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1. Catapano JS, Labib MA, Srinivasan VM, et al. Saccular aneurysms in the post–Barrow Ruptured Aneurysm Trial era. J Neurosurg 2021;137(July):1–8

The Barrow Ruptured Aneurysm Trial (BRAT) was a single-center trial that compared endovascular coiling to microsurgical clipping in patients treated for aneurysmal subarachnoid hemorrhage (aSAH). However, because patients in the BRAT were treated more than 15 years ago, and because there have been advances since then—particularly in endovascular techniques—the relevance of the BRAT today remains controversial. Some hypothesize that these technical advances may reduce retreatment rates for endovascular intervention. In this study, the authors analyzed data for the post-BRAT (PBRAT) era to compare microsurgical clipping with endovascular embolization (coiling and flow diverters) in the two time periods and to examine how the results of the original BRAT have influenced the practice of neurosurgeons at the study institution.

Of the 1014 patients with aSAH during the study period, 798 (79%) were confirmed to have saccular aneurysms. Neurological outcomes at ≥ 1-year follow-up did not differ between patients treated with microsurgery (n = 451) and those who received endovascular (n = 347) treatment (p = 0.51). The number of retreatments was significantly higher among patients treated endovascularly (32/347, 9%) than among patients treated microsurgically (6/451, 1%). The retreatment rate after endovascular treatment was lower in the post BRAT era (9%) than in the BRAT (18%).

Similarly to the BRAT results, the post BRAT-era results showed no significant difference in neurological outcomes between endovascular and microsurgical intervention for saccular aneurysms. Hence, in quaternary centers with expert neurosurgeons, neurological outcomes in aSAH patients are likely associated with the inherent risk of the hemorrhage and, to a lesser extent, with the specific treatment modality. For example, in the present analysis, the average aneurysm size was 5.5 mm, and 35% of aneurysms were < 5 mm in size. The substantial number of small aneurysms argues for more aggressive treatment of these lesions, particularly in patients at an increased risk for aneurysm rupture.

In patients with saccular aneurysms in the BRAT, endovascular surgery was found to be associated with a retreatment rate of 18% compared with only 0.4% in the microsurgery cohort. The PBRAT-era analysis found similar results, with a significantly higher percentage of endovascular patients than microsurgery patients requiring retreatment. However, the percentage of endovascular patients in the post BRAT era requiring retreatment was half that in the BRAT study (9% vs 18%). In patients with anterior circulation aneurysms, only 7% of endovascular patients required retreatment in the post BRAT era cohort. The substantial decrease in retreatment is likely due to the advances in endovascular techniques over the past decade, especially improved coil and catheter technology.

2 figures, 5 tables, no imaging

2. Kresbach C, Neyazi S, Schüller U. Updates in the classification of ependymal neoplasms: The 2021 WHO Classification and beyond. Brain Pathol 2022;(February):1–11

Clinically, ependymomas represent a very heterogeneous group of tumors from rather benign subependymomas to very aggressive and often deadly childhood ependymomas of the posterior fossa. Newly identified biological markers and classification schemes, e. g. based on global DNA methylation profiling, have led to the definition of 10 types of ependymal tumors and an improved prediction of patients’ outcome by applying the new classification system. While the exact genetic basis for several ependymoma types still remains unclear, the knowledge about ependymoma driving events has significantly increased within the last decade and contributed to a classification based on molecular characteristics and localization rather than histological features alone. Convincing evidence is now pointing towards gene fusions involving ZFTA or YAP1 causing the development of supratentorial ependymomas. Also, H3, EZHIP, or TERT mutations have been detected in a fraction of infratentorial ependymal tumors. Finally, MYCN amplifications have recently been identified in spinal ependymomas, in addition to the previously known mutations in NF2.

A major improvement presented by the 2021 WHO Classification is the taxonomy within the tumor family of ependymoma. Whereas the previous edition primarily defined ependymoma subtypes based on clinico-pathological characteristics (with the exception of RELA-fusion positive ependymoma), the current update mainly comprises molecular subtypes instead. More precisely, the types of subependymomas (SE), myxopapillary ependymomas (MPE), and RELA-fusion positive (now: ZFTA-fusion positive) ependymomas have been maintained in the 2021 classification, although some changes have been applied. The previously used terms of ependymoma and anaplastic ependymoma are not used to define an entity anymore. Instead, PFA and PFB ependymoma in the posterior fossa, YAP1-fusion positive ependymoma in the cerebrum, and spinal ependymoma as well as spinal ependymoma, MYCN-amplified, in the spinal cord have been newly defined. This not only provides an objective molecular basis for the diagnosis and classification of ependymomas, but is also intended to better predict the clinical outcome of the patients.

4 figures with histology

3. Whitfield BT, Huse JT. Classification of adult-type diffuse gliomas: impact of the World Health Organization 2021 update. Brain Pathol 2022;(February):1–12

WHO 2021 expands upon the trend started in 2016, using key molecular biomarkers to define neoplastic entities and greatly reducing the dependency on morphologic features for tumor classification. Terminology around tumor grading has also been simplified, with molecular features dictating classification and joint histopathologic and molecular analysis determining grade. The classification of diffuse gliomas under the 2021 update is dependent largely on isocitrate dehydrogenase (IDH1/2) mutation status and 1p/19q codeletion status, resulting in 3 primary disease groups: IDH-mutant, 1p/19q codeleted oligodendroglioma; IDH-mutant, non-codeleted astrocytoma; and IDH-wildtype glioblastoma.

Astrocytoma, IDH-mutant is now the preferred designation for all adult-type gliomas that are IDH1-or IDH2-mutant with absence of 1p/19q codeletion. These diffusely infiltrating gliomas frequently harbor inactivating mutations in TP53 and ATRX and can be defined as either CNS WHO grade 2, grade 3, or grade 4. Designations such as diffuse astrocytoma, IDH-mutant; anaplastic astrocytoma, IDH-mutant; and glioblastoma, IDH-mutant are no longer preferred, having been replaced with astrocytoma, IDH-mutant grade 2, grade 3, and grade 4, respectively.

WHO 2021 reserves the term glioblastoma specifically for IDH-wildtype tumors, with IDH-mutant glioblastoma having been effectively renamed astrocytoma, WHO grade 4. Microvascular proliferation and/or necrosis are both sufficient to establish a diagnosis of glioblastoma in an IDH-wildtype, H3-wildtype diffuse glioma. However, WHO 2021 also delineates multiple defining molecular features for IDH-wildtype glioblastoma, namely TERT promoter mutation, epidermal growth factor receptor (EGFR) amplification, and combined chromosome 7 gain/chromosome 10 loss.

7 figures with histology

4. Budd Haeberlein S, Aisen PS, Barkhof F, et al. Two randomized phase 3 studies of aducanumab in early Alzheimer’s disease. J Prev Alzheimer’s Dis 2022;9:19 7–210. (Journal of Prevention of Alzheimer’s Disease)

EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer’s disease, funded by Biogen. These studies involved 348 sites in 20 countries. Participants included 1638 (EMERGE) and 1647 (ENGAGE) patients (aged 50–85 years, confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease dementia, of which 1812 (55.2%) completed the study. Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (10 mg/kg target dose), or placebo via IV infusion once every 4 weeks over 76 weeks. The primary outcome measure was change from baseline to week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; and biomarker endpoints. EMERGE and ENGAGE were halted based on fu