

BACKGROUND AND OBJECTIVES: The pathophysiology of spontaneous vertebral artery dissecting aneurysms (SVADA) is poorly understood. Our goal is to investigate the hemodynamic factors contributing to their formation using computational fluid dynamics (CFD) and deep learning algorithms. METHODS: We have developed software that can use patient imagery as input to recreate the vertebrobasilar arterial system, both with and without SVADA, which we used in a series of three patients. To obtain the kinematic blood flow data before and after the aneurysm forms, we utilized numerical methods to solve the complex Navier-Stokes partial differential equations. This was accomplished through the application of a finite volume solver (OpenFoam/Helyx OS). Additionally, we trained a neural ordinary differential equation (NODE) to learn and replicate the dynamical streamlines obtained from the computational fluid dynamics (CFD) simulations. RESULTS: In all three cases, we observed that the equilibrium of blood pressure distributions across the VAs, at a specific vertical level, accurately predicted the future SVADA location. In the two cases where there was a dominant VA, the dissection occurred on the dominant artery where blood pressure was lower compared to the contralateral side. The SVADA sac was characterized by reduced wall shear stress (WSS) and decreased velocity magnitude related to increased turbulence. The presence of a high WSS gradient at the boundary of the SVADA may explain its extension. Streamlines generated by CFD were learned with a neural ordinary differential equation (NODE) capable of capturing the system's dynamics to output meaningful predictions of the flow vector field upon aneurysm formation. CONCLUSION: In our series, asymmetry in the vertebrobasilar blood pressure distributions at and proximal to the site of the future SVADA accurately predicted its location in all patients. Deep learning algorithms can be trained to model blood flow patterns within biological systems, offering an alternative to the computationally intensive CFD. This technology has the potential to find practical applications in clinical settings.

Craniovertebral and spinal adhesive arachnoiditis: a late complication of ruptured vertebral and posterior inferior cerebellar arteries aneurysms.

BACKGROUND: Adhesive arachnoiditis is a rare yet serious complication that may occur following subarachnoid hemorrhage (SAH). In this circumstance, it is mainly due to ruptured vertebral artery (VA) or posterior inferior artery (PICA) aneurysms. It disrupts cerebrospinal fluid (CSF) flow leading to complications such as spinal arachnoiditis, syringomyelia, trapped 4th ventricle, or a combination of these conditions. Evidence for effective treatment strategies is currently limited. We aimed to review the epidemiology, clinical characteristics, treatment, complications, outcomes, and prognosis of cranio-vertebral junction and spinal adhesive arachnoiditis resulting from ruptured VA and PICA aneurysms. METHODS: This study involved a comprehensive literature review and complemented by our own case. We focused on adult cases of arachnoiditis, syringomyelia, and trapped 4th ventricle with SAH caused by ruptured VA or PICA aneurysms, excluding cases unrelated to these aneurysms and those with insufficient data. RESULTS: The study included 22 patients, with a mean age of 52.4 years. Symptoms commonly manifest within the first year after SAH and timely diagnosis requires a high index of suspicion. Treatment approaches included lysis of adhesions and various shunt procedures. Most patients showed improvement post-treatment, though symptom recurrence is significant. CONCLUSION: Adhesive arachnoiditis is a critical complication following SAH, most commonly from ruptured VA and PICA aneurysms. Early detection and individualized treatment based on the type of arachnoiditis and CSF flow impact are crucial for effective management. This study underscores the need for tailored treatment strategies and further research in this field.

Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

BACKGROUND: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients. METHODS: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients. RESULTS: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%). CONCLUSIONS: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs.

Surgical treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial.

OBJECTIVE: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS: TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS: From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I-II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%-93%) and 105/110 low-grade (95%, 95% CI 90%-98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%-18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%-28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%-9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS: The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov).

Endovascular treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial.

OBJECTIVE: The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. METHODS: Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. RESULTS: From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%-22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%-28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%-25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%-21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%-37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%-20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%-40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%-21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%-35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%-29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%-33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%-34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%-26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%-34%). CONCLUSIONS: Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.

Pregnancy as a Subgroup in the Pathophysiologic Classification of Spinal Aneurysms.

