The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.

The ketogenic diet, a high fat, adequate protein, low carbohydrate diet, has, during the past decade, had a resurgence of interest for the treatment of difficult-to-control seizures in children. This review traces its history, reviews its uses and side effects, and discusses possible alternatives and the diet's possible mechanisms of action. Finally, this review looks toward possible future uses of the ketogenic diet for conditions other than epilepsy.

Summary:Purpose: Rasmussen syndrome (RS) is a rare form of epilepsy characterized by progressive destruction of a single hemisphere. To characterize the profile of cortical involvement in RS, we studied the pathological changes in the cerebral cortex of 45 hemispherectomies performed at Johns Hopkins Hospital between 1985 and 2002.Methods: The patterns of pathologic changes and stages of cortical abnormalities were studied by histology and immunocy to chemistry methods. The burden of pathology (BP) was quantified in all brain regions of each of the 45 hemispheres.Results: Our study demonstrated significant heterogeneity in the stages of cortical pathology and the multifocal nature of the disease. These stages varied from early inflammation defined by infiltration of T lymphocytes and neuroglial reactions, to more severe stages with extensive neuronal cell death and cavitation of the cerebral cortex. A greater BP was significantly associated with an early age at onset (p = 0.01) and longer duration of disease (p ≤ 0.001). The BP was similar in all brain regions except the occipital lobe, where the BP was significantly lower (p = 0.032).Conclusions: The multifocal distribution of pathologic changes, as well as the heterogeneity in the stages of cortical damage in each patient, is consistent with an ongoing and progressive immune-mediated process of neuronal damage that involves neuroglial and lymphocytic responses, resembling other autoimmune CNS disorders such as multiple sclerosis.

HE KETOGENIC DIET IS A HIGHfat low-carbohydrate adequate protein diet first developed 8 decades ago for the management of difficult-to-control seizures in children. 1 Recent studies have documented the short-term and longterm benefits of this diet in improving seizure control. 2-4 An evaluation by the Blue Cross/Blue Shield Technology Center reported 5 ". .. the diet's effectiveness in providing seizure control for children with difficult-to-control seizures has remained as good, or better than any of the newer medications." Although the mechanisms by which the diet decreases seizures remain unknown, 6,7 the level of ketosis produced by the incomplete oxidation of fats when carbohydrates are in short supply appears to play a critical role in the effectiveness of this diet. 1 The classic ketogenic diet consists of a 4:1 ratio of fat to carbohydrate and protein combined. 3 Because there are 9 calories/g of fat compared with 4 calories/g of either carbohydrate or protein, the fat content of such a ketogenic diet provides 90% of the child's calorie intake. Carbohydrates are severely restricted and are usually less than 10 g/d. Younger rapidly growing children and adolescents are often started in treatment by receiving a less stringent 3:1 ratio of fat to carbohydrate plus protein to allow sufficient protein (1-1.5 g/kg per day) for growth. Growth while receiving the ketogenic diet remains within the normal range. 8

Paralysis seen in children with myelomeningocele has been attributed to congenital myelodysplasia. We suspected that paralysis may be due in part to a spinal cord injury caused by exposure of the neural tube to the amniotic fluid. This hypothesis was tested using a fetal rat model of surgically created dysraphism. Each pup from the experimental group of rats in which the spinal cord was intentionally exposed to the amniotic fluid was born with severe deformity and weakness of the hind limbs and tail. Control fetal rats, subjected to the same procedure without directly exposing the spinal cord to the intrauterine environment, were normal at birth. Histological studies of the exposed spinal cord revealed extensive erosion and necrosis, findings similar to those described in children with myelomeningocele. We therefore propose a “two-hit” hypothesis to explain the paralysis seen in children with myelomeningocele: congenital myelodysplasia complicated by an intrauterine spinal cord injury. Intrauterine protection of the exposed spinal cord might prevent some or all of the paralysis. The possible implications of these findings for the future treatment of myelomeningocele are discussed.