Mean daily plasma concentrations of beta-endorphin, leu-enkephalin, ACTH, cortisol, and DHEAS in epileptic patients with complex partial seizures evolving to generalized tonic-clonic seizures.

INTRODUCTION: A multitude of mechanisms have been implicated in the pathophysiology of epilepsy. OBJECTIVE: To assess mean daily plasma concentrations of ACTH, cortisol, DHEAS, leu-enkephalin, and beta-endorphin in epileptic patients with complex partial seizures evolving to tonic-clonic in relation to frequency of seizure occurrence (groups with seizure occurrences - several per week and several per year) and duration of the disease (groups less than and more than 10 years). We decided to analyse mean daily values of beta-endorphin and leu-enkephalin because of significant differences in concentrations of these substances in blood during the day. MATERIAL AND METHODS: The study was performed on 17 patients (14 males + 3 females; mean age 31.8 yrs) treated with carbamazepine (300-1800 mg/day). The control group consisted of six age-matched healthy volunteers. Blood was collected at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. Intergroup analysis was performed with the use of ANOVA Kruskal-Wallis test. RESULTS: Mean daily concentrations of ACTH and cortisol in the blood of the patients with epilepsy were higher in comparison with those of the healthy volunteers, independently of the frequency of seizures and duration of the disease. Mean daily concentrations of beta-endorphin in the blood of the patients with epilepsy were higher in the groups of patients with more severe clinical course of disease (with more frequently occurring epilepsy seizures and longer duration of the disease) in comparison with healthy subjects. Mean daily concentrations of leu-enkephalin in the blood of the patients with epilepsy were higher in the group of patients with short duration of the disease in comparison with the group with long duration of the disease. CONCLUSIONS: 1. Pituitary-adrenal axis hyperactivity is observed in patients with clinically active epilepsy, independently of the frequency of seizures and duration of the disease. 2. Changes in endogenous opioid system activity are related to the clinical activity of epilepsy - beta-endorphin concentrations are connected with frequency of seizures and duration of the disease and leu-enkephalin concentrations with duration of the disease. 3. Endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy. (Pol J Endocrinol 2010; 61 (1): 103-110).

Levetiracetam pharmacokinetics in neonates at birth.

Based on blood sampling in a formula-fed pair of twins, the estimated serum half-life of levetiracetam (LEV) at birth is 16-18 h.

A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures.

The aim of the present work was to assess serum melatonin levels and melatonin circadian rhythm in patients with diurnal and nocturnal complex partial epilepsy. Daily rhythms of melatonin were studied in patients with diurnal complex partial epilepsy (n=10), patients with nocturnal complex partial epilepsy (n=10), and a control group (n=10). All patients were under carbamazepine treatment. Serum melatonin samples were taken at 1000, 2200, 0100, and 0500 hours. We found that melatonin circadian rhythm was normal in all patients when compared with controls. Melatonin levels were low in both patients with nocturnal and patients with diurnal complex partial epilepsy compared with the control group at 1000, 2200, 0100, and 0500 hours; a statistically significant decrease in melatonin levels was observed in the patients with epilepsy at 1000 hours only. These findings suggest that melatonin levels and circadian rhythm of melatonin do not differ between patients with nocturnal and patients with diurnal complex partial epilepsy. Further detailed research is necessary to determine the factors that govern the nocturnal or diurnal occurrence of complex partial seizures.

Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis. METHODS: The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate. RESULTS: Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic-clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic-clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test-induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures. RECOMMENDATIONS: Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic-clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).

Serum prolactin levels for differentiation of nonepileptic versus true seizures: limited utility.

