The authors report the 6-year results of the Barrow Ruptured Aneurysm Trial (BRAT). This ongoing randomized trial, with the final goal of a 10-year follow-up, compares the safety and efficacy of ...surgical clip occlusion and endovascular coil embolization in patients presenting with subarachnoid hemorrhage (SAH) from a ruptured aneurysm. The 1- and 3-year results of this trial have been previously reported.
In total, 500 patients with an SAH met the entry criteria and were enrolled in the study. Of these patients, 471 were randomly assigned to the treatments: 238 to surgical clipping and 233 to endovascular coiling. Six patients who died before treatment and 57 patients with nonaneurysmal SAHs were excluded, leaving a total of 408 patients who underwent clipping (209 assigned) or coiling (199 assigned). Whether to treat patients within the assigned group or to cross over patients to the other group was at the discretion of the treating physician; 38% (75/199) of the patients assigned to coiling were crossed over to clipping and 1.9% (4/209) assigned to clipping were crossed over to coiling. The outcome data were collected by a dedicated nurse practitioner. The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. Six years after randomization, 336 (82%) of 408 patients who had been treated were available for examination.
On the basis of an mRS score of > 2, and similar to the results at the 3-year follow-up, no significant difference in outcomes (p = 0.24) was detected between the 2 treatment groups. Complete aneurysm obliteration at 6 years was achieved in 96% (111/116) of the clipping group and in 48% (23/48) of the coiling group (p < 0.0001). In the period between the 3- and 6-year follow-ups, 3 additional patients assigned to coiling and none assigned to clipping received retreatment, for overall retreatment rates of 4.6% (13/280) for clipping and 16.4% (21/128) for coiling (p < 0.0001). When aneurysm location was considered, the 6-year results continued to match the previously reported results, with no difference in outcome for anterior circulation aneurysms at most time points. Of the anterior circulation aneurysms assigned to coiling treatment, 42% (70/168) were crossed over to clipping treatment. The outcomes for posterior circulation aneurysms continued to favor coiling. The randomization process was unexpectedly skewed, with 18 of 21 treated aneurysms of the posterior inferior cerebellar artery (PICA) being assigned to clipping, but even when PICA aneurysms were removed from the analysis, outcomes for the posterior circulation aneurysms still favored coiling.
Although BRAT was statistically underpowered to detect small differences, these results suggest little difference in outcome between the 2 treatments for anterior circulation aneurysms. This was not the case for the posterior circulation aneurysms, where coil embolization appeared to provide a sustained advantage over clipping. Aneurysm obliteration rates in BRAT were significantly lower and retreatment rates significantly higher in the patients undergoing coiling than in those undergoing clipping. However, despite the fact that retreatment rates were higher after coiling, no recurrent hemorrhages were known to have occurred in patients undergoing coiling in BRAT who were followed up for 6 years. Sufficient questions remain about the relative benefits of the 2 treatment modalities to warrant further well-designed randomized trials.
Cerebral cavernous malformations (CCMs) are vascular anomalies of the central nervous system, comprising dilated blood-filled capillaries lacking structural support. The lesions are prone to rupture, ...resulting in seizures or hemorrhagic stroke. CCM can occur sporadically, manifesting as solitary lesions, but also in families, where multiple lesions generally occur. Familial cases follow autosomal-dominant inheritance due to mutations in one of three genes, CCM1/KRIT1, CCM2/malcavernin or CCM3/PDCD10. The difference in lesion burden between familial and sporadic CCM, combined with limited molecular data, suggests that CCM pathogenesis may follow a two-hit molecular mechanism, similar to that seen for tumor suppressor genes. In this study, we investigate the two-hit hypothesis for CCM pathogenesis. Through repeated cycles of amplification, subcloning and sequencing of multiple clones per amplicon, we identify somatic mutations that are otherwise invisible by direct sequencing of the bulk amplicon. Biallelic germline and somatic mutations were identified in CCM lesions from all three forms of inherited CCMs. The somatic mutations are found only in a subset of the endothelial cells lining the cavernous vessels and not in interstitial lesion cells. These data suggest that CCM lesion genesis requires complete loss of function for one of the CCM genes. Although widely expressed in the different cell types of the brain, these data also suggest a unique role for the CCM proteins in endothelial cell biology.
