Combined treatment of nerve growth factor and transcranical direct current stimulations to improve outcome in children with vegetative state after out-of-hospital cardiac arrest

Antonietta Curatola, Benedetta Graglia, Giuseppe Granata, Giorgio Conti, Lavinia Capossela, Luigi Manni, Serena Ferretti, Daniela Di Giuda, Domenico Marco Romeo, Maria Lucia Calcagni, Marzia Soligo, Enrico Castelli, Marco Piastra, Flavio Mantelli, Giacomo Della Marca, Susanna Staccioli, Tiziana Romeo, Marcello Pani, Fabrizio Cocciolillo, Aldo MancinoAntonio Gatto, Antonio Chiaretti

Research output: Contribution to journalArticlepeer-review

Abstract

BackgroundOut-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.ResultsThree children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS 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 finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported.ConclusionsThese promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalBiology Direct
Volume18
DOIs
Publication statusPublished - 2023

Keywords

  • Human-recombinant nerve growth factor
  • Intranasal Administration
  • Transcranial Direct current stimulations
  • Out-Off Hospital Cardiac arrest
  • Neuroprotection

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