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L’autisme est un trouble du développement caractérisé par des perturbations dans les domaines de la communication, des interactions sociales et par des intérêts et comportements restreints et répétitifs.

Il est aujourd’hui clairement établi que les troubles du neurodéveloppement (TSA, DI, TDAH, troubles DYS, etc.) sont souvent associés à l’épilepsie, surtout si celle-ci est précoce et pharmacorésistante.

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Epilepsie et autisme. Maison de l'autisme, 2024, 9 p.

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Epilepsie et autisme. Maison de l'autisme, 2024, 9 p.

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Synthèse de 9 diapos réalisée par la Maison de l'autisme à l'occasion de la journée internationale de l'épilepsie, le 12 février 2024.

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Epilepsie & autisme - Maison de l'autisme - 2024

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Epilepsie et autisme : une association complexe. Article de la revue Archives de pédiatrie, n°2010/17, 2010

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Epilepsie et autisme : une association complexe. Article de la revue Archives de pédiatrie, n°2010/17, 2010

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Epilepsy and autism : is there a special relationship ? Article de la revue Epilepsy and behavior n°3/2012, 2012.

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Epilepsy and autism : is there a special relationship ? Article de la revue Epilepsy and behavior n°3/2012, 2012.

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The co-occurrence of epilepsy with autism spectrum disorders (ASD or autism) has been the subject of frequent reviews [ 1- 6]. This has understandably led to speculation that there are common mechanisms linking the two types of disorders. Indeed, some epilepsy syndromes and specific genetic factors involved in those syndromes are associated with a high risk of ASD. For example, patients with tuberous sclerosis, particularly when associated with TSC2 mutations [ 7, 8] Dravet syndrome, usually caused by mutations in the voltage- gated neuronal sodium channel gene SCN1A[ 9], and epilepsy in females with mental retardation or EFMR, found to be secondary to PCDH19 mutations [ 10] tend to have very high occurrence of autistic like features if not autism proper. As Brooks-Kayal points out, these and other genetic factors are implicated in specific early-onset epileptic encephalopathies and the mechanisms involved in producing the epilepsy might play a role in producing autistic features [ 1]. While this possibility needs investigation, an obvious factor linking epilepsy and autism, intellectual disability (ID), must first be carefully considered. The role of ID is potent and could potentially explain most if not all of the association between epilepsy and autism. This is not a new concept [ 3, 4, 11]; however, in the context of the increasing use of genomic technology and other methods for exploring causation and mechanisms, and capability to mount complex, large scale investigations as well as the changing definitions and understanding of autism, the role of ID in the association between epilepsy and autism must be thoroughly accounted for.

To appreciate the complexity of the epilepsy-autism-ID triad, one must first understand what autism is, how it has been defined and diagnosed over time. In this context, we examine the relationships between autism and intellectual impairment, epilepsy and intellectual impairment, autism and epilepsy, and the implications for the three together. This review does not cover causes of autism per se which are covered in detail by others elsewhere, for example, Hughes (2009) [ 12] . As much as possible, we focus on data from population-based studies and regional centers to ensure the findings are robust and representative of affected individuals in the general population.

Features and diagnosis of autism and changes over time

Autism is a developmental disorder characterized by a specific pattern of persistent deficits in social reciprocity, communication, and fixed interests, and repetitive behaviors. These fundamental features are conceptualized similarly in all diagnostic frameworks, such as DSM-IV-TR , ICD-10 and the proposed DSM-5 [ 13]. Although the cardinal features used in diagnosing autism have remained relatively stable over time, there has been a broadening in the concept of autism spectrum disorders (ASD) to include milder forms of autism, particularly Asperger syndrome and pervasive developmental disorders not otherwise specified (PDD-NOS) and to recognize autism in the context of intellectual impairment. The proposed DSM-V could result in yet further changes in autism diagnosis as these separate diagnostic categories will be merged into a single entity, "autistic spectrum disorder."

Ideally, the clinical diagnosis of autism should be reached by conducting an observation and patient examination, and obtaining information from multiple sources such as parents and teachers. It requires the presence of full diagnostic criteria and differentiation from typical development, language delay, and other "non-spectrum" psychiatric disorders (DSM-V). To this day, no diagnostic biological markers or specific tests for ASD are available, thus diagnosis depends on the individual clinician's interpretation of diagnostic criteria, which can be affected by multiple factors, most notably level of training and clinical expertise, and conceptualization of ASD [ 14]. Generally, autism cannot be confidently diagnosed before the age of about 36 months although early detection of at least some forms is possible [ 15].

Studies published in the last ten years, report a prevalence of autism in the population on the order of 6 to 11/1000 [ 16- 19]; however there is some evidence that the prevalence may have increased over the last 30 or more years [ 16, 20, 21], and estimates within the US find rates rising recently even during the early to mid 2000s [ 22, 23]. Many factors can influence these figures including the availability of resources to treat and manage children with ASD. Palmer et al. found that the prevalence of ASD diagnoses in the school system was directly tied to the wealth of the community with lower prevalences found in poorer communities [ 24]. Definitions are important as well. A general population study from the UK [ 19] reported an overall prevalence of 116.1/10,000 which dropped to 24.8/10,000 when narrow definition and more rigorous criteria were employed. Within a single population, strikingly different estimates of prevalence were obtained in two consecutive birth cohorts. Autism in the first cohort, born in 1974-1983, was diagnosed based on ICD-9 criteria with a resulting prevalence of 3.8/10,000. In the second cohort (born in 1984-1993), ICD-10 criteria with the addition of some other criteria were used with a resulting prevalence of 8.6/10,000. The diagnosis of Asperger syndrome was explicitly excluded in both cohorts [ 25]. One could argue for changes in the underlying prevalence over time; however, a separate research group in a single region measured the prevalence of autism during two consecutive time periods using the same methods and criteria and found highly consistent estimates across the two periods [ 17, 26]. Both ID and epilepsy occur in comparably small proportions of the population. As part of its definition, ID may generally be considered when IQ drops below 70 (2 standard deviations below the mean) which statistically should occur in roughly 2% of the population. This is likely an overestimate as criteria for functional impairment must also be met [ 13]. Over the course of childhood and early adolescence, the cumulative risk of developing epilepsy is approximately 6-7/1000 [ 27].

Key to the discussion of autism and epilepsy, the diagnosis of autism requires that the autistic features cannot be fully explained by developmental delays or related impairments. They must also be present since early childhood, although some may not become fully apparent until later when social expectations for an older child result in the deficits becoming evident. The last point is more strongly emphasized in the recent revisions to the DSM [ 28] and is crucial because the strong association and overlapping symptomatology between autism and ID can lead to both the over- and under-diagnosis of autism. Deficits in communication and social skills due to cognitive delay and repetitive self-stimulatory behaviors are frequently observed in ID patients without necessarily constituting the basis for diagnosing autism. This has been emphasized in the autism screening literature. For example, in toddlers born very prematurely (<28 weeks), the Modified Checklist for Autism in Toddlers (mCHAT) scores were strongly correlated with motor and sensory impairments. Of those with vision impairments or hearing impairments, 71% scored positive on the mCHAT autism screen versus 20-21% without such impairments. Cerebral palsy was strongly associated with positive autism screening results including 76% of children with quadreparesis, 30% with diparesis, and 44% of those with hemiparesis. This is in contrast to 22% screening positive in the absence of cerebral palsy [ 29]. A population-based study found a 40% false positive rate for an autism screening program with intellectual disabilities, language disorders, and specific behavioral disorders being common reasons for the error [ 30]. A preliminary report from a tertiary epilepsy center found that 16/44 children screened positive for autism with the mCHAT. All 16 also had developmental delays, and in 12, the neurological and developmental impairments were found to explain the positive autism screening results [ 31].

The potential errors in the over-interpretation of autistic symptoms and use of the diagnosis of autism in individuals with ID was highlighted by Sevin et al [ 32]. They assessed the initial (at admission) prevalence of DSM-IV based psychiatric diagnoses and longitudinal outcome in 150 adolescents (aged 11 to 19 years) with ID admitted to an inpatient psychiatric specialty unit. After 15 months, PDD was identified in 8.6% of sample whereas the initial prevalence had been 16.0%, an almost halving in the prevalence of PDD in just over a year. Considering the persistent course of ASD symptoms and unlikely resolution of ASD over 15 months of treatment in adolescence, these data likely reflect diagnostic disagreement between clinicians or an over interpretation of transient autistic symptoms which may be temporary due to emerging medical or neurological disorders. When developmental difficulties improve over time and the child is able to communicate more effectively and negotiate social situations, the autistic symptoms may weaken and previously diagnosed ASD resolve. This is not true in primary autism, where impairment persists. Consequently, one must be concerned about the over-interpretation of autistic features in individuals with ID, especially if assessed at only one point in time.

Diagnoses of autism can also be missed in people with intellectual disabilities. Saemundsen reported a 21% prevalence of autism in adults (18-87 years old) with intellectual disability [ 33]. Only 11 of the 25 cases of autism identified had been previously diagnosed as having autism, all during childhood. The other 14 cases with autism were found by the investigators through screening and diagnostic procedures. Possibly individuals whose diagnoses of autism were missed during childhood were older patients who were children during a time when the concepts surrounding autism were somewhat different and many considered that intellectual disability excluded the diagnosis [ 34]. Once in an adult care setting, the diagnosis was likely never revisited. La Malfa et al. reported similar observations with an initial ASD prevalence of 7.8% rising to 39.2% with more thorough investigation of a single group of intellectually disabled adults patients [ 35].

There is currently a lack of consensus regarding how best to conceptualize autism with and without ID [ 36] as none of the existing psychiatric diagnostic criteria have been specifically developed for use in people with ID [ 37 32]. This is reflected in the different yields of standardized screening and diagnostic instruments. For example, De Bildt et al. applied several autism screening and diagnostic instruments to the same group of individuals with intellectual disability [ 38]. Although two different screening instruments identified similar proportions of subjects as having autism (18.4% for the Scale of Pervasive Developmental Disorders in Mentally Retarded Persons or PDD-MRS and 17.2% for the Autism Behavior Checklist or ABC), only 7.8% were identified with autism according to both instruments.

An additional source for the increase in the prevalence of autism may be the special education laws in the US and elsewhere that require special educational assistance for children with autism [ 36, 39, 40] . These concerns see some validation in the striking increase in children receiving special educational services for autism in the United States from 1992 through 2008. This increase was reported starting in the early 1990s in different states [ 41- 43] and followed the signing into law of the Individuals with Disabilities in Education Act which specifically identified autism as a disorder that entitled a child to special education services [ 44]. Similar phenomena have been observed in Australia [ 45] and Israel, [ 46] and investigators have suggested that changes in diagnostic criteria as well as qualifying for services and greater availability of services were likely factors in the increase. In this context, the evolution in the understanding of autism over time and the consequences for diagnostic practices has likely contributed to several trends. These include a shift from the narrow definition of classical autism with severe functional impairment to a broader range of expression for autistic symptoms with less severe functional impairment on the one hand as well as inclusion of those with more severe intellectual impairment on the other [ 30].

Related to these trends, there is evidence that diagnostic substitution (i.e., using the ASD diagnosis instead of another diagnosis), may occur [ 21, 39, 40]. Shattuck reported an increasing administrative prevalence of autism to be significantly associated with corresponding declines in the prevalence of mental retardation and learning disabilities. From 1994 to 2003, the average prevalence of autism (based on administrative data) increased from 0.6 to 3.1 per 1000 [ 39]. During the same period, the prevalence of mental retardation and learning disabilities declined by 2.8 and 8.3 per 1000, respectively. He suggested that declines in ID prevalence may have been offset by the increase in autism prevalence. King and Bearman [ 21] estimated that, in California, about a quarter of the increased case load of autism from 1992 to 2005 was due solely to changes in diagnostic practices, substitution in particular.

Another concern with diagnoses, especially when used for educational purposes, is diagnosis "augmentation," application of the diagnosis to children with autistic features who do not truly meet diagnostic criteria for autism as described above in order to enable a child to receive necessary educational services [ 36, 47]. While understandable from a patient advocacy perspective, this hampers research investigations as these individuals do not meet rigorous diagnostic criteria, and many do not have autism by such standards.

Autism and Intellectual Disability

Despite the temporal trends and differences in application of diagnostic criteria and the concept of autism itself, virtually all studies find a higher prevalence of autism in individuals with intellectual disability than in those whose intellectual function is within the normal range. Studies have examined the prevalence of autism in relation to intellectual disability both by looking at the prevalence of intellectual disability in series of people with autism and conversely the prevalence of autism in people with ID.

