A modified ketogenic diet could help resolve super refractory status epilepticus (SRSE) in adults, and may be safer than the traditional regimen, Australian researchers suggest.

Their retrospective study of 12 hospitalised SRSE patients found a lower-ratio ketogenic diet (two versus four grams of fat to one non-fat gram), with 20–30% of calories coming from medium-chain triglycerides, helped stop seizures in most participants and had less adverse outcomes than recorded with the classic diet in previous studies.

It’s the latest in a limited, but growing body of evidence supporting ketogenic therapy in adults with drug-resistant seizures — an approach that’s widely used in similarly-affected children.

Published in the Journal of Parenteral and Enteral Nutrition, the study assessed outcomes of SRSE patients who received the 2:1 diet plus medication in the Alfred and Royal Melbourne hospitals’ ICUs between 2015 and 2020.

It found patients received four to eight anti-seizure drugs and up to five anaesthetic agents prior to starting a ketogenic diet, with no reprieve.

Within 21 (median nine) days of starting the diet, however, 10 of 12 cases resolved, with patients achieving blood beta-hydroxy-butyrate levels of 0.0 to 6.1 mmol/L (median 0.5 mmol/L), Ms Neha Kaul, lead author and senior dietician, Department of Neuroscience, Monash University, wrote with her colleagues.

Five patients experienced diet-related adverse effects, including vomiting, diarrhoea, hypoglycaemia and hypertriglyceridaemia, the last of which, led two patients to stop treatment, though there were no cases of metabolic acidosis, they reported.

Although, this is “very preliminary data” and its lack of control arm or control for adjuvant therapies prevent it saying how much the diet contributed to patients’ recovery, the results appear positive and reflect conventional wisdom, Ms Kaul and the study suggested.

“Ketogenic therapy for epilepsy has been around for 100 years,” she told the limbic.

To date, most research has been done in children with drug-resistant epilepsy, however, and evidence supporting ketogenic therapy in SRSE is limited to small, uncontrolled studies and subject to publication bias, she shared.

Despite this, medium-chain triglyceride ketogenic diet, modified Atkin’s, modified ketogenic and low-glycemic index diets have all been used to help adults with drug-resistant epilepsy.

Ketogenic therapies have shown some success in adults outside this study; a pooled analysis of four observational studies saw SRSE resolve in 82% of patients following treatment with 3:1 or 4:1 diets, Ms Kaul’s paper read.

The result is similar to this study’s, where 87% of patients respond to therapy, it added.

Why it works

“The underlying mechanism of ketogenic therapy is likely due to a combination of factors and not ketogenesis alone, including increased fatty acid oxidation, metabolic shift, hormonal changes and modulation of gut microbiota,” the study read.

Ketogenesis is key though since it generates beta-hydroxy-butyrate which has been associated with seizure reduction at levels over 2 mmol/L and “may still be of some clinical benefit” at lower levels.

Patients likely benefited from the medium-chain triglycerides too. These are “readily [metabolised] to ketone bodies, thereby increasing ketosis”, and their associated caprylic (C8) and capric (C10) fatty acids have anti-convulsant therapies that “may be beneficial in treating SRSE”, the study read.

They can cause gastrointestinal problems though, and may have contributed to the adverse events observed in the study, it suggested.

Tolerability and use

The 2:1, triglyceride-containing diet is likely still more tolerable than the 4:1, which, in enteral nutrition, may further slow gastric emptying, worsen enteral feed intolerance and reduce nutrient absorption, the paper noted.

It also better matches patients’ nutritional requirements. The 4:1 diet prescribes 0.5 g of protein per kilogram of body weight, per day — less than half the recommended daily protein load of 1.2–2.0 g/kg body weight/day for critically ill patients.

Balancing patients’ therapeutic and nutritional needs is vital to recovery, Ms Kaul said.

“Given that patients are very sick, we want to make sure that they’re preserving their muscle mass for recovery,” she added.

While more research needs to be done on ketogenic therapy in SRSE, Ms Kaul said greater neurologist-dietician collaboration would be worthwhile in-clinic.

“We’re seeing a growing number of patients that are looking for alternatives to medication treatment.”

“They’ve often tried a lot of medication in the past and we really need to be thinking about non-drug options for these patients,” Ms Kaul said.

There is currently little evidence guiding medicinal treatments in SRSE and ketogenic therapies may be effective and tolerable without exposing patients to sedating effects or drug-drug interactions, the study noted.