Many patients with epilepsy are nonreponsive to medications. The ketogenic diet and other dietary therapies, such as the modified Atkins diet, are back in the forefront as viable nonpharmacological treatment options for medication refractory epilepsy. Following are illustrative fictional accounts of patients with medical problems with co-occurring epilepsy.
Glucose Transporter Deficiency Syndrome
Three-year-old Matt with history of motor delay presents with episodes of head drop and movement abnormality that seem to worsen with longer duration after a meal. Cerebrospinal fluid glucose is 304, with concurrent serum glucose of 90. Atonic seizures are ultimately controlled on a combination of 2 antiseizure medications, including a carbonic anhydrase inhibitor, although electroencephalogram remains abnormal. Genetic testing reveals SLC2A1 mutation.
Matt is admitted to the hospital to initiate a 4:1 ketogenic diet. He is not fasted, however by the second day, he produces 4+ urine ketones, is not drinking well, and vomits with meals. Blood glucose nadir is 30 and bicarbonate level drops from 18 to 12. Intravenous hydration is provided and potassium citrate/citric acid is started. By hospital day 5, bicarbonate level has stabilized and he is discharged.
The initial month is difficult for his family, as they struggle to find foods that Matt consistently enjoys. However, with the support of the dietitian and another “keto family,” as well as cookbooks and online recipes, he tolerates the diet. The family is also motivated by the observation that seizures are no longer seen and balance is improved. EEG normalizes and gradually he is weaned off of antiseizure medications.
Five-year-old Téa with history of febrile seizures, intellectual disability, ataxia, and refractory myoclonic, generalized-tonic-clonic, and complex partial seizures, presents for transfer of care. She has an SCN1A mutation, and seizures persist despite numerous medication trials, often occurring as status epilepticus requiring multiple rescue medications. Height is at the 50th percentile for age; weight is at the 5th percentile for age.
She is admitted for initiation of 4:1 KD. No short-term complications arise, however she is resistant to the foods offered to her. Authorization for a manufactured ketogenic formula is obtained and she accepts the drink. She is discharged home after family receives education regarding food preparation and use of an online program to assist with calculation of food proportions, and recipes and resources for further meal options. They suspect that once in familiar surroundings at home, she will be more willing to eat.
At home she continues to be resistant to offered meals and will not drink plain water or flavored sugar-free drinks. She may have 4 days between bowel movements. She will not eat avocado or flaxseed, but will take polyethylene glycol (Miralax). Weight gain stagnates. The KD ratio is gradually decreased, to allow for greater amounts of protein/carbohydrate, and caloric goal is increased.
At a subsequent visit, the dietary therapies program social worker elicits that there is inconsistency and disagreement at home between family members regarding the use of the KD. Treatment is changed to MAD, to allow for more flexibility since precise calculations and weighing of food is not necessary. However, administration continues to be difficult, the patient continues to resist foods given to her, and dietary changes are abandoned.
Formula-Fed Patient with Epileptic Encephalopathy
Seven-year-old Robbie with diffuse cerebral malformation, and daily myoclonic and tonic seizures is referred by his primary neurologist. He has spastic quadriplegia, is non-ambulatory, and is on 3 antiseizure medications. Nutrition is provided via gastrostomy tube due to oral motor dyscoordination and aspiration.
Robbie is admitted for initiation of 4:1 KD. No immediate complications arise, and his family is comfortable with formula preparation and monitoring of blood sugar and urine ketones. Robbie is discharged after 3 days, with multivitamin, calcium, and vitamin D3 supplementation. His family observes a 75% decrease in seizures within 2 weeks, however fat malabsorption and diarrhea occur. This improves with a decrease in the ratio, ultimately to 2.5:1. Seizure control decreases, however family observes that he is more alert and feel that the balance between benefits and adverse effects of the KD is positive.
Within the next year, he has multiple femur fractures. Twenty-five-hydroxyvitamin D is low at 24. A Bone density scan demonstrates severely low bone density for age. He is weaned off of KD to minimize factors contributing to his fracture risk.
Febrile Infection-Related Epilepsy Syndrome
Jennie, a 16-year-old, presents with fever, symptoms of upper respiratory infection, with progressive alteration of mental status and status epilepticus. A full evaluation, including testing for infectious, postinfectious, autoimmune, paraneoplastic, vascular, and structural etiologies is negative. Seizures persist despite medication trials including steroids, intravenous immunoglobulin, midazolam, pentobarbital, ketamine, plasma exchange, and rituximab. Medical complications include transaminitis, elevated pancreatic enzymes, and hemodynamic instability.
The initial attempt at enteral KD fails because of poor tolerance related to ileus. Subsequently, parenteral KD is attempted, however ratio is low due to limitation of lipid administration; significantly elevated triglycerides are seen and parenteral KD is aborted. When able to be enterally fed, enteral KD is re-attempted, with close monitoring of electrolytes, bicarbonate, liver functions, triglycerides. Ketone levels remain nil to trace; all potential sources of sugar are identified, and ultimately ketone levels rise to 3+ in the urine, confirmed by a betahydroxybutyrate level of 50 in the blood. Approximately one week after KD is initiated, pentobarbital is weaned. Two months later, Jennie is transferred to the rehabilitation unit.