Low glycemic index treatment for seizures in Angelman syndrome

Abstract

SUMMARYPurpose: The low glycemic index treatment (LGIT) is a high fat, limited carbohydrate diet used in the treatment of epilepsy. The purpose of this study was to assess the efficacy and tolerability of the LGIT for the treatment of refractory seizures in pediatric patients with Angelman syndrome. Methods: A pediatric Angelman syndrome cohort with refractory epilepsy was treated with the LGIT and followed prospectively over 4 months. Parents recorded a daily seizure log for a minimum of 1 month prior to the start of treatment as well as throughout the LGIT trial. Electroencephalography (EEG) and neuropsychological assessments (Scales of Independent Behavior-Revised and the Vineland Adaptive Behavior Scales-2nd Edition were obtained for each subject at both baseline and 4-month follow-up time points. Clinical evaluations of subjects were completed by a neurologist and dietitian at the time of enrollment, as well as following both the first and fourth months of dietary therapy. At each time point, blood for laboratory chemistries was drawn and anthropometric measures were obtained. Key Findings: Six children (mean age 3.3 years, range 1.1-4.8) with genetically confirmed Angelman syndrome initiated the LGIT, and completed the trial with no significant adverse events. Cohort averages for indices of seizure severity were as follows: age of 1.6 years at seizure onset, 3 lifetime antiepileptic drugs tried (range 1-6), and baseline seizure frequency of 10.1 events/week (range: 0.4-30.9). All subjects had a decrease in seizure frequency on the LGIT, with five of six exhibiting >80% seizure frequency reduction. All posttrial EEG studies showed improvement and three of four children with epileptiform activity on his or her baseline EEG had no discharges present on follow-up EEG. Developmental gains were noted by parents in all cases, although few of these neurocognitive gains were statistically significant on neuropsychological assessment. Significance: This is the first prospective study assessing the LGIT for epilepsy. Our results indicate that this dietary therapy is highly effective in treating Angelman syndrome-related seizures. The diet was well tolerated by subjects as evidenced by five of six subjects remaining on the LGIT after completion of the trial. Beyond the prospective trial window, all five subjects who remained on the diet had >90% seizure reduction after 1 year of LGIT therapy. Despite the small sample size in this prospective study, the results indicate a potentially higher degree of efficacy of the LGIT for the Angelman syndrome population than that observed in the general epilepsy population. Although this study is too small to make definitive recommendations, these results suggest that the LGIT is a promising treatment option for Angelman syndromerelated epilepsy.

Angelman syndrome: Current and emerging therapies in 2016

“…LGIT limits the amount of carbohydrates to 10% of the diet and the type of carbohydrates to those with a glycemic index less than 50, while permitting up to 30% protein. In a small prospective study of LGIT in AS, five of six patients experienced a more than 80% reduction in seizures (including one patient who did not achieve the target carbohydrate reduction), and 50% became seizure free [Thibert et al, ].…”

The role for ketogenic diets in epilepsy and status epilepticus in adults

“…Similarly, for patients with pyruvate dehydrogenase deficiency, where the diet overcomes the deficiencies in the catalytic component of the mitochondrial enzyme pyruvate dehydrogenase complex by providing an alternative source of acetyl coenzyme A, the ketogenic diet is considered first-line therapy and should be implemented as soon as the patient is identified (Kass et al, 2016, Klepper and Leiendecker, 2007, Pong et al, 2012). There is also general agreement that patients with infantile spasms, Lennox-Gaustat syndrome, Dravet syndrome, Angelman syndrome (particularly with the LGIT) and myoclonic-astatic epilepsy benefit from a trial of diet therapy once there epilepsy has become refractory to medication (Nangia et al, 2012, Thibert et al, 2012). While there is a paucity of scientific evidence supporting efficacy of diet treatment as first-line therapy for these epilepsy syndromes given their relative rarity (Cervenka et al, 2017a, Rubenstein et al, 2005), there is evidence of particular effectiveness suggesting it may be appropriate to introduce the diet early (Barañano and Hartman, 2008, Bergin, 2017, Lee and Kossoff, 2011).…”

Angelman syndrome: review of clinical and molecular aspects

“…Efficacy appears to be highest with valproate and clonazepam and lowest with phenobarbital and carbamazepine;28 vigabatrin and carbamazepine may exacerbate seizures 26,29. Some patients have responded to vagal nerve stimulation or ketogenic diet30 for seizures that were medically refractory 28,29. There can be attenuation of seizure activity in adolescents 27–29.…”