Frequently occurring nonepileptic psychogenic seizures (PNES) are a cause of substantial morbidity. Differentiation of these from true seizures may sometimes be very difficult. Serum prolactin level estimation following the event has been described as a useful test for this purpose. We conducted this study to assess the role of this test in diagnosis of PNES. Serum prolactin was estimated from venous blood samples of 19 patients (13 females, 6 males) with PNES and 17 patients (5 females, 12 males) with true complex partial seizures with or without secondary generalization. The age range was 12-39 years in the PNES group and 9-42 years in the true seizure group. Five patients (all females) in the PNES group (26.3%) had raised prolactin levels, all of them having greater than twice normal levels. In the true seizure group, 10 of 17 (58.8%) patients had raised levels; only 3 (17.6%) of these had greater than twice normal levels. The difference in percentage of patients with abnormal prolactin levels between these groups was not found to be significant. We demonstrate that serum prolactin level estimation is not a useful method for differentiation of psychogenic nonepileptic from true epileptic seizures.

Thrombophilia interpretation in childhood stroke: a cautionary tale.

Several authors have reported a link between childhood stroke and inherited thrombophilia in recent years. The impact of such a relationship on management and outcome is yet to be determined, as is the potential cost-benefit ratio associated with the performance of thrombophilic screening in children presenting with ischemic stroke. We present a case that highlights the need for clinical and radiologic examinations to remain the definitive criteria used to diagnose stroke in children. The diagnosis should not be influenced by the finding of a thrombophilic marker.

Rapid infusion of sodium valproate in acutely ill children.

The purpose of this study was to investigate the clinical safety of sodium valproate and total and unbound valproic acid plasma concentrations after rapid infusion in hospitalized, acutely ill children. Four children (5-15 years) completed the study. Sodium valproate doses (8.3-15.4 mg/kg) were administered in

Possible oxcarbazepine interaction with cyclosporine serum levels: a single case study.

We studied the influence of an add-on medication with oxcarbazepine on the cyclosporine trough level in a kidney transplant recipient with pharmacoresistant epilepsy. Two weeks after the beginning of the trial we observed a decrease of the cyclosporine trough and the Na serum levels. Both could be corrected by a small-dose reduction of oxcarbazepine, an augmentation of the cyclosporine dosis, and oral sodium chloride substitution. After this episode the cyclosporine trough and the Na serum levels remained stable. Seizure frequency was reduced by 95%. The influence of oxcarbazepine on the cyclosporine serum level has to be studied carefully in other patients after transplantation before the use of oxcarbazepine can be recommended in patients with an immunosuppressive medication with cyclosporine. Our data suggest that oxcarbazepine may be an effective drug with tolerable side effects in this group of patients.

Peripheral WBC count and serum prolactin level in various seizure types and nonepileptic events.

PURPOSE: To analyze effects of different types of seizures and nonepileptic events as well as effects of seizure duration and lapse between the time of seizure and blood collection on serum prolactin level and peripheral white blood cell (WBC) count. METHODS: We prospectively collected blood samples from all patients admitted to our Epilepsy Monitoring Unit at baseline and after an event. Blood samples were analyzed, and serum prolactin level and WBC count were determined. Statistical analyses were performed to evaluate the relation of each type of seizure, its duration, and time lapse between a seizure and collection of blood sample to the serum prolactin level and peripheral WBC count. RESULTS: Serum prolactin level increases above twice the level at baseline after a complex partial seizure or a generalized seizure. Peripheral WBC count is elevated above the upper limit of normal in about one third of cases after a generalized seizure. In generalized seizures, the length of a seizure is positively associated, whereas the lapse time between the seizure onset and blood draw is negatively correlated with the increase in WBC count. Thus the longer the seizure and quicker the blood draw, the higher the WBC count. CONCLUSIONS: We conclude that complex partial or generalized seizures are associated with an increase in serum prolactin level. Peripheral WBC count increases significantly after a generalized seizure and is probably transient in nature.

Near infrared spectroscopy (NIRS) distinguishes seizure types.

