Thursday, March 10, 2016

Ketogenic diet redux

Eric H. Kossoff, Sarah C. Doerrer, Steven P. Winesett, Zahava Turner, Bobbie J. Henry, Stacey Bessone, Anthony Stanfield, Mackenzie C. Cervenka.  Diet Redux.  Outcomes from Reattempting Dietary Therapy for Epilepsy.   Journal of Child Neurology.  Published online ahead of print.

The outcome for patients attempting dietary therapy for epilepsy a second time is unknown. Twenty-six subjects treated with the ketogenic diet as children who then began either the ketogenic diet or a Modified Atkins Diet (MAD) at least 6 months later were evaluated. The mean age at the first diet trial was 5.6 years and at the second diet trial was 11.5 years. Most restarted dietary therapy because of persistent seizures (65%) or recurrence after seizure freedom (19%). Overall, 77% had a ≥50% seizure reduction with the first diet, and 50% with the second diet, P = .04. Individual subject responses were largely similar, with 14 (54%) having identical seizure reduction both times, 9 worse (35%) with the second attempt, and 3 (16%) improved. The second diet trial was more likely to lead to >50% seizure reduction if the first trial was started at a later age (7.4 vs 3.9 years, P = .04).

From the manuscript:

Typically, due to concerns about metabolic side effects and the fact that a significant residual effect of seizure reduction occurs after the ketogenic diet is discontinued, the ketogenic diet is discontinued in children after approximately 2 years and other options (eg, further antiepileptic drug trials or vagus nerve stimulation) are then implemented…

For some, the ketogenic diet was short-lived secondary to side effects, problems with restrictiveness, and/or rapid recognition of inefficacy. However, there are other patients who had positive experiences with the ketogenic diet, including periods of seizure freedom, but for various reasons the ketogenic diet was eventually discontinued. Both types of patients may reconsider the use of dietary therapy years later should seizures recur or remain uncontrolled…

Of the 7 children who were on the first diet for fewer than 6 months, all were on the second diet slightly longer (14.1 vs 2.4 months, P = .3). However, there was no clear improvement concurrently in seizure control, with only 1 patient having 50% to 90% seizure reduction. Six of these 7 children with brief first diet durations discontinued the second diet because of inefficacy again…

Our study suggests that a variety of patients start dietary therapy a second time, often years later. The majority did so for continued seizures after an initial positive response to the ketogenic diet and failed response to further antiepileptic drug trials and/or vagus nerve stimulation. Many of these patients had Lennox-Gastaut syndrome or other childhood-onset epilepsies that would not be expected to resolve, and two-thirds were intellectually disabled. Having a gastrostomy tube for the ketogenic diet or utilizing the Modified Atkins Diet for adults likely helped influence the decision to retry dietary therapy because of perceived improved tolerability and limited negative effect on lifestyle.

Although as a group, the chances of improvement were less overall with the second diet attempt, when examined individually, approximately half of patients had identical responses, including 12% who had a greater reduction in seizures during the second trial. If a child was seizure-free during the first diet attempt, the majority became seizure-free again. If a child had poor seizure response with the first diet attempt, nearly all had a poor response again. Based on these findings, a neurologist can counsel a family or patient that the first response is likely to predict the outcome with repeat treatment. Older children at the time of the first diet attempt were more likely to respond the second time (or perhaps younger children are less likely to improve). This may reflect the severe nature of some infantile-onset epilepsies (eg, Ohtahara syndrome, infantile spasms) and that their epilepsy may be just as intractable later in life and not respond well to dietary therapy.

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