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Cerebral venous thrombosis in traumatic brain injury: a cause of secondary insults and added mortality

Dag Ferner Netteland, Magnus Mejlænder-Evjensvold, Nils O. Skaga, Else Charlotte Sandset, Mads Aarhus, and Eirik Helseth

OBJECTIVE

Cerebral venous thrombosis (CVT) is increasingly recognized in traumatic brain injury (TBI), but its complications and effect on outcome remain undetermined. In this study, the authors characterize the complications and outcome effect of CVT in TBI patients.

METHODS

In a retrospective, case-control study of patients included in the Oslo University Hospital trauma registry and radiology registry from 2008 to 2014, the authors identified TBI patients with CVT (cases) and without CVT (controls). The groups were matched regarding Abbreviated Injury Scale 1990, update 1998 (AIS’98) head region severity score 3–6. Cases were identified by AIS’98 or ICD-10 code for CVT and CT or MR venography findings confirmed to be positive for CVT, whereas controls had no AIS’98 or ICD-10 code for CVT and CT venography or MR venography findings confirmed to be negative for CVT. All images were reviewed by a neuroradiologist. Rates of complications due to CVT were recorded, and mortality was assessed both unadjusted and in a multivariable logistic regression analysis adjusting for initial Glasgow Coma Scale score, Rotterdam CT score, and Injury Severity Score. Complications and mortality were also assessed in prespecified subgroup analysis according to CVT location and degree of occlusion from CVT. Lastly, mortality was assessed in an exploratory subgroup analysis according to the presence of complications from CVT.

RESULTS

The CVT group (73 patients) and control group (120 patients) were well matched regarding baseline characteristics. In the CVT group, 18% developed venous infarction, 11% developed intracerebral hemorrhage, and 19% developed edema, all representing complications secondary to CVT. Unadjusted 30-day mortality was 16% in the CVT group and 4% in the no-CVT group (p = 0.004); however, the difference was no longer significant in the adjusted analysis (OR 2.24, 95% CI 0.63–8.03; p = 0.215). Subgroup analysis by CVT location showed an association between CVT location and rate of complications and an unadjusted 30-day mortality of 50% for midline or bilateral CVT and 8% for unilateral CVT compared with 4% for no CVT (p < 0.001). The adjusted analysis showed a significantly higher mortality in the midline/bilateral CVT group than in the no-CVT group (OR 8.41, 95% CI 1.56–45.25; p = 0.032).

CONCLUSIONS

There is a significant rate of complications from CVT in TBI patients, leading to secondary brain insults. The rate of complications is dependent on the anatomical location of the CVT, and midline and bilateral CVT is associated with an increased 30-day mortality in TBI patients.

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Genetic landscape of sporadic vestibular schwannoma

Aril Løge Håvik, Ove Bruland, Erling Myrseth, Hrvoje Miletic, Mads Aarhus, Per-Morten Knappskog, and Morten Lund-Johansen

OBJECTIVE

Vestibular schwannoma (VS) is a benign tumor with associated morbidities and reduced quality of life. Except for mutations in NF2, the genetic landscape of VS remains to be elucidated. Little is known about the effect of Gamma Knife radiosurgery (GKRS) on the VS genome. The aim of this study was to characterize mutations occurring in this tumor to identify new genes and signaling pathways important for the development of VS. In addition, the authors sought to evaluate whether GKRS resulted in an increase in the number of mutations.

METHODS

Forty-six sporadic VSs, including 8 GKRS-treated tumors and corresponding blood samples, were subjected to whole-exome sequencing and tumor-specific DNA variants were called. Pathway analysis was performed using the Ingenuity Pathway Analysis software. In addition, multiplex ligation-dependent probe amplification was performed to characterize copy number variations in the NF2 gene, and microsatellite instability testing was done to investigate for DNA replication error.

RESULTS

With the exception of a single sample with an aggressive phenotype that harbored a large number of mutations, most samples showed a relatively low number of mutations. A median of 14 tumor-specific mutations in each sample were identified. The GKRS-treated tumors harbored no more mutations than the rest of the group. A clustering of mutations in the cancer-related axonal guidance pathway was identified (25 patients), as well as mutations in the CDC27 (5 patients) and USP8 (3 patients) genes. Thirty-five tumors harbored mutations in NF2 and 16 tumors had 2 mutational hits. The samples without detectable NF2 mutations harbored mutations in genes that could be linked to NF2 or to NF2-related functions. None of the tumors showed microsatellite instability.

CONCLUSIONS

The genetic landscape of VS seems to be quite heterogeneous; however, most samples had mutations in NF2 or in genes that could be linked to NF2. The results of this study do not link GKRS to an increased number of mutations.