Near infrared spectroscopy (NIRS) is a noninvasive method for bedside measurement of cerebral oxygenation (SaO(2)). The purpose of this study was to establish differences in SaO(2)for complex partial seizures (CPS) and rapidly secondarily generalized CPS (RCPS). We studied eight adults with medically refractory epilepsy undergoing evaluation for temporal lobectomy. We continually measured cerebral SaO(2)via a Somanetic Invos 3100a cerebral oximeter, pre-ictal (5 minutes), ictal, immediate (30 seconds) post-ictal, and late post-ictal (5 minutes after ictus). Seventeen seizures (12 CPS, four RCPS and one subclinical) were recorded in eight patients. The percentage change in cerebral SaO(2)from pre-ictal to ictal periods was derived. Cerebral SaO(2)increased (percentage change, mean: 16.6, SD: 13.9) for CPS and decreased (percentage change, mean: 51.1, SD: 18.1) for RCPS. No change in cerebral oximetry was recorded for the subclinical seizure. Post-ictal (immediate and late) increase in cerebral SaO(2)was seen for 11 of the 17 seizures (nine CPS and two RCPS). Peripheral SaO(2)rose greater than 93% for all CPS and the subclinical seizure, but decreased between 78 and 84% during RCPS. These results suggest NIRS distinguishes cerebral SaO(2)patterns between CPS and RCPS. The decrease in peripheral SaO(2), however, may account for the decrease in cerebral SaO(2)seen in generalized seizures.

Treatment of refractory complex-partial status epilepticus with propofol: case report.

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.

Remacemide hydrochloride: a placebo-controlled, one month, double-blind assessment of its safety, tolerability and pharmacokinetics as adjunctive therapy in patients with epilepsy.

Forty patients (33 male, 7 female) with refractory epilepsy were randomized to receive ascending weekly doses of adjunctive remacemide hydrochloride in a b.i.d. or q.i.d. regimen, or placebo for up to 1 month. Assessments included routine physical examination and laboratory tests, recording of adverse events and seizure frequency, and neuropsychological tests. Trough plasma concentrations of concomitant AEDs were measured at weekly intervals. Trough plasma concentrations of remacemide and its desglycinyl metabolite were measured before each dose increment, and complete 24-hour profiles were measured at steady state following administration of 600 mg day(-1)and 1200 mg day(-1). A daily dose of 1200 mg was well tolerated in a q.i.d. regimen and up to 800 mg was well tolerated in a b.i.d. regimen. The most common adverse events were dizziness, diplopia, dyspepsia and abdominal pain. On some occasions, these were considered to be related to raised concentrations of concomitant AEDs. No adverse effects were observed on seizure frequency. Neuropsychology tests revealed no significant changes. Remacemide and the desglycinyl metabolite demonstrated dose proportional pharmacokinetics over the dose range tested.

Serum prolactin levels after seizure and syncopal attacks.

Loss of consciousness and falling are the key features of syncope. Common accompaniments include tonic and myoclonic muscle activity, eye deviations, automatisms, vocalizations and hallucinations that may render the distinction from epileptic seizures difficult. The frequently increased levels of serum prolactin (SPRL) were observed immediately after generalized and complex partial seizures. Presumably, the hormone release is caused by the propagation of epileptic activity, usually from the temporal lobe to the hypothalamic pituitary axis. Numerous reports have demonstrated that the post-ictal SPRL level may be used to differentiate between epileptic and syncopal, non-epileptic attacks. In order to confirm the hypothesis, the SPRL levels were measured in patients with complex partial seizures (CPS) and patients with vaso-vagal syncopal attacks (VVS). The SPRL levels were prospectively measured for each patient as soon as possible after the event (within 1 hour), then 1 hour after the first determination and finally blood was sampled 24 hours later. During the study period (18 months), 18 patients with CPS and 15 patients with VVS were investigated in total. The mean values of SPRL levels in both groups were increased immediately after the event (CPS group: 1142 +/- 305 mIU/l; VVS group: 874 +/- 208 mIU/l). The elevated SPRL levels were found in 14 (78%) patients immediately after CPS and in 9 (60%) patients immediately after VVS. After examining the results of the present study we conclude that the elevated serum prolactin level after an epileptic attack is of no significant value in differential diagnosis between epileptic and vaso-vagal syncopal attacks.