BACKGROUND: Aneurysms of spinal arteries not associated with any known predisposing condition are referred to as isolated spinal aneurysms (SAs). In our series, an SA was found in 2 patients during the postpartum period. The goal of this study is to determine whether an occurrence of an SA may be related to puerperium. METHODS: In a retrospective analysis of our consecutive series of 10 cases of SAs from 2008 to 2020, we identified 2 cases of SAs during puerperium. Patients' charts and imaging were reviewed, for potential predisposing factors. RESULTS: In both cases, angiography showed fusiform aneurysms of the anterior SA with concomitant bilateral vertebral artery (VA) dissections. Serum vasculitis and inflammatory panel and genetic testing for collagen disorders were negative in both cases. Review of the literature showed that pregnancy is associated with an increased risk of arterial dissections in various locations and supports the hypothesis that hemodynamic and hormonal changes may play a role in the formation of SAs. CONCLUSIONS: Pregnancy and peripartum state may be a distinct cause of the formation of SAs, possibly as a result of increased hemodynamic stress and hormonal changes that may alter the arterial wall. It would be appropriate to add pregnancy as a subgroup in the classification of SAs. In our series, both cases were associated with bilateral VA dissections; it is possible that the bilateral VA stenosis may have contributed to the formation of the SAs. It is important to recognize this possibility when considering the occlusion of a dissected VA.

Fatal hemorrhagic complication after coil embolization of a petrosal arteriovenous shunt.

BACKGROUND: Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF. CASE PRESENTATION: A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve. CONCLUSION: CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

Recruitment in a Pragmatic Randomized Trial on the Management of Unruptured Intracranial Aneurysms.

OBJECTIVES: The Comprehensive Aneurysm Management (CAM) study is a pragmatic trial designed to manage unruptured intracranial aneurysm (UIA) patients within a care research framework. METHODS: CAM is an all-inclusive study. Management options are allocated according to an algorithm combining pre-randomization and clinical judgment. Eligible patients are offered 1:1 randomized allocation of intervention versus conservative management and 1:1 randomization allocation of surgical versus endovascular treatment. Ineligible patients are registered. The primary outcome is survival without dependency (modified Rankin Scale score <3) at 10 years. All UIA patients at 1 center are reported. RESULTS: Between February 2020 and July 2021, 403 UIA patients were recruited: 179 (44%) in one of the randomized controlled trials (RCTs) and 224 (56%) in one of the registries. Conservative management was recommended for 205 of 403 patients (51%); of 198 (49%) patients considered for curative treatment, 159 (80%) were randomly allocated conservative (n = 81) or curative treatment (n = 78). These patients were younger and had larger aneurysms than those in the observation registry (P = 0.004). In 39 of 198 patients (20%), conservative management was not considered reasonable (17 patients were recommended endovascular, 2 surgery, and 20 the RCT comparing endovascular with surgical treatment). In total, 70 patients were recruited in the RCT comparing surgery and endovascular treatment. After informed discussion at time of consent, 141 of 159 patients (89%) agreed with the randomly allocated management plan, while 11% crossed over to the alternative management option. CONCLUSIONS: CAM was successfully integrated into routine practice. Meaningful conclusions can be obtained if multiple centers actively participate in the trial.

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.

Repeated Retching and Vomiting in the Pathophysiology of Isolated Spinal Aneurysms.

BACKGROUND: Rupture of spinal aneurysms is a rare cause of subarachnoid hemorrhage. These aneurysms are often associated with a variety of vascular malformations that increase blood flow in the spinal circulation or with disorders that compromise the vessel wall. However, spinal aneurysms may be isolated, not associated with any known predisposing condition. The objective of this study is to explore the possible mechanisms associated with the formation and rupture of isolated spinal aneurysms (ISAs). METHODS: We conducted a retrospective review of a series of consecutive patients admitted for a ruptured ISA. In all cases, spinal angiography confirmed the presence of a spinal aneurysm responsible for the bleeding. Particular attention was paid to medical history and symptoms before bleeding, for potential factors predisposing to their formation and rupture. RESULTS: Between 2008 and 2020, ten cases of spinal aneurysms were seen at our institution including 4 cases of ISA. All patients with ISA were female, and in 3 cases the aneurysm involved the territory of the posterior spinal artery. In 3 of these 4 (75%) ISA cases, there was a strikingly similar history of retching and vomiting preceding the thunderclap headache. In 1 patient, the aneurysm was surgically resected; pathologic analysis revealed a fusiform dissecting aneurysm. All 4 patients had a favorable outcome. CONCLUSIONS: We suggest that the straining during prolonged retching and vomiting plays a role in the formation and rupture of some ISAs, possibly because of pressure spikes, increased transmural arterial pressure, and increased wall shear stress during straining.

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.