Do children with autism and developmental regression need EEG investigation in the absence of clinical seizures?
Date First Published:
July 31, 2007
Last Updated:
November 5, 2008
Report by:
Dr Choong Yi Fong, Paediatric Neurology Specialist Registrar (Evelina Children's Hospital, London, UK and Guy's Hospital)
Search checked by:
G. Baird, E Wraige, Evelina Children's Hospital, London, UK and Guy's Hospital
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
Primary sources: searched Medline (1966 – 2007)
Secondary sources: Cochrane library
Search Details:
-"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).
-"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).
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):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Regression in Pervasive Developmental Disorders: Seizures and Epileptiform Electroencephalogram Correlates. Tuchman R, Rapin I. 1997 United States of America | Children diagnosed with autistic spectrum disorder (ASD) with no clinical epilepsy who had sleep EEG from 1990 - 1995. Mean age of sample group 5.8 yrs old (range 1.6 – 28 yrs old).Total n=519. 335 / 519 (65%) children with ASD without epilepsy were analysed as EEG data only available in these patients. 113/335 (34%) had autistic regression. | Retrospective case series, Level 4 | EEG not all performed in same centre and was not independently reviewed by the same panel. This can cause inter-observer bias. Cohort including higher functioning ASD accounting for 27% of children in sample. This can cause sampling bias. | ||
| Epilepsy, Electroencephalogram Abnormalities, and Regression in Children with Autism. Canitano R, Luchetti A, Zappela M. 2005 Italy | Children diagnosed with autism who had routine awake and sleep EEG as part of diagnostic work-up over 1 year period. Mean age of sample group 7.8 yrs old (range 5.1 – 10.5 yrs old).Total n= 46. 24/46 (52%) had autistic regression. | Prospective cohort study, Level 1b | Small sample size. | ||
| Sleep electroencephalograms in young children with autism with and without regression. Baird G, Robinson R, Boyd S, Charman T. 2006 United Kingdom | Children diagnosed with autism without epilepsy that had sleep EEG between 18mths – 4yrs old. Mean age of sample group 3 yrs old (range 1.5 – 4 yrs old).Total n= 64. 39/64 (61%) children had regressive autism. | Retrospective case series, Level 2b | Sample was obtained from tertiary referral centre causing bias for sample to have high proportion of autistic regression compared with population-based studies. Small sample size. |
||
| Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A. 2006 United States of America | Children diagnosed with autism that had routine sleep EEG as screening tool with no known epilepsy from 1996–2005. Mean age of sample group 5.8 yrs old (range 1.3 – 35 yrs old). Total n= 889. 177/889 (20%) children had autistic regression. | Retrospective case series, Level 2b | Largest known retrospective collection of EEG data in an autistic population-based study. Only study using ambulatory 24hr digital EEG when compared with other studies allowing more accurate EEG identification of epileptiform abnormalities. |
Author Commentary:
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.
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.
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).
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:
- American Psychiatric Association. . Diagnostic and statistical manual of mental disorders - fourth edition .
- Kurita H. . Infantile autism with speech loss before the age of thirty months.
- Lord C, Shulman C, DiLavore P. . Regression and word loss in autistic spectrum disorders.
- Ballaban-Gil K, Tuchman R.. Epilepsy and epileptiform EEG: association with autism and language disorders.
- Tuchman R, Rapin I.. Regression in Pervasive Developmental Disorders: Seizures and Epileptiform Electroencephalogram Correlates.
- Canitano R, Luchetti A, Zappela M.. Epilepsy, Electroencephalogram Abnormalities, and Regression in Children with Autism.
- Baird G, Robinson R, Boyd S, Charman T.. Sleep electroencephalograms in young children with autism with and without regression.
- 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.