Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: Two years' experience

Abstract

Recent data indicate that melatonin inhibits brain glutamate receptors and nitric oxide production, thus suggesting that it may exert a neuroprotective and antiexcitotoxic effect. Melatonin has been seen to prevent seizures in several animal models and to decrease epileptic manifestations in humans. The lack of response to conventional anticonvulsants in an epileptic child led us to use melatonin in this case. A female child who began to have convulsive seizures at the age of 1.5 months and was diagnosed as having severe myoclonic epilepsy was unsuccessfully treated with different combinations of anticonvulsants, including valproic acid, phenobarbital, clonazepam, vigabatrin, lamotrigin, and clobazam. Melatonin was thus added to the treatment. Imaging studies (CT, SPECT, and MNR), EEG recordings, blood biochemical, and hematological analyses, including measures of the circadian rhythm of melatonin, were made. The child was initially treated with various anticonvulsants. Severe neurological and psychomotor deterioration combined with increased seizure activity showed a lack of response to the treatment. At the age of 29 mon the patient was in a pre-comatose stage at which time melatonin was added to treatment. After 1 month of melatonin plus phenobarbital therapy and for a year thereafter, the child's seizures were under control. On reducing the melatonin dose after this time, however, seizures resumed and the patient's condition was re-stabilized after restoring melatonin. Prior to our attempts to reduce melatonin, all analyses, including EEG recordings and SPECT, were normal. As far as the results of neurological examination are concerned, only mild hypotony without focalization remained. Changes in the therapeutic schedules during the second year of melatonin treatment, including the withdrawal of phenobarbital, did not result in the same degree of seizure control, although progressively the child became satisfactorily controlled. At the present moment the child continues to have mild hypotony and shows attention disorder and irritability. Melatonin has proven to be useful as adjunctive therapy in the clinical control of this case of severe infantile myoclonic epilepsy. The results suggest that melatonin may have a useful role in mechanisms of neuroprotection and also indicate its use in other cases of untreatable epilepsy. Further studies using more patients and placebo-treatment would be beneficial in understanding the potential use of melatonin as a co-therapy in some cases of seizures.

Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress

“…Therefore, the decrease in L-kynurenine, with an increase in kynurenic acid, xanturenic acid and 3-hydroxyantranilic acid, in the group of patients with fetal distress could be interpreted as an endogenous compensatory mechanism. The increase in umbilical vein concentration of melatonin in this group of neonates may contribute to this compensatory mechanism, as a result of the antistress and anticonvulsant properties of the indoleamine (7).…”

Melatonin, mitochondria, and cellular bioenergetics

“…Both experimental and clinical anticonvulsant activity of melatonin was reported [Molina-Carballo et al, 1997;Lapin et al, 1998]. Reduced melatonin levels are related to increased brain damage after stroke or excitotoxic seizures in rats [Manev et al, 1996], whereas melatonin protected the brain against kainic acid or quinolinic acid oxidative damage Tan et al, 1998;Cabrera et al, 2000].…”

Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

“…Melatonin as a strong antioxidant was an effective anticonvulsant in intractable epilepsy patients (Molina-Carballo et al, 1997). Plasma melatonin was also decreased in epileptic patients by epileptic and febrile convulsions (Molina-Carballo et al, 1994).…”