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Ketogenic Diet May Help in Tough-to-Treat Epilespy

— Literature review suggests benefit in refractory status epilepticus

MedpageToday

WASHINGTON -- The ketogenic diet may work as a treatment for refractory status epilepticus (RSE), researchers reported here.

In a review of the literature involving 77 cases of RSE treated with the ketogenic diet, 90% had complete resolution, according to Neha Kaul, RD, of the Royal Melbourne Hospital in Parkville, Australia, and colleagues in a poster at the American Epilepsy Society meeting.

She cautioned that there were no randomized controlled trials included in the review, and that the positive findings could be confounded by publication bias. Still, the results suggest the diet "might work for this difficult-to-treat situation, with very few side effects."

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

RSE is notoriously difficult to treat and is associated with high mortality. Currently available evidence for its treatment is lacking, and is often guided by clinical experience and expert opinion. Treatment options include sedative agents, anti-epileptic drugs (AED), surgery, plasma exchange, hypothermia, and magnesium infusion.

There's also emerging evidence that the ketogenic diet may also be an effective treatment option, Kaul said. The high-fat, low-carbohydrate diet and has become a well-established treatment option in pediatric drug-resistant epilepsy, but its role in RSE is yet to be established.

Kaul's group reviewed studies published in MEDLINE and EMBASE from January 1946 to May 2017, ultimately including 18 studies in their final analysis: one prospective trial, four retrospective studies, seven case series, and six case reports totaling 77 participants.

Mean age was 11, the mean number of treatments prior to diet was seven, and mean duration of RSE prior to starting the diet was 8 days.

Overall, they found that RSE completely resolved in 69 cases (90%). However, Kaul warned, there's "a lot of publication bias because looking at the quality of the studies, there was only one prospective trial, so we have to be cautious about that."

Death occurred in eight patients, and in six of these patients, RSE remained uncontrolled. Kaul noted that mortality was significantly lower in these studies than previously reported, which likely reflects patient selection bias.

Complications of the ketogenic diet were reported in 36% of patients, including gastrointestinal effects (11%), metabolic acidosis (9%), dyslipidemia (7%), and hypoglycemia (3%).

The exact mechanisms by which the diet might work in RSE aren't known, but given that "we know it works in drug-resistant epilepsy, the mechanism is probably similar in RSE, too," Kaul said.

Although it's not possible to draw conclusions about the efficacy of the ketogenic diet for the treatment of RSE based on the findings, Kaul's group recommended that physicians consider using it in this difficult-to-treat population. They also called for a large randomized controlled trial to put its efficacy to the test in RSE.

"We should be thinking about designing a very big, robust trial to test it. It shows promise," she said.

The popularity of the ketogenic diet in epilepsy has expanded rapidly in recent years, Kaul explained. "Looking at some of the evidence that's coming out with newer AEDs, we still haven't seen a reduction in the incidence of drug-resistant epilepsy, so we really need to be looking at other treatments such as diet, cannabidiol, surgery, and deep brain stimulation."

"All of these are being investigated more closely because the new drugs aren't targeting patients with drug-resistant epilepsy," she said. "Plus, we're seeing a shift in culture for patients in the community who really want to look at the self-empowerment model. They want to be able to use diet, to feel in control of their treatment, and they're looking for an alternative to medications. Patients are very motivated to look at other options."

Disclosures

Kaul disclosed no relevant relationships with industry.

Primary Source

American Epilepsy Society

Kaul N, et al "Is the ketogenic diet a safe and tolerable treatment for refractory status epilepticus? A systematic review" AES 2017; Abstract 3.336.