Variations in EEG discharges predict ADHD severity within individual Smith-Lemli-Opitz patients

Abstract

Objective: We sought to examine the prevalence of EEG abnormalities in Smith-Lemli-Opitz syndrome (SLOS) as well as the relationship between interictal epileptiform discharges (IEDs) and within-subject variations in attentional symptom severity. Methods:In the context of a clinical trial for SLOS, we performed cross-sectional and repeatedmeasure observational studies of the relationship between EEG findings and cognitive/behavioral factors on 23 children (aged 4-17 years). EEGs were reviewed for clinical abnormalities, including IEDs, by readers blinded to participants' behavioral symptoms. Between-group differences in baseline characteristics of participants with and without IEDs were analyzed. Within-subject analyses examined the association between the presence of IEDs and changes in attentiondeficit/hyperactivity disorder (ADHD) symptoms.Results: Of 85 EEGs, 43 (51%) were abnormal, predominantly because of IEDs. Only one subject had documented clinical seizures. IEDs clustered in 13 subjects (57%), whereas 9 subjects (39%) had EEGs consistently free of IEDs. While there were no significant group differences in sex, age, intellectual disability, language level, or baseline ADHD symptoms, autistic symptoms tended to be more prevalent in the "IED" group (according to Autism Diagnostic Observation Schedule-2 criteria). Within individuals, the presence of IEDs on a particular EEG predicted, on average, a 27% increase in ADHD symptom severity. Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by an inborn error of cholesterol biosynthesis, which may result in intellectual disability; attention-deficit/ hyperactivity disorder (ADHD); autistic features; and brain, facial, and limb malformations. While seizures are uncommon, 1,2 EEG abnormalities have not been examined systematically. As part of a clinical trial to assess the efficacy of simvastatin, an HMG CoA-reductase inhibitor, serial clinical EEGs, and neuropsychological testing were performed, thus providing a unique opportunity to examine the characteristics of EEG in SLOS, as well as the relationship between interictal epileptiform discharges (IEDs) and behavioral symptoms in a neurodevelopmental Conclusions: