Abstract Details

Title The BDNF Val66Met Polymorphism Influences Motor System Function and Plasticity after Stroke

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S41 - (-)

Poster/Presentation
Number 004

Objective

Background The BDNF val66met polymorphism is common (30%) and when present associated with altered short-term plasticity in healthy subjects, and slower behavioral recovery after stroke.

Design/Methods Patients with stroke 11-26 weeks prior and mild-severe distal arm deficits enrolled in a trial (NCT01244243) that provided 3 weeks of robotic therapy targeting distal arm motor function. Functional MRI scan during affected hand movement was obtained before/after therapy.

Results At baseline (n=28), mean age=56 years, time post-stroke=4.3 months, Fugl-Meyer score=36, and infarct volume=35cc, with no significant differences between those with (BDNF+, n=8) and without (BDNF-, n=20) the polymorphism. At baseline, the task activated bilateral motor networks. The BDNF- group showed larger activation than the BDNF+ group (SPM, p<0.001), for example, whole brain (247 vs 66 cc) and in ipsilesional motor cortex (0.9 vs 0.5 cc). Across therapy, mean change in Fugl-Meyer score=4.7 points (no significant difference between BDNF subgroups) and activation overall decreased (repeat imaging available in 18). A timeXgroup interaction term (p<0.01) found significantly greater activity reduction in BDNF- subjects within medial prefrontal and contralesional parietal regions.

Conclusions The BDNF val66met polymorphism is associated with differences in motor system function and plasticity. Findings at baseline mirror those reported among healthy controls; subjects with the polymorphism present (BDNF+) showed smaller brain activation, which can be interpreted in several different ways. Subjects with the polymorphism (BDNF+) showed less activation consolidation, but this must be interpreted in light of baseline differences. Genetic polymorphisms that affect the function of the healthy brain continue to influence brain function after stroke. The impact of these findings on clinical course requires further study, but could suggest a means to optimize restorative therapies after stroke.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Steven C. Cramer, MD, FAAN	Dr. Cramer has received personal compensation for serving as an employee of University of California. An immediate family member of Dr. Cramer has received personal compensation for serving as an employee of University of California. Dr. Cramer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alevian, BrainQ, Helius, Insight Global, Janssen Global Services, Medtronic, Mobia, Myomo, and Simcere. Dr. Cramer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MUSC. Dr. Cramer has or had stock in Alevian, Constant Therapeutics, Panaxium, and TRCare. The institution of Dr. Cramer has received research support from NIH; PCORI; Veterans Administration.
Bruno Dubois, MD (Hopital La Salpetriere)	No disclosure on file

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