Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome
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Published:2023-10-03
Issue:1
Volume:18
Page:
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ISSN:1745-6150
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Container-title:Biology Direct
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language:en
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Short-container-title:Biol Direct
Author:
Gatto Antonio,Capossela Lavinia,Conti Giorgio,Eftimiadi Gemma,Ferretti Serena,Manni Luigi,Curatola Antonietta,Graglia Benedetta,Di Sarno Lorenzo,Calcagni Maria Lucia,Di Giuda Daniela,Cecere Stefano,Romeo Domenico Marco,Soligo Marzia,Picconi Enzo,Piastra Marco,Della Marca Giacomo,Staccioli Susanna,Ruggiero Antonio,Cocciolillo Fabrizio,Pulitanò Silvia,Chiaretti Antonio
Abstract
Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Publisher
Springer Science and Business Media LLC
Subject
Applied Mathematics,General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics,Immunology
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