Narayanan Vairavan, Veeramuthu Vigneswaran, Ahmad-Annuar Azlina, Ramli Norlisah, Waran Vicknes, Chinna Karuthan, Bondi Mark William, Delano-Wood Lisa, Ganesan Dharmendra
Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Wilayah Persekutuan, Malaysia.
PLoS One. 2016 Jul 20;11(7):e0158838. doi: 10.1371/journal.pone.0158838. eCollection 2016.
The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen's d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers.
创伤性脑损伤患者神经认知结果的可预测性并非一目了然。轻度创伤性脑损伤（mTBI）患者的恢复程度和性质通常是异质性的，尽管遭受了相似的损伤或损伤严重程度，但常见的人口统计学和损伤相关预后因素并不能充分解释这种情况。因此，本研究评估了脑源性神经营养因子（BDNF）错义突变对mTBI患者神经认知表现的影响及相关性。前瞻性招募了48例mTBI患者，在创伤后平均10.1（标准差4.2）小时内进行脑部MRI扫描，并在格拉斯哥昏迷量表（GCS）完全恢复后评估其神经心理表现。在6个月随访时再次进行神经认知评估。采用配对t检验、科恩d效应量和重复测量方差分析来确定两组[野生型G等位基因（Val纯合子）与次要A等位基因（Met携带者）]之间及其在各时间点（T1 = 基线/入院 vs. T2 = 6个月随访）的神经心理表现的统计学显著差异。在本研究中，次要A等位基因携带者在两个时间点的神经心理测试中总体表现均比野生型G等位基因组差。在野生型组中，在记忆领域（M = -11.44，标准差 = 10.0，p = .01，d = 1.22）、执行功能领域（M = -11.56，标准差 = 11.7，p = .02，d = 1.05）和总体表现领域（M = -6.89，标准差 = 5.3，p = .00，d = 1.39）观察到显著的平均差异，而次要A等位基因携带者在注意力领域（M = -11.0，标准差 = 13.1，p = .00，d = .86）和总体认知表现领域（M = -5.25，标准差 = 8.1，p = .01，d = .66）显示出显著的平均差异。与野生型G等位基因组相比，次要A等位基因携带者在入院时得分明显较低，并且在各个时间点的大多数领域仍存在受损情况，尽管在注意力和总体认知领域观察到恢复的延迟迹象具有显著性。总之，本研究证明了BDNF rs6265 Val66Met多态性在影响mTBI患者特定神经认知结果中的作用。在Met等位基因携带者中，研究结果的不利影响更为显著。
