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Ketogenic Diet Effective, Well Tolerated in Infants With Refractory Epilepsy

Adverse effects were common but manageable among patients and were not identified as a reason to discontinue treatment in those with refractory disease.

Results from a recent prospective study at a single center in Argentina suggest that ketogenic diet therapy (KDT) was effective and well-tolerated in infants with treatment-refractory epilepsy. Although adverse effects (AEs) were commonly reported, they did not provide reason to discontinue treatment, investigators found.

A total of 56 infants with treatment-refractory epilepsy were included in the study, 29 of whom (51%) were under 1 year of age upon initiation of KDT. In terms of etiology, 21.4% had genetic (n = 12), 26.8% had structural (n = 16), 44.7% were unknown (n = 25), and 5.4% had metabolic (n = 3). Ketosis was achieved in 2 patients (3.6%) in less than 24 hours after initiating the diet, achieved in 22 patients (39.3%) between 24 and 48 hours, and achieved in 13 patients (23.2%) in more than 49 hours. All participants achieved ketosis within the therapeutic range. 

Follow-up was conducted at 3 months, 6 months, 1 year, and 2 years. At 3 months (n =56), 35 patients (62.4%) had a 50% decrease in seizure frequency, and 11 of those patients (19.6%) became seizure-free. At 6 months (n = 52), 34 patients (60.7%) had a 50% decrease in seizure frequency, and 10 of those patients (17.8%) became seizure-free. At the 1-year mark (n = 34), 27 patients (48.2%) had a 50% decrease in seizure frequency, and 6 of those patients (10.7%) were seizure-free. The 2-year mark (n = 21) found that 14 patients (25%) had greater than 50% seizure control, 4 of whom (7.1%) were seizure-free. 

“Our study confirms that KDT is a useful option in infants with treatment-resistant epilepsy,” lead author Marisa Armeno, MD, Ketogenic Diet Team Coordinator, department of clinical nutrition, Garrahan National Pediatric Hospital, Buenos Aires, Argentina, et al wrote. “Further studies are necessary to evaluate in which epilepsy syndromes, beyond West syndrome, and etiologies the KDT is more effective, for early referral in order to start treatment earlier.”

READ MORE: Perampanel Shows Real-World Benefit in Epilepsy With Comorbid Intellectual Disability 

Epileptic syndromes were defined in approximately 46 patients (82.2%). Thirty patients (53.6%) had West syndrome, 7 patients (12.5%) had migrating focal seizure of infancy, 4 patients (7.1) had Dravet syndrome, 2 patients (3.6%) had Ohtahara syndrome, 1 patient (1.8%) had myoclonic epilepsy, and 1 patient (1.8%) had infantile spasms without hypsarrhythmia. None of the patients were eligible for epilepsy surgery. 

A statistically significant difference in response to the KDT was observed in patients with genetic etiology (10/12; 83.33%) when excluding patients with metabolic etiology and comparing to the remaining etiologies (21/41; 51.22%) (response rate = 1.627 [95% CI, 1.1-2.4]; P = .04591). In addition, patients with unknown etiology had a trend towards a better response to the KDT (P = .1033). Investigators did not identify a statistically significant different in diet response between patients with West syndrome and those with other syndromes. 

Of AEs reported, the most common were hypoglycemia and vomiting, with 13 patients each (23.2%), followed by transient hypertriglyceridemia in 8 patients (14.3%). Following 1 month of KDT, the most common AEs were metabolic acidosis in 18 patients (32%), constipation in 10 patients (17.9%), and hypercalciuria in 8 patients (14.3%). Also frequent were gastrointestinal symptoms, namely vomiting in 7 patients (12.5%) and gastroesophageal reflux disease in 5 patients (8.9%). Patients who were younger than 1 year had a higher rate of acute AEs (52%), compared with those older than 1 year (28%), but the different was not statistically significant (P = .087). 

Reasons for discontinuing KDT were identified as noncompliance for 12 participants, ineffectiveness for 6, death due to unrelated causes in 3, and seizure freedom in 8. All 29 participants discontinued before 2 years. 

The KDT approach has been widely studied in patients with epilepsy, and data presented recently at the American Epilepsy Society Annual Meeting, December 3-7, 2021, in Chicago and virtually, suggested dietary therapies such as KDT, as well as vagal nerve stimulation were effective in reducing seizures in children with tuberous sclerosis complex and drug refractory epilepsy. Comparably, another recent study identified a significant reduction in sleep anxiety in children with drug-resistant epilepsy after completing 3 months of KDT. 

The use of diet is being further explored in several neurologic conditions, including mild cognitive impairment and multiple sclerosis (MS). While there is no evidence that a particular diet can prevent, treat, or cure MS, research efforts have suggested dietary adjustments may be beneficial for this patient population. Tyler Titcomb, PhD, RDN, IFMCP, recently spoke with NeurologyLive® on the need to incorporate registered dietitians into the standard interdisciplinary care model for patients with MS. Hear more about what he had to say in the video below.

REFERENCE
Armeno M, Verini A, Cresta A, Valenzuela GR, Caraballo R. Long-term effectiveness and adverse effects of ketogenic diet therapy in infants with drug-resistant epilepsy treated at a single center in Argentina. Epilepsy Res. 2021;178:106793. doi:10.1016/j.eplepsyres.2021.106793