[Relationship between the effect of carbamazepine on SCE frequencies and folic acid in epileptic patients].

Peripheral blood lymphocyte sister chromatid exchange(SCE) frequencies, serum folic acid(FA) levels were examined in 15 epileptic patients treated with carbamazepine(CBZ), and another 15 epileptic patients treated with CBZ and folic acid(FA). The untreated epileptic patients and the healthy subjects served as control. The results showed that SCE frequencies were significantly higher in CBZ Group, compared with CBZ plus FA Group and control(P < 0.01). Serum FA levels were lower in CBZ Group compared with healthy control(P < 0.01). It suggests that CBZ can induce the increase of SCE frequencies. Supplementation with FA may effectively prevent chromosome DNA damage induced by CBZ.

Serum prolactin levels are elevated also after pseudo-epileptic seizures.

The aim of the study was to evaluate the sensitivity, specificity and the predictive values of repeated serum prolactin measurements in relation to epileptic seizures versus pseudoseizures. The method used was prospective measuring of serum prolactin from blood samples drawn (1) 15 min after seizure and (2) 2 hr after the first sample. Two parameters were used: the absolute maximal level; and the relative rise in blood level. In the study 38 had epilepsy (simple or complex partial seizures with or without secondary generalisation); and 20 had pseudo-epileptic seizures. In all cases, the diagnoses were made independent of the prolactin levels. In 30/38 (79%) of epilepsy patients and 17/20 (85%) of pseudoseizure patients, the diagnoses were corroborated by intensive EEG monitoring (video or cassette telemetry). There was a statistically significant rise in prolactin levels in both groups (p < 0.0001 and < 0.02, respectively), and also a significant difference between the two groups. However, repeated measurements in a number of patients (epilepsy: mean 1.5 measurements; pseudo; mean 2.1) showed also considerable intra-patient variations. The sensitivity for the maximal rise in pseudoseizures (5.5x) was only 20% and the negative predictive value 40%. For the cut-off in absolute level (1025 microU/ml), the corresponding figures were 34% and 44%, respectively. The rather limited discriminative power of prolactin measurements makes it of questionable value in discerning between epileptic and pseudo-epileptic seizures.

Three patterns of catamenial epilepsy.

PURPOSE: On the basis of the neuroactive properties of estradiol and progesterone and the menstrually related cyclic variations of their serum concentrations, we propose the existence of three hormonally based patterns of seizure exacerbation. Because previous reports both support and refute the concept of catamenial epilepsy, we test the hypothesis by charting seizures and menses and measuring midluteal serum progesterone levels to estimate the frequency of epileptic women with catamenial seizure exacerbation. METHODS: One hundred eighty-four women with intractable complex partial seizures (CPS) charted their seizure occurrence and onset of menstruation on a calendar for one cycle during which they had a midluteal blood sample taken for serum progesterone determination on day 22. Levels >5 ng/ml were considered ovulatory. The cycle was divided into four phases with onset of menstruation being day 1: menstrual (M) = -3 to +3, follicular (F) = 4 to 9, ovulatory (O) = 10 to -13, and luteal (L) = -12 to -4. Average daily seizure frequency for each phase was calculated and compared among phases by repeated-measures analysis of variance (ANOVA) and the Student-Newman-Keul's test, separately for ovulatory and anovulatory cycles. RESULTS: The 1,324 seizures recorded during 98 ovulatory cycles occurred with significantly greater (p < 0.001) average daily frequency during the M (0.59) and O (0.50) phases than during the F (0.41) and L (0.40) phases, offering support for perimenstrual (catamenial 1) and preovulatory (catamenial 2) patterns of seizure exacerbation. The 1,523 seizures recorded during 86 anovulatory cycles occurred with significantly lower (p < 0.001) average daily frequency during the F phase (0.49) than during all other phases (M = 0.78, O = 0.74, L = 0.74), offering support for seizure exacerbation throughout the second half of inadequate luteal phase cycles (catamenial pattern 3). Although 71.4% of the women with ovulatory cycles and 77.9% with inadequate luteal phase cycles had seizure exacerbation in relation to one of the three patterns of catamenial epilepsy, approximately one third of the women showed at least a twofold increase in average daily seizure frequency. We propose a twofold or greater increase as a reasonable definition of catamenial epilepsy. CONCLUSIONS: Charting of seizures and menses and determination of day 22 progesterone levels during each cycle may be sufficient to establish the existence of three distinct patterns of catamenial epilepsy. Approximately one third of women with intractable CPS may have catamenial epilepsy.

