FMZ-PET to assess the efficacy and the mechanism of ketogenic diet for patients with intractable infantile spasms

Objectives Ketogenic diet (KD), a strict diet with high-fat, low-protein and low-carbohydrate, has been recognized as an eventual and an effective treatment strategy for medically refractory epilepsy. Although several theories how the KD could have the anticonvulsant efficacy have been hypothesized, the most important anticonvulsant mechanism of the KD is still unknown. This study is a first report to speculate the mechanism underlying the effect of KD in patients with intractable epilepsy focusing on the alternations of the binding potentials (BP) of a specific ligand [C-11]flumazenil (FMZ) to benzodiazepine receptor (BZR) relating GABA_A-R function based on FMZ- PET studies.

Methods We had precious experiences with four patients of infantile spasms whose seizures disappeared or were markedly reduced after KD, who underwent FMZ-PET before KD and after improvement of seizures. Dynamic FMZ-PET scanning was acquired, followed by assessment of BP images using the graphic plot method of Logan.

Results A significantly increased BP of FMZ was observed in the FMZ-PET images obtained after the initiation of the KD (mean BP; 2.5-3.5), compared with the images obtained before the start of the KD (mean BP; 1.0-2.0) in all cases. The increased the BP of FMZ after initiation of KD perhaps reflect the improvement of brain function followed by seizure reduction dramatically. It was considered KD induced increase of GABA levels and enhanced the affinity of GABA_A-R for benzodiazepine ligands.

Conclusions This is the first imaging report suggesting that KD might control seizures by increasing the BP of BZR relating GABA_A-R, which may represent the enhancement of GABA density after KD