Credit: Juergen Ritterbach / Alamy Stock Photo.
Cardiac arrest is rare in children, but when it happens outside an hospital setting (an event that clinicians call Out of Hospital Cardiac Arrest, OHCA) it can lead to brain damage caused by the temporary lack of oxygen. The result is often a progressive decrease in cognitive and motor functions. There are no effective therapies are available to restore neuronal loss or produce clinical improvements in these patients. In a new study1, a group led by Antonio Chiaretti, at Policlinico Gemelli, in Rome, tested for the first time a new therapy in three children in a vegetative state following OHCA.
The team has a long history of pioneering therapeutic interventions for brain damage. They previously demonstrated that intranasal injection of nerve growth factor (NGF) helped children suffering severe brain damage from traumatic brain injuries and meningitis. NGF is a well-studied neurotrophin that can restore the function of injured neurons acting on different levels. It was discovered in the 1950s by Rita Levi-Montalcini and Stanley Cohen, who in 1986 won the Nobel Prize for their work. The new study combined NGF injections with transcranial direct current stimulation (tDCS). This non-invasive method delivers direct current to the brain through electrodes placed on the scalp, and has been successfully tested in various neurological conditions, but never in children with severe brain damage. As tDCS stimulate brain plasticity by inducing an endogenous production of NGF and other neurotrophic factors, “we combined them to boost the chances of responses in an extreme case,” says Chiaretti, senior study author. “The rationale was to take advantage of the neurotrophin’s capacity to simultaneously block the death of neurons and the inflammatory processes that causes it, while favouring neuronal repair and regeneration,” explains Chiaretti.
The team selected three children in a chronic vegetative state following OHCA during infancy. The children have been stable for an average of three years since the initial event. They underwent two cycles, each 10 days long, of intranasal NGF injection associated with tDCS. Then, through instrumental and clinical analyses, the team looked for signs of improvement. Using functional and electrophysiological studies, they showed an increase in blood flow and glucose uptake in specific brain regions, which are signs of brain functionality. Clinicians and carers also reported some improvements, such as reduced involuntary movements and the ability to briefly maintain a semi-sitting position. “We saw a similar path in all three children, who continue improving without signs of regression,” says Chiaretti.
Ericka Fink, Professor of Pediatric Critical Care Medicine at the University of Pittsburgh and Dr Fredrik Hessulf, from the University of Gothenburg in Sweden, who were not involved in the study, praise the authors for their work in a field lacking effective treatments. “It’s remarkable to see studies trying to innovate this area,” says Fink.
The team plans to confirm the results in a multi-centre study and target less severe conditions, where the results might be more noticeable.
