Erythropoietin in the serum and cerebrospinal fluid of epileptic children

ABSTRACT

Recent years' research has revealed a specific, neuroprotective enythropoietin [EPO] system in the central and peripheral nervous system, that is upregulated by neuronal damage due to brain hypoxia. Few studies have investigated the endogenous production of EPO in human nervous system. The presence, origin and clinical importance of EPO in epileptic children are investigated for the first time. Forty-five children divided into 3 groups were studied. Group I included 15 recently diagnosed epileptics, not receiving antiepileptic drugs [AEDs], aged 3.8-15 years. Group II consisted of 15 refractory epileptics on AEDs for more than 1 year, aged 3.5-14.7 years. Fifteen healthy children of matched age, sex and socioeconomic status represented groups III [control group]. All children were suffering no hematological, neurological or renal diseases. They were subjected to detailed history, thorough clinical examination an routine investigations [CBC, urea, creatinine, ESR, CRP]. CT brain and EEG were done for epileptic children. Serum levels of albumin [by a colorimetric reaction] and serum prealbumin levels and CSF levels of albumin and prealbumin [by nephelometry] were measured for all children. Serum and CSF levels of EPO were assessed 12 hours after epileptic fits and on admission of control children [using erythropoietin ELISA kit]. Family history was positive for epilepsy in 16.67% of our epileptic children. Their most common types of convulsions were generalized tonic-clonic [GTC], generalized tonic [GT], myoclonic then focal seizures. CT brain was normal in the majority. A minority showed brain atrophy, calcification, hemorrhage, and infarction. EEG showed focal [FEA], generalized [GEA] and multifiocal epileptic activities among our recent epileptics while diffuse slowing [DS] and burst suppression were additional EGG findings among refractory epileptics. The serum and CSF levels of albumin, and prealbumin were normal just as control levels with no correlation with other demographic, clinical and laboratory studied variables. Q albumin was normal in epileptic children indicating the integrity of the blood brain barrier [BBB]. Q prealbumin was as expected markedly higher than Q albumin among epileptic and control children as it has a well known CNS synthesis. The serum levels of EPO were not significantly different in epileptic children, while its CSF levels were significantly higher compared to control children. The degree of elevation of the CSF levels of EPO among refractory epileptics was significantly lesser than that observed among recent epileptics. The CSF levels of EPO in recent epileptics were directly proportionate to the duration of the epileptic fits, while they were inversely proportionate to it in refractory epileptics; a disturbed and/or exhausted neuroprotective role of EPO among prolonged and refractory epileptics may be an explanation. So far; as the Q EPO is much higher [as Q prealbumin] than Q albumin, as there is no significant correlation between CSF and serum levels of EPO among epileptics, as there is no significant correlation between CSF levels EPO and Q albumin and as there is no significant correlation between Q EPO and Q albumin among epileptics and control children; it is concluded that the origin of this CSF erythropoietin is the brain; as a neuroprotective cytokine against neuronal damage caused by the epileptic fits, with the duration of the fit as a determinant factor. As commercially available forms of genetically engineered EPO are safely used for several indications in pediatrics; it is concluded that EPO is an ideal compound to study and it should be thoroughly evaluated in epileptic children, specially the refractory epilepsies and those with prolonged epileptic fits considering a possible therapeutic potential for EPO. It is also concluded that EPO in the CSF of epileptic children is a marker of epileptic fits and has its clinical indications in prognosis and therapeutic intervention