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  • Cognitive and MRI Correlates of Brain Derived Neurotrophic Factor Val66Met Gene Polymorpism in Adults With Intrinsic Brain Tumors

    Final Number:

    David Altshuler MD; Lin Wang M.D.; Guarang Shah; Karen Kluin; Amanda Brezzell; Daniel A. Orringer MD; Shawn L. Hervey-Jumper MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: 70,000 people in the United Stated states are living with a primary or secondary brain tumor. The majority of patients experience language, motor, or cognitive disability, which limits their survival, ability to work, and maintain productive lives. Functional impairments are largely due to disruption of cortical and subcortical pathways, which occur as result of both tumor growth and oncological therapies. CNS plasticity is the process by which functional pathways repair and is influenced by patient genetics. BDNF is the most abundant growth factor in the brain and the primary neurotrophin responsible for white matter reorganization. A genetic polymorphism of BDNF results in the val/met or met/met genotype, which results in diminished intracellular trafficking and BDNF secretion, which has an effect on white matter repair. Therefore, the goal of this study is to examine BDNFval/met polymorphism and its significance on language reorganization.

    Methods: 87 adult patients were included in the study population. Study subjects underwent a full language and neurocognitive assessment, language and motor task functional MRI, 32 direction DTI MRI, and BDNF genotyping, and plasma BDNF quantification.

    Results: The “high performance allele” BDNF val/val genotype (HPA) represented 77% of the study population while the “low performance allele” BDNF val/met and met/met polymorphism (LPA) represented 20 and 3% respectively. Bilateral language activation identified in subjects with dominant hemisphere tumors confirmed greater contralateral language task activation in the HPA cohort (45% HPA vs. 13% LPA, p=0.02)(fig.1). ELISA confirmed elevated plasma BDNF in HPA population (1160.31 pg/ml vs. 395.5 pg/ml in LPA, p=0.05)(fig.2). While there was difference in global cognitive and language task performance (BDAE severity scores not significant), HPA cohort revealed a greater NIH PROMIS Depression scores (p=0.03, R2= .478).

    Conclusions: We used the common BDNFval/met polymorphism to illustrate genetic influences on language remodeling and neurocognitive function in adults with glioma and brain metastasis.

    Patient Care: This research will improve patient care by discovering actionable mechanisms underlying functional recovery surgery for intrinsic brain tumors.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of BDNF role in functional recovery, 2) Discuss common mutations in BDNF and their clinical significance 3) Describe clinical and radiographic methods for assessment of language function pre- and post-operatively in patients with brain tumors.


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