Abstracts

Rationale: Seizures occur at some time in 25% to 50% of patients with brain tumors. Seizures occur more often in low-grade astrocytomas, oligodendrogliomas, or oligoastrocytomas (60% to 80%) than in high-grade gliomas (20% to 40%) or metastases (15% to 20%). Isocitrate dehydrogenase 1 (IDH-1) mutations were discovered in 2008. Mutations in IDH-1 occur in almost all low-grade gliomas and secondary high-grade gliomas. Most glial tumors are tested for IDH-1 mutations and it is associated with prolonged survival. The aim of this study is to investigate whether a specific mutation, IDH-1, found in brain tumor patients, is associated with increased risk of seizure. This study hypothesizes that if low grade glial tumors are associated with increased seizure frequency, and IDH-1 is found in 85% of all grade II and III gliomas (compared to 10% of grade IV), then the prevalence of seizure is expected to be greater in IDH-1 positive tumors.Methods: This was a retrospective case control study. Using “PennSeek”, a tool to search unstructured or semi-structured medical documents across all electronic medical record domains at the Hospital of the University of Pennsylvania, 551 patients with “IDH-1” were identified. Patients with non-glial pathology were excluded. Using ICD9 codes, patients with seizures were identified. Comparisons between these two groups were made with t-test s and Chi-square where appropriate.Results: The odds of having seizures in the IDH-1 positive group are 1.4 times that of the IDH1-1 negative group (95% CI 0.782-2.536, p=0.22). There were more males than females overall, and more males than females in the IDH-1 positive and IDH-1 negative groups, this difference was not statistically significant. There was a statistically significant difference (p< 0.0001) between the mean age of IDH-1 positive patients (45.66 years), compared to IDH-1 negative patients (58.58 years). The most common pathology in IDH-1 positive patients who had seizure activity is oligodendroglioma (27.8%) compared to IDH-1 negative patients with seizures, which are made up overwhelmingly by GBM (54.3%).Conclusions: There was an increased odds ratio of seizure in IDH-1 positive patients. However, this was not a statistically significant finding. A statistically significant difference between the mean age of IDH-1 positive patients (45.66 years), compared to IDH-1 negative patients (58.58 years) corresponds with existing epidemiological data comparing median age of diagnosis between oligodendroglioma (median age at diagnosis=42) and glioblastoma (median age at diagnosis=64). Using this same methodology, and applying it to additional molecular markers, will allow screening of multiple potential biomarkers (EGFR, P53, 1p19q co-deletion) in brain tumor patients that may help predict independent risk factors for seizure activity.