May 27, 2010 — The ketogenic diet is an effective alternative for pediatric patients with persistent seizures who have not responded to other therapies, say investigators. Reporting results from the largest analysis to date, researchers from Johns Hopkins Children's Center, Baltimore, Maryland, show that about two-thirds of refractory patients respond to the high-fat, low-carbohydrate diet.
"Stopping or reducing the number of seizures can go a long way toward preserving neurological function, and the ketogenic diet should be our immediate next line of defense in children with persistent infantile spasms who don’t improve with medication," senior investigator Eric Kossoff, MD, a pediatric neurologist and director of the ketogenic diet program at Hopkins, said in a news release.
The new study is a follow-up of a 2002 report that showed the diet worked well in a small number of children with infantile spasms. The current report, published online in Epilepsia, includes 104 pediatric patients.
The ketogenic diet provides just enough protein for body growth and repair and sufficient calories to maintain a healthy weight. The classic ketogenic diet contains a 4:1 ratio of fat to combined protein and carbohydrate.
"We have seen a significant increase in referrals for the ketogenic diet for intractable infantile spasms," note the study authors. They have also started using the diet in new-onset cases. "The purpose of this study was to use the increased patient cohort to evaluate for predictive factors for success, compare results over time, and evaluate long-term seizure, electroencephalogram, and developmental outcomes."
The researchers show that nearly 40% of children became seizure free for at least 6 months. Most of these have remained seizure free for at least 2 years.
Table. Spasm Reduction at Each Follow-up
Reduction,% 3 Months,% 6 Months,% 9 Months,% 1 Year,% 2 Years,%
Seizure free 18 28 32 30 33
>90 13 11 14 13 11
50–90 32 25 27 34 33
<50 37 36 27 23 23
The investigators also report significant improvements in development and electroencephalograms, as well as a reduction in the number of concurrent anticonvulsants.
The mean age of patients was 1.2 years. Previous therapy included on average 3.6 anticonvulsants. Most patients had tried corticosteroids or vigabatrin.
The researchers used the diet first line in 18 patients with newly diagnosed seizures never treated with drugs. Ten of these patients became seizure free within 2 weeks of starting the diet.
The finding suggests that in some children the diet may work well as first-line therapy. Debating at the American Epilepsy Society 63rd Annual Scientific Conference in December, experts weighed the pros and cons of this approach.
Speaker Elizabeth Donner, MD, from the Hospital for Sick Children in Toronto, Ontario, Canada, argued at the meeting that the ketogenic diet is effective and should be considered first line in infantile spasms and especially in GLUT1 and pyruvate dehydrogenase deficiency.
First Line In GLUT1 and Pyruvate Dehydrogenase Deficiency
"Antiepileptic drugs do bad things to children," Dr. Donner said, naming a long list of adverse effects — many serious and some involving cognitive impairment. "In some cases, antiepileptic drugs can even make seizures worse," she said.
Dr. Donner suggested that since the ketogenic diet works quickly, it makes sense to try it first line.
Speaker Douglas Nordli, MD, from the Children's Memorial Hospital in Chicago, Illinois, agreed the ketogenic diet can be used first line in patients with GLUT1 or pyruvate dehydrogenase deficiency. However, he argued there is otherwise limited evidence confirming the benefits of the diet.
Dr. Nordli says it is not easy for dieticians and families to start a ketogenic diet emergently, so he will continue to try 1 or 2 medications first.
"The diet is not completely innocuous," he added, noting that it can be especially dangerous for patients with underlying metabolic defects.
Common adverse effects include constipation, heartburn, diarrhea, behavior problems, kidney stones, and temporary spikes in cholesterol levels. In this study, adverse effects were observed in a third of children. Some also experienced diminished growth (6%).
"We would do a disservice to the ketogenic diet to propose it first line without sufficient prospective comparative data," Dr. Nordli said. "Articles showing a probable beneficial effect are not the same as comparative superiority to existing agents."
Speaking to Medscape Neurology, lead study author Amanda Hong, a medical student at Hopkins, said her team agrees. "Additional prospective, multicenter studies are needed."
This study was funded by Johns Hopkins University and the National Institutes of Health. Dr. Kossoff has received financial support from Nutricia Inc for unrelated research pertaining to their products.
Epilepsia. Published online April 30, 2010.
Source: Medscape
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