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Three Part Question

In [a seizure-free child with autism presenting with developmental regression] is [EEG] necessary to [rule out subclinical epilepsy]?

Clinical Scenario

A child presents to your developmental clinic at 30 months old. His mother reports developmental regression of previously acquired developmental milestones. He has now lost his previously acquired language skills and only makes incomprehensible babbles. He is otherwise clinically well and does not have any clinical seizures. From his early history and current behaviour your clinical diagnosis is autism. You wonder whether an electroencephalogram (EEG) should be performed to rule out possible underlying subclinical epilepsy that may contribute to his developmental regression.

Search Strategy

Search date: March 2007
Primary sources: searched Medline (1966 – 2007)
Secondary sources: Cochrane library
-"autism" AND "developmental delay" AND "EEG"
-"autism" AND "developmental delay" AND "EEG" OR "epilepsy"
-"autism regression" AND "EEG" OR "epilepsy"
-"autism" and "developmental regression" AND "EEG" OR "epilepsy"
-"pervasive developmental delay" AND "EEG" OR "epilepsy"
Limits: human, English language, all children (0 – 18 years).

Search Outcome

No systematic reviews. 258 papers identified, of which 4 were relevant. There were 3 retrospective studies and 1 prospective study examining EEG abnormalities between children with regressive autism and non-regressive autism who did not have epilepsy (see Table).

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses

Comment(s)

Autism refers to an early onset childhood developmental disorder with core symptoms of qualitative impairment of social interaction, communication disorder affecting language and non-verbal expressive skills, and different patterns of repetitive behaviour varying from stereotypies to restricted interests and activities (American Psychiatric Association). In majority of children with autism the disabilities and cognitive difficulties are present from infancy or are acquired following a period of normal or near-normal development. 15% to 40% of children with autism undergo a pattern of apparently normal development followed by cessation of development with frequent loss of existing language, social, and occasionally manipulative skills also known as 'autistic regression'. The regression usually occurs under the age of 2 years (Kurita, Lord). Children with autism are at a greater risk of developing epilepsy. The prevalence of epilepsy is approximately 11% to 39% in children with autistic spectrum disorder (ASD)(Ballaban-Gil). The relationship of epilepsy and epileptiform EEG abnormalities to language and behavioural regression in autism is unclear and it is uncertain how closely epilepsy (clinical or subclinical) and autistic regression are related. The management of children with regressive autism without clinical seizures remains debatable. There is a concern among some clinicians that subclinical epilepsy might be undetected and is the primary cause of the autistic regression. Recent studies have attempted to study the relationship between subclinical epilepsy in children with autism without regression compared with children with autism and regression. Four published studies evaluating the relationship between subclinical epilepsy in children with autism without regression compared with children with autism and regression are appraised here. These four papers use slightly different approaches to compare epileptiform EEG abnormalities between regressive or non-regressive children with autism who do not have clinical seizures. This can make comparison of their findings challenging. Important aspects of the methodology used by these papers need to be taken into consideration that will determine the accuracy and reliability of these results. These include firstly the method of EEG monitoring. The ideal method for analysis of EEG would be using a 24-hour EEG monitoring. This will prevent underestimation of EEG abnormalities. Secondly, independent blinded EEG review by a designated panel of neurophysiologist in the same center is important to prevent inter-observer bias, avoid differing quality in EEG tracing and improve the consistency of the reporting. Thirdly, the sample of children with autism analysed is also an important factor, for example inclusion of children with autistic spectrum disorder (ASD) and degree of cognitive difficulties. The sample group should exclude children with higher functioning ASD as these children are at a lower risk of developing epilepsy compared to classical autism. The largest study by Chez et al showed no significant difference in epileptiform EEG abnormalities between these two groups. It is the only study that uses an ambulatory 24-hour digital EEG monitoring compared to other studies that lack prolonged sleep EEG monitoring. The results by Baird et al and Canitona et al support the findings by Chez et al. The study conducted by Tuchman and Rapin is the only study showing a statistically significant proportion of subclinical epileptiform EEG changes seen in children with regressive autism. This study however may be subject to biases that include inter-observer bias and sampling bias. Thus, the results should be interpreted in the light of this. Based on our critical appraisal on the current published evidence, the overall weight of evidence show no significant difference in the presence of epileptiform EEG abnormality between children with regressive and non-regressive autism who do not have clinical seizures. We conclude that in the absence of clinical seizures children with regressive autism have EEG findings that are similar to children with non-regressive autism. Hence carrying out EEG in children with regressive autism without clinical seizures is not justified as it does not allow for prediction of the presence of subclinical epilepsy and will not alter the management strategy in these patients.

Clinical Bottom Line

In the absence of clinical seizures, children with autism and developmental regression have EEG findings that are similar to those with non-regressive autism (Grade B). There is no significant association between subclinical epileptiform EEG abnormalities and children with autistic regression (Grade B). There is insufficient evidence to screen a child with autism and developmental regression without clinical seizures with an EEG to rule out underlying subclinical epilepsy (Grade B).

References

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders - fourth edition . Washington, DC: APA, 1994.
2. Kurita H. Infantile autism with speech loss before the age of thirty months. J Am Child Psychiatry 1985;24:191–6.
3. Lord C, Shulman C, DiLavore P. Regression and word loss in autistic spectrum disorders. J Child Psychol Psychiatry 2004;45:936–55.
4. Ballaban-Gil K, Tuchman R. Epilepsy and epileptiform EEG: association with autism and language disorders. Ment Retard Dev Disabil Res Rev . 2000;6:300–8.
5. Tuchman R, Rapin I. Regression in Pervasive Developmental Disorders: Seizures and Epileptiform Electroencephalogram Correlates. Pediatrics 1997;99:560 - 566.
6. Canitano R, Luchetti A, Zappela M. Epilepsy, Electroencephalogram Abnormalities, and Regression in Children with Autism. J Child Neurol 2005;20:27 - 31.
7. Baird G, Robinson R, Boyd S, Charman T. Sleep electroencephalograms in young children with autism with and without regression. Dev Med Child Neurol 2006;48:604 - 608.
8. Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A. Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy & Behaviour 2006;8:267 - 271.