In large-scale studies of children with autism, half or more are reported to have some degree of intellectual disability (consistent with IQ<70). Steffenburg and Gillberg's found that 88% of children with infantile autism or autistic-like conditions (the terms used then) had an IQ<70 with 58% having IQ<50. In more recent studies, this has lessened somewhat [ 48]. For example, Nichols et al. reported that 60.4% of 8 year-olds meeting their criteria for autism had an IQ score <70 placing them in the intellectual disability range [ 18]. In the Special Needs and Autism Project series, 55% of children identified as having autism had an intellectual disability, again defined as IQ<70 [ 49]. The definitions used are important. A population-based study in Brick Township, NJ, considered all children 3 to 10 years of age. Of those with autism spectrum disorder, 49% had IQ scores <70; however, if only those who met strict criteria for autism were considered along with those too impaired to be tested, this figure rose to 63% [ 16]. A single surveillance network found varying degrees of overlap between autism and epilepsy across different states within the US [ 22]. In children with ASD, ID was present in anywhere from 29% to 51%.

One would expect the association between autism and ID to depend heavily on the definition of autism, specifically whether it includes Asperger syndrome and PDD-NOS. In one British study, 69% of children meeting criteria for autism had some degree of intellectual disability in contrast to 7.6% of those with PDD-NOS and none of the children with Asperger [ 26]. These latter two categories constituted about two-thirds (65/91) of the children identified with an autism spectrum disorder in that study and support Bryson and Smith's conclusion that most people with autism, broadly defined, do not have intellectual disability [ 50].

When considered from the perspective of intellectual disability, the prevalence of autism increases with the severity of the ID. De Bildt et al. specifically examined individuals with known intellectual disability. Depending on the diagnostic criteria and instruments used, they found a four to ten-fold increase in prevalence of ASD in people with mild to severe/profound mental retardation [ 38]. For example, using the PDD-MRS, the prevalence of autism was 2% for people with mild MR rising to 28.2% for severe-profound MR. Very similar trends, although somewhat higher absolute values, were reported by an Italian group [ 35]. For adults with mild, moderate, severe, and profound ID, the prevalence of autism was 8.3%, 24.1%, 37.1% and 59.6% respectively.

The other feature in the population that is strongly associated with autism is male gender with virtually every study demonstrating a 3 to 6 fold higher prevalence in males than in females [ 16- 19, 25, 26, 41, 46, 48]. Current theories about the "male brain" as well as assortative mating and delayed age at parenthood have been proposed [ 51]. Notably, this association diminishes and, in some studies even disappears in individuals with intellectual disability [ 18, 49]. A general impression from a review of the epidemiology of autism concluded that the sex ratio depended on the presence of intellectual disability and dropped to about 2 in those with ID [ 52]. This pattern suggests that autism in association with intellectual impairment may be a different phenomenon from autism in someone of normal intellect. The diagnostic issues discussed above need to be considered as well as there may be a surfeit of autism diagnoses due to autistic features associated with ID (in both boys and girls) which are over interpreted as autism and thus obscure any gender difference.

Epilepsy and Intellectual Disability

Epilepsy is recognized as a large group of disorders which, although characterized by the occurrence of epileptic seizures, are also strongly associated with a range of behavioral and cognitive comorbidities [ 53]. Intellectual disability per se is very common in children with epilepsy. Four population-based or population-representative studies reported that approximately a quarter (20-27%) of children with epilepsy also had some degree of intellectual disability [ 54- 57]. The prevalence is highest in children with the youngest age at onset of epilepsy and in association with structural brain lesions. ID is especially high in a group of epilepsy syndromes often referred to collectively as the epileptic encephalopathies because of their strong association with developmental and behavioral disabilities [ 56, 58]. These syndromes include several disorders such as (but not limited to) West syndrome, Dravet, Ohtahara, and Lennox-Gastaut syndromes. Developmental and cognitive outcomes in these syndromes are rarely within the normal range [ 9, 55, 56]. Increasingly, investigations are targeting underlying genetic factors involved in intellectual disability syndromes closely associated with epilepsy [ 59]. In general, however, and apparently regardless of underlying cause, younger age at onset of epilepsy, particularly when drug-resistant, appears to place a child at substantially increased risk of intellectual impairment although autistic features and the diagnosis of autism per se are not always described [ 60, 61]. It is in the children with the youngest age at onset of seizures that one would expect to see the highest levels of autism because of their increased burden of intellectual disability and also because this is the age when autism begins to manifest itself.

Autism and Epilepsy

Many investigators have approached the issue of epilepsy and autism from the vantage point of the latter. In people with autism, estimates range from a few to as much as a quarter also having epilepsy [ 4]. In a prevalent sample of 286 children with autism evaluated at a tertiary center specializing in both autism and epilepsy, in children diagnosed with autism, the prevalence of epilepsy was 7% among those with no motor deficits or severe intellectual disability [ 62]. By contrast the prevalence of epilepsy was as high as 42% in those with motor deficits and severe ID. Figures for children with clearly "normal" intellect were not provided, however. In a population-register study, a quarter of individuals diagnosed with infantile autism also had epilepsy in contrast to 1.5% of population-based controlled [ 63]. With the exception of cerebral palsy, other neurological disorders did not occur more often in the autism group than in controls. The prevalence of epilepsy was greater in association with severity of intellectual impairment; 34% of children with autism and severe intellectual disability (IQ<50) had epilepsy as compared to 27% of those with moderate ID (IQ 50-69) and 9% of those with IQ>=70. In both of these last studies, males out-numbered females overall by about 3:1; however, gender was not clearly associated with being diagnosed with epilepsy. This is largely because, at the most severe end of the intellectual disability spectrum, where the risks of developing epilepsy and of autism are highest, and the gender differential for autism is diminished.

Using patient data from a regional disabilities center, Wong et al. (1993) found that only 11 of 145 (7.6%) children diagnosed with infantile autism were also diagnosed with epilepsy [ 64]. Of the 11, only one was of normal intellect. Another study from a regional center reported epilepsy in 72 patients with autism [ 65]. Epilepsy occurred in 15% of the group with IQ<55, 55% of those with "secondary" autism (i.e. with other underlying neurological conditions) but in only 3% (1/34) of those with "primary" autism and IQ>55. Their conclusion was that epilepsy was not a common occurrence in primary autism [ 65]. In a novel approach to question of epilepsy and autism, Mouridsen et al. looked at the prevalence of epilepsy in parents of children with infantile autism and in parents of controls (children without autism) [ 66]. The rationale behind the design being that, if epilepsy and autism share genetic mechanisms, then family members of probands with one disorder should be at increased risk for the other disorder. While this is a somewhat novel approach, it has been used in other settings, for example, nocturnal frontal lobe epilepsy and sleep disorders [ 67]. No evidence of a greater prevalence of epilepsy or other neurological disorders was found in case parents compared to control parents.

Of note, while the diagnosis of autism in these studies was often very sophisticated, that for epilepsy was typically based upon the observation of aberrant, episodic behaviors combined with an abnormal scalp EEG. Since then, studies using video-EEG monitoring have demonstrated that children with autism who are evaluated for epilepsy because of events of concern often have epileptiform abnormalities; however, their clinical events are not associated with electrographic evidence of seizure activity [ 68- 70]. There is another substantial literature on the relationship between epileptiform discharges and ASD, autistic regression, and language disorders in the absence of epileptic seizures. Epilepsy is not, however, diagnosed solely on the basis of interictal findings. There are many comparisons made with Landau-Kleffner syndrome, a severe encephalopathy characterized by language impairment and electrographic status epilepticus in sleep, although seizures may not even occur [ 2, 4]. This is a relatively rare disorder, however, and it is not necessarily the best model for studying autism and epilepsy.

Viewed from the other perspective, there are several small series reporting the occurrence of autism in patients with selected types of epilepsy that are strongly associated with autism and autistic features. For example, in a population-based study of seizures with onset in the first year of life, 35% of children with infantile spasms developed autism versus 9% with other forms of epilepsy [ 71]. Most of the association between spasms and autism was due to the underlying structural lesions associated with the spasms themselves. A separate study reported infantile spasms, relative to all other forms of childhood epilepsy and regardless of age at onset, to be a strong correlate of autism [ 72]. In patients seen at a tuberous sclerosis clinic, autism was reportedly more likely to occur in patients whose mutation was in theTSC2 gene than in TSC1. Mutations in TSC2 were also more likely to be associated with infantile spasms so the relative importance of the spasms phenotype versus the TSC genotype was not clear [ 7, 8]. Animal models, however, have also implicated TSC2 mutations as being particularly important in both severe epilepsy and autism [ 73, 74]. A high prevalence of autistic features although not necessarily classical autism per se is also reported in association with Dravet syndrome [ 9, 75, 76] and in Epilepsy in Females with Mental Retardation [ 10]. Finally, in a tertiary clinic, children with established epilepsy were screened for autism and 32% screened positive for autism although cognitive status was not specifically described. Only 9 of 31 with positive screening results had been previously diagnosed with autism. Diagnostic results for the other 22 were not reported [ 77].

Epilepsy-Autism-ID

While repeated studies report a high prevalence of autism in children with epilepsy and of epilepsy in children with autism, these studies, virtually always also point to the importance of intellectual disability (however labeled) as being the connection between autism and epilepsy. Definitional issues aside, individuals with autism who have ID are at substantially higher risk of epilepsy than are those with relatively normal intellectual function. This general pattern is seen across multiple studies and was the focus and conclusion of an extensive meta-analysis [ 11]. The complement is true as well. Children with epilepsy and ID are at substantially increased risk of autism relative to those with epilepsy who are of normal intellect [ 72]. To our knowledge, only two large prospective cohort studies have examined autism in representative series of children with epilepsy [ 57, 72]. The first reported that 3.9% of a representative cohort of children with epilepsy developed autism but did not provide any breakdowns by level of cognitive function. The second found that 5% of all children in the cohort met criteria for autism; however, only 2% of those with IQ≥80 met criteria. These had almost exclusively Asperger syndrome and involved a range of different epilepsy syndromes. While this estimate is higher than population-based estimates of ASD, all of the concerns regarding diagnostic criteria, substitution and augmentation must be considered. In the end, these findings do not suggest a large additional burden of autism in otherwise cognitively normal children with epilepsy.

Together, the many studies reviewed above have taken complementary approaches to the epilepsy-autism-ID puzzle and have provided different pieces of information that help resolve this question, although not entirely. Collectively, the literature provides clear evidence that intellectual disability is the main and possibly the only reason that studies find a higher than expected level of autism in children with epilepsy. The changing concept of autism and other factors affecting how the diagnosis is used complicate any investigations into these issues. In the context of US Federal spending on the genetics of autism having neared 1 billion dollars in the last decade [ 78], and given that advances that have been made in the genetics of ID syndrome [ 79] as well as specific epilepsy syndromes [ 80], it is imperative that any further investigations, especially of epilepsy and autism, consider the role of ID. Given how sensitive the yield of ASD diagnoses can be to the methods for ascertaining and diagnosing ASD, any future studies that wish to advance our knowledge of this field will need to have clinically meaningful, standardized approaches for accurately diagnosing autism, epilepsy and intellectual disability in a large enough sample or using a clever enough design so that the role of intellectual disability can be teased apart from the role of epilepsy and its underlying causes. This will allow us to determine the extent to which any association between autism and epilepsy is solely a function of ID (). Only then can we seriously entertain the other possibility, that, above and beyond any contribution from ID, autism and epilepsy truly have a special relationship ().

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Epilepsy and Autism: Is there a special relationship?

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Increasingly, there has been an interest in the association between epilepsy and autism. The high frequency of autism in some of the early-onset developmental encephalopathic epilepsies is frequently cited as evidence of the relationship between autism ...

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Epilepsie et autisme [dossier]. Les cahiers d’épilepsie 2012 ; 2 (1) .

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Epilepsie et autisme [dossier]. Les cahiers d’épilepsie 2012 ; 2 (1) .

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Dossier spécial de la revue "Les cahiers d'épilepsies" consacré au sujet "Epilepsie et autisme".

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Epilepsies et autismes - parcours de sensibilisation. CRA Ile-de France, 2022.

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Epilepsies et autismes - parcours de sensibilisation. CRA Ile-de France, 2022.

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Le CRAIF organise un parcours de sensibilisation tous publics sur "Autisme et épilepsie".

Ce parcours en 2 temps comprend :

Une vidéo e-learning « Autisme et Epilepsie » accessible dès maintenant : accéder à la vidéo

Contenu du parcours :

Qu’est-ce que l’épilepsie ? symptomatologie de l’épilepsie, formes particulières d’expression dans l’autisme ?

Les signes évocateurs (avant le diagnostic d’épilepsie)

Epilepsie et Autisme

La démarche diagnostique d’épilepsie chez une personne TSA (examens ; délai d’accès aux examens ; habituation aux soins (préparer les examens))

Prise en charge thérapeutique

Quelles attitudes adopter ?

