Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the selective loss of spinal motor neurons due to the depletion of the survival of motor neuron (SMN) protein. No therapy is currently available for SMA, which represents the leading genetic cause of death in childhood. In the present study, we report that insulin-like growth factor-1 receptor (Igf-1r) gene expression is enhanced in the spinal cords of SMA-like mice. The reduction of expression, either at the physiological (through physical exercise) or genetic level, resulted in the following: (1) a significant improvement in lifespan and motor behavior, (2) a significant motor neuron protection, and (3) an increase in SMN expression in spinal cord and skeletal muscles through both transcriptional and posttranscriptional mechanisms. Furthermore, we have found that reducing IGF-1R expression is sufficient to restore intracellular signaling pathway activation profile lying downstream of IGF-1R, resulting in both the powerful activation of the neuroprotective AKT/CREB pathway and the inhibition of the ERK and JAK pathways. Therefore, reducing rather than enhancing the IGF-1 pathway could constitute a useful strategy to limit neurodegeneration in SMA.

Predicting the functional recovery of patients with severe neurological condition due to coronavirus disease 2019 (COVID-19) is a challenging task. Only limited outcome data are available, the pathophysiology is poorly understood, and the time-course of recovery is still largely unknown. Here, we report the case of a patient with COVID-19 associated encephalitis presenting as a prolonged state of unresponsiveness for two months, who finally fully recovered consciousness, functional communication, and autonomy after immunotherapy. In a multimodal approach, a high-density resting state EEG revealed a rich brain activity in spite of a severe clinical presentation. Using our previously validated algorithms, we could predict a possible improvement of consciousness in this patient. This case report illustrates the value of a multimodal approach capitalizing on advanced brain-imaging and bedside electrophysiology techniques to improve prognosis accuracy in this complex and new aetiology.