Melatonin Response in Active Epilepsy

Abstract

Urinary excretion of 6-sulfatoxymelatonin (aMT.6S), the hepatic metabolite of melatonin, was measured for three consecutive 8-h intervals, beginning at 0600 h, in 30 patients with untreated active epilepsy and in 19 healthy subjects. Excretion of aMT.6S in a 24-h period in patients with active epilepsy was 77.3 +/- 55 nmol (median 68.0, range 8.7-280 nmol), significantly higher (p < 0.05) than that of healthy subjects (49.1 +/- 14 nmol, median 49.0, range 19.7-68.0 nmol). Sequential 8-h urinary aMT.6S excretion rates in patients with active epilepsy were 2.45 +/- 2.8 nmol/h (0600-1400 h), 0.83 +/- 0.5 nmol (1400-2200 h) and 6.38 +/- 5.0 nmol/h (2200-0600 h) as compared with 1.43 +/- 0.8, 1.10 +/- 0.8 and 3.81 +/- 1.3 nmol/h, respectively, in healthy subjects. Analysis of variance (ANOVA) indicated that the difference in total output resulted from greater nocturnal excretion (F = 5.58, p = 0.018). Melatonin production in untreated patients with active epilepsy is increased and has a circadian pattern with a phase difference as compared with that of normal subjects.

Melatonin secretion in children with epilepsy

“…No cases of severe epilepsy with morphological brain abnormalities were included, which may be the reason for loss of circadian rhythms, described in Lennox-Gastaut syndrome [12]. The MLT measurement scheme used in the present study enabled data interpretation in the context of high inter-individual variability and observed late offset of urinary MLT metabolite concentrations [33], contrary to a sparse data sampling which may have led to the finding of shift in MLT excretion rhythm [15]. Thus, the present findings suggest that in the most typical cases of epilepsy in childhood, the MLT system responds to the light/dark cycle.…”

“…We could not identify any factors that may have induced such high nocturnal salivary MLT peaks. Antiepileptic treatment, e.g., valproic acid (VPA) is thought to interact with GABA transmission at the suprachiasmatic nucleus and decrease endogenous levels of MLT, and carbamazepine (CBZ) may increase MLT metabolite excretion [15,37]; however, no relation between antiepileptic drugs and MLT concentrations was found in the present study. Melatonin levels are known to depend on genotype (e.g., mutations in genes encoding for enzymes of melatonin biosynthesis) as well as environmental factors during the early development of the pineal gland [38][39][40].…”

“…Examination of the MLT system in children and adults with epilepsy has shown higher nocturnal MLT concentrations than in controls, increase in MLT concentrations during/directly after seizures and shift or loss of MLT circadian rhythm [12][13][14][15][16][17]. Conversely, a number of studies have demonstrated MLT rhythm and plasma concentrations in epilepsy comparable to those of control populations [18][19][20][21].…”

Sudden death in epileptic rats exposed to nocturnal magnetic fields that simulate the shape and the intensity of sudden changes in geomagnetic activity: an experiment in response to Schnabel, Beblo and May

“…Fig. 1 Proportions of sudden death in rats during the three 24 h intervals (24, 48, 72) after induction of seizures, as a function of intensities of the experimentally simulated geomagnetic activity to which the rats had been exposed during the previous three nights Increased melatonin production (Schapel et al 1995) has been measured in untreated epileptic patients and clustering of seizures with circadian peaks between 2200 and 0600 hours local time are well known. Increased levels of nocturnal melatonin are induced by consumption of moderately low dosages of ethanol (Myers and Badia 1993) and by sleep deprivation (Badia et al 1994).…”

Progress in neuroprotective strategies for preventing epilepsy

“…The dose dependant anticonvulsant property of melatonin was shown to be associated with decreased aspartate, glutamate, nitrite and elevated GABA and taurin levels in various brain regions (Bikjdaouene et al, 2003). In untreated epileptic patients, melatonin production is shown to be increased (Schapel et al, 1995) and its diurnal variation in epileptic children is altered (Molina-Carballo et al, 1994). Moreover, it is administered as adjunctive anticonvulsant therapy in severe infantile myoclonic epilepsy (Molina-Carballo et al, 1997).…”