Avant, pendant et après la crise

Les traitements antiépileptiques

Conclusion et ressources complémentaires

Des supports à télécharger

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BIENVENUE SUR CE PADLET !

L'autisme, et les troubles envahissants du développement, sont très souvent associés à l'épilepsie. Retrouvez ici une sélection de supports d'informations traitant de cette association.

Nous enrichissons ce Padlet au fur et à mesure de nouvelles publications, recherches et "trouvailles".

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Vous pouvez alimenter ce padlet en ajoutant des références qui vous semblent pertinentes. Celles-ci seront validées avant leur publication.

Abonnez vous à ce Padlet pour être informé de ses mises à jour ! (en cliquant sur la petit icone "cloche" à droite du Padlet, puis sur "suivre").

Pour compléter vos recherches, rendez-vous sur notre portail documentaire : https://doc.handicapsrares.fr/fahres

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Trouble du spectre de l'autisme et épilepsie. CHU Sainte-Justine, 2017

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Trouble du spectre de l'autisme et épilepsie. CHU Sainte-Justine, 2017

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Le trouble du spectre de l’autisme et l’épilepsie sont deux pathologies distinctes, mais qui deviennent parfois la comorbidité de l’autre. La prévalence de l’autisme chez les personnes atteintes d'épilepsie varie beaucoup. Toutefois, on retrouve certains facteurs de risques plus susceptibles au développement de l’autisme chez les enfants atteints d’épilepsie.

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Le trouble du spectre de l'autisme et l'épilepsie sont deux pathologies distinctes, mais qui deviennent parfois la comorbidité de l'autre. La prévalence de l'autisme chez les personnes atteintes d'épilepsie varie beaucoup. Toutefois, on retrouve certains facteurs de risques plus susceptibles au développement de l'autisme chez les enfants atteints d'épilepsie.

Facteurs de risques
Âge au développement de l'épilepsie
Lorsque les crises débutent dans la première année de vie, on estime à 14% le risque de développer également un trouble du spectre de l'autisme. Un fait intéressant est que l'épilepsie débutant à l'adolescence semble également avoir un lien avec la présence de l'autisme. Toutefois, cette association reste encore peu expliquée si ce n'est qu'elle serait liée à l'autisme idiopathique.
Retard intellectuel
Le retard intellectuel est également un facteur de risque puisque les enfants avec une épilepsie et présentant un retard intellectuel sont dans 30% des cas également d'autiste.
Syndrome de West
Le syndrome de West est une forme rare d'épilepsie. Plus particulièrement, celui-ci se caractérise par des contractions involontaires " spasmes infantiles ", par un ralentissement du développement de l'enfant pouvant aller vers une régression. On calcule que 46% des enfants atteints de ce syndrome développent également un trouble de spectre de l'autisme. Ces deux diagnostics sont donc fortement corrélés.

Pourquoi une corrélation entre ces deux pathologies ?

Le lien entre les deux maladies est encore très mal compris. Certains chercheurs suggèrent qu'une mutation génétique pourrait jouer un rôle dans l'apparition de ces deux troubles.

Difficultés lors de la présence de l'épilepsie et de l'autisme

Moins grande motricité fine et globale

Difficulté sociale

Difficulté comportementale

Possible rémission de l'épilepsie plus faible

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Trouble du spectre de l'autisme et épilepsie : Comorbidités

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Le trouble du spectre de l'autisme et l'épilepsie sont deux pathologies distinctes, mais qui deviennent parfois la comorbidité de l'autre. La prévalence de l'autisme chez les p

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Autism spectrum disorder and epilepsy : two sides of the same coin ? Article de la revue Journal of child neurology, n°14 vol 30, 2015.

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Autism spectrum disorder and epilepsy : two sides of the same coin ? Article de la revue Journal of child neurology, n°14 vol 30, 2015.

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Abstract

Autism spectrum disorders (ASD) and epilepsy commonly co-occur. In this review, we consider some unresolved questions regarding the temporal relationship, causal mechanisms, and clinical stratification of this comorbidity, highlighting throughout the interplay between ASD, epilepsy and intellectual disability. We present data on the clinical characterization of children with ASD and epilepsy, discussing distinctive phenotypes in children with this comorbidity. While some distinctive clinical features emerge, this comorbidity also informs convergent pathways in genetic variants that cause synaptic dysfunction. We then move beyond diagnostic categorization and consider the extent to which electrophysiology as a quantitative biomarker may help guide efforts in clinical stratification and outcome prediction. Epilepsy, and atypical electrophysiological patterns, in ASD may inform the definition of biologically meaningful subgroups within the spectrum that, in turn, can shed light on potential targets for intervention.

Keywords: autism spectrum disorder, electroencephalography, epilepsy, intellectual disability, biomarkers

Introduction

The co-occurrence of epilepsy and autism spectrum disorder (ASD) has been well-established through large-scale prevalence studies. As the field of ASD research moves toward the elucidation of mechanism-based clinical stratification and targeted treatments, studies have begun to focus more deeply on understanding the clinical and biological basis of this comorbidity. In this review, we first present the most recent literature on the prevalence of epilepsy in ASD, and ASD in epilepsy. Throughout the discussion we consider the additional role of global developmental delay/intellectual disability, both the temporal relationship between these comorbidities and whether there are defined clinical phenotypes that define individuals with this triad. We then move beyond diagnostic stratification and discuss the relationship between ASD and epileptiform discharges, and we introduce the emerging concept of electrophysiology to help guide intervention and predict outcome in ASD. Lastly, we discuss the controversy surrounding the possibility of electrophysiological abnormalities serving as a treatment target in ASD. Throughout the review, we consider the following question: Can the presence of epilepsy or atypical electrophysiological patterns in ASD inform the definition of biologically meaningful subgroups within the spectrum and, in turn, shed light on potential targets for intervention?

What is the Risk of Developing Epilepsy in ASD?

The rate of epilepsy in individuals with an ASD diagnosis ranges from 6% to 27%,1-7 with no single type of epilepsy more consistently reported. The range in rates is due, in large part, to the heterogeneity of the groups being studied, particularly with regard to cognitive function and age. Additionally, methodological differences in the measures used to diagnose ASD, from retrospective chart reviews to prospective parent questionnaires and clinician-performed diagnostic assessments, lead to differences in prevalence rates. Several factors have been associated with a greater risk of developing epilepsy, including regression of skills (language and social function) and female sex; however, the most robust data indicate that the single most important risk factor is overall cognitive function.8 Of note, although efforts have been made to characterize the ASD phenotype in these studies, few have taken similar efforts to define the epilepsy phenotype, either patterns in the electroencephalogram (EEG) or seizure semiology.

A meta-analysis by Amiet and colleagues attempted to disentangle the relationship between intellectual disability, ASD, and epilepsy. They compared rates of epilepsy between subgroups of subjects based on IQ (<40, 40-50, 50-70, >70) and found that epilepsy rates increased as IQ decreased. The highest rate of epilepsy (46%) occurred in the group with an IQ <40. Furthermore, they found that the male-to-female ratio in ASD with epilepsy was 2:1, compared with the 3.5:1 ratio in non-epilepsy ASD. The authors were unable to determine whether sex, IQ, or the interaction between IQ and sex mediated the ASD-epilepsy relationship. In a subsequent study in a sample of 2644 children with simplex ASD, these same investigators found no significant increase of epilepsy associated with sex, but did confirm the association between epilepsy severity and cognitive impairment.9 This strong relationship between epilepsy and cognition was replicated by Viscidi and colleagues in a sample of 5185 children of ASD, where they demonstrated that in children over age 10, for every one standard deviation increase in IQ, the odds of having epilepsy decreased by 47%.6

Age is the only other risk factor strongly associated with the development of seizures in individuals with ASD. Several studies have suggested there are 2 peaks of epilepsy, one in early childhood and a second in adolescence.5,10,11 Other large cross-sectional studies have found that the risk of epilepsy increases with age, with peak in early adolescence.12,13 In a population of children diagnosed as having ASD in the first decade, most seizures developed after age 10, and the risk of developing epilepsy continued to increase into the third decade of life.2 In the cross-sectional study by Viscidi and colleagues, the average prevalence of epilepsy was 12% in children with ASD, with the rate reaching 26% by adolescence.6 Furthermore, in a meta-analysis by Woolfenden, the pooled estimate of developing epilepsy was highest, 23.7%, in those with intellectual disability and age >12 years.7 To summarize the findings from these large recent studies, the prevalence of epilepsy in ASD is greatest among those with intellectual disability and in children in the second decade of life, and the risk of developing epilepsy continues into adulthood.

What is the Risk of Developing ASD in Epilepsy?

In studies of children with an epilepsy diagnosis, rates of ASD or positive screens for ASD symptoms have ranged from 5% to 37%.14-19 The strong association with intellectual disability is supported in these studies as well, with ASD rates higher in children with both epilepsy and intellectual disability. Data from several studies support the utility of developmental screening in children with epilepsy, as it is likely that neurodevelopmental disorders may already be present at the onset of the epilepsy. Fisher and colleagues conducted a widespread developmental screening program of patients with epilepsy in a tertiary medical center, with focus on symptoms of social communication impairment (ASD-related symptoms).16 Of 66 children under age 5 years screened (mean age, 2.5 years), 72% screened positive on a global developmental survey, the Ages and Stages Questionnaire, and 65% of those with an abnormal developmental screen also scored positive for ASD. The severity of developmental delay was highly related to autism risk. The authors then sought to disentangle the developmental delay from ASD through formal clinical evaluations, and they concluded, quite notably, that in 20 of 24 children, the positive ASD screening results could be explained by underlying developmental delays. In an extension of their previous work, this same group found that in 236 children with epilepsy screened with multiple instruments for ASD, approximately 7% had a clinical diagnosis of ASD, and 12 of these 15 children had other developmental delays or intellectual disability.20 Moreover, 20% of these children showed red flags that required further evaluation and potential intervention.

There exists no ambiguity in the fact that ASD, intellectual disability, and epilepsy co-occur. However, 2 critical questions require further investigation, the first regarding timing and the second regarding phenotype. First, in children with epilepsy, does atypical development precede or follow the onset of epilepsy and, to unpack the question further, does intellectual disability precede ASD, does ASD contribute to intellectual disability, or do the 2 develop synergistically? Second, can we identify specific behavioral, cognitive, and developmental characteristics in children with ASD and epilepsy, particularly in the setting of co-morbid intellectual disability, that inform specific treatment targets? In other words, is there a distinctive ASD/epilepsy phenotype?

What is the Temporal Relationship of ASD, Epilepsy, and Intellectual Disability?

With regard to the first question, several studies have documented that epilepsy can both precede and follow a diagnosis of a neurodevelopmental disorder such as global developmental delay/intellectual disability or ASD. Matsuo and colleagues17 described a cohort of 79 patients with ASD and epilepsy and found that in 46.8% of cases, epilepsy was diagnosed prior to ASD. Similarly, in the Finnish cohort, more than half of the cohort was diagnosed with epilepsy prior to ASD or intellectual disability. It is possible that formal diagnoses of neurodevelopmental disorders are deferred because of the initial focus on epilepsy management. However, it is also possible that subtle or subclinical signs of atypical development do occur early in infancy, but they are not identified until a formal clinical evaluation is performed. The second question regarding the temporal relationship between intellectual disability and ASD becomes much more complicated to understand, as the diagnosis of one can easily confound the other. Prospective studies of infants at risk for ASD and epilepsy are required to tease apart this phenomenon.

A recent longitudinal study of infants with tuberous sclerosis complex was designed to characterize early developmental trajectories and predictors of ASD. Children with tuberous sclerosis complex are at high risk for ASD (up to 50%)21 and epilepsy (up to 80%),22,23 and they can be studied from early infancy because of prenatal diagnosis of tuberous sclerosis complex.24 In this multi-site study, the investigators followed infants with tuberous sclerosis complex from ages 3 to 36 months, performing comprehensive behavioral assessments (focused on cognition and social communication skills), clinical history, and resting state and event-related EEG.25,26 Ninety-five percent of infants had a diagnosis of epilepsy by age 24 months, and 55% met criteria for ASD based on standardized testing and clinical confirmation. By 12 months of age, infants who developed ASD had a significantly lower verbal and nonverbal IQ. Controlling for seizure severity, as defined by proportion of life with active epilepsy, infants diagnosed as having ASD demonstrated a significant decline in nonverbal IQ between ages 12 and 36 months. Moreover, only in infants later diagnosed with ASD was there a significant interaction between seizure severity and decline in nonverbal IQ.

