Prediction of responders to ketogenic diet based on syndrome
and etiology: identiﬁcation of a new target population?
Pediatric Neurology Department & INSERM U1141, Robert-Debr
Hospital, Paris, France.
This commentary is on the original article by Villaluz et al. on pages
718–723 of this issue.
The ketogenic diet therapy is now an established evidence-
based treatment for pharmacoresistant epilepsies. Initially
it was thought that the ketogenic diet was a more effective
treatment of epilepsies with generalized-onset seizures and
the encephalopathies. Some pediatric epilepsy syndromes
have been identiﬁed as interesting target populations
because of the efﬁcacy of the ketogenic diet when conven-
tional antiepileptic drugs have limited effects. The keto-
genic diet is favorably considered in cases of West
syndrome, Dravet syndrome, Lennox-Gastaut syndrome,
pharmacoresistant childhood absence epilepsy, and epilepsy
with myoclonic-atonic seizures. A good responder rate to
the ketogenic diet has also been found in children with
epilepsy with focal-onset seizures, when the etiology is a
malformation of the cortical development. In a study
including children with focal cortical dysplasia, 29 of 47
were responders after 3 months on the ketogenic diet,
suggesting that the diet could be a good treatment option
for seizure control before epilepsy surgery or during the
Villaluz et al.
report a dramatic 3-month responders
rate (7/9) in developmental and epileptic encephalopathy
due to acquired structural abnormalities. After 2 years of
the ketogenic diet, ﬁve patients remained on the diet and
were still responders. Despite the limitation of the retro-
spective nature of the study and the limited number of
patients, this report could have a signiﬁcant impact in the
ﬁeld. The data suggest the ketogenic diet is particularly
effective in refractory epilepsy due to acquired structural
abnormalities. Further studies might conﬁrm new target
populations as good responders to the ketogenic diet. In
this group of patients (primarily epilepsy after hypoxic-
ischemic encephalopathy), the ketogenic diet could be an
interesting option for patients other than the group with
refractory epilepsy. Most of the time these patients have
several neurological sequelae, including intellectual disabil-
ity. An early use of the ketogenic diet as an anti-seizure
option might become a strategy to avoid the worsening of
cognitive function, which can be observed with some
In their study, Villaluz et al. note that the families
observed a signiﬁcant gain in children’s development and
quality of life during the ketogenic diet treatment. This has
been reported previously.
Until now, it has been method-
ologically difﬁcult to conﬁrm any positive effect on cogni-
tion of the ketogenic diet. The population studied by
Villaluz et al. might represent an interesting population for
such evaluation. It would be of great interest to validate the
effects of the ketogenic diet by controlled prospective trials.
These trials could explore the positive effect of the keto-
genic diet on cognition in cases of epileptic encephalopathy
or its effectiveness in maintaining cognition versus
antiepileptic drugs. New imaging techniques could provide
additional tools to evaluate whether the anti-inﬂammatory
properties of the ketogenic diet contribute to its ability to
modify the epileptic encephalopathy process.
1. Jung DE, Kang HC, Kim HD. Long-term outcome of
the ketogenic diet for intractable childhood epilepsy with
focal malformation of cortical development. Pediatrics
2008; 122: e330–3.
2. Villaluz MM, Boiss
e Lomax L, Jadhav T, Cross JH, Sch-
effer IE. The ketogenic diet is effective for refractory epi-
lepsy associated with acquired structural epileptic
encephalopathy. Dev Med Child Neurol 2018; 60: 718–23.
3. Pulsifer MB, Gordon JM, Brandt J, Vining EP, Freeman
JM. Effects of ketogenic diet on development and behav-
ior: preliminary report of a prospective study. Dev Med
Child Neurol 2001; 43: 301–6.
4. Kostoula C, Pascente R, Ravizza T, et al. Development
of in vivo imaging tools for investigating astrocyte acti-
vation in epileptogenesis. Mol Neurobiol 2017; https://d
oi.org/10.1007/s12035-017-0660-x. [Epub ahead of
5. Scott G, Mahmud M, Owen DR, Johnson MR. Micro-
glial positron emission tomography (PET) imaging in
epilepsy: applications, opportunities and pitfalls. Seizure
644 Developmental Medicine & Child Neurology 2018, 60: 636–644