NCOG-14. WHITE MATTER CHANGES LINKED TO LANGUAGE RECOVERY IN ADULT GLIOMA

Abstract

INTRODUCTION: CNS neoplasms are a major cause of morbidity and mortality in the US. Current treatments focus on enhancing survival, however >70% of patients experience language, motor, or cognitive dysfunction resulting in impaired quality of life. Little is known about the mechanisms of CNS plasticity and the effect on language impairment and recovery in glioma patients. We are studying the influence of a polymorphism in the brain derived neurotrophic factor (BDNF) gene on these processes. A BDNF val66met genotype “low performance allele”(LPA) results in diminished BDNF secretion compared to the more prevalent val/val genotype “high performance allele”(HPA). The objective of this study is to characterize the influence of this polymorphism on white matter integrity and functional language outcomes in patients with glioma. METHODS: 87 adult patients were included in the study. Subjects underwent longitudinal language assessments, tissue immunohistochemistry, DTI MRI, BDNF genotyping, and plasma BDNF quantification. RESULTS: The HPA genotype represented 77% of the study population while the LPA genotype represented 23%, replicating prevalence in the general population. ELISA confirmed elevated plasma BDNF in the HPA population (1160.31 pg/ml vs. 395.5 pg/ml, p=0.05). Peritumor myelinogensis markers GAP43, CNPase, and O4 were diminished in the LPA population by immunohistochemistry and western blot (p<0.05). DTI revealed decreased integrity of the superior longitudinal fasciculus, an important language tract in the LPA population compared to HPA and control. A greater percentage of LPA patients were severely aphasic both pre and post-operatively by Boston Diagnostic Aphasia Examination score (P<0.05). CONCLUSION: The results demonstrate the significance of BDNF on language function in adult glioma patients. BDNF polymorphisms are implicated in white matter repair processes by plasma level, tissue expression, DTI, and functional language outcomes. Targeting BDNF and the mechanisms underlying white matter repair may lead to improved quality of life and functional recovery in patients with glioma.