1) Background: The Aicardi-Goutières syndrome (AGS) is a rare congenital disease which courses with severe psychomotor delay in neurodevelopment. We studied a 3-years and 4-months old child with very important growth and weight affectation, microcephaly and loss of his developmental skills from 16-months of age, in which previous metabolic and genetic studies discarded any abnormality. Therefore diagnosis was cerebral palsy of unknown etiology. He presented spastic paraparesia, poor fine motricity, cognitive impairment and absence of oral communication. One year after discharge, a de novo mutation was detected in a single nucleotide in the gene IFIH1: c.2317G>C, being then diagnosed of AGS. 2) Methods: Blood analysis showed very low IGF-1 and slightly elevated liver transaminases. Treatment consisted in GH (0.04 mg/kg/day), melatonin (20 mg/day, and after 3-months 50 mg/day), and daily intense neurorehabilitation (5 days/week). Tests for evaluating childhood developmental milestones (GMFM-88, BDIST and the WeeFim test) were carried out every 3-months. 3) Results: The equivalent age at admission (10-months) increased to 24-months at discharge. There were clear improvements in spasticity, fine motor function, swallowing, cognition and autonomy as well as in communication, growth and weight. 4) Conclusion: Most likely melatonin blocked or decreased the interferon signature, allowing GH and neurorehabiltation to act on neurodevelopment.

Caudal regression syndrome (CRS) is a congenital abnormality characterized by an incomplete development of the spinal cord (SC) and other abnormalities. We studied a 9-months old CRS child presenting: interruption of SC at L2-L3 level, sacral agenesis, lack of innervation of the inferior limbs (flaccid paraplegia) and neurogenic bladder and bowel. Given the effects of growth hormone (GH) on the proliferation, differentiation and migration of neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce the recovery of main sequelae. GMFM-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed during 5 years, being the last GH dose 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and every 6 months later. Six months after commencing the treatment GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved any muscle over the knees and controlled his sphincters. Three years later he walked with the help of canes, there was plantar flexion and GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal territories, below the level of the incomplete spinal cord in CRS. Most likely, GH acts on ependymal SC NSCs, as the hormone does in the neurogenic niches in the brain.