The ketogenic diet: it’s about ‘time’

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The year 2008 may have been one of the most exciting years in the history of the ketogenic diet since its origin in 1921. In April 2008, a 4-day internationally-organized symposium was held in Phoenix, Arizona, USA which was solely focused on dietary therapies for epilepsy. Just 2 months later, in June, the first published randomized, controlled trial of the ketogenic diet demonstrated strong evidence for its efficacy.1 Lastly, in September, a 26-member international panel published the first consensus statement guiding management of children receiving the diet.2

Over the past decade, there has been considerable research into who should be started on the ketogenic diet, such as children with infantile spasms, tuberous sclerosis complex, and myoclonic-astatic epilepsy. Studies have also attempted to improve how to implement the diet (e.g. not fasting upon admission, outpatient initiation, using ‘alternative’ diets such as the modified Atkins diet, and low glycemic index treatments). Researchers have even made great strides in determining why the diet works.

In the study by Dr Villeneuve et al. published in this issue of DMCN, the fascinating question of when the ketogenic diet should be started was investigated. It is traditional to use the diet in children with epilepsy who have failed to respond to at least two anticonvulsants,2 but this recommendation applies to pediatric epilepsy overall. These investigators attempted to determine the ideal timing for beginning the diet for a given child.

Results demonstrated that children with ‘recently worsened’ epilepsy, defined by the authors as a doubling of their individual baseline seizure frequency within the past month, were nearly three times as likely to respond to the ketogenic diet as those with a more stable seizure frequency (70 vs 25%). Despite only 22 children included in this retrospective trial, this was statistically significant. What may be even more impressive was the level of response seen, with four of five children with status epilepticus becoming seizure-free, and nearly all children who responded doing so within a week. This rapid improvement has been previously reported,3 but is even more remarkable considering that all children had focal epilepsy, which is less likely to have such a dramatic, seizure-free response with the diet.

The potential value of the ketogenic diet for status epilepticus, although not the primary focus of this study, is strongly implied. Interestingly, similar success using the diet for a 54-year-old male with refractory partial status epilepticus was described recently by other investigators from France.4 Should the diet therefore be a considered a valuable adjunctive therapy to intravenous benzodiazepines, phenytoin, and phenobarbital for status epilepticus? This novel use for the ketogenic diet is definitely worth validating prospectively. All patients with status epilepticus require nutrition, and the ketogenic diet can be provided as a formula via a nasogastric catheter. Neonates with frequent seizures as a result of hypoxic–ischemic encephalopathy, meningitis, or other etiologies could similarly have their infant formulas switched from standard ones to ketogenic.

This approach is not without its difficulties. The ketogenic diet requires time and effort to convince parents as to its value; it is not a simple therapy to maintain and needs a team approach by a neurologist and nutritionist.2 Creating and providing basic informational pamphlets and materials may aid in this educational process during emergency situations. Also, for how long should one provide the ketogenic diet should it prove successful for a patient with status epilepticus? The traditional 2-year seizure-free period may not be necessary; however, as many of the children in this study did have seizures recur, it would likely be at least several months. Lastly, immediate-term side effects of the diet, which include acidosis, vomiting, hypoglycemia, and weight loss, were seen in the majority of children in this study. This could have serious ramifications for a medically-fragile child in an intensive care unit.

This research is to be commended for its originality and represents a new avenue of investigation. It is further evidence that research into the diet has continued to move beyond simply proving efficacy into maximizing it. For basic and clinical ketogenic diet scientists, the ‘time’ could not be more perfect.

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