Vigabatrin dosing during haemodialysis.

The antiepileptic drug vigabatrin has shown efficacy in the treatment of patients with refractory epilepsy. Unlike many other antiepileptics it is not bound to plasma protein and mainly eliminated by the kidney. Although the therapeutic and toxic serum concentration range is not clearly defined and efficacy and toxicity are not closely correlated with the dose, factors decreasing vigabatrin elimination such as advanced age or renal failure may pose risk of untoward effects. Thus far there are no dose recommendations available for patients on haemodialysis. We report on an epileptic patient who experienced severe, partially reversible renal failure as a consequence of near-drowning. In this patient serum concentrations of vigabatrin were measured repeatedly both during haemodialysis and after partial recovery of renal function. The terminal elimination half-life in this patient was 41 hours during the period of severe renal failure (creatinine clearance < 5 ml/min). As about 60% of vigabatrin was removed from the blood pool by haemodialysis in these patients the antiepileptic should be administered after dialysis. To maintain serum concentrations in the usual range and to control seizure activity only 500 mg vigabatrin every 3 days were necessary.

Neuron-specific enolase, a marker of acute neuronal injury, is increased in complex partial status epilepticus.

PURPOSE: To determine whether complex partial status epilepticus (CPSE) causes brain injury in humans. Serum neuron-specific enolase (s-NSE) is an accepted marker of acute brain injury, and increases in s-NSE have been correlated with the duration and outcome of generalized convulsive status epilepticus. s-NSE levels in CPSE are unknown. Increase in s-NSE in CPSE would provide new information about the degree of brain injury in CPSE and would help confirm that CPSE is a medical emergency. METHODS: This was a pilot prospective study of serial levels of s-NSE and outcome in CPSE. Eight patients with confirmed CPSE and no acute neurologic deficit were identified prospectively. Results were compared with those of normal and epileptic control groups, and outcome was assessed at hospital discharge or at 7 days with the Glasgow Oucome Scale (GOS). RESULTS: The mean peak s-NSE was 21.81 ng/ml, which for the 8 patients with CPSE was four times higher than that of normal controls (mean s-NSE = 5.36 SD = 1.66, p = 0.0003) and epileptic controls (mean s-NSE = 4.61 SD = 1.74, p. = 0.001). CONCLUSION: The increase in s-NSE provides new evidence that CPSE causes brain injury in humans.

Deliberate overdose with the novel anticonvulsant tiagabine.

Tiagabine is a novel antiepileptic drug which acts by decreasing gamma aminobutyric acid uptake in astrocytes and neurones. Here the first case of deliberate overdose with this compound in a patient on concomitant phenytoin is reported. On admission to hospital his conscious level deteriorated to grade III coma. No changes in the electrocardiogram were noted. Recovery from the initial effects was rapid, and there were no sequelae. Plasma levels of tiagabine (3.1 micrograms/ml) 4 hours after ingestion were 30 times higher than at typical steady state during therapeutic dosing. The effects of poisoning with current first-line antiepileptic drugs are reviewed. The newer agents, particularly those with greater biochemical specificity, may be safer in overdose than the more established anticonvulsants.