Identification of cerebral acetone by 1H-MRS in patients with epilepsy controlled by ketogenic diet

Ketogenic diet (KD) is highly effective in controlling epileptic seizures in children. One of the mechanisms postulated, the accumulation of ketone bodies, acetoacetate (AcAc) and/or betahydroxybutyrate (beta-OHB) in the brain, would be detectable by non-invasive proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS was performed in occipital cortical grey matter in 14 epileptics (E); ages 3.8-48.3 years), seven KD and seven without, and 16 healthy age-matched subjects. One E was examined before and after KD. A singlet resonance (sigma = 2.22 ppm), distinct from AcAc (sigma = 2.26 and 3.46 ppm), and identified as acetone was present in all spectra of children on KD (nine spectra in five children; concentration 0.7 +/- 0.2 mM). This resonance was absent from Control and E without diet. AcAc and beta-OHB, which were not detectable in KD brain, were found in urine or blood of all KD. Seizures were well controlled in all E in whom acetone was detected. Two of seven E, both adults, were seizure-free without detectable acetone. Cerebral acetone may contribute to seizure control in KD, but is unlikely to be the sole mechanism.