Someone who has persistent seizures that last more than 24 hours, despite treatment, is in super refractory status epilepticus. The condition is rare, but often results in death or disability. Bringing someone out of status usually involves treatment with anti-seizure medications and anesthetics, but other therapies are beginning to gain attention. One of those therapies is the ketogenic diet.
A recent paper in Neurology Clinical Practice offers practical considerations for the use of the ketogenic diet in patients with super-refractory status epilepticus. ILAE spoke with two of the paper’s authors – dietitian Neha Kaul and epileptologist Joshua Laing.
Neha Kaul: I’m Neha Kaul, senior dietitian at the Alfred Hospital and researcher in the Central Clinical School, Department of Neurosciences at Monash University.
The reason the paper came about is that we’re seeing an increase in the number of centers using the ketogenic diet as a treatment for adults in super refractory status epilepticus. As a community of dietitians, intensivists, neurologists, we have been communicating with each other to try to find advice to guide treatment. We now more commonly use the diet to treat these patients, who have a very difficult to treat condition. We put this paper together to guide some of the practical considerations for other centers and to guide practice.
ILAE: What is the evidence base for using the ketogenic diet in this group?
Kaul: The first publication looking at the ketogenic diet to treat super refractory status epilepticus dates back to 2008. Since then there’ve been about a dozen publications on using the diet to treat adults. These studies are mainly small and retrospective, so they are not controlled for other treatments that patients are receiving. But a lot of the studies don’t show any major harm to the patients when the diet was administered, and in the majority of patients the status resolved within about a week of starting the diet.
When we pulled the data on all of the cases that have been reported, 41 of 47 patients responded to the diet. I think that’s a very convincing number, but we do need to think about the level of evidence and having more controlled studies.
Joshua Laing: I’m Joshua Laing, a neurologist and epileptology from the Alfred Hospital as well as Peninsula Health in Melbourne, and I also do clinical research at Monash University’s Department of Neurosciences.
Certainly in the field of refractory and super refractory status epilepticus, we don’t have very much high-level evidence for any therapies. So once we have a patient who has failed the first round of anesthetic treatment, we consider them to be in super-refractory status, and start to think about alternative therapies. In terms of patient selection, we think of other contributing factors that may cause the patient to have a more prolonged course in hospital.
Patients who have an acute neurological insult, such as autoimmune encephalitis, traumatic brain injury, cerebral infection – these are the sorts of patients we expect will have pretty resistant seizures and we may need therapies other than anti-seizure medications. It’s at that point we think about the ketogenic diet, and work with a neuro-dietitian to get it started and monitor it over time.
With medications and anesthetics, the common property of all of them is sedation. The ketogenic diet is non-sedative. To have a treatment that is non-sedative when you’re aiming to wake a patient up out of anesthetics, as well as having the confidence that the therapy can continue whilst you’re waking up the patient, is very reassuring.
ILAE: Are there people that should not receive this therapy? What are the contraindications?
Kaul: The main contraindications are metabolic disorders, any disorder related to impaired fatty acid oxidation. And any diets that require someone to have a high carbohydrate intake. For medications, the first thing to consider is propofol. It’s a commonly used anesthetic in status epilepticus. But when used with KD, it can increase the risk of propofol syndrome, which can be fatal. So often the first thing will be stopping a propofol infusion and switching to an alternative agent.
ILAE: What are the steps to initiating the diet in someone who’s in super refractory status?
Kaul: It’s a team approach – the dietitian, the neurologist, and the intensive care unit (ICU) working together to make sure it’s administered correctly and safely. Usually it starts with the neurologist deciding the ketogenic diet is the next treatment to start. This will be discussed with the care team, and a dietitian will screen the patient for contraindications or concerns, and then make a ketogenic diet prescription based on the patient’s needs and communicate that to the intensive care unit team, making sure doctors, nurses, pharmacists have all reviewed the treatment plan. Then monitoring – the neurologist, ICU team and dietitian all review this to ensure the diet is at a therapeutic level.
ILAE: When do you decide to stop treatment?
Kaul: This varies from patient to patient. It takes 24 to 48 hours for the diet to come into therapeutic range. We need to carefully monitor the clinical situation, review the tolerance to the diet as well as the other treatments the patient is receiving. We usually reassess at the two-week mark to see if the patient is improving. We’ll consult with a neurologist and if the patient is responding, we’ll aim to continue the diet as long as possible, even after recovery – we may switch them to an oral version, such as classical ketogenic diet or modified Atkins. But if the patient is having side effects or complications, we’ll aim to stop the diet earlier.
ILAE: Are there other logistical issues in using the ketogenic diet with status epilepticus? What are the challenges?
Laing: From an epilepsy perspective, once we get to a situation of super refractory status, we know that anti-seizure medications are not that effective. These patients often have inflammatory conditions, and there’s also a theory that nonconvulsive seizures are related to a metabolic crisis in the brain. These concurrent ailments the patient may have, we believe the ketogenic diet may help to treat those. There’s not a lot of evidence for the success of anti-seizure medications, so it’s really using the ketogenic diet as an anti-inflammatory treatment.
We’re lucky to have a large, experienced team, headed by Neha who does a lot of research with the ketogenic diet, and we feel quite comfortable with it. With this paper, we hope to educate others that it’s a safe and effective treatment.
Kaul: I think it does come down to the confidence of the team in administering the diet and knowing what the side effects are to look out for, how to adjust the diet prescription, how to review all the medications, it does take a bit of practice. There is a big learning curve in the beginning – I think back to the first couple of patients we treated, and now we feel much more comfortable. A lot of people have been involved in developing this paper but also our own local guidelines. And now we’re likely to start the diet much earlier in the treatment course, which is something important to consider. This is not the last treatment option.
We’re very happy to be contacted as well for advice on these patients. We regularly provide advice to other centers on ketogenic diet management. So I would encourage intensivists, neurologists, dietitians to contact centers with more experience if they need advice.
Practical considerations for ketogenic diet in adults with super refractory status epilepticus (N Kaul et al., Neurology Clinical Practice 2020. )
Food for thought: The ketogenic diet as epilepsy treatment (ILAE Epigraph, Fall 2020)
Ketogenic Diet Therapies: ILAE website resources on the ketogenic diet
Founded in 1909, the International League Against Epilepsy (ILAE) is a global organization with more than 120 national chapters.
Through promoting research, education and training to improve the diagnosis, treatment and prevention of the disease, ILAE is working toward a world where no person’s life is limited by epilepsy.