BANGKOK – For a form of epilepsy treatment that’s been around since the 1920s, ketogenic diet therapy has lately been the focus of a surprising wealth of clinical research and development, Suvasini Sharma, MD, observed at the International Epilepsy Congress.
Bruce Jancin/MDedge News
Dr. Suvasini Sharma
This high-fat, low-carbohydrate diet is now well established as a valid and effective treatment option for children and adults with drug-refractory epilepsy who aren’t candidates for surgery. That’s about a third of all epilepsy patients. And as the recently overhauled pediatric ketogenic diet therapy (KDT) best practice consensus guidelines emphasize, KDT should be strongly considered after two antiepileptic drugs have failed, and even earlier for several epilepsy syndromes, noted Dr. Sharma, a pediatric neurologist at Lady Hardinge Medical College and Kalawati Saran Children’s Hospital in New Delhi, and a coauthor of the updated guidelines.
“The consensus guidelines recommend that you start thinking about the diet early, without waiting for every drug to fail,” she said at the congress, sponsored by the International League Against Epilepsy.
Among the KDT-related topics she highlighted were the recently revised best practice consensus guidelines; an expanding role for KDT in infants, critical care settings, and in epileptic encephalopathies; mounting evidence that KDT provides additional benefits beyond seizure control; and promising new alternative diet therapies. She also described the challenges of using KDT in a low-resource nation such as India, where most of the 1.3 billion people shop in markets where food isn’t packaged with the nutritional content labels essential to traditional KDTs, and low literacy is common.
KDT best practice guidelines
The latest guidelines, which include the details of standardized KDT protocols as well as a summary of recent translational research into mechanisms of action, replace the previous 10-year-old version. Flexibility is now the watchword. While the classic KDT was started as an inpatient intervention involving several days of fasting followed by multiday gradual reintroduction of calories, that approach is now deemed optional (Epilepsia Open. 2018 May 21;3[2]:175-92).
“By and large, the trend now is going to nonfasting initiation on an outpatient basis, but with more stringent monitoring,” according to Dr. Sharma.
The guidelines note that while the research literature shows that, on average, KDT results in about a 50% chance of at least a 50% reduction in seizure frequency in patients with drug-refractory epilepsy, there are a dozen specific conditions with 70% or greater responder rates: infantile spasms, tuberous sclerosis, epilepsy with myoclonic-atonic seizures, Dravet syndrome, glucose transporter 1 deficiency syndrome (Glut 1DS), pyruvate dehydrogenase deficiency (PDHD), febrile infection-related epilepsy syndrome (FIRES), super-refractory status epilepticus (SRSE), Ohtahara syndrome, complex I mitochondrial disorders, Angelman syndrome, and children with gastrostomy tubes. For Glut1DS and PDHD, KDTs should be considered the treatment of first choice.
Traditionally, KDTs weren’t recommended for children younger than age 2 years. There were concerns that maintaining ketosis and meeting growth requirements were contradictory goals. That’s no longer believed to be so. Indeed, current evidence shows that KDT is highly effective and well tolerated in infants with refractory epilepsy. European guidelines address patient selection, pre-KDT counseling, preferred methods of initiation and KDT discontinuation, and other key issues (Eur J Paediatr Neurol. 2016 Nov;20[6]:798-809).
The guidelines recognize four major, well-studied types of KDT: the classic long-chain triglyceride-centric diet; the medium-chain triglyceride diet; the more user-friendly modified Atkins diet; and low glycemic index therapy. Except in children younger than 2 years old, who should be started on the classic KDT, the consensus panel recommended that the specific KDT selected should be based on the family and child situation and the expertise at the local KDT center. Perceived differences in efficacy between the diets aren’t supported by persuasive evidence.