Short- and long-term seizure-free outcomes of dietary treatment in infants according to etiology

Abstract

It is important to determine whether specific etiology is more effective to dietary treatment so that the diet can be started earlier for infants. We evaluated etiology-specific, seizure-free outcomes of dietary treatment in infants < 1 year of age. Methods: We conducted a 10-year, retrospective, longitudinal observational study of 115 infants treated with ketogenic diet (KD) or modified Atkins diet (MAD). Results: Most patients (70%) received classical KD; 30% received MAD. During follow-up, 90%, 73%, and 61% of the patients remained on the diet at 3, 6, and 12 months, respectively. Seizure-free outcomes were reported in 50%, 44%, and 50% of the patients at 3, 6, and 12 months, respectively. Long-term seizure-free outcomes over 12 months were reported in 43 (74%) of 58 infants who were seizure-free at 3 months. Etiologies were mostly symptomatic (structural brain abnormalities, genetic, or metabolic) in 83 (72%) of 115 patients. According to underlying etiology, long-term seizure-free outcomes were observed in 14 (33%) of 42 patients with structural brain abnormalities, 7 (33%) of 21 with genetic etiologies, 7 (35%) of 20 with metabolic etiologies, and 15 (47%) of 32 with unknown etiologies. There were no etiology-based differences with respect to long-term seizure-free outcomes (P = 0.63). Conclusion:The high rate of long-term seizure-free outcomes can be predicted based on the seizure freedom at 3 months regardless of etiology. Early dietary treatment is beneficial, even in infants < 1 year of age with specific symptomatic etiologies such as genetic, structural brain abnormalities, and metabolic etiology.

Efficacy and Safety of a Ketogenic Diet in Children and Adolescents with Refractory Epilepsy—A Review

“…In the past, KDTs were not recommended for infants because infancy is a critical period for neurodevelopment and due to the perceived risk of inadequate nutrition [ 39 ]. Compared with adults, neonates and infants have the advantage of having a metabolism associated with the use of ketone bodies [ 40 , 41 , 42 ].…”

Diet in the Treatment of Epilepsy: What We Know So Far

“…In this regard, infancy and neonatal age represent a target population as "fragile" as promising for the use of KD. In a 10-year, retrospective, observational study involving 115 infants treated with KD (70%) or MAD (30%), the authors found a high rate of long-term seizure-free outcomes (37% of the patients at 12 months), which can be predicted based on the seizure freedom at three months (50% of the patients) regardless of etiology (genetic, structural brain abnormalities, and metabolic pathologies) [118]. In fact, the higher amounts of enzymes that metabolize ketones and the production of monocarboxylic acid transporters, leading to more ketone bodies that can cross the blood-brain barrier, are responsible for the greater efficacy of such dietary treatment in infants.…”

Advances in Ketogenic Diet Therapies in Pediatric Epilepsy

“…At that time, 10 retrospective studies including 32 children and adults with RSE showed dramatic beneficial effects of stable at long-term follow-up. Another study reports specific etiologic differences in long-term seizure-free outcomes among 115 patients who initiated KDTs before 1 year of age and shows that seizure freedom within the first 3 months could be a predictor of long-term seizure freedom [55]. A similar study including 109 patients with RE under 3 years of age with different etiologies reports that patients with a genetic etiology were particularly good responders to KDTs [54], with nearly half of patients with a confirmed genetic abnormality showing more than a 50% reduction in seizure frequency.…”

“…Contrary to a conventional view, under 2 years of age may be the optimum time to initiate a KDT because of the metabolic advantages of infants [50][51][52][53][54][55]. Numerous studies provide evidence for the advantages of using KDTs in infants with RE.…”