PracticeUpdate Neurology Best of 2018

EDITOR’S PICKS 15

Effect of Modified Atkins Diet in AdultsWith Drug-Resistant Focal Epilepsy Epilepsia Take-home message • High-fat, low-carbohydrate diets are gaining attention. The authors argue that, while these diets have shown a seizure-reducing effect in children, there is a lack of strong evidence for a similar effect in adults. In this randomized controlled trial of a modified Atkins diet after a period of 12 weeks, using a cutoff of 25% seizure frequency reduction, but not 50%, there was a significant reduction in seizures in the 24 patients who completed the diet. While there were no serious adverse events, 3 of the 28 patients who were on the diet for at least 1 week terminated the diet early due to increased seizure frequency; problems including reduced exercise capacity and reduced energy were reported. • This is good information for the practicing provider, advocating for a possible benefit of a modified Atkins diet in patients with refractory epilepsy. However, interestingly, the authors do note that the seizure response varied considerably among individuals and was perhaps negatively influenced by a drop in serum concentrations of antiepileptic drugs, raising caution to the provider that it may be necessary to measure drug levels carefully while patients are on these diets. Omar Khan MD

Abstract OBJECTIVE Ketogenic diets reduce seizures in children with drug-resistant epilepsy. Whether adults benefit from similar treatment has not been clarified. We therefore examined the effi- cacy of the modified Atkins diet in adults with drug-resistant focal epilepsy. METHODS We performed a randomized clinical trial (RCT) with patients >16 years who had at least 3 seizures per month despite having tried at least 3 antiepileptic drugs. They were ran- domized to either 12 weeks on the modified Atkins diet (diet group) or habitual diet (control group). Primary endpoint was a change in sei- zure frequency from baseline to the intervention period, comparing those on diet with controls. RESULTS We assigned 37 patients to the diet group and 38 to the control group. Nine of the patients in the diet group and 4 controls were excluded. Of those who completed the dietary intervention (n = 24), median seizure change was -1.0 (interquartile range [IQR] -13.7-8.8), while in the control group (n = 32) the median change was 4.5 (IQR -4.8-33.5). The median difference between the groups was -7.0 (95% confidence interval [CI] -37.0-3.0; P = .21). In the intention-to-treat analysis, the relative risk (RR) for achieving >50% seizure reduction was 1.8 (95%CI 0.3-10.2; P = .65), while for achieving >25% seizure reduction RR was 2.43 (95% CI 0.94-6.28; P = .06). We observed no serious adverse events. SIGNIFICANCE In this RCT investigating the effect of an adjunctive modified Atkins diet on seizure frequency in adults with difficult-to-treat focal epilepsy, we found a significant reduction in sei- zure frequency in the diet group compared to the controls, but only for moderate benefit (>25% seizure reduction) among those who completed the intervention. However, seizure response var- ied considerably between individuals, perhaps negatively influenced by a drop in serum con- centrations of antiepileptic drugs. Effect of Modified Atkins Diet in Adults With Drug-Resistant Focal Epilepsy: A Randomized Clinical Trial. Epilepsia 2018 Jun 14;[EPub Ahead of Print], M Kverneland, E Molteberg, PO Iversen, et al. www.practiceupdate.com/c/70012

COMMENT By Amal Satte MD T he Atkins diet is widely used to treat drug-resistant epilepsy in children. However, there are few studies on the effect of this diet on refrac- tory epilepsy in adults. On the other hand, most of these studies don’t spec- ify the response to the diet with respect to epilepsy type. The objective of this trial was to evaluate the impact of adjunctive Atkins diet on refractory focal epilepsy in adults. One of the strengths of this study is that it was a randomized clinical trial with two arms: a diet group and a control group. But, because of slow recruitment, the number of participants was relatively low: 24 patients in the diet group versus 32 patients in the control group. This may be the reason why there was no signif- icant seizure-reducing effect seen with the diet, although the individual varia- tion in seizure response was important. In practice: • As the diet was effective in some patients, it might be worth trying in adult focal epilepsy. • A close follow-up and support may improve adherence to the diet. In this trial, there were few dropouts com- pared with other studies. This may be explained by a shorter trial period, but also the close follow-up (information,

training, recipes, etc). • Efficacy in some patients in this study was seen after 2 to 3 months, which may suggest the need to prolong the diet duration. • Some patients on the Atkins diet may experience an increased seizure fre- quency. This effect can be transient and is sometimes related to a drop-in serum concentration of antiepileptic drugs (AED). Thus, it can be important to monitor AED serum levels in patients on the Atkins diet. • In this study, there were no serious adverse events. • Finally, there’s a need for further studies with a larger number of participants and long follow-up, which would also take into account other factors such as seizure history, the effect on different types of seizures, quality of life, inter- actions between specific AEDs and the diet, AED serum concentration, any protective and triggering factors (especially stressful events linked or not to the diet). Dr. Satte is from the Neurophysiology Department of Mohammed V Teaching Military Hospital Mohammed V University in Rabat, Morocco.

VOL. 3 • NO. 4 • 2018