The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.

HE KETOGENIC DIET IS A HIGHfat low-carbohydrate adequate protein diet first developed 8 decades ago for the management of difficult-to-control seizures in children. 1 Recent studies have documented the short-term and longterm benefits of this diet in improving seizure control. 2-4 An evaluation by the Blue Cross/Blue Shield Technology Center reported 5 ". .. the diet's effectiveness in providing seizure control for children with difficult-to-control seizures has remained as good, or better than any of the newer medications." Although the mechanisms by which the diet decreases seizures remain unknown, 6,7 the level of ketosis produced by the incomplete oxidation of fats when carbohydrates are in short supply appears to play a critical role in the effectiveness of this diet. 1 The classic ketogenic diet consists of a 4:1 ratio of fat to carbohydrate and protein combined. 3 Because there are 9 calories/g of fat compared with 4 calories/g of either carbohydrate or protein, the fat content of such a ketogenic diet provides 90% of the child's calorie intake. Carbohydrates are severely restricted and are usually less than 10 g/d. Younger rapidly growing children and adolescents are often started in treatment by receiving a less stringent 3:1 ratio of fat to carbohydrate plus protein to allow sufficient protein (1-1.5 g/kg per day) for growth. Growth while receiving the ketogenic diet remains within the normal range. 8

Hemidecortication continues to be a beneficial procedure in reducing seizure frequency in cases of unilateral cortical epilepsy. Fewer children with migrational disorders are seizure-free.

The ketogenic diet is a safe, well-tolerated, and possibly effective potential alternative to other therapies for infantile spasms.

The objective of this study was to determine the relationship between β-hydroxybutyrate levels and seizure control in children on the ketogenic diet. Seventy-four children on the ketogenic diet presenting for routine follow-up visits had blood levels of β-hydroxybutyrate correlated with their seizure control. Forty-two children admitted for initiation of the ketogenic diet had urine ketones measured by dipstick and correlated with simultaneous blood levels of β-hydroxybutyrate. Blood β-hydroxybutyrate levels statistically correlated with seizure control (P = .003). Children with blood β-hydroxybutyrate levels greater than 4 mmol/L were significantly more likely to have a decrease in seizure frequency than those with levels less than 4 mmol/L. Urine ketones of 4+ (160 mmol/L) were found on dipstick when blood β-hydroxybutyrate levels exceeded 2 mmol/L. Seizure control correlates with blood β-hydroxybutyrate levels and is more likely when blood β-hydroxybutyrate levels are greater than 4 mmol/L. The traditional measurement of urine ketones by dipsticks in children on the ketogenic diet provides a less than optimal assessment of the degree of blood ketosis. Three to four plus (80-160 mmol/L) urine ketones are necessary, but not necessarily sufficient, to achieve optimal seizure control in children on the ketogenic diet. At present, however, urine ketones are the only readily available inexpensive approach to ketone assessment. (J Child Neurol 2000; 15:787-790).

Kidney stones have been associated with use of the ketogenic diet in children with refractory seizure disorders. We performed a case-control study examining risk factors for the development of stones on the ketogenic diet, and prospectively followed children initiating the ketogenic diet to evaluate the incidence of urolithiasis. Clinical characteristics of 18 children presenting with stones (8 uric acid stones, 6 mixed calcium/uric acid stones, 1 calcium oxalate/phosphate stone, 3 stones not evaluated) were compared with characteristics of non-stone-forming children initiating the ketogenic diet at Johns Hopkins since July 1996. Since July 1996, 112 children initiating the ketogenic diet have been followed for development of stones. Follow-up times on the diet range from 2 months to 2.5 years. Of 112 children, 6 have developed stones (3 uric acid, 3 mixed calcium/uric acid stones) (0.8 children developing stones/ 100 patient-months at risk). Comparisons of children presenting with stones on the ketogenic diet with characteristics of the entire cohort initiating the ketogenic diet suggest younger age at diet initiation and hypercalciuria are risk factors for the development of stones. Prospective evaluation of children initiating the ketogenic diet revealed that almost 40% of patients had elevated fasting urine calcium: creatinine ratios at baseline; this increased to 75% after 6 months on the diet. Median urine pH was 5.5 at diet initiation, and remained at 6.0 thereafter. In a subset of patients tested, urinary citrate excretion fell from a mean of 252 mg/24 h pre diet initiation to 52 mg/24 h while on the diet. Uric acid excretion remained normal. Patients maintained on the ketogenic diet often have evidence of hypercalciuria, acid urine, and low urinary citrate excretion. In conjunction with low fluid intake, these patients are at high risk for both uric acid and calcium stone formation.

Three to 6 years after initiation, the ketogenic diet had proven to be effective in the control of difficult-to-control seizures in children. The diet often allows decrease or discontinuation of medication. It is more effective than many of the newer anticonvulsants and is well-tolerated when it is effective.

A cohort study was performed of children started on the ketogenic diet for intractable epilepsy from 2000 to 2005 (n = 195). Children who developed kidney stones were compared with those without in terms of demographics, urine laboratory markers, and intervention with urine alkalinization (potassium citrate). Thirteen children (6.7%) developed kidney stones. The use of oral potassium citrate significantly decreased the prevalence of stones (3.2% vs 10.0%, P = .049) and increased the mean time on the ketogenic diet before a stone was first noted (260 vs 149 patient-months, P = .29). The prevalence of kidney stones did not correlate with younger age or use of carbonic anhydrate inhibitors (eg, topiramate or zonisamide) but trended toward higher correlation with the presence of hypercalciuria (92% vs 71%, P = .08). No child stopped the diet due to stones; in fact, the total diet duration was longer (median 26 vs 12 months, P < .001). Kidney stones continue to occur in approximately 1 in 20 children on the ketogenic diet, and no statistically significant risk factors were identified in this cohort. As oral potassium citrate was preventative, prospective studies using this medication empirically are warranted.