Safety and Tolerability of the Ketogenic Diet in Pediatric Epilepsy: Effects of Valproate Combination Therapy

Abstract

Summary:Purpose: To evaluate safety and tolerability of ketogenic diet (KGD) and valproate (VPA) cotherapy in the treatment of intractable seizures.Methods: The patient records of children who underwent KGD initiation at the Massachusetts General Hospital for Children from February 2002 to September 2004 were retrospectively assessed. Efficacy was measured by comparing reported seizure frequency at baseline and at 3-month intervals thereafter. Adverse events and reasons for terminating the diet were tabulated.Results: Of 71 patients who underwent KGD initiation, 24 were concomitantly using VPA at the time of initiation. The most serious adverse events were two cases of acute pancreatitis (2.8%), both of which occurred in patients not taking VPA. The most common complications in both groups were acidosis (39.4%), nausea and vomiting (23.9%), hypertriglyceridemia (21.1%), lethargy (18.3%), and behavioral changes and irritability (15.5%). No significant difference in adverse-event profiles was found between the VPA group and the non-VPA group. At 1 year, 32 patients remained on the diet, including 11 in the VPA group. Efficacy was nearly identical in these two groups.Conclusions: KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy. Adverse-event profiles of patients on KGD and VPA cotherapy are similar to those of patients on the KGD without VPA. In considering possible treatment options for intractable seizures, cotherapy with these two modalities should not be excluded for safety or tolerability concerns. In some patients, this combination may provide optimal seizure control.

Long-Term Outcome of the Ketogenic Diet for Intractable Childhood Epilepsy With Focal Malformation of Cortical Development

“…In the administration of the KD, various complications occurred, but most were transient and could easily be managed by conservative treatments. 13,19 Even serious complications could be resolved after stopping the diet. 13 Contrary to the complications of diet therapy, we experienced sustained hemiparesis in 3 patients who had hemispherec(o)tomy.…”

Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy

“…Volume restriction or depletion during acute illness heightens the risk of urolithiasis by concentrating the urine and its stone-forming solutes. Within the past decade, renal calculi have been reported in 1.4—8.7% of children on the KD (Freeman et al, 1998; Hassan et al, 1999; Furth et al, 2000; Maydell et al, 2001; Nordli et al, 2001; Kossoff et al, 2002a,b; Vaisleib et al, 2004; Sampath et al, 2007) and hematuria in as many as 10% (Lyczkowski et al, 2005). In general, lower rates are reported when GU imaging is restricted to patients with pain or macroscopic hematuria, whereas higher rates of urolithiasis are detected when imaging is also performed in cases of occult hematuria or hypercalciuric hypocitraturia.…”

The Influence of Ketogenic Diet on Liver Function in Children and Adolescents with Intractable Epilepsy

“…In the study that was done by Lyczkowski et al, 2 patients who took KD and VPA concomitantly experienced raises of the serum liver function enzymes (14). In 1 patient after 3 weeks, the serum levels of ALT and AST were increased to 201 U/L and 161 U/L, respectively.…”

“…The 2nd patient experienced the elevation of liver function tests after 2 weeks on the diet (ALT, 229 U/L; AST, 238 U/L). Albeit, after comparison of the adverse effects of patients who got the combination of KD and VPA and the patients who took exclusively KD, they concluded that concomitant introduction of KD and VPA did not increase the chance of hepatotoxicity (14). In addition, Ballaban-Gil et al reported 2 cases that had the marked elevation of liver function biomarkers during initiation of the diet and 13 months after commencement of KD (15).…”