These findings suggest that, in infants at high risk for both ASD and epilepsy, delays can be quantified in the first year of life, and these delays are highly associated with the diagnosis of ASD. However, there is a dynamic interaction between cognition, ASD, and epilepsy in this population, as infants later diagnosed with ASD may be more vulnerable to the effects of epilepsy on cognitive and social development. It is also possible, consistent with the findings from the study by Fisher and colleagues, that the diagnostic process and standardized testing for ASD become confounded by global developmental delay. To address these concerns, this group has begun to focus on the characterization of discrete behaviors (joint attention) and event-related EEG domains (face processing) that may be more sensitive and specific to the social cognitive impairments that define ASD, especially in high-risk groups such as infants with epilepsy. These discrete measures, along with continued investigation of infants in the first year of life, will help us to understand both the timing and specific deficits in social cognition and communication skills in these high-risk infants which, in turn, will facilitate implementation of early interventions for children who are at highest risk for ASD.

Is There a Distinctive ASD/Epilepsy Phenotype?

The clinical heterogeneity in ASD presents the greatest barrier to the establishment of reliable prognostic indicators and targeted treatment strategies. Efforts have been made to identify symptom clusters within the autism spectrum, in order to define clinically meaningful subgroups that may share a common mechanism of disease and therefore could benefit from a common treatment. The presence of epilepsy could serve as an entry point to the identification of a subgroup within the spectrum. In a recent study, Cuccaro and colleagues3 performed a latent class cluster analysis on a cohort of children with ASD to identify biologically and clinically meaningful subgroups. They identified 5 clusters based on IQ, ASD severity, and ASD symptoms. The cluster with the highest rate of epilepsy was characterized by early onset of ASD, greatest repetitive object use and unusual sensory interests, and highest frequency of gross motor coordination problems. Although these characteristics could actually relate to comorbid intellectual disability and perhaps reflect a global developmental delay, the prominent impairments in the repetitive behaviors/restricted interests domain, and in motor function, could serve as a quantifiable target for intervention. The results from this cluster analysis should spark future efforts in the characterization of social communication impairments in children with ASD and epilepsy, with focus on core deficits and features that not only would inform treatment targets but also could be measured longitudinally for treatment monitoring and for evaluation of outcomes with intervention.

The focus of research must move beyond diagnostic categories and toward the discrimination of behaviors and developmental features that can be improved or at least ameliorated by specific intervention strategies. In future analyses, addition of genetics data and, particularly, any known genetic variations in the patients, would enhance our understanding of the common mechanisms underlying these clusters.

Are There Convergent Pathways to Epilepsy, Intellectual Disability, and ASD?

With regard to pathophysiological mechanisms of ASD and epilepsy, 2 primary hypotheses exist in the literature that, in fact, may not be mutually exclusive. First, both may reflect outcomes from common processes, such as dysregulation of excitation/inhibition imbalance, either due to defects in GABAergic fibers or in γ-aminobutyric acid (GABA)-receptor function. Several genetic syndromes and variants that cause such dysregulation lead to epilepsy and to ASD.25 Second, primary epilepsy may impact synaptic plasticity and cortical connectivity, which, in turn, may predispose a developing brain to cognitive delays and behavioral impairments.27,28 Advances in our understanding of genetic causes of ASD have facilitated the investigation of these 2 hypotheses and, in fact, it is likely both mechanisms are at play.

ASD is a heritable disorder, as has been identified convincingly in twin and sibling studies.29 With advances in genetic testing methods over the past decade, and routine use of chromosomal microarray analysis and, now, whole-exome and -genome sequencing, more than 30% of individuals with ASD have identifiable genetic correlates.30-33 Genetic causes of ASD include well-recognized single gene disorders, such as Fragile X and tuberous sclerosis complex, as well as de novo copy number variations and single gene mutations (See Table ). Many of these single gene disorders and de novo variations are highly penetrant for comorbid epilepsy and intellectual disability, leading to the coining of the term "syndromic autism."34

Figure 1

Genetic variant or
syndrome

Relevant genes

Epilepsy features

Developmental
features

Potential
treatments

7q35 deletion (cortical dysplasia-focal epilepsy)
CNTNAP2

Both focal and generalized epilepsy

Profound ID
Profound language impairment

Oxytocin

15q11.2-13.1 duplication
UBE3A, GABA A receptors

Varied: Generalized and partial, multi-focal, infantile spasms, possibly resistant to typical benzodiazepenes

Hypotonia
Comorbid ID and ASD
Profound language impairment Excessive beta band activity

Benzodiazepenes may be less effective

18q12.1 duplication or deletion
DTNA
Cadherin superfamily genes

Focal and generalized

ID, language delay, deletions associated with motor delay

22q13.3 deletion
SHANK3

Varied: generalized, focal, absence

Hypotonia
Comorbid ID and ASD Profound language impairment

IGF-1

Not surprisingly, the genes implicated in many of these syndromes and variants cause impairments at the level of the synapse, both structural and functional, thereby likely serving as a causative mechanism for epilepsy and for atypical development.35 For instance, copy-number variation alterations in genomic regions or associated genes were recently reported in children with continuous spike and waves during slow-wave sleep syndrome and Landau-Kleffner syndrome, suggesting genetic pathway overlaps may exist between ASD and this group of epilepsies.36 Specific mutations in the GRIN2A gene have been associated with Landau-Kleffner syndrome37 and are also associated with neurodevelopmental disorders, such as ASD.38

From a clinical standpoint, these genetic variants and syndromes can be studied as a biologically based subgroup, with the goal of identifying clinical patterns that can help clinicians provide concrete information about prognosis and treatment (see Table ). A timely example of this opportunity arises from maternal duplications on chromosome 15q11.2-q13.1 (Dup15q syndrome), as this syndrome confers a high risk for early onset epilepsy, ASD, hypotonia, and intellectual disability.39-41 In fact, Dup15q syndrome is considered one of the most highly penetrant variants for intellectual disability and ASD. Duplication of this region leads to the overexpression of several genes, most notably UBE3A (E3 ubiquitin ligase gene) and a cluster of alpha-receptor subunits for the neurotransmitter GABA.

A recent large cohort study of 95 children with Dup15q syndrome sought to identify common characteristics and potential treatments for epilepsy in this population.42 Investigators identified multiple seizure types, both generalized and focal, with infantile spasms present in 42% of cases. Both broad spectrum and focal antiepileptic medications (such as carbamazepine) demonstrated efficacy for seizure reduction, suggesting a multifocal etiology to the epilepsy. However, GABAergic medications, such as benzodiazepines, were relatively ineffective, possibly due to abnormalities in GABA transmission in the setting of duplications in GABA A receptor genes in the duplicated 15q region. This trend has led to the recommendation that traditional benzodiazepines should not be considered as a first-line agent for these patients.

In parallel to the efforts in epilepsy, investigators have begun to better characterize the social communication abilities and impairments in children with Dup15q syndrome. In particular, given the ubiquitous finding of hypotonia in these children, investigators are studying the link between motor impairment and both language and social development. Elucidation of the nature of the core deficits of intellectual disability and ASD in Dup15q syndrome will facilitate the design and implementation of targeted behavioral interventions, such as those that focus on motor development, that will specifically benefit this subgroup within the spectrum of neurodevelopmental disorders.

What is the Relationship of ASD to Epileptic Encephalopathy?

Epileptic encephalopathy is a conceptual term suggesting that epileptic activity, seizures, or interictal epileptiform discharges can lead to cognitive and behavioral impairment above and beyond what might be expected from the underlying pathology.43 Because of case reports of children with early onset seizures and autistic regression,44-47 parallels have been drawn between children with "autistic regression" and Landau-Kleffner syndrome, an epileptic encephalopathy in which children (usually after age 3) lose language skills in association with an epileptiform EEG showing continuous spike-and-wave pattern in sleep.48 In clinical disorders where regression, epilepsy, and ASD overlap, multiple variables need to be considered, such as type of regression (language versus autistic), age of onset of seizures or epileptiform activity, and the location, orientation, and quantity of the epileptiform activity, which can guide clinical management.

There is no quantifiable definition of autistic regression, and there continues to be debate in the field regarding its true prevalence, as it is a rather descriptive term that refers to children who seem to lose skills in language and social communication and who develop a restricted and repetitive pattern of behaviors and interests consistent with a diagnosis of ASD. There are 3 major differences between children with autistic regression and those with an epileptic encephalopathy such as Landau-Kleffner syndrome. The first is age of onset. The mean age of language or social communication regression in ASD is 18 months to 24 months, and over 90% of children with ASD who undergo a regression do so before age 3 years.49 In Landau-Kleffner syndrome, only 12% to 14% of children regress before age 3 years.50 Age at regression may explain the second difference, which lies in the features of language loss. Because autistic regression occurs in a stage of development that precedes the emergence of full phrased speech, the regression can be clinically subtle (eg, loss of single words, decreased gesturing), whereas in Landau-Kleffner syndrome the loss is dramatic, with loss of fully developed language.

The second difference lies in the behavioral profiles. In ASD, regression affects social communication skills, repetitive behaviors, and language, and it results in the behavioral profile that typifies ASD. In Landau-Kleffner syndrome, regression primarily affects language, whereas behavioral abnormalities are much less pervasive and may be attributable to the inability to communicate or cognitive regression.51 Lastly, there are differences in the EEG findings. In ASD, the epileptiform activity associated with regression is characterized by centrotemporal spikes that can be infrequent and intermittent.52 In Landau-Kleffner syndrome, the EEG is characterized by frequent temporoparietal spikes, strikingly activated by slow sleep and with the EEG pattern of electrical status epilepictus of sleep.53 Furthermore, it has been shown that children with isolated language regression, as would be seen in Landau-Kleffner syndrome, have a significantly higher frequency of epileptic disorders (60%) versus those with language regression in the context of autistic regression (31%).54

Despite studies showing that the prevalence of epileptic disorders in individuals with ASD and no clinical history of seizures range from 6% to 60%,55,56 there is significant controversy regarding the specificity of these findings to the ASD phenotype, with or without regression.57-59 On the basis of the current literature, the prognostic implications of epileptic disorders in individuals with ASD and the utility of a baseline EEG in individuals with ASD without epilepsy, with or without regression, is dubious. There have not been prospective studies of infants prior to onset of ASD that can definitively demonstrate that epileptic disorders are causative of ASD or autistic regression. Despite studies showing that antiepileptic medications (AEDS) can have a positive impact on behavior,57,60 no studies have yet demonstrated that treatment of epileptic disorders positively impact social, language, cognitive, or behavioral outcomes.55,61,62-66 The comprehensive treatment of ASD and epilepsy has recently been reviewed.59,67

Despite the fact that children with an epileptic encephalopathy are more likely to develop ASD, it is important to point out that ASD is not an epileptic encephalopathy and, therefore, routine EEG is not warranted for an ASD diagnosis. An overnight EEG is clinically appropriate if there is a suspicion of seizures or a clear regression. Treatment with AEDs is warranted if seizures are diagnosed. If electrical status epilepticus of sleep is diagnosed based on overnight EEG, then treatment with protocols for epileptic encephalopathy would be indicated. However, there exists no evidence that supports the treatment of a child with ASD or with regression if the EEG is normal or only demonstrates infrequent spikes. However, as discussed earlier, children with an epileptic encephalopathy are at increased risk for developing ASD and, therefore, early implementation of behavioral, communication, and educational interventions should be considered a part of their comprehensive management.

Independent of Epileptiform Activity, is There an EEG Biomarker in ASD?

Recently there has been tremendous research interest in the identification of EEG biomarkers that could identify biologic correlates of ASD. The hope is that these biological correlates in ASD can predict outcomes and inform treatment monitoring. EEG is not only a more feasible, motion-tolerant imaging tool, but it also provides a temporally sensitive measures cortical connectivity, likely to be aberrant in ASD. Perhaps not surprisingly, because of the wide range in ages and phenotype of the ASD group being studied, no single EEG biomarker has been identified that consistently distinguishes individuals with ASD from those without ASD. In the most comprehensive review of resting-state EEG studies in ASD, Wang and colleagues identified a possible "U-shaped" profile of EEG power alterations, with excess power displayed in theta frequency and gamma frequency bands and reduced power in mid-frequency bands compared with typically developing individuals.68 The authors speculated that, in part, this profile results from abnormal GABAergic tone in inhibitory circuits.

