Efficacy of the ketogenic diet: Which epilepsies respond? *ySasipa Thammongkol, zDanya F. Vears, *Jillian Bicknell-Royle, *xJudy Nation, {Kellie Draffin, #Karen G. Stewart, z#**yyIngrid E. Scheffer, and *yyzzMark T. Mackay *Children’s Neuroscience Centre, Royal Children’s Hospital, Parkville, Victoria, Australia; yPediatric Neurology Department, Prasat Neurological Institute, Bangkok, Thailand; zEpilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, West Heidelberg, Victoria, Australia; xDepartment of Nutrition and Dietetics, Royal Children’s Hospital, Parkville, Victoria, Australia; {Department of Nutrition and Dietetics, Austin Health, West Heidelberg, Victoria, Australia; #Department of Paediatrics, Austin Health, West Heidelberg, Victoria, Australia; **Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; yyFlorey Neuroscience Institutes, Melbourne, Victoria, Australia; and zzMurdoch Childrens Research Institute, Parkville, Victoria, Australia SUMMARY We report the efficacy of the ketogenic diet in refrac- tory epilepsies focusing on outcomes with regard to epi- lepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty-four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbo- hydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) clas- sification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty-nine (48%) of 61 patients were responders at 3 months. Two children became seizure-free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epi- lepsy of infancy, childhood absence epilepsy, focal epi- lepsy, epilepsy with myoclonic-atonic seizures, and Dravet syndrome. Children with lissencephaly and hyp- oxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syn- drome is an important factor in decisions about timing of initiation of the ketogenic diet. KEY WORDS: Seizure, Epilepsy, Syndrome, Etiology, Treatment, Ketogenic diet, Side effects, Refractory, Etiology. The ketogenic diet (KD) is a medically supervised, high- fat, low–carbohydrate, and moderate-protein diet, which has been used successfully in patients with refractory epi- lepsy. The majority of published studies describe response in terms of the seizure type rather than epilepsy syndrome (Henderson et al., 2006). It is important to determine whether specific epilepsy syndromes and etiologies are more responsive to the KD so that the diet can be initiated earlier in the syndrome’s course rather than being a last resort after conventional antiepileptic drugs (AEDs) have failed. Our aim was to prospectively investigate the efficacy of the KD with regard to electroclinical syndromes and etiolo- gies in children and adults with refractory epilepsy. Patients and Methods Patients with refractory epilepsy (defined as failure to respond to two or more anticonvulsants) were prospectively enrolled between 2002 and 2009. The KD was initiated as an inpatient following a modified Johns Hopkins protocol with dietary ratio ranging from 2:1 to 4:1 fat to carbohydrate and protein. Continuing adjustments to dietary ratio, energy, and protein intake were made while children remained on the diet in order to optimize ketone levels, minimize side effects, and maintain appropriate growth. Urinary ketones were monitored in all patients with a goal of 8 mM in the mornings and 16 mM in the evenings. Blood ketones were also measured in children younger than 2 years of age, aim- ing for levels of 2.4–5.0 mM. Accepted December 13, 2011; Early View publication February 6, 2012. Address correspondence to Mark Mackay, Children’s Neuroscience Centre, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, Australia. E-mail: mark.mackay@rch.org.au Wiley Periodicals, Inc. ª 2012 International League Against Epilepsy Epilepsia, 53(3):e55–e59, 2012 doi: 10.1111/j.1528-1167.2011.03394.x BRIEF COMMUNICATION e55