Abstract
BACKGROUND
Ruptured wide-neck aneurysms (WNAs) are difficult to treat and few publications have compared clipping to coiling.
OBJECTIVE
To determine, using Barrow Ruptured Aneurysm Trial ...(BRAT) data: (1) How many aneurysms had a wide neck? (2) Did wide-neck status influence treatment? (3) How did clipping compare to coiling for WNAs?
METHODS
A post hoc analysis was conducted of saccular WNAs in the BRAT. A WNA was defined as maximum neck width ≥ 4 mm or maximum aneurysm dome-diameter–to–neck-width ratio < 2. Both intent-to-treat and as-treated analyses were performed.
RESULTS
Of the 327 patients analyzed, 177 (54.1%) had a WNA. WNAs were more likely to occur in older patients (P = .03) with worse presenting clinical grade (P = .02), were more likely to arise from the middle cerebral artery, basilar tip, or internal carotid artery other than the junction with the posterior communicating artery (P = .001) and were associated with worse clinical outcomes at all time points (P ≤ .01). WNAs were equally distributed in assigned treatment groups (clip 56.6% vs coil 51.8%; P = .38), but were overrepresented in the actual clipping group (clip 62.4% vs coil 37.6%, P < .001). Most patients (76.7%) in the coil-to-clip crossover group had a WNA. Comparing clipping to coiling, there was no difference in clinical outcomes at any time point in either analysis (P ≥ .33). The aneurysm obliteration rate was lower (P < .001) and the retreatment rate higher (P < .001) in the actual coiling group.
CONCLUSION
Wide-neck status significantly impacted treatment strategy in the BRAT, favoring clipping. Clipping and coiling of ruptured WNAs resulted in statistically similar long-term clinical outcomes.
10.1093/neuros/nyy439
Video Abstract
10.1093.neuros.nyy439
5850292551001
OBJECTIVE The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial in which treatment with clipping was compared to treatment with coil embolization. Patients were randomized to ...treatment on presentation with any nontraumatic subarachnoid hemorrhage (SAH). Because all other randomized trials comparing these 2 types of treatments have been limited to saccular aneurysms, the authors analyzed the current BRAT data for this subgroup of lesions. METHODS The primary BRAT analysis included all sources of SAH: nonaneurysmal lesions; saccular, blister, fusiform, and dissecting aneurysms; and SAHs from an aneurysm associated with either an arteriovenous malformation or a fistula. In this post hoc review, the outcomes for the subgroup of patients with saccular aneurysms were further analyzed by type of treatment. The extent of aneurysm obliteration was adjudicated by an independent neuroradiologist not involved in treatment. RESULTS Of the 471 patients enrolled in the BRAT, 362 (77%) had an SAH from a saccular aneurysm. Patients with saccular aneurysms were assigned equally to the clipping and the coiling cohorts (181 each). In each cohort, 3 patients died before treatment and 178 were treated. Of the 178 clip-assigned patients with saccular aneurysms, 1 (1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. There was no statistically significant difference in poor outcome (modified Rankin Scale score > 2) between these 2 treatment arms at any recorded time point during 6 years of follow-up. After the initial hospitalization, 1 of 241 (0.4%) clipped saccular aneurysms and 21 of 115 (18%) coiled saccular aneurysms required retreatment (p < 0.001). At the 6-year follow-up, 95% (95/100) of the clipped aneurysms were completely obliterated, compared with 40% (16/40) of the coiled aneurysms (p < 0.001). There was no difference in morbidity between the 2 treatment groups (p = 0.10). CONCLUSIONS In the subgroup of patients with saccular aneurysms enrolled in the BRAT, there was no significant difference between modified Rankin Scale outcomes at any follow-up time in patients with saccular aneurysms assigned to clipping compared with those assigned to coiling (intent-to-treat analysis). At the 6-year follow-up evaluation, rates of retreatment and complete aneurysm obliteration significantly favored patients who underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).
