Cerebral palsy is an important health issue that has a strong socioeconomic impact. There is no cure for cerebral palsy, and therapeutic approaches only report small benefits for affected people. In this study we assessed the effects of growth hormone treatment (0.3 μg/kg/day) combined with physical rehabilitation in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy (four males and six females, mean age 5.63 ± 2.32 years) as compared with that observed in a similar population of cerebral palsy children (five males, five females, mean age 5.9 ± 2.18 years) without growth hormone deficiency treated only with physical rehabilitation for two months. The Gross Motor Function Measure (GMFM-88) and Modified Ashworth Scale were performed before commencing the treatment and after completion thereof. In children with cerebral palsy and growth hormone deficiency, Dimension A (P < 0.02), dimension B (P < 0.02), and dimension C (P < 0.02) of the GMFM-88, and the total score of the test (P < 0.01) significantly improved after the treatment; dimension D and dimension E did not increase, and four of five spastic patients showed a reduction in spasticity. However, in children with cerebral palsy and without growth hormone deficiency, only the total score of the test improved significantly after the treatment period. This indicates that growth hormone replacement therapy was responsible for the large differences observed between both groups in response to physical rehabilitation. We propose that the combined therapy involving growth hormone administration and physical rehabilitation may be a useful therapeutic approach in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy.

Caudal regression syndrome (CRS) is a malformation occurring during the fetal period and mainly characterized by an incomplete development of the spinal cord (SC), which is often accompanied by other developmental anomalies. We studied a 9-month old child with CRS who presented interruption of the SC at the L2–L3 level, sacral agenesis, a lack of innervation of the inferior limbs (flaccid paraplegia), and neurogenic bladder and bowel. Given the known positive effects of growth hormone (GH) on neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce recovery from the aforementioned sequelae. The Gross Motor Function Test (GMFM)-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, during 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed for 5 years, the last GH dose being 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and then every 6 months. Six months after commencing the treatment the 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 all muscles over the knees and controlled his sphincters. Three years later he began to walk with crutches, there was plantar flexion, and the GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal areas below the level of the incomplete spinal cord in CRS. It is likely that GH acted on the ependymal SC NSCs, as the hormone does in the neurogenic niches of the brain, and rehabilitation helped to achieve practically full functionality.

Neonatal hearing loss is one of the most common anomalies and is frequently associated with delivery problems. The effects of growth hormone (GH) on brain regeneration after an injury are well known. This paper looks at a male child diagnosed with cerebral palsy, psychomotor affectation, left spastic hemiparesis, and bilateral sensorineural hearing loss after fetal distress due to ruptured membranes before the delivery of more than 30 hours of evolution and several episodes of severe hypoglycemia. From 3.5 months of age, we treated him with GH (0.04 mg/kg/day), Melatonin (5 mg/day and 6 months later 10 mg/day) and rehabilitation, for a period of 14 months; at discharge, the child fully recovered all the disabilities produced by his cerebral palsy, including normal hearing; GMFM-88 increased from 7.84% to 48.23%; Battelle scores increased from 2 to 9 after 7 months of treatment, and to 30, 1 year after discharge. Most likely hearing loss was recovered due to the effect of GH on the production of hair cells from stem cells (only present in very young children) in the cochlear sensory epithelium. This is the first case of recovery of hearing loss in humans after GH administration. Moreover, GH administration is useful and safe for early treatment of cerebral palsy.

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 17incomplete development of the spinal cord (SC) and other abnormalities. We studied a 9-months 18 old CRS child presenting: interruption of SC at L2-L3 level, sacral agenesis, lack of innervation of 21(NSCs), we treated him with GH and rehabilitation, trying to induce the recovery of main sequelae. 22GMFM-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, 3 23 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed 24 during 5 years, being the last GH dose 1 mg/day. Blood analysis and physical exams were performed