EEG can also inform neurophysiological mechanisms of disease in high-risk genetic variants, therefore bridging the gap from genes to behavior. For instance, in duplications on chromosome 15q11.2-q13.1, a subgroup of children exhibit a classic EEG pattern of excessive beta frequency activity, a feature often found in patients treated with GABAergic medications such as benzodiazepines.41 This signature in Dup15q syndrome likely reflects the upregulation of several GABA receptor genes located in the duplicated region. Studies are currently underway to better characterize this excessive beta activity, both in mouse models and in patients, in order to understand the mechanism underlying this EEG pattern and to investigate whether this EEG signature relates to or predicts clinical outcomes, particularly the development of epilepsy or ASD. Furthermore, recent efforts have been focused on relating specific EEG patterns to core deficits or individual behaviors within ASD, in order to facilitate clinical stratification. In fact, EEG patterns could be extremely informative in the separation of intellectual disability from ASD in genetic syndromes where the 2 are highly related.

There has been more success recently in the identification of EEG patterns that distinguish infants at high and low risk for ASD, with risk conferred by having an older sibling with ASD. Studies have quantified differences in the developmental trajectories of EEG power, particularly in the gamma band, which reflect the binding of neural information from different networks.69,70 Other studies have identified atypical pattern of hemispheric organization, based on alpha band asymmetry,71 as well as lower functional connectivity between frontal and parietal regions,72 in high-risk infants compared with low-risk infants, independent of ASD diagnosis.

Failure to identify consistently predictive patterns of ASD diagnosis stems from the fact that a variety of genetic variants contribute to the development of ASD in infant siblings, each of which may result in a unique electrophysiological signature that represents distinctive neural mechanisms of disease. Nevertheless, if electrophysiological patterns can reliably place infants into risk categories, such categorization could facilitate the initiation of early interventions, prior to the onset of symptoms, which could enhance cognitive and behavioral outcomes. The potential relationship, if any, between these electrophysiological patterns and the development of epilepsy has not yet been investigated.

If EEG patterns can detect risk for developing ASD and can be tracked reliably across development, it seems feasible that quantitative EEG could be used to inform treatment outcomes, especially when standardized clinical measures are less sensitive to change over short intervals. Only one study has attempted to integrate EEG measures with behavioral outcomes after intervention. Dawson and colleagues studied a standardized intervention called the Early Start Denver Model in toddlers with ASD. They found that after 2 years of treatment, toddlers receiving the treatment demonstrated an EEG pattern (based on an alpha: theta ratio) similar to that of typically developing children.

Moreover, this EEG pattern related to gains in social behavior.73 The study did not include an EEG measure prior to intervention, which would have been informative in the characterization of changes with treatment, but the study did generate considerable dialogue about the potential for an EEG biomarker to refine the definition of outcome measures, especially in very young or impaired children. More controversial in this area of treatment is the potential utility for treatments to target EEG patterns in an effort to improve behavior or cognition. In other words, can spike suppression or modulation of oscillatory patterns change a child's functioning? The answer to this question leads us back to the original questions regarding mechanism of EEG abnormalities, and epilepsy, in ASD. If EEG patterns reflect the same underlying pathophysiological process causing the atypical development, then spike suppression or modification of the EEG pattern should not improve behavior. However, if these atypical patterns do truly precede and, in turn, cause atypical development, then an EEG modifier could, in fact, be effective. Carefully designed, hypothesis-driven studies in homogeneous subgroups of infants and young children must be performed to truly disentangle this issue.

Future Directions

In this review, we have examined the relationship between epilepsy and ASD, raising several themes that require further investigation, with the potential for insights that could elucidate mechanisms of disease, early detection, and, ultimately, treatment of these comorbidities. How do we disentangle intellectual disability from ASD in children with epilepsy? Is there an ASD phenotype that is specific to children with epilepsy? Are there characteristic phenotypes within genetic variant syndromes, both from the standpoint of epilepsy and behavior, that can give clues to earlier diagnoses and treatment? Are there electrophysiological precursors to epilepsy and ASD that can be quantified and provide accurate risk markers of disease? When and how should we treat atypical electrophysiological patterns in children with ASD?

The goal of precision medicine in neurodevelopmental disorders will be realized when we define mechanisms of disease that inform specific treatment targets. The comorbidity of epilepsy and ASD is a clue into such neural mechanisms, and through more rigorous methodology that moves beyond cross-sectional descriptions toward a quantification of the timing of onset, electrophysiological and behavioral characteristics, and underlying genetic etiologies, we will move one step closer toward identifying treatment targets for individuals within the heterogeneous autism spectrum.

Acknowledgments

The authors also wish to thank Melanie Fridl Ross, MSJ, ELS, for editing the initial draft of this paper.
Funding (Financial Disclosure)
SSJ is funded by National Institute of Mental Health grant 1K23MH094517 (principal investigator, Dr Jeste), National Institute of Child Health and Human Development grant 2P50HD055784-06 (principal investigator, Dr Bookheimer), and the Department of Defense Congressionally Directed Medical Research Programs, Tuberous Sclerosis Complex Research Program (principal investigator, Dr Nelson).

Footnotes

This work was presented in part at the 2014 Neurobiology of Disease in Children Symposium: Autism, held in conjunction with the 43rd Annual Meeting of the Child Neurology Society, Columbus, Ohio, October 22-25, 2014.
Declaration of Conflicting Interests
The authors have no conflicts of interest to declare.

References

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Autism Spectrum Disorder and Epilepsy: Two Sides of the Same Coin?

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Autism spectrum disorders (ASD) and epilepsy commonly co-occur. In this review, we consider some unresolved questions regarding the temporal relationship, causal mechanisms, and clinical stratification of this comorbidity, highlighting throughout the ...

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Epilepsy in patients with autism : links, risks and treatment challenges. Article de la revue Neuropsychiatric disease and treatment, vol 14, 2018.

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Epilepsy in patients with autism : links, risks and treatment challenges. Article de la revue Neuropsychiatric disease and treatment, vol 14, 2018.

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Frank MC Besag

Neurodevelopmental Team, East London Foundation NHS Trust, Family Consultation Clinic, Bedford, UK

Abstract: Autism is more common in people with epilepsy, approximately 20%, and epilepsy is more common in people with autism with reported rates of approximately 20%. However, these figures are likely to be affected by the current broader criteria for autism spectrum disorder (ASD), which have contributed to an increased prevalence of autism, with the result that the rate for ASD in epilepsy is likely to be higher and the figure for epilepsy in ASD is likely to be lower. Some evidence suggests that there are two peaks of epilepsy onset in autism, in infancy and adolescence. The rate of autism in epilepsy is much higher in those with intellectual disability. In conditions such as the Landau-Kleffner syndrome and nonconvulsive status epilepticus, the epilepsy itself may present with autistic features. There is no plausible mechanism for autism causing epilepsy, however. The co-occurrence of autism and epilepsy is almost certainly the result of underlying factors predisposing to both conditions, including both genetic and environmental factors. Conditions such as attention deficit hyperactivity disorder, anxiety and sleep disorders are common in both epilepsy and autism. Epilepsy is generally not a contraindication to treating these conditions with suitable medication, but it is important to take account of relevant drug interactions. One of the greatest challenges in autism is to determine why early childhood regression occurs in perhaps 25%. Further research should focus on finding the cause for such regression. Whether epilepsy plays a role in the regression of a subgroup of children with autism who lose skills remains to be determined.

Keywords: epilepsy, autism, regression, genetics, environment, Landau-Kleffner, CSWS

Introduction

Compared with the general population, the increased prevalence of epilepsy in people with autism and the increased prevalence of autism in epilepsy are now well established. Kanner's original paper describing 11 children with "autistic disturbances of affective contact" included one child with a history of seizures and an abnormal encephalogram (EEG). Several epidemiologic studies have since confirmed the relatively common co-occurrence of these two conditions. A review by Tuchman and Rapin stated that the reported frequency of epilepsy in autism ranged from 5% to about 40%. Amiet et al, in a meta-analysis of epilepsy in autism, demonstrated a relationship with intellectual disability; epilepsy was present in 21.5% of subjects with autism who also had intellectual disability and 8% of subjects without intellectual disability. The relationships between epilepsy and autism continue to be debated. This relationship is tantalizing from the scientific point of view and challenging from the management point of view. It is anticipated that a greater understanding of the relationship between these two conditions could have profound effects on the management of patients. If the risk factors for developing epilepsy in people with autism were known, perhaps the epilepsy could be prevented, or at least recognized early and managed better, as a result. Knowing that certain disorders, for example, metabolic disorders, can lead both to autism and epilepsy should result in early recognition and possible amelioration of the effects of both epilepsy and autism. In previous reviews, the current author had asked a number of questions. These questions remain relevant to the discussion of the relationship between epilepsy and autism. They include the following. Does epilepsy cause autism? Does autism cause epilepsy? Are there underlying brain mechanisms that predispose to both conditions? What is the role of genetics in determining conditions that underlie both autism and epilepsy? What is the importance of prenatal, perinatal and postnatal environmental factors? Do any of the proposed relationships between autism and epilepsy provide insight into useful management or treatment? Is the prognosis of either autism or epilepsy different when the other condition is present? What is the role of additional comorbidities, such as intellectual disability or attention deficit hyperactivity disorder (ADHD), in the relationship between the two conditions and in influencing treatment choices? What research is recommended for the future? Many of the issues reflected in these questions remain controversial. However, a confounding factor that is likely to affect not only the quoted percentages of the co-occurrence of the two conditions, but also the prevalence of additional comorbidities is the major change in the quoted prevalence of autism spectrum disorder (ASD) itself. These issues will be discussed and updated in this review.

The effect of the changing prevalence of ASD

Early studies, for example, Lotter, quoted an autism prevalence of about 4 per 10,000. In contrast, recent epidemiologic studies, for example, Baird et al, and the various estimates of Fombonne and coworkers have indicated that the prevalence of ASD in children is greater than 1% and the prevalence of Diagnostic and Statistical Manual of Mental Disorders, 5th revision (DSM-5) ASD together with social communication disorder might be >2%. It is quite clear that the early, narrow diagnostic criteria included only children with more severe autism and, by implication, children with more severe disability overall. The rate of intellectual disability and, consequently, epilepsy would have been much higher in this group of severely affected children than in the much larger group identified by the broader diagnostic criteria in recent studies. However, reviews in the literature have taken little or no account of this major factor. The quoted figures of epilepsy in autism using previous narrow criteria will be much higher than the prevalence using the current criteria. If children with intellectual disability (defined as an intelligence quotient [IQ] <70) are excluded, because even the population of children with autism with IQ >70 will be skewed toward a lower-than-average IQ, the prevalence of epilepsy is still likely to be higher than that in the general population. In other words, this increased prevalence of epilepsy in children with autism and IQ >70 might be because of the distribution tending toward a lower IQ, rather than because of any specific relationship to autism. In contrast, the broader definition of "ASD" implies that the prevalence of this condition in children with epilepsy might be considerably higher using the current criteria in place of the narrow "Kanner autism" criteria. These issues require a detailed critical review which is beyond the scope of the current overview.

In summary, the previous narrow diagnostic criteria of severe "Kanner" autism were associated with a high rate of intellectual disability and a high rate of epilepsy, whereas the current broader "ASD" criteria would be expected to lead to a lower rate of intellectual disability and a lower rate of epilepsy, but the frequency of ASD in epilepsy would be expected to be higher using the current broader criteria. Most published papers do not take account of the changing ASD criteria, implying that the rates of intellectual disability and epilepsy may be misleading. When quoting such figures, it is important not only to know what diagnostic criteria were used for autism/ASD, but also to note the date of publication because of the increased awareness of autism. The consequence of the changing prevalence of ASD is that past statements about the rate of epilepsy in autism are now almost certainly inaccurate.

At what age does epilepsy develop in children with autism?

In one of the classic studies, Gillberg and Steffenburg followed up 46 young people of age between 16 and 23 years with infantile autism (diagnosed by DSM-III criteria) and "autistic-like conditions". Approximately one third developed epilepsy. There were two peaks of epilepsy: in infancy and around puberty, the majority being around puberty. Subsequent studies have yielded conflicting results, but there is some evidence, for example, the publication by Volkmar and Nelson, that the original conclusions of Gillberg and Steffenburg apply. Subsequent studies have yielded differing results for the age of onset of epilepsy in autism, as recently reviewed by El Achkar and Spence, and Bolton et al, in a long-term follow-up study of 150 individuals with childhood autism, found that 22% developed epilepsy; the majority were over 10 years of age and some developed epilepsy in adulthood.

What is the influence of intellectual disability on the rate of epilepsy in children with autism?

