Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

中文翻译：

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鼻内人类重组 NGF 给药可改善患有创伤后无反应觉醒综合征的儿童的预后

严重创伤性脑损伤（TBI）是儿科最严重的事件之一，尽管有先进的神经重症监护，这些患者的存活率仍然很低。患有严重 TBI 的儿童会表现出长期后遗症，在行为、神经和神经心理功能方面更为明显，在最严重的情况下，会导致反应迟钝综合征 (UWS)。目前，没有有效的治疗方法可以恢复这些患者的神经元损失或产生显着的改善。在实验动物模型中，人重组神经生长因子 (hr-NGF) 促进神经恢复，支持神经元生长、脑细胞分化和存活，并上调神经发生相关过程。只有少数研究报告了鼻内 hr-NGF 给药对创伤后 UWS 儿童的疗效。诊断为创伤后 UWS 的儿童被纳入研究。这些患者接受鼻内hr-NGF给药治疗，总剂量为50γ/kg，每天3次，连续7天。治疗方案进行 4 个周期，每个周期间隔 1 个月。在治疗前和治疗结束后一个月，通过正电子发射断层扫描（PET）、单光子发射计算机断层扫描（SPECT）、脑电图（EEG）和功率谱密度（PSD）进行神经放射学评估。还通过使用改良的 Ashworth 量表、粗大运动功能测量和残疾评定量表加深了神经学评估。三名患有创伤后 UWS 的儿童接受了治疗。hr-NGF 给药改善了功能（PET 和 SPECT）和电生理（EEG 和 PSD）评估。临床状况也得到改善，主要表现为痉挛减少，并获得随意运动、面部模仿、注意力和语言理解、哭泣能力、咳嗽反射、口腔运动和进食能力，神经系统评分显着改善。没有副作用的报道。这些有希望的结果和这种治疗的易于管理使得值得进一步研究，主要是在严重 TBI 的早期阶段和基线神经系统状况较好的患者中，以更彻底地探索这种新方法对神经元功能恢复的益处脑外伤后。