Dravet Syndrome (DS)

Dravet syndrome (DS) is a rare form of childhood epilepsy that often manifests within the first year of life. It is a type of epileptic encephalopathy in which recurrent, intractable seizures cause developmental delays, cognitive impairment, behavioral changes, and motor deficits.¹ 

Seizures in DS are often refractory to treatment with antiseizure medications (ASMs). One alternative, nonpharmacologic treatment that has shown efficacy in the reduction of seizures in this patient population is the ketogenic, or “keto,” diet.¹ 

Classical Ketogenic Diet

Several studies have shown that at least 65% of patients with DS respond to the keto diet with an over 50% reduction in seizure activity within the first year of initiation. A small percentage of patients in these studies even became seizure free.^2-4

Principles of the Keto Diet

The keto diet is a diet high in fat, adequate in protein, and very low in carbohydrates. The normal breakdown of macronutrients in the keto diet is 70% to 80% fat, 20% protein, and 5% to 10% carbohydrates.⁵ 

The ratio of fat to carbohydrates and protein may vary depending on the age of the child. Infants, adolescents, and children who need higher protein intake may stick to a 3:1 ratio for the keto diet. Most children with epilepsy are on an even stricter keto diet with a 4:1 ratio.⁶

Mechanism of Action

The keto diet works by altering the source of energy for the brain. Instead of the energy coming from carbohydrates, it comes from fats. Although the mechanism of action of the keto diet is poorly understood as an alternative treatment for refractory epilepsy, it has been shown to uniquely change the excitability of the brain, reducing the triggering of seizures.⁵ The keto diet produces ketones in the body when fats are used as a source of energy. Higher ketone concentrations in the body may potentially explain improvements in seizure control.⁶

Read more about DS pathophysiology 

Management of DS With the Keto Diet

While on the keto diet, children and adults will require follow-up visits every month to 3 months for blood and urine testing to assess for nutritional problems or other conditions that might be related to the diet.⁵ 

The keto diet is usually used in conjunction with antiseizure medications for optimal outcomes, but sometimes the keto diet can reduce or eliminate the need for ASMs.⁶

Read more about DS therapies

Adverse Effects of the Keto Diet

Possible side effects of a long-term keto diet include constipation, kidney stones, hypercholesterolemia, osteopenia or osteoporosis leading to fractures, fatigue, and impaired growth.⁵ 

Warnings and Precautions

Children with DS who have specific comorbid metabolic or mitochondrial disorders may not be the best candidates for the keto diet.⁶ 

Johns Hopkins Hospital Protocol

Some centers choose to initiate the keto diet with an 18- to 24-hour fast (except for water) under close medical supervision and monitoring in the hospital. Then, the keto diet is started slowly by increasing the ratio of fats to carbohydrates to achieve ketosis more quickly. The children are monitored for any increase in seizure activity while on the diet.⁶ 

Modified Atkins Diet

The modified Atkins diet (MAD) is a less restrictive version of the keto diet that often produces a state of ketosis in patients who have trouble following the strict guidelines of the keto diet. Its more flexible guidelines allow a greater variety of choices and amounts, as patients have unrestricted access to both fat and protein and are allowed unlimited fluids and calories.⁷

There have been limited studies comparing the efficacy of the classical keto diet and the modified Atkins diet. However, MAD is especially recommended for older children and adolescents.⁷ 

Read more about DS experimental therapies

Growth and Nutrition Problems

Approximately 60% of children with DS exhibit problems with growth or nutrition including⁸:

• Failure to thrive, resulting in small stature, slow growth, and being underweight
• Spinal scoliosis
• Osteopenia
• Malabsorption
• Feeding difficulties
• Poor appetite

Consultation with a registered dietitian may benefit children with DS, both to optimize nutrition and growth and to guide initiation of the keto diet, if it is recommended as a treatment option. This expertise makes meal planning and diet management much easier for caregivers and parents.⁹ 

Read more about the DS care team

In severe cases of malnutrition or malabsorption, doctors may recommend the placement of a gastrostomy feeding tube to ensure adequate nutrition.⁸ Children with DS who have feeding tubes may be treated with a formula-only ketogenic diet, resulting in improved efficacy and compliance with the diet.⁶

Read more about DS treatment

References 

1. Joshi C, Wirrell E. Dravet syndrome. Epilepsy Foundation. August 24, 2020. Accessed March 17, 2023.
2. Tian X, Chen J, Zhang J, et al. The efficacy of ketogenic diet in 60 Chinese patients with Dravet syndrome. Front Neurol. 2019;10:625. doi:10.3389/fneur.2019.00625
3. Laux L, Blackford R. The ketogenic diet in Dravet syndrome. J Child Neurol. 2013;28(8):1041-1044. doi:10.1177/0883073813487599
4. Caraballo RH, Cersósimo RO, Sakr D, Cresta A, Escobal N, Fejerman N. Ketogenic diet in patients with Dravet syndrome. Epilepsia. 2005;46(9):1539-1544. doi:10.1111/j.1528-1167.2005.05705.x
5. Ketogenic diet (keto diet) for epilepsy. Cleveland Clinic. Accessed March 17, 2023.
6. Kossoff E. Ketogenic diet. Epilepsy Foundation. October 25, 2017. Accessed March 17, 2023.
7. Sharma S, Jain P. The modified Atkins diet in refractory epilepsy. Epilepsy Res Treat. 2014;2014:404202. doi:10.1155/2014/404202 
8. Growth and nutrition concerns. Dravet Syndrome UK. Accessed March 17, 2023.
9. Understanding Dravet syndrome. Amber Specialty Pharmacy. Accessed March 17, 2023.

Reviewed by Harshi Dhingra, MD, on 3/27/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.