External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD ...insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors’ view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.
A direct comparison of endovascular versus microsurgical treatment of ruptured middle cerebral artery (MCA) aneurysms in randomized trials is lacking. As endovascular treatment strategies continue to ...evolve, the number of reports of endovascular treatment of these lesions is increasing. Herein, the authors report a detailed post hoc analysis of ruptured MCA aneurysms treated by microsurgical clipping from the Barrow Ruptured Aneurysm Trial (BRAT).
The cases of patients enrolled in the BRAT who underwent microsurgical clipping for a ruptured MCA aneurysm were reviewed. Characteristics of patients and their clinical outcomes and long-term angiographic results were analyzed.
Fifty patients underwent microsurgical clipping of a ruptured MCA aneurysm in the BRAT, including 21 who crossed over from the endovascular treatment arm. Four patients with nonsaccular (e.g., dissecting, fusiform, or blister) aneurysms were excluded, leaving 46 patients for analysis. Most (n = 32; 70%) patients presented with a Hunt and Hess grade II or III subarachnoid hemorrhage, with a high prevalence of intraparenchymal blood (n = 23; 50%), intraventricular blood (n = 21; 46%), or both. At the last follow-up (up to 6 years after treatment), clinical outcomes were good (modified Rankin Scale score 0–2) in 70% (n = 19) of 27 Hunt and Hess grades I–III patients and in 36% (n = 4) of 11 Hunt and Hess grade IV or V patients. There were no instances of rebleeding after the surgical clipping of aneurysms in this series at the time of last clinical follow-up.
Microsurgical clipping of ruptured MCA aneurysms has several advantages over endovascular treatment, including durability over time. The authors report detailed outcome data of patients with ruptured MCA aneurysms who underwent microsurgical clipping as part of a prospective, randomized trial. These results should be used for comparison with future endovascular and surgical series to ensure that the best results are being achieved for patients with ruptured MCA aneurysms.
Abstract Background Ethmoidal dural arteriovenous fistulas (dAVFs) have a malignant natural history and anatomy that makes endovascular therapy challenging. Their uniqueness begs for stratified ...analyses, but this has largely been precluded by their rarity. We sought to summarize the anatomic presentation, treatment approaches, and clinical outcomes of patients with these lesions. Methods We reviewed our prospectively maintained institutional database to identify patients diagnosed with ethmoidal dAVFs from January 1, 2000 to December 31, 2015. We evaluated demographic, presentation, angiographic, treatment, and follow-up data. Results In total, 27 patients with ethmoidal dAVFs underwent endovascular and/or surgical treatment. Mean patient age was 62 years old and there was a male sex predilection (67% male; 2:1 male-female ratio). All dAVFs exhibited direct cortical venous drainage; venous ectasia was present in 59% of cases. Of the dAVFs, 30% drained posteriorly into the basal vein of Rosenthal or sylvian veins. Embolization with casting of the draining vein was successful in 2 of 9 cases (22%), including one successful transvenous case. There were no clinical or permanent complications from embolization; specifically, no patients experienced visual loss after treatment. Surgical treatment with successful dAVF obliteration was carried out in 24 of 24 patients (100%). One patient declined surgical treatment after attempted endovascular embolization. There were no permanent complications after surgical treatment and no cases of wound infection or cerebrospinal fluid leakage. Conclusion Surgical disconnection remains the gold standard in the treatment of ethmoidal dAVFs. Embolization is a consideration for well-selected cases with favorable arterial or venous access anatomy.
External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD ...insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors’ view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.
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