Mathematical evaluation of melatonin secretion in Hypoxic ischemic encephalopathy

BACKGROUND: Hypoxic-ischemic brain injury is caused by a cascade of molecular reactions and mechanisms concerning calcium influx, free radical formation, free iron accumulation, nitric oxide production, apoptosis activation. THE AIM OF THE STUDY: The authors access the endogenous melatonin diurnal secretion in the hypoxic-ischemic group and compare the results with the results obtained for children with epilepsy (EG) and children from the comparison group (CG). MATERIAL AND METHODS: The hypoxic-ischemic encephalopathy group (HIE) consists of 9 prematurely born children at the mean age of 6.5 years, all diagnosed with epilepsy and suffering because of sleep problems. The parameters of the melatonin secretion model obtained for this group were interpreted and compared with data from the patients with epilepsy (n=78) and the children from the non-epileptic group (n=38). The melatonin level was assessed by a radioimmunoassay method. RESULTS: Among the model parameters, the phase shift of melatonin release is one that strongly differentiates the HIE and CG groups (p-value = 0.001157). DLMOon50 and both offset parameters: DLMOoff50 and DLMOoff25 are helpful in distinguishing HIE from CG, whereas DLMOoff50 is found to differentiate statistically two epileptic groups: HIE and EG. CONCLUSIONS: The characteristic feature of the HIE melatonin secretion is delayed melatonin phase release and shift of the DLMO parameters to the later morning hours. HIE secretion is even more disturbed than in EG. Our mathematical modelling of circadian melatonin cycle facilitates statistical analysis of the patients' hormone levels offering a set of parameters that enable objectification of the secretion description.