Ronald Thibert, DO, MsPH is a pediatric epileptologist in the Pediatric Epilepsy Program at MGHfC and the Lurie Center for Autism, specializing in the treatment of children with difficult to control seizures. He has a special interest in children with autistic spectrum disorders, especially those with Angelman syndrome and duplications of chromosome 15q (Dup15q). He is the director of both the Angelman syndrome clinic and the Dup15q Center at MGHfC and the Lurie Center and the majority of his clinical research focuses on the treatment of seizures in these 2 genetic disorders.

Research of Ronald Thibert, DO, MsPH


Ronald L. Thibert, DO, MsPH, Assistant in Neurology, Massachusetts General Hospital, Instructor in Neurology, Harvard Medical School

Ronald L. Thibert, DO, MsPH, Assistant in Neurology, Massachusetts General Hospital, Instructor in Neurology, Harvard Medical School

1. Epilepsy in Angelman Syndrome: A Questionnaire Based Assessment of the Natural History and Current Treatment Options

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the deletion or mutation of the maternal copy of UBE3A on chromosome 15q11.2-q13. AS is characterized by global developmental delays, severe speech impairment, disorders of balance or movement (usually ataxia and tremor), and behavioral uniqueness including frequent laughter. Seizures have been reported in up to 80% of individuals so we conducted a survey of family members of individuals with Amgelman syndrome through the Angelman Syndrome Foundation. The survey assessed the natural history of epilepsy in AS as well as various treatments for seizures in this population.

There were responses from 461 family members making this the largest study to date assessing seizures in AS. Approximately 86% of respondents reported seizures in their family member with AS with 60% reporting multiple seizure types. Seizure types typically present in Lennox-Gastaut syndrome were most common including atonic (41%), atypical absence (37%), complex partial (32%) and myoclonic (12%). Those with maternal deletions had the highest rate of seizures (89%) followed by those with uniparental disomy (UPD) and UBE3A mutations (~75%) and those with imprinting center defects (55%). Seizures were most common in those ages 3-11 with lower seizure rates during puberty and before the preschool years.

Seizures in AS are typically refractory to mediations with only 23% responding (>90% seizure reduction) to either the first or second medication tried. Broad spectrum antiepileptic drugs (AED) are most effective with non-broad spectrum medications such as phenobarbital and carbamazepine having the lowest efficacy and highest rates of seizure exacerbation. Newer broad spectrum AED such as lamotrigine and levetiracetam appeared to be as effective as older, more commonly used medications such as valproic acid and clonazepam but with fewer side effects.

2. Low Glycemic Index Treatment for Seizures in Angelman Syndrome

The Low glycemic index treatment (LGIT) is a high fat, limited carbohydrate diet used in the treatment of epilepsy. This diet was developed in 2005 at MGH as an alternative to the classic ketogenic diet which is more restrictive. The structure of this treatment aims to maintain a stable serum glucose level by limiting carbohydrates to ~10% of an individual’s daily caloric intake and by limiting the types of carbohydrates to those with a glycemic index of <50.

The literature on dietary therapy in AS was limited to a few case reports of children on the classic ketogenic diet so we performed a prospective study in which we placed children with AS on the LGIT for 4 months. Inclusion required a genetic diagnosis of AS, more than 2 seizures per month at baseline and no prior treatment with dietary therapy. Daily seizure logs were kept for one month prior to starting the diet and during the 4 months of dietary therapy. EEG’s were obtained prior to starting dietary therapy and upon completion of the 4 months. Laboratories were drawn and height and weight recorded prior to beginning therapy, at one month and at 4 months (Table 1).

There were 6 children that completed the study and 5/6 had at least 80% seizure reduction from baseline with 3 becoming seizure-free on dietary therapy (Table 2). EEG’s were overall improved after 4 months of dietary therapy with 3/4 children who had epileptiform discharges on initial EEG not having discharges present on the follow-up study. After completion of the study, 5/6 children stayed on the diet and at the one year mark all 5 had >90% seizure reduction as compared to prior to dietary therapy.

Table 2. Average weekly seizure frequency on the low glycemic index treatment for Angelman syndrome cohort


1. Thibert RL, Conant KD, Braun EK, Bruno P, Said RR, Nespeca MP, Thiele EA. Epilepsy in Angelman syndrome: A questionnaire-based assessment of the natural history and current treatment options. Epilepsia. 2009;50(11):2369-2376.
2. Thibert RL, Pfeifer HH, Larson AM, Raby AR, Reynolds AA, Morgan AK, Thiele EA. Low glycemic index treatment for seizures in Angelman syndrome. Epilepsia. 2012. Sept;53(9):1498-502.