Chiaretti Antonio, Capozzi Domenico, Mariotti Paolo, Valentini Piero, Manni Luigi, Buonsenso Danilo, Fantacci Claudia, Ferrara Pietro
Department of Pediatrics, Catholic University of the Sacred Heart, A. Gemelli Hospital, Largo Gemelli, I-00168 Rome, Italy.
Department of Pediatrics, Catholic University of the Sacred Heart, A. Gemelli Hospital, Largo Gemelli, I-00168 Rome, Italy.
Int J Infect Dis. 2014 Mar;20:52-7. doi: 10.1016/j.ijid.2013.11.006. Epub 2014 Jan 7.
The aim of this study was to evaluate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) of children with Epstein-Barr virus (EBV)-induced meningoencephalitis (ME) in order to establish a possible correlation with laboratory findings and neurological manifestations.
A prospective observational clinical study was performed on 10 children with viral ME, five of them with EBV-induced ME. As controls, we used CSF samples collected from children admitted with febrile seizures. Neurotrophin levels were measured using an enzyme immunoassay.
Significantly higher levels of BDNF and NGF were detected in all patients with viral ME compared to controls. Moreover, in patients with EBV-induced ME, the neurotrophin levels were higher than in those with other viral ME. Of note, in children with EBV-induced ME, we found a significant correlation between neurotrophic factor levels and the number of lymphocytes in the CSF (p<0.001). In these patients we also found a significant correlation between BDNF expression and the blood platelet count (p<0.001). Interestingly, two patients with EBV-induced ME showed a correlation between neurotrophin increase and persistent brain abnormalities, such as prolonged alteration of mental status, psychomotor agitation, and athetosis.
Viral ME induces an early and strong increased biosynthesis of neurotrophic factors. This neurotrophin over-expression is likely to play a key role in the mechanisms of neuronal inflammation and in the severity of brain damage, particularly in EBV-induced ME.
本研究旨在评估爱泼斯坦 - 巴尔病毒(EBV)所致脑膜脑炎(ME)患儿脑脊液(CSF)中神经生长因子(NGF)和脑源性神经营养因子(BDNF)的表达,以确定其与实验室检查结果及神经学表现之间的可能关联。
对10例病毒性ME患儿进行了一项前瞻性观察性临床研究,其中5例为EBV所致ME。作为对照,我们使用了从热性惊厥患儿收集的脑脊液样本。采用酶免疫测定法测量神经营养因子水平。
与对照组相比,所有病毒性ME患者脑脊液中BDNF和NGF水平均显著升高。此外,EBV所致ME患者的神经营养因子水平高于其他病毒性ME患者。值得注意的是,在EBV所致ME患儿中,我们发现神经营养因子水平与脑脊液中淋巴细胞数量之间存在显著相关性(p<0.001)。在这些患者中,我们还发现BDNF表达与血小板计数之间存在显著相关性(p<0.001)。有趣的是,2例EBV所致ME患者的神经营养因子升高与持续性脑异常之间存在相关性,如精神状态长期改变、精神运动性激越和手足徐动症。
病毒性ME可诱导神经营养因子早期且强烈的生物合成增加。这种神经营养因子的过度表达可能在神经元炎症机制及脑损伤严重程度中起关键作用,尤其是在EBV所致ME中。