CSF levels of dopamine and serotonin, but not norepinephrine, metabolites are influenced by the ketogenic diet in children with epilepsy

The ketogenic diet (KD) is a non-pharmacological treatment of medically refractory epilepsy in children. Its mechanisms of action are still unclear but monoamine neurotransmitters have been proposed to be involved. Norepinephrine, dopamine, and serotonin are known to modulate seizure susceptibility in many animal models. We examined whether the concentrations of norepinephrine, dopamine, and serotonin metabolites were affected by the KD in children with pharmacoresistant epilepsy. The metabolites of norepinephrine, HMPG, of dopamine, HVA, and of serotonin, 5-HIAA, were analyzed in cerebrospinal fluid (CSF) before and 3 months after starting the KD. Twenty-six children (mean age 5.9 years) participated. Twenty-one children had generalized epilepsy and five partial. CSF was sampled by lumbar puncture. Seizure frequency before and during the diet was determined. Highly significant changes were found for HVA (p = 0.0002) and 5-HIAA (p = 0.004), which were both decreased during the KD compared to before diet. The levels of HMPG were unchanged. However, no differences were found between response groups. Valproate medication affected the levels of HMPG during diet with decreased levels in children on valproate and increased in those not on valproate (p = 0.04). Our study indicates that the KD significantly alters the levels of metabolites of dopamine and serotonin but with a stable ratio HVA/5-HIAA in the CSF of children with refractory epilepsy, which finding may be of importance for the mechanism of action.