Autistic regression with and without EEG abnormalities followed by favourable outcome

doi:10.1016/j.braindev.2010.05.004

Brain and Development

Volume 32, Issue 9, October 2010, Pages 739-745

https://doi.org/10.1016/j.braindev.2010.05.004 Get rights and content

Abstract

Objectives

To explore the relationship between autistic regression (AR) with and without EEG abnormalities and favourable outcome. Methods: Follow up data on children with favourable outcome in a series of 534 cases aged below 5 years and diagnosed as ASD. Results: Cases with regression were 167 (31.8%), usually with persistent ASD, intellectual disabilities and EEG abnormalities. Thirty nine children (7.3%) went off autism and recovered entirely their intellectual and social abilities. Few of them included examples of pharmacologically treated Landau and Kleffner syndrome and other similar complex cases with abnormal EEG. The majority was represented by 36 (6.7%) children, mostly males, with a dysmaturational syndrome: their development was initially normal up to 18 months when an autistic regression occurred accompanied by the appearance of motor and vocal tics. Relational therapies were followed by rapid improvement. By 6 years all children had lost features of ASD and their I.Q. was in most cases between 90 and 110. Convulsions were absent and EEG was normal in all cases except one. In a few of them recovery was spontaneous. Seventeen children were followed after 5 years 6 months: 12 (70%) had ADHD, 10 (56%) persistent tics. Tics were often present in parents and relatives, ASD absent, suggesting a genetic background different from cases with persistent ASD. With one exception all “off autism” children had a previous autistic regression. Conclusions: In this series “off autism” children had either early onset epilepsy and/or EEG abnormalities or cases of dysmaturational syndrome. Autistic regression was present in almost all.

Introduction

Autism and epilepsy are defined by behaviour, paroxysmal in the latter, based on socio-communicative difficulties and repetitive modalities in the former. Epilepsy and EEG abnormalities are also a frequent finding in autism spectrum disorders (ASD) [1]. Both disorders have a composite, varied etiology and share the presence of subgroups of children where the disorder is benign with a favourable outcome.

ASD can have a positive outcome and affected children go “off autism” in two basic situations. One is represented by children affected by a disorder where epilepsy plays a crucial role and appropriate pharmacological treatment may lead to recovery: a number of studies have given the corresponding evidence [2], [3], [4], [5], [6], [7], [8]. The second situation is represented by children where physical abnormalities and/or epilepsy are never mentioned: the present author has reported them in previous studies, evaluating neurological symptoms, family history, presence or absence of regression and other details, included them among developmental disorders and defined them as a dysmaturational syndrome [9], [10], [11], [12], [13], [14], [15], [16]. The literature, however, has several descriptions of children with ASD with favourable outcome described essentially by their psychological features [17], [18], [19].

Children falling within these categories are usually taken from relatively small series of children with ASD. The study of a large population of young children with ASD seen in the outpatient clinic of a child neuropsychiatrist, as the present report, can give additional knowledge and suggest the appropriate steps to professionals working with children affected by ASD and searching for cases potentially reversible.

Section snippets

Methods

All children aged 5 years or below examined by the author in his private outpatient clinic between the beginning of 2000 and the end of 2008 were evaluated and those with an initial diagnosis of ASD became the object of the present study. Children belonging to specific syndromes such as tuberous sclerosis, fragile X, and Down syndrome were excluded from this study. In every child a number of data had been systematically collected, including information concerning the mental health of parents

Results

Five hundred and thirty four children had ASD: 446 were males and 88 were females (see Table 1). The ratio of males to females was 5.06, slightly divergent from common data, usually around 3.5:1 [23], but consistent with other reports ranging, for example, from 3.4:1 to 6.5:1 in different states of US [24]. Within this population 167 children (31.8%) had an AR, usually during their second year of life. In the subgroup with AR motor and/or vocal tics appeared within 1 year from the beginning of

Case 1

A girl with a normal development up to 3 years and a half had a severe regression at this age losing language and social skills. This disorder was accompanied by the appearance of myoclonic jerks of her head. She was seen at 4 years 6 months when she was found mute with no verbal comprehension, accompanied by a severe disorder involving relationships and communication. She scored 35 at CARS and 60 at ABC with a full autistic picture at a DSM IV R evaluation: the EEG showed multifocal frontal and

Discussion

The present study shows that children with favourable outcome have had previously an AR in all cases except one: this was true for those belonging to the dysmaturational syndrome as well as for two cases with epilepsy and/or abnormal EEG. The latter subgroup includes children with a clear epileptic disorder as in case 1 (LKS). In this case epilepsy apparently originates in brain networks responsible for communication and interaction causing as a consequence autistic behaviour, due to multiple

Limitations

This study has the limitations implicit in data collected in an outpatient clinic by the author alone: in contrast with a hospital population, observations and collection of data are not confirmed by another professional. The time of observation is more limited; in addition the family can be less compliant and, if the child is definitely better, avoid another consultation and follow up with a possible, consequent reduction in the number of children who went off autism.

Acknowledgment

This paper was presented at the International Symposium on Epilepsy in Autism Spectrum Disorders and Related Conditions (The 12th Annual Meeting of the Infantile Seizure Society), Kurume Japan, May 9–10, 2009.

References (44)

R. Tuchman et al.
Epilepsy in autism
Lancet Neurol
(2002)
T. Deonna
Cognitive and behavioural disturbances as epileptic manifestations in children: an overview
Semin Pediatr Neurol
(1995)
A. Renieri et al.
Diagnostic criteria for the Zappella variant of the Rett syndrome (the preserved speech variant)
Brain Dev
(2009)
T. Kanaumi et al.
Developmental changes in KCNQ2 and KCNQ3 expression in human brain: possible contribution to the age dependent etiology of benign familial neonatal convulsions
Brain Dev
(2008)
S. Volkl-Kernstock et al.
Spatial perception and spatial memory in children with benign childhood epilepsy with centro-temporal spikes (BCECTS)
Epilepsy Res
(2006)
Deonna T. Autistic regression of epileptic origin. Presented at MacKeith’s meetings, The Royal Society of Medicine,...
T. Deonna et al.
Autistic regression in relation to limbic pathology and epilepsy: report of two cases
Dev Med Child Neurol
(1993)
T. Deonna et al.
Reversible behavioural autistic-like regression: a manifestation of a special (new?) epileptic syndrome in a 28-month-old child. A 2 year longitudinal study
Neurocase
(1995)
R. Canitano et al.
Autistic epileptiform regression
Funct Neurol
(2005)
R. Canitano et al.
Epilepsy, electroencephalographic abnormalities, and regression in children with autism
J Child Neurol
(2005)

R. Canitano et al.

Epilepsy in autism spectrum disorders: clinical aspects and implications for treatment

M. Zappella

Bambini autistici che guariscono: L’esempio dei tic complessi familiari

Ter Famil

(1994)

M. Zappella

Autismo infantile: studi sulla affettività e le emozioni

(1996)

M. Zappella

Familial complex tics and autistic behaviour with favourable out come in young children

Infanto Rev Neuropsych Infan Adolesc

(1999)

M. Zappella

Early interventions in autistic disorders

M. Zappella

Early-onset Tourette syndrome with reversible autistic behaviour: a dysmaturational disorder

Eur Child Adolesc Psychiatry

(2002)

M. Zappella

The question of reversible autistic behaviour in autism

M. Zappella

Clinical and genetic observations on early-onset Tourette syndrome with reversible autistic behaviour (dysmaturational syndrome)

Zappella M. Regression and progression in autistic spectrum disorders. In “A World of possibilities”, 8th International...

I.O. Lovaas

Behavioural treatment and normal educational and intellectual functioning in young autistic children

J Consult Clin Psychol

(1987)

J.J. McEachin et al.

Long-term outcome for children with autism who received early intensive behavioural treatment

Am J Ment Retard

(1993)

G.O. Sallows et al.

Intensive behavioural treatment for children with autism: Four year outcome and predictors

Am J Ment Retard

(2005)

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Review articleAutistic regression with and without EEG abnormalities followed by favourable outcome

Abstract

Objectives

Introduction

Section snippets

Methods

Results

Case 1

Discussion

Limitations

Acknowledgment

Lancet Neurol

Semin Pediatr Neurol

Brain Dev

Brain Dev

Epilepsy Res

Autistic regression in relation to limbic pathology and epilepsy: report of two cases

Dev Med Child Neurol

Reversible behavioural autistic-like regression: a manifestation of a special (new?) epileptic syndrome in a 28-month-old child. A 2 year longitudinal study

Neurocase

Autistic epileptiform regression

Funct Neurol

Epilepsy, electroencephalographic abnormalities, and regression in children with autism

J Child Neurol

Epilepsy in autism spectrum disorders: clinical aspects and implications for treatment

Bambini autistici che guariscono: L’esempio dei tic complessi familiari

Ter Famil

Autismo infantile: studi sulla affettività e le emozioni

Familial complex tics and autistic behaviour with favourable out come in young children

Infanto Rev Neuropsych Infan Adolesc

Early interventions in autistic disorders

Early-onset Tourette syndrome with reversible autistic behaviour: a dysmaturational disorder

Eur Child Adolesc Psychiatry

The question of reversible autistic behaviour in autism

Clinical and genetic observations on early-onset Tourette syndrome with reversible autistic behaviour (dysmaturational syndrome)

Behavioural treatment and normal educational and intellectual functioning in young autistic children

J Consult Clin Psychol

Long-term outcome for children with autism who received early intensive behavioural treatment

Am J Ment Retard

Intensive behavioural treatment for children with autism: Four year outcome and predictors

Am J Ment Retard

Review article
Autistic regression with and without EEG abnormalities followed by favourable outcome