study of some clinical and biochemical markers of epileptic seizures

The adverse effects of anticonvulsant drugs, duration and expense of therapy and social implications make it essential for accurate discrimination of epileptic from non epileptic seizures [NES]. There is still no single biochemical marker for epileptic seizures and many patients being treated as epileptics are not actually so. Moreover, the coexistence of pseudoseizures with epilepsy is high. Recently few studies had investigated the neuroprotective erythropoietin [EPO] system in the central and peripheral nervous systems. However, the clinical importance of EPO as a specific biochemical marker for epileptic fits is not yet investigated. Sixty children divided into 3 groups were studied. Group I included 20 recently diagnosed epileptics, aged 3.5-15 years. Group II involved 20 children with recent NES, aged 2-14 years. Twenty children suffering fever of unknown origin with lumbar puncture as part of its diagnostic work up, aged 3-15 years represented group III [control group]. All children were suffering no other neurological, hematological or renal diseases. Thorough history, clinical examination and routine investigations, confirmed diagnosis and established exclusion criteria. CT brain, EEG and EMG were done for all patients. Peripheral white blood cells [WBCs], serum creatine kinase [CK] and serum and CSF albumin and erythropoietin [EPO] were measured 24 hours Post-ictally for all patients and on admission of control children. Family history was positive for epilepsy in 20% of epileptic children. Post-ictal symptoms followed more than a half of epileptic seizures and less than a quarter of NES. The most common types of epileptic seizures were generalized tonic-clonic [GTC], generalized tonic [GT], myoclonic then focal seizures. CT brain was normal among most epileptic and all non epileptic patients; with hemorrhage in two epileptics and calcification in only one. EEG showed focal [FEA], generalized [GEA] and multifocal epileptogenic activities [MFEA] among our recent epileptics. Peripheral WBCs, serum CK and CSF levels of EPO showed a significant elevation 24 hours Post-ictally following generalized tonic-clonic epileptic fits and to a lower extent following focal and non epileptic fits. The 3 parameters showed a significant positive correlation with seizure duration. Serum CK levels were markedly elevated [more than 200 U/L] and CSF levels of EPO increased by more than 2 standard deviations in a high percentage of epileptic seizures especially so; GTC seizures, with this marked degree of elevation as a more sensitive factor discriminating epileptic from non epileptic seizures. Post-ictal symptoms, peripheral WBCs, serum CK and CSF levels of EPO are important discriminative factors between epileptic and non epileptic seizures before proceeding to more sophisticated and expensive investigations

Erythropoietin in the serum and cerebrospinal fluid of epileptic children

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

Serum prolactin and creatine kinase levels in epileptic and non-epileptic seizures

The adverse effects of anticonvulsant drugs, duration and expense of therapy and social implications, make it essential for accurate diagnosis before starting treatment. Many patients being treated as epileptics are not actually so. Moreover the coexistence of pseudoseizures with epilepsy is high. There is no single exposure, biochemical marker to differentiate between epileptic and non epileptic seizures [NES]. Ninety children were studied. They were subgrouped into 4 groups. Group I included 30 children with recent epileptic fits, aged 2-12 years. Group II consisted of 15 children with recent typical febrile seizures, aged 1-4.75 years. Group III involved 15 children with recent non-epileptic seizures, aged 5.2-12.7 years. Thirty clinically healthy children aged 3-12 years represented group IV [control group]. Thorough history and clinical examination confirmed diagnosis and established exclusion criteria. CT brain, EEG and EMG imaging studies were done for all patients. Peripheral white blood cell count [WBCs], serum creatine kinase [CK] and prolactin levels were measured within lapse time [15-120 minutes] and 24 hrs post-ictally for all patients and once for control children. Post-ictal symptoms were present in more than 2/3 of epileptic seizures and 20% only of non-epileptic fits. WBCs and serum prolactin levels showed a transient early; while serum CK levels had a late post-ictal significant increase after generalized epileptic fits and to a much lower extent following focal and nonepileptic fits. The generalized tonic-clonic seizures [GTCS] showed higher elevation than other types of generalized epileptic fits. The three parameters showed a positive correlation with duration of seizures and a negative correlation with lapse time. Peripheral WBCs and serum prolactin returned to near normal levels one day post-ictally, while serum CK started to show a significant increase only 24 hrs after seizures. Serum prolactin levels were elevated more than twice and serum CK levels increased by more than 20 U/L in a high percentage of epileptic GTC seizures. The integrated interpretation of post-ictal symptoms, early assessment of peripheral WBCs and serum prolactin [<2 hrs] and late measurement of serum CK levels [>24 hrs] can compensate for our clinical uncertainty between epileptic and non-epileptic seizures before having to resort to more sophisticated and expensive investigations