Amiet et al carried out a meta-analysis on data available from published reports between 1963 and 2006 on autism and epilepsy to assess the relative risk of epilepsy in autism with respect to intellectual disability and gender. More subjects with autism who also had intellectual disability developed epilepsy than those who did not have an intellectual disability ( p<0.001). The pooled prevalence of epilepsy was 21.5% in those with autism and intellectual disability, compared with 8% in those with autism who did not have intellectual disability. They also noted that the male:female ratio of autism in those with epilepsy was close to 2:1, compared to a ratio of 3.5:1 in those without epilepsy. This analysis established very clearly that intellectual disability greatly increases the risk of epilepsy in people with autism. It also appeared to show that the rate of epilepsy in people with autism who did not have intellectual disability was higher, that is, 8%, than in the general population, but this figure needs to be interpreted carefully. As already stated, it is highly likely that the IQ distribution of those who have autism but do not have intellectual disability is, nevertheless, shifted to the left, implying that the mean or median IQ would be considerably less than that of the general population and, consequently, the risk of epilepsy would be higher.

The prevalence of autism in people with epilepsy, in these and other studies, depends very much on the presence of intellectual disability and also on the definition of autism/ASD used.

Does epilepsy cause autism?

In certain circumstances, for example, nonconvulsive status epilepticus and the Landau-Kleffner syndrome, epilepsy may cause features that have a strong resemblance to autism. The child may exhibit poor reciprocal social interaction, poor verbal and nonverbal communication and may cope with change poorly. However, this is not autism. Autism is a pervasive developmental disorder that persists over time. If either nonconvulsive status epilepticus or the Landau-Kleffner syndrome is treated effectively, the features of autism may decrease or even resolve. Would it be possible for nonconvulsive status epilepticus to continue, unabated, for several years, resulting in a clinical picture that was indistinguishable from autism? In theory, this possibility should be considered, although in practice, it is unlikely to occur. The models of the Landau-Kleffner syndrome and the closely allied continuous spike-waves in slow-wave sleep (CSWS) syndrome are particularly interesting. In the Landau-Kleffner syndrome, the child typically has normal early language development and then, apparently in association with electrical status epilepticus of slow-wave sleep (ESES), loses language skills. The pattern of loss of skills after normal early development also typically occurs in CSWS syndrome, but the loss of skills is not necessarily in the area of language. The typical case of the Landau-Kleffner syndrome would present with a verbal agnosia or a broader auditory agnosia (including the inability to recognize environmental sounds). Because the child cannot recognize his or her own speech, expressive language difficulties or even mutism can result. Children with the Landau-Kleffner syndrome can recover spontaneously with or without some permanent impairment of language or may continue to have severe language impairment. In cases in which there is no recovery, it is possible that the child could be misdiagnosed as having autism. Since ~25% of children with autism appear to develop normally and then lose skills under 3 years of age, it would clearly be very important to distinguish between the loss of skills in autism, for which the cause remains unknown, and the loss of skills in the Landau-Kleffner syndrome, which is potentially treatable with recovery of skills if the treatment is instituted promptly.

In summary, the weight of the current evidence is against epilepsy being the cause of autism in the majority of cases. Whether there is a subgroup of children in whom undiagnosed epilepsy might have a role in causing autistic regression and in whom antiepileptic treatment might reverse the regression still remains undetermined, although attempts to establish such a link have not been successful so far.

While on one hand, it is important to treat the epilepsy early and effectively if it is suspected as being the cause of the autistic features, on the other hand, the epilepsy in most children will not be the cause of any autistic features. However, in both situations, good management of the epilepsy is strongly to be recommended because even if the epilepsy is not the cause of the autistic features, treating it effectively may improve the quality of the life of the individual and family greatly.

Are specific epilepsy syndromes associated with autism?

The behavioural aspects of pediatric epilepsy syndromes have been reviewed by the current author. Although several epilepsy syndromes are said to be associated with autistic features, in many cases, the diagnosis of autism has not been made according to rigorous criteria and the quality of the data is questionable.

Can autism cause epilepsy?

From the available evidence, it appears that epilepsy is rarely the cause of autistic features, although when it is, it is important to treat it promptly and effectively. There is no plausible explanation for a link in the other direction; in other words, there is no plausible argument for suggesting that autism could cause epilepsy. It seems that the weight of evidence now favors a common underlying cause for both conditions. Broadly speaking, such underlying causes could be divided into genetic and environmental.

What is the role of genetics in determining conditions that underlie both epilepsy and autism?

There have been remarkable advances in genetics over recent years. With regard to autism, these advances are epitomized in the title of the paper by Betancur, "Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting". Although not all of these disorders would necessarily have been associated with epilepsy, many of them would have been. Intellectual disability is strongly associated with epilepsy. The lower the intellectual ability, the higher the prevalence of both epilepsy and autism. Much attention has rightly been given to the obvious example of a genetic disorder that can result in both autism and epilepsy, namely, tuberous sclerosis. In this particular case, a new type of treatment, namely, mTOR inhibitors such as sirolimus (rapamycin, Rapamune, Pfizer) and everolimus (Afinitor, Novartis) that limit cell growth, can also have an effect in ameliorating seizures, in at least some cases.

Advances in chromosomal microarray analysis have made detection of small chromosomal variations possible. In the past, clinicians would examine the patient, perhaps with dysmorphic features, intellectual disability, autism and epilepsy, expressing the view that a chromosomal abnormality was highly likely, only to find that chromosomal investigations revealed no such abnormality. The reverse is now true. Chromosomal microanalysis often yields unsuspected abnormalities, the significance of which may be difficult to interpret.

An interesting population-based, nationwide cohort study was carried out in Sweden by Sundelin et al. The study design was unusual. They examined follow-up data for 85,201 individuals with epilepsy, 80,511 siblings of these individuals and 98,534 offspring. In addition, those with epilepsy were compared with five controls, matched for age, sex, calendar period and county. Siblings and offspring were compared with siblings and offspring of controls. They excluded siblings and offspring with epilepsy. Because they were only interested in those who developed ASD, the percentages do not represent an overall prevalence, but do provide a relative a risk. During the follow-up period, 1,381 (1.6%) of those with epilepsy and 700 (0.2%) controls were diagnosed with ASD. The hazard ratio for developing ASD in those with epilepsy was 10.49, and 95% CI was 9.55-11.53. The highest risk was in those who had epilepsy diagnosed in childhood. It was of interest to note that both siblings and offspring of epilepsy patients had an increased risk of developing ASD, suggesting that both epilepsy and ASD had "shared etiology". This is likely to be interpreted as a shared genetic risk, although environmental factors might also play a role. A commentary on this study was provided by the current author.

There are many genetically determined metabolic conditions that lead to intellectual disability and the combination of both autism and epilepsy. The classic example is phenylketonuria, the deleterious effects of which have largely been eliminated in developed countries by neonatal screening.

Environmental factors

Schmidt et al have reviewed the environmental factors associated with autism, some of which may also be associated with epilepsy. There is evidence for a deleterious effect of air pollution. There is less convincing evidence for the role of organophosphate pesticides and phthalate exposure. They have pointed to evidence for a protective environmental effect of maternal folate during pregnancy. There is an increasing recognition of gene-environment interactions in general. If the offspring has a genetic predisposition and the mother is exposed to a relevant environmental toxin, the combination might result in a child with ASD who could also have epilepsy. Much further work needs to be performed in this area to provide definitive answers.

Brain damage arising during delivery and through neonatal factors such as severe neonatal jaundice should be avoidable, but if treated inadequately can predispose both to epilepsy and autism. In a recent large (N=874), 10-year follow-up study of children born under 28 weeks gestation, Kuban et al reported a high ASD rate: 9% in boys and 5% in girls. Singh et al have recently reviewed the shared features of the effects of traumatic brain injury and autism.

There are many metabolic conditions that can lead to brain damage if inadequately treated. The total number of these that could lead to intellectual disability, epilepsy and autism, especially if inadequately treated, remains unclear. However, Frye has provided a strong argument for treating any underlying metabolic disorders, both for ameliorating autism and epilepsy. Some studies have suggested that autistic features could be improved by appropriate treatment of the metabolic disorder. This raises an important question that continues to be debated, namely, how extensively should a child with autism and loss of skills be investigated? Again, it should be emphasized that the greater the level of intellectual disability, the higher the probability of epilepsy developing.

How should the individual with both epilepsy and autism be managed?

As a general principle, both conditions should be managed as they would be when occurring individually, but with certain reservations. This management will include ensuring that the cause of the epilepsy is appropriately investigated.

First, as has already been emphasized, ensure that the autistic features are not the result of ESES or frequent epileptiform discharges.

The diagnosis of epilepsy may be more difficult in someone with autism, especially if there is accompanying intellectual disability. Autism alone or in combination with intellectual disability can prove to be an obstacle in history taking.

There are special cases, for example, tuberous sclerosis, where specific treatment - in this case with sirolimus (rapamycin) or everolimus - may decrease the seizures (see earlier).

Some antiepileptic drugs can have negative effects on mood, behavior or cognition. For example, levetiracetam is sometimes associated with deterioration in children, whereas lamotrigine tends to be a mood-leveling antiepileptic drug. Topiramate can be associated with word-finding difficulties. For more details, see recent reviews by Aldenkamp et al and Brodie et al.

One of the most dramatic developments in recent years in the field of neurology has been the discovery of the role of neuronal autoantibodies, which can result in seizures, loss of skills, which can sometimes be dramatic, behavioral changes and even psychosis. Prompt, effective immunotherapy can, in at least some cases, reverse all these changes. Very few studies consider the possibility that neuronal antibodies might be a cause for at least some cases of autistic regression. This is an area that requires further consideration.

How should additional comorbidities be treated in the presence of both epilepsy and autism?

In addition to intellectual disability, which has already been discussed, three common comorbidities with autism and epilepsy are ADHD, anxiety and sleep problems.

Attention deficit hyperactivity disorder

ADHD is common in children with epilepsy, children with autism and children with both conditions together. Should children with autism who have both epilepsy and ADHD be considered for ADHD treatment? The answer to this question depends on the circumstances. Some children with epilepsy present with features of ADHD that are the result of frequent epileptiform discharges. In those cases, treating the epileptiform discharges may improve the ADHD features and this would be the treatment of choice. A few children may have inattention, distractibility and excitability as a result of inappropriate antiepileptic medication; for example, treatment with phenobarbital, benzodiazepines or vigabatrin can result in this situation. In those cases, a review of the antiepileptic medication and treatment with an antiepileptic drug that does not cause these features would be appropriate. However, many children with epilepsy and autism appear to have genuine underlying ADHD. In those cases, standard treatment with ADHD medication can be of great benefit. There are several research papers and reviews that have come to the conclusion that ADHD treatment is very unlikely to precipitate seizures. The current author has reviewed this topic elsewhere. One of the most convincing studies is that of Gucuyener et al, who treated 57 children with ADHD and active seizures and 62 children with ADHD and EEG abnormalities. They concluded that the ADHD symptoms improved significantly, but seizure frequency did not change from baseline. Methylphenidate appeared to have a beneficial effect on the EEG. They concluded that methylphenidate is safe and effective in children with ADHD and concomitant active seizures or EEG abnormalities. When endeavoring to assess the effect of ADHD medication on seizures, there are at least two confounding factors. First, epilepsy is a highly variable condition. If no change is made to treatment, some subjects will have an increase in seizure frequency, some will have a decrease and others will have no change, if the seizure frequency is monitored over a relatively short period of time. If ADHD medication is instituted, it may consequently be incorrectly concluded that those who had an increase in seizures did so because of the ADHD treatment, whereas, in fact, it was simply a variation in the epilepsy that would have been expected in any case. A different situation is that of the child who has no history of seizures, but develops seizures while taking ADHD medication. Can it be concluded that the ADHD medication caused the seizure? Hemmer et al investigated 234 children with "uncomplicated ADHD" who had no history of seizures. Thirty-six (15.4%) had epileptiform abnormalities. Studies on children with ADHD consistently reveal a high proportion of epileptiform abnormalities, implying that ADHD itself is a risk factor for having seizures. Consequently, even if a child with ADHD has no previous history of seizures and develops seizures after ADHD medication is commenced, it cannot necessarily be concluded that the ADHD medication was the cause of the seizures; ADHD itself predisposes to seizures.

Are there any additional factors that should be taken into account when considering methylphenidate treatment for a child with autism, epilepsy and ADHD? Methylphenidate can sometimes increase "obsessionality", with the implication that some of the rituals in a child with autism may become more intrusive. In the experience of the current author, the advantages of ADHD treatment usually outweigh this disadvantage; but occasionally, the "obsessionality" can become so intrusive that it is necessary to review the ADHD medication and to prescribe an alternative to methylphenidate.

In children with autism, epilepsy and ADHD, there is relatively little evidence on other ADHD treatments, such as atomoxetine, guanfacine and clonidine. However, there seems to be no clear evidence that these medications exacerbate seizures either. The current author has used atomoxetine and clonidine in children with autism, uncontrolled epilepsy and ADHD, without the occurrence of any seizure exacerbations.

