Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005
Introduction
Autism spectrum disorders (ASDs) are devastating conditions with an onset in early childhood and core symptoms of varying degree involving communication and social and cognitive development, and usually sparing gross motor development. In 1943, Kanner [1] first described the case of an autistic individual who developed epilepsy, and since then, multiple case reports or population series have described an association of abnormal EEG findings within autistic individuals [2], [3], [4], [5]. The incidence of these findings has ranged from 6 to 74% [2], [3], [4], [5], [6] depending on the level of mental retardation, age, incidence of older regression, and presence of clinical seizures, with the incidence of seizures rising to 30% by adolescence [3], [5], [6], [7]. Traditionally, the highest risk associated with epilepsy has been puberty, but this was observed in previously unscreened patients who had not had an EEG prior to their seizure onset [6], [7]. One population-based study in Sweden routinely screened children with autism with EEGs [5]. This study also suggested the incidence of abnormal EEGs to be around 30%, with seizures occurring in 10%. Other studies have suggested that epilepsy occurs in higher percentages (26–49%) [8], [9].
Current neurology guidelines suggest maintaining a high suspicion for epilepsy in this population as a guide for screening [10], [11]. Recently, a fairly large study involving 585 children was described by Tuchman and Rapin [12]. They reviewed autistic patients with regression and found the incidence of abnormal EEGs to be higher in those who regressed without epilepsy than previously believed (19% vs 10%), but among those who developed epilepsy clinically, there was no differentiation between those with and those without regression. The incidence of EEG abnormalities in their nonepileptic patients with autism was 8%, but 59% with clinical seizures had abnormal EEGs. In a more recent study, Hughes and Melyn reported that in a group of 59 autistic children with suspected or known clinical seizures, the rate of EEG abnormalities was 75%, with 46% having clinical epilepsy [9]. In the group without epilepsy, 20% had epileptic discharges. Other authors have shown localization of the EEG abnormalities in autistic children to be variable [8], [12], [13], ranging from centrotemporal spikes to similarities to benign focal epilepsies [12], [13], [14]. These studies did not use prolonged EEGs, such as 24- to 48-hour studies. Only one consensus group has recommended prolonged EEG sleep recording in the screening of autistic patients [15]. Authors using prolonged EEG recordings often report incidences of EEG abnormalities higher than those in routine study recordings [10], [12], [16]. The validity of routine EEG without prolonged sleep can be questioned, as many authors describe EEG abnormalities in autistic patients only during sleep [12], [16].
This study was conducted with a large number of screened autistic patients and a unique methodology to acquire data as a routine part of a neurology evaluation for autism. An ambulatory digital EEG system (Sleep Med DigiTrace, Boston, MA, USA) was used to collect prolonged overnight EEG data. This technology allowed free movement and eliminated the need for hospitalization or sedation to restrain patients during EEG data acquisition. It also allowed for prolonged sleep sampling of EEGs in these autistic patients. The large number of patients studied showed the practicality in obtaining high-quality digital EEG data in autistic patients without severe hardship or the need for risky sedation, as only six studies failed in 10 years (two because they pulled off the leads, and four because of battery malfunction). This study evaluated the incidence of EEG abnormalities in autistic patients who had no previous seizures and were not taking anticonvulsant medications for seizures or behavior. This population is also younger than populations in prior studies of patients with ASDs who had clinical seizures, and should reflect more accurately the incidence of EEG abnormalities at baseline in early childhood autism.
Section snippets
Methods
Successful 24-hour DigiTrace ambulatory digital EEGs were recorded for 1268 patients with ASDs between 1996 and 2005. Patients were diagnosed as having an ASD (autism or pervasive developmental disorder) by DSM-IV criteria [17]. Those known to have a genetic disorder, such as fragile X syndrome, Rett’s syndrome, Angelmann’s syndrome, or tuberous sclerosis, were excluded from the study, as were patients with congenital brain malformations or a prior history of known childhood epileptic syndromes
Results
The rate of EEG abnormalities in this population was 60.7% (540/889). The number who did not regress and the number who regressed between 12 and 18 months of age were similar, 434/712 (60.9%) and 106/177 (59.9%), respectively. The neurologist/epileptologist reader defined abnormalities that met criteria for spikes or sharp wave discharge, sharp slow waves, generalized spike–wave, generalized polyspikes, or paradoxical rhythmic delta activity. There was no difference between those who regressed
Discussion
This study represents the largest known retrospective collection, to date, of EEG data in an autistic population. It is the only study that has been done using ambulatory digital overnight EEGs uniformly, and is the first extended EEG study of 889 consecutive patients with ASDs, with regression and nonregression. The patients in this study were also young (average age = 5.8 years; range = 1.3–35). Most prior studies of large populations may have underestimated the frequency of abnormalities due to
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