Neurotransmitter Depletion in Early Epileptic Encephalopathies and Possible Therapeutic Options

The role of monoamines in epilepsy is not clearly reported in the literature. Seizures are associated with the release of catecholamines when the cerebrospinal fluid (CSF) is analyzed in a less than 2 hours period after the epileptic event. However, no detailed studies regarding intercritical alterations have been described. Clinical data and levels of neurotransmitters (biogenic amines) in CSF of 90 patients with early epileptic encephalopathies followed in HSJD, Barcelona, were recruited. Data about the epileptic syndrome type and other neurological features, electroencephalography, genetic studies, brain magnetic resonance imaging, and extensive metabolic screening were collected. The series was composed by 51 females and 39 males with a median age of 1.37 years at the moment of lumbar puncture and 0.52 years at the epilepsy onset. Thirty-one patients had abnormal levels of biogenic amines (34.4%). Sixteen patients had isolated alteration of 5-HIAA (serotonin metabolite) and 10 abnormal isolated HVA levels (dopamine metabolite); five patients had a combined HVA+5-HIAA decrease. Twenty-five patients had a positive genetic diagnosis. Onset age was the only factor related to higher probability of NT depletion. So far only four patients with low CSF NT levels have been treated (one with 5-hidroxytriptophan and three with combined L-dopa+carbidopa and 5-hydroxytriptophan). All of them showed a sustained reduction in seizures (very striking in two patients and moderate in the other two) and improvement in other neurodevelopmental skills. Although this is an ongoing study and requires further analysis, biogenic amines seem to be importantly affected in EE, in particular in very young children. Studies about therapeutic replacement in long series of patients are badly needed to establish formal treatment recommendations, but these preliminary results are promising.