In summary, the evidence reveals that about 30% of children with epilepsy have ADHD and about 70% of those with epilepsy and ADHD will benefit from treatment of the ADHD with methylphenidate. There has been a suggestion that the proportion might be slightly smaller in those who also have autism, but the proportion that responds favorably to standard ADHD medication is, nevertheless, high. Children with epilepsy and autism who also have ADHD should not be denied treatment for the ADHD, which can be of great benefit to them.

Anxiety

Anxiety is common in young people who have both epilepsy and autism. The RUPP study has shown that behavior in children with autism and intellectual disability can be improved with low-dose risperidone. The mechanism is probably through decreasing anxiety. Is epilepsy a contraindication to such treatment? Although there are anecdotal reports of seizure exacerbations with risperidone, it appears that low-dose risperidone is very unlikely to exacerbate seizures. As with many medications, the risk almost certainly increases with increasing dose; but since the doses required for treating anxiety in children with autism are low, the chances of seizure exacerbations are also low, even in children with uncontrolled epilepsy and autism. However, it is important to be aware of the interactions between antiepileptic and antipsychotic drugs. In particular, enzyme-inducing drugs such as carbamazepine, phenobarbital and phenytoin may decrease the blood levels of antipsychotic medication. For example, carbamazepine decreases the serum levels of both risperidone and its active metabolite. This implies that larger doses of risperidone may be required in those who are also taking carbamazepine or possibly other enzyme-inducing AEDs.

Cognitive-behavioral therapy and other psychologic interventions should be the first-line approach to managing anxiety. Although selective serotonin reuptake inhibitors are generally effective in decreasing anxiety in adults and teenagers, a Cochrane review has concluded that there is a lack of evidence for a beneficial role of selective serotonin reuptake inhibitors in treating anxiety in children with autism.

Sleep

Sleep problems are very common in children with autism, with or without epilepsy. If sleep problems present in a child with both epilepsy and autism, it is clearly important to ensure that nocturnal seizures are not the reason for the sleep disturbance. If they are, a review of antiepileptic medication is required. If the sleep disturbance is not due to nocturnal seizures, is melatonin a contraindication? The current author reviewed the question of whether melatonin exacerbates seizures. Although the literature is sparse, there appears to be no good evidence that melatonin exacerbates seizures. The current author has used melatonin in many children with uncontrolled epilepsy, with no reports of seizure exacerbations. Animal work suggests that melatonin might have an antiepileptic effect. Based on the current, albeit incomplete, evidence, there seems to be no reason for avoiding melatonin as a treatment for sleep-onset insomnia in children with epilepsy and autism.

Future research

Based on the limited evidence that is available in many areas of research on epilepsy and autism, the following recommendations may be made.

With regard to autism with regression, there is a pressing need for carefully conducted, prospective, population-based studies particularly to investigate the child as soon as any regression is detected. Such investigation should include the following:

1. Genetic and chromosomal studies

2. Search for metabolic and mitochondrial disorders

3. EEGs including at least a sleep EEG and preferably an overnight EEG

4. Testing for possible neuronal antibodies.

With regard to autism in general, in addition to the first two investigations listed above, a search should be made for possible environmental factors, including prenatal factors such as maternal exposure to infection, pollution, toxic chemicals, alcohol and drugs, both illicit and therapeutic. The history of drug exposure in mothers who also have epilepsy should include a history of exposure to antiepileptic drugs in view of the link between maternal valproate and learning problems/probable autism in the offspring.

Obstetric and neonatal factors will form an essential part of the data.

As stratification into the various subcategories is likely to result in small numbers, there is a strong case for international research collaboration with agreed and standardized protocols. The aim will be that focused research studies provide answers that significantly improve the future outlook for people with epilepsy and autism.

Conclusion

1. The risk of epilepsy in people with autism is high, around 20% based on previous criteria of autism, and the risk of ASD in epilepsy is also high, probably around 20%, based on recent epidemiologic studies.

2. Although, in most cases, the link between epilepsy and autism arises from a common underlying factor, it is essential to ensure that the autistic features are not the result of inadequately treated epilepsy.

3. Good management of autism, epilepsy and comorbidities can greatly improve the quality of life of both the child and the family.

There are major challenges both in the future research and in the current management of people who have both epilepsy and autism. However, prompt, appropriate management, with a good understanding of the importance of focused investigations and correct treatment, can be of significant benefit.

Disclosure

The author reports no conflicts of interest in this work.

References

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Epilepsy in patients with autism: links, risks and treatment challenge | NDT

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Epilepsy in patients with autism: links, risks and treatment challenges Frank MC Besag Neurodevelopmental Team, East London Foundation NHS Trust, Family Consultation Clinic, Bedford, UK Abstract: Autism is more common in people with epilepsy, approximately 20%, and epilepsy is more common in people with autism with reported rates of approximately 20%.

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Prevalence and risk factors for autism spectrum disorder in epilepsy : a systematic review and meta-analysis. Article de la revue Developmental medecine & child neurology, vol 60 n°1, 2018.

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The association between epilepsy and autisme symptoms and maladaptive behaviors in children with Autisme Spectrum Disorders. Article de la revue Autism, vol 18 n°8, 2013.

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The association between epilepsy and autisme symptoms and maladaptive behaviors in children with Autisme Spectrum Disorders. Article de la revue Autism, vol 18 n°8, 2013.

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Autisme associé à une épilepsie ou une déficience sensorielle.

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Autisme associé à une épilepsie ou une déficience sensorielle.

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Chapitre extraite de l'expertise collective INSERM "Handicaps rares : contextes, enjeux et perspectives". 2013, pp. 293-319.

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L'autisme : de l'enfance à l'âge adulte. Ouvrage de 2012 paru chez Lavoisier.

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L'autisme : de l'enfance à l'âge adulte. Ouvrage de 2012 paru chez Lavoisier.

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Longtemps méconnu, ignoré, mal compris, l'autisme fait actuellement l'objet de nouvelles définitions et de nouvelles approches thérapeutiques concernant sa forme chez l'enfant et, surtout, sa forme chez l'adulte, que la pathologie soit de révélation tardive ou qu'elle s'inscrive dans le parcours du patient depuis son enfance. Ainsi, une attention particulière est actuellement portée sur les mécanismes à l'origine de la maladie, sur la sémiologie, la prise en charge médicale, mais aussi sociale, pour accompagner au mieux les personnes avec autisme et leur famille. Fruit d'une longue expérience clinique des auteurs et de leur implication dans la recherche, cet ouvrage présente en cinq parties : l'historique, le modèle neurodéveloppemental et la physiopathologie génétique, la sémiologie chez l'enfant, l'adolescent et l'adulte, les examens cliniques et les explorations fonctionnelles pour diagnostic, nécessitant une collaboration pluridisciplinaire, la thérapeutique et l'accompagnement depuis l'enfance jusqu'à l'âge adulte, les stratégies et les outils d'exploration clinique et neurofonctionnelle pour la recherche. [Résumé d'Auteur/Editeur]

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L'autisme : de l'enfance à l'âge adulteDoc Handicaps Rares

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Faites nous part de ce que vous avez pensé de ce Padlet !

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Epilepsie & autisme - Bibliographie. Fahres, 2024

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Epilepsie & autisme - Bibliographie. Fahres, 2024

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Autisme : ouvrages de base pour les parents, témoignages. Bibliographie, CRA Rhône-Alpes, 2024

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Autisme : ouvrages de base pour les parents, témoignages. Bibliographie, CRA Rhône-Alpes, 2024

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Bibliographie réalisée par le Centre de Ressources Autisme Rhône-Alpes.

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Les troubles du spectre de l'autisme : ressources documentaires. CRA Bretagne

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Les troubles du spectre de l'autisme : ressources documentaires. CRA Bretagne

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Dans le cadre de sa mission d’information, le CRA Bretagne mettra régulièrement à jour la présente page, où vous pourrez trouver une liste actualisée d’ouvrages de références, ainsi que les liens vers les principaux textes en ligne ou sites d’intérêt, ou encadrant les bonnes pratiques associées à l’autisme.

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Dans le cadre de sa mission d’information, le CRA Bretagne mettra régulièrement à jour la présente page, où vous pourrez trouver une liste actualisée d’ouvrages de références, ainsi que les liens vers les principaux textes en ligne ou sites d’intérêt, ou encadrant les bonnes pratiques associées à l’autisme.

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Comment collaborer sur notre Padlet ? Tutoriel rapide

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Comment collaborer sur notre Padlet ? Tutoriel rapide

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Nous avons souhaité que nos Padlets soient évolutifs, collaboratifs et participatifs.

Vous avez la possibilité de soumettre à la documentaliste de Fahres des publications ou supports de tous types (pdf, vidéo, podcast etc.) que vous trouveriez pertinent d’ajouter à ce Padlets pour l'enrichir. Une fois soumise, votre demande d’ajout sera étudiée, validée et intégrée au Padlet si tel est le cas !

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Troubles du spectre de l'autisme : glossaire. CléPsy, équipe du service de psychiatrie de l'hôpital Robert Debré

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Troubles du spectre de l'autisme : glossaire. CléPsy, équipe du service de psychiatrie de l'hôpital Robert Debré

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Cette fiche est à destination des familles et aidants afin qu'ils se familiarisent avec les termes régulièrement utilisés par les professionnels lors des bilans et prises en soin des troubles du spectre de l'autisme. Il est important de rappeler que chaque enfant a un profil unique, et donc, chaque terme ne s’applique pas nécessairement à tous les enfants ayant un diagnostic de trouble du spectre de l’autisme. Ces termes servent à orienter les familles, sans réduire la personne à un diagnostic.

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Cette fiche est à destination des familles et aidants afin qu'ils se familiarisent avec les termes régulièrement utilisés par les professionnels lors des bilans et prises en charge des troubles du spectre de l'autisme.
Il est important de rappeler que chaque enfant a un profil unique, et donc, chaque terme ne s'applique pas nécessairement à tous les enfants ayant un diagnostic de trouble du spectre de l'autisme. Ces termes servent à orienter les familles, sans réduire la personne à un diagnostic.
Trouble du spectre de l'Autisme (TSA), (anciennement appelé Trouble envahissant du développement (TED) ou Autisme) : sont couramment utilisés comme synonymes et correspondent à des variations successives des définitions des Troubles du Spectre de l'autisme dans les classifications internationales (DSM et CIM).

Trouble du spectre de l'Autisme sans trouble du développement intellectuel (anciennement appelé Syndrome d'Asperger ou Trouble du spectre de l'autisme sans déficience intellectuelle) : sont couramment utilisés comme synonymes et correspondent à des variations successives des définitions des Troubles du Spectre de l'autisme sans trouble du développement intellectuel.

Trouble du développement intellectuel (TDI), (anciennement appelé déficience intellectuel ou retard mental) : signifie un fonctionnement intellectuel global inférieur à la moyenne pour ce qui est attendu pour l'âge et apparaissant dès l'enfance :

Constat de déficits des fonctions intellectuelles : Cela inclut des déficits dans le raisonnement, la résolution de problèmes, la planification, la pensée abstraite, le jugement, l'apprentissage académique et l'apprentissage par l'expérience.

Constat de déficits des fonctions adaptatives : dans les habiletés conceptuelles, sociales et pratiques apprises qui permettent de fonctionner dans la vie quotidienne dans divers environnements tels que le domicile, l'école ou le travail.

Troubles associés, comorbidités : présence simultanée de plusieurs troubles ou maladies chez une même personne.

Fonctionnement intellectuel

Défaut de généralisation : difficulté à réutiliser ses connaissances/capacités dans un autre contexte social

Fonctions cognitives/fonctionnement intellectuel : fonctionnement du cerveau : percevoir, se concentrer, acquérir des connaissances, raisonner, s'adapter et interagir avec les autres.

Fonctions exécutives : elles font partie des fonctions cognitives et permettent la mise en place de stratégies pour arriver à un but (mémoire, attention, initiation, planification, organisation, flexibilité et inhibition).

Lenteur exécutive : c'est la difficulté à accomplir rapidement des tâches impliquant la planification, l'organisation et la prise de décision. Elle se manifeste par un retard dans l'initiation ou la réalisation des activités, souvent lié à des difficultés à gérer plusieurs informations ou à s'adapter aux changements.

Théorie de l'esprit : Capacité à comprendre et attribuer des pensées, croyances, intentions, sentiments et désirs aux autres et à soi-même.

Langage, communication et interaction sociale

Attention conjointe : attirer l'attention de l'autre vers une cible avec le regard ou le pointage. L'attention conjointe peut être initiée (l'enfant pointe en direction d'une cible) ou suivie (l'enfant regarde ce qui est pointé par l'autre). Exemple : l'enfant voit un chien dans la rue et souhaite vous le montrer : il vous interpelle peut être verbalement "maman, papa" et vous le montre du doigt (pointe).

