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  • Author or Editor: Roland Goldbrunner x
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Lukas Goertz, Muriel Pflaeging, Christina Hamisch, Christoph Kabbasch, Lenhard Pennig, Niklas von Spreckelsen, Kai Laukamp, Marco Timmer, Roland Goldbrunner, Gerrit Brinker and Boris Krischek

OBJECTIVE

Timely aneurysm occlusion and neurointensive care treatment are key principles in the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent secondary brain injury. Patients with early (EHA) and delayed hospital admission (DHA) were compared in terms of clinical presentation, treatment strategies, aSAH-related complications, and outcome.

METHODS

In this retrospective study, consecutive aSAH patients were treated at a single neurovascular center between 2009 and 2019. Propensity score matching was performed to account for divergent baseline characteristics.

RESULTS

Among 509 included patients, 55 were admitted more than 48 hours after ictus (DHA group). DHA patients were significantly younger (52 ± 11 vs 56 ± 14 years, p = 0.03) and had lower World Federation of Neurosurgical Societies scores (p < 0.01) than EHA patients. In 54.5% of the cases, DHA patients presented with neurological deterioration or aggravated symptoms. Propensity score matching revealed a higher vasospastic infarction rate in the DHA group (41.5%) than in the EHA group (22.6%) (p = 0.04). A similar portion of patients in both groups achieved favorable outcome at midterm follow-up (77.3% vs 73.6%, p = 0.87). DHA patients (62.3%) received conventional coiling more often than EHA patients (41.5%) (p = 0.03).

CONCLUSIONS

DHA patients are at an increased risk of cerebral infarction. Nevertheless, state-of-the-art neurointensive care treatment can result in a good clinical outcome.

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Lukas Goertz, Christina Hamisch, Christoph Kabbasch, Jan Borggrefe, Marion Hof, Anna-Katharina Dempfle, Moritz Lenschow, Pantelis Stavrinou, Marco Timmer, Gerrit Brinker, Roland Goldbrunner and Boris Krischek

OBJECTIVE

Cerebral infarction is a significant cause of morbidity and mortality related to microsurgical clipping of intracranial aneurysms. The objective of this study was to determine the impact of aneurysm shape and neck configuration on cerebral infarction after aneurysm surgery.

METHODS

The authors retrospectively reviewed consecutive cases of ruptured and unruptured aneurysms treated with microsurgical clipping at their institution between 2010 and 2018. Three-dimensional reconstructions from preoperative computed tomography and digital subtraction angiography were used to determine aneurysm shape (regular/complex) and neck configuration (regular/irregular). Morphological and procedure-related risk factors for cerebral infarction were identified using univariate and multivariate statistical analyses.

RESULTS

Among 243 patients with 252 aneurysms (148 ruptured, 104 unruptured), the overall cerebral infarction rate was 17.1%. Infarction tended to occur more often in aneurysms with complex shape (p = 0.084). Likewise, aneurysms with an irregular neck had a significantly higher rate of infarction (37.5%) than aneurysms with regular neck configuration (10.1%, p < 0.001). Aneurysms with an irregular neck were associated with a higher rate of intraoperative rupture (p = 0.003) and temporary parent artery occlusion (p = 0.037). In the multivariate analysis, irregular neck configuration was identified as an independent risk factor for infarction (OR 4.2, 95% CI 1.9–9.4, p < 0.001), whereas the association between aneurysm shape and infarction was not significant (p = 0.966).

CONCLUSIONS

Irregular aneurysm neck configuration represents an independent risk factor for cerebral infarction during microsurgical clipping of both ruptured and unruptured aneurysms.

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Pantelis Stavrinou, Aristotelis Kalyvas, Stefan Grau, Christina Hamisch, Norbert Galldiks, Sotirios Katsigiannis, Christoph Kabbasch, Marco Timmer, Roland Goldbrunner and George Stranjalis

OBJECTIVE

Data on the survival effects of supportive care compared to second-line multimodal treatment for glioblastoma progression are scarce. Thus, the authors assessed survival in two population-based, similar cohorts from two European university hospitals with different treatment strategies at first progression.

METHODS

The authors retrospectively identified patients with newly diagnosed glioblastoma treated at two neurooncological centers. After diagnosis, patients from both centers received identical treatments, but at tumor progression each center used a different approach. In the majority of cases, at center A (Greece), supportive care or a single therapeutic modality was offered at progression, whereas center B (Germany) provided multimodal second-line therapy. The main outcome measure was survival after progression (SaP). The influence of the treatment strategy on SaP was assessed by multivariate analysis.

RESULTS

One hundred three patients from center A and 156 from center B were included. Tumor progression was observed in 86 patients (center A) and 136 patients (center B). At center A, 53 patients (72.6%) received supportive care alone, while at center B, 91 patients (80.5%) received second-line treatment. Progression-free survival at both centers was similar (9.4 months [center A] vs 9.0 months [center B]; p = 0.97), but SaP was significantly improved in the patients treated with multimodal second-line therapy at center B (7 months, 95% CI 5.3–8.7 months) compared to those treated with supportive care or a single therapeutic modality at center A (4.5 months, 95% CI 3.5–5.5 months; p = 0.003). In the multivariate analysis, the treatment center was an independent prognostic factor for overall survival (HR 1.59, 95% CI 0.17–2.15; p = 0.002).

CONCLUSIONS

Treatment strategy favoring multimodal second-line treatment over minimal treatment or supportive care at glioblastoma progression is associated with significantly better overall survival.

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Mark W. Youngblood, Daniel Duran, Julio D. Montejo, Chang Li, Sacit Bulent Omay, Koray Özduman, Amar H. Sheth, Amy Y. Zhao, Evgeniya Tyrtova, Danielle F. Miyagishima, Elena I. Fomchenko, Christopher S. Hong, Victoria E. Clark, Maximilien Riche, Matthieu Peyre, Julien Boetto, Sadaf Sohrabi, Sarah Koljaka, Jacob F. Baranoski, James Knight, Hongda Zhu, M. Necmettin Pamir, Timuçin Avşar, Türker Kilic, Johannes Schramm, Marco Timmer, Roland Goldbrunner, Ye Gong, Yaşar Bayri, Nduka Amankulor, Ronald L. Hamilton, Kaya Bilguvar, Irina Tikhonova, Patrick R. Tomak, Anita Huttner, Matthias Simon, Boris Krischek, Michel Kalamarides, E. Zeynep Erson-Omay, Jennifer Moliterno and Murat Günel

OBJECTIVE

Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

METHODS

Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher’s exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.

RESULTS

Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among “mutation unknown” samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor’s underlying driver mutation.

CONCLUSIONS

Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.