Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study

Shala G Berntsson, Ryan T Merrell, E Susan Amirian, Georgina N Armstrong, Daniel Lachance, Anja Smits, Renke Zhou, Daniel I Jacobs, Margaret R Wrensch, Sara H Olson, Dora Il'yasova, Elizabeth B Claus, Jill S Barnholtz-Sloan, Joellen Schildkraut, Siegal Sadetzki, Christoffer Johansen, Richard S Houlston, Robert B Jenkins, Jonine L Bernstein, Rose Lai, Sanjay Shete, Christopher I Amos, Melissa L Bondy, Beatrice S Melin, Shala G Berntsson, Ryan T Merrell, E Susan Amirian, Georgina N Armstrong, Daniel Lachance, Anja Smits, Renke Zhou, Daniel I Jacobs, Margaret R Wrensch, Sara H Olson, Dora Il'yasova, Elizabeth B Claus, Jill S Barnholtz-Sloan, Joellen Schildkraut, Siegal Sadetzki, Christoffer Johansen, Richard S Houlston, Robert B Jenkins, Jonine L Bernstein, Rose Lai, Sanjay Shete, Christopher I Amos, Melissa L Bondy, Beatrice S Melin

Abstract

Background: The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.

Methods: The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures.

Results: Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.

Conclusions: Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

Keywords: Epileptic seizures; Glioma-related seizures; Observational study (cohort, case–control); Primary brain tumor.

Conflict of interest statement

Funding

This work was supported by Grants from the NIH, Bethesda, MD:R01CA139020 (to M.L. Bondy), R01CA52689, P50CA97257 (to M.R. Wrensch). All authors received support from R01CA139020 (to M.L. Bondy). Additional support was provided by the McNair Medical Institute and the Population Sciences Biorepository at Baylor College of Medicine (P30CA125123).

Conflicts of interest

The authors declare no competing financial interests.

Informed consent

Written informed consent was obtained from each subject or from his or her guardian. Approval from local institutional review boards was received at each Gliogene participating institution. This study was conducted in accordance with the Declaration of Helsinki.

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