Contact visuel : contact qui s'établit par le regard.

Discours plaqués : Utilisation répétée de mots ou de phrases déjà entendus, puis réutilisés de manière appropriée ou non, avec le même ton de voix.

Écholalie : répétition involontaire des paroles d'un individu. Elles peuvent être immédiates ( exemple : l'enfant répète après vous "bonjour, comment vas-tu ?" instantanément) ou différées ( exemple : l'enfant répète mot pour mot une phrase entendue dans un dessin animé la veille).

Interaction sociale : échange entre deux ou plusieurs individus. Des informations doivent être partagées par chaque individu, oralement ou par le regard, les gestes, etc.

Jargon : langage créé par un individu, incompréhensible par les autres.

Langage idiosyncratique : utilisation inhabituelle de mots ou phrases ayant un sens pour l'enfant mais pas pour son interlocuteur.

Langage plaqué : utilisation répétée de phrases ou d'expressions apprises, souvent sans lien direct avec le contexte ou l'interaction en cours. Ces phrases sont souvent reprises de manière rigide, avec le même ton ou intonation, sans modification, et peuvent sembler mécaniques ou inadaptées à la situation.

Logorrhée : flot ininterrompu et rapide de parole.

Prosodie : ton, débit et rythme de la parole.

Main-outil ou main-objet : répondre à ses besoins en utilisant la main de l'autre ( exemple : utiliser la main d'un parent pour attraper quelque chose).

Mutisme : attitude, état d'une personne qui se tait, refuse ou n'est pas en mesure de parler.

Néologisme : mot inventé.

Palilalie : répétition automatique de nos propres paroles.

Pointage : montrer du doigt :

Proto-impératif : demander un objet en le montrant du doigt.

Proto-déclaratif : montrer une situation ou un objet en pointant du doigt dans le but d'attirer l'attention, de partager son intérêt.

Pragmatique : capacité à adapter son langage et à comprendre celui des autres selon le contexte dans lequel on se trouve : exemple "bravo, je te félicite" n'aura pas la même signification selon le ton employé par la personne (premier degré ou ironie) et selon l'action commentée (comportement positif ou négatif).

Rituels verbaux : répétition d'une production vocale ou d'une séquence de mots devant toujours être énoncée dans le même ordre. La personne peut imposer l'ordre aux autres.

Stéréotypie vocale : production inappropriée et répétée de sons ou de mots qui n'a pas pour objectif de communiquer avec l'autre. l'enfant répète la même syllabe lorsqu'il joue "nonononono".

Manifestations comportementales et réactions émotionnelles

Amimie : absence de variation des expressions du visage/mimiques selon l'état émotionnel de l'enfant.

Auto-agressivité : être agressif envers soi-même (se mordre le bras ou la main, se taper la tête contre le mur...).

Désinhibition : difficulté à freiner un comportement.

Dysrégulation émotionnelle : émotions ressenties ou exprimées trop fortement ou trop faiblement par rapport à la situation. Passage rapide d'une émotion à l'autre (ex : passer du rire aux larmes).

Hétéro-agressivité : être agressif envers les autres.

Intérêt restreint : intérêt qui occupe un temps très important dans la vie de l'enfant, au détriment de certaines activités parfois (exemple: passion envahissante pour les plans du métro, que l'enfant peut étudier et dessiner pendant de longues heures) mais dont le thème n'est pas forcément inhabituel pour l'âge (exemple: voiture, chevaux, ...).

Intolérance à la frustration : réaction excessive face à l'impossibilité d'obtenir ce que l'on souhaite.

Inhibition : freiner ou empêcher l'apparition d'un comportement.

Impulsivité : action rapide et non contrôlée de l'individu.

Préoccupations inhabituelles: intérêts particuliers/inhabituels pour l'âge et qui peuvent difficilement être partagés avec les autres enfants ( exemple : panneaux de signalisation, mécanisme des chasses d'eaux, etc.).

Rigidité comportementale : Résistance à tout changement, nécessité de suivre des routines précises, entraînant une détresse en cas de modifications des horaires, des habitudes ou des routines.

Rituels, routines : séquence d'actions qui doit s'effectuer régulièrement et dans un ordre précis ( par exemple, routine du coucher, rituel du matin, du repas).

Troubles instinctuels et physiologiques : alimentation, sommeil, propreté et sexualité

Comportement masturbatoire: auto-stimulation sexuelle, qui peut survenir de manière inappropriée en public ou de façon répétitive.

Cauchemar : rêve effrayant ou angoissant qui survient généralement pendant le sommeil paradoxal.

Encoprésie : émission de selles dans les sous-vêtements ou dans des endroits inappropriés, volontaires ou non.

Énurésie : Émission involontaire d'urine. Elle peut être primaire (l'enfant n'a jamais acquis la propreté) ou secondaire (l'enfant a acquis la propreté au préalable).

Hypersomnie : excès du temps total de sommeil sur 24 heures, souvent accompagné de somnolence excessive la journée.

Insomnie : difficultés à s'endormir, à rester endormi toute la nuit, ou réveils très précoces.

PICA : fait de mettre en bouche et d'ingérer des matériaux non alimentaires.

Sélectivité alimentaire : refus de manger certains aliments, selon leur goût, leur odeur, leur forme, leur couleur ou leur texture.

Terreur nocturne : trouble du sommeil caractérisé par des épisodes soudains au cours du sommeil lent profond de cris, d'agitation, et d'une peur intense, avec un réveil incomplet et souvent sans que la personne en soit consciente. Contrairement aux cauchemars, la personne ne se souvient généralement pas de l'épisode au réveil.

Troubles du sommeil : concernent les difficultés d'endormissement, les réveils matinaux précoces et les réveils nocturnes.

Jeu de cause à effet : jeux pop-up, jeux qui s'actionnent en appuyant sur des boutons.

Jeu de faire-semblant: imitation d'action observées dans l'entourage pour jouer ( exemple : jeux de dinette avec un faire-semblant de cuisiner), jeu avec les poupées avec un faire semblant de s'occuper de son bébé malade).

Jeu fonctionnel : utilisation des objets pour leur fonction première (empiler des cubes, porter le téléphone à l'oreille).

Utilisation symbolique des objets : capacité de détourner les objets de leur fonction première ( exemple : un bloc pour une voiture).

Mouvements et comportements moteurs

Crispations : contraction volontaire d'un membre, parfois lors d'émotions fortes

Échopraxie : répétition involontaire d'un geste observé chez l'autre.

Flapping : mouvements répétitifs des mains ou bras.

Hyperactivité motrice : besoin excessif de bouger constamment. Cela se manifeste par une agitation physique, une incapacité à rester immobile et des mouvements fréquents et intenses.

Instabilité motrice / agitation motrice / excitabilité : besoin important de bouger.

Maniérismes des mains / doigts : mouvements inhabituels et répétitifs des mains ou des doigts sans raison apparente.

Stéréotypie motrice : ensemble de gestes et mouvements répétitifs, rythmés sans but apparent (balancement, flapping...).

Auto-stimulation : recherche de sensation à travers différents sens.

Aversion sensorielle : fait de ne pas supporter certaines stimulations sensorielles.

Bruxisme : grincement des dents, volontaire ou involontaire, notamment au cours du sommeil.

Hypersensibilité : sensibilité exagérée à certaines sensations.

Hyposensibilité : sensibilité réduite à certaines sensations (lumière, froid, douleur...).

Recherche sensorielle : recherche de sensation plaisante pour l'enfant. Elles peuvent concerner tous les sens :

Nociceptif : stimulation par la douleur (morsure des mains).

Guttural : stimulation par la gorge (bruits de gorge).

Olfactive : stimulation par l'odorat (flairage : sentir les objets ou les personnes).

Orale : stimulations par la bouche (bruits de bouche, bruxisme, mises en bouche, léchage, ...).

Tactile : stimulation par le toucher (frottement, caresser les murs).

Vestibulaire : stimulations entraînant un mouvement, une accélération ou un changement de direction pour maintenir l'équilibre (tourner sur soi-même, balancements).

Visuel : stimulation par la vue.

Visées : regarder de très près un objet ou un mouvement.

Regards périphériques : regarder de côté.

Plafonnement du regard : regarder en haut (lumières).

Retrouvez nos vidéos en suivant ce lien.

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Elise MARTIN, Albane VIGNON, Laure GIORDAN, Keissa SEFIANE, Amélie PIERRET, Valérie VANTALON

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Troubles du Spectre de l'Autisme : Glossaire

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Voici une fiche comprenant tous les termes régulièrement utilisés par les professionnels dans le cadre des Troubles du Spectre de l'Autisme.

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Pour aller plus loin dans vos investigations et recherches d'informations, rendez-vous sur le portail documentaire de Fahres : porte d'entrée unique vers les ressources sélectionnées et validées par le CNRHR Fahres. Cet espace documentaire en ligne est libre d'accès pour tous.

Le centre de documentation du CNRHR Fahres a pour vocation de constituer et mettre à disposition un pôle d’information spécialisé sur les épilepsies, épilepsies sévères et les handicaps associés.

Le centre de documentation informe et conseille toute personne étant concernée/intéressée par l’épilepsie et les déficiences graves pouvant y être associées. Il met également à disposition des acteurs du soin et de l’accompagnement des ressources expertes.

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L'autisme : un spectre, pas une échelle ! 

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L'autisme : un spectre, pas une échelle ! 

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Lorsque l’on parle d’autisme, un réflexe fréquent est de vouloir le classer : « autisme de haut niveau », « autisme de bas niveau », « léger », « sévère », etc. Pourtant, on sait qu’il y a autant d’autismes que d’autistes, et qu’il n’y a pas de hiérarchie ! Dans cet article, on vous propose deux infographies en téléchargement gratuit pour sensibiliser le plus grand nombre aux Troubles du Spectre de l’Autisme.

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L’autisme : un spectre, pas une échelle !

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On vous propose deux infographies en téléchargement gratuit pour sensibiliser le plus grand nombre aux Troubles du Spectre de l’Autisme.

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KIT'AUTISME 2025. CRA Midi Pyrénées, CRA Languedoc-Roussilon, 2025.

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KIT'AUTISME 2025. CRA Midi Pyrénées, CRA Languedoc-Roussilon, 2025.

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À l’occasion de la Journée mondiale de sensibilisation à l’autisme du 2 avril, les Centres de Ressources Autisme du Languedoc-Roussillon et de Midi-Pyrénées ont collaboré à la création d’un tout nouvel outil pratique : le Kit’Autisme 2025.

Ce kit rassemble des ressources soigneusement sélectionnées par les documentalistes des centres de ressources afin de mieux comprendre l’autisme.

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A l’occasion de la Journée mondiale de l’autisme, le CRA Languedoc-Roussillon et le CRA Midi-Pyrénées proposent un Kit’Autisme pour faciliter la diffusion des informations auprès du plus grand nombre.

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Fiches pratiques pour l'accompagnement des personnes présentant un TSA

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Fiches pratiques pour l'accompagnement des personnes présentant un TSA

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Ces fiches pratiques, développées par EDI Formation, sont destinées aux professionnels accompagnants de terrain et à tous les partenaires (médicaux, paramédicaux) mais aussi aux familles et aidants d’enfants ou d’adultes présentant un Trouble du Spectre de l’Autisme.

Cet outil a été créé dans le but de mettre en œuvre ou consolider une méthodologie d’accompagnement basée sur les évaluations fonctionnelles (informelles) suivies d’apprentissages. Il reprend les domaines prioritaires à développer chez les personnes présentant un TSA, ainsi que tous les thèmes abordés lors de nos formations théoriques et supervisions.

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Fiches pratiques pour l’accompagnement de personnes présentant un TSA - EDI FORMATION

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Fiches pratiques pour l’accompagnement de personnes présentant un TSA EDI FORMATION Organisme de formation : Autisme et Stratégies Educatives TSA. Formations intra/inter établissements

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Epilepsies et troubles du neuro-développement : comprendre et agir. Délégation interministérielle à la stratégie nationale pour les troubles du neurodéveloppement, février 2026.

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Epilepsies et troubles du neuro-développement : comprendre et agir. Délégation interministérielle à la stratégie nationale pour les troubles du neurodéveloppement, février 2026.

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À l’occasion de la Journée internationale de l’épilepsie, la Délégation interministérielle à la stratégie nationale pour les troubles du neurodéveloppement (autisme, troubles DYS, TDAH, TDI) met en ligne un guide pour mieux comprendre et appréhender les épilepsies liées aux TND.

Près d’une personne sur six est concernée par un trouble du neurodéveloppement. Pour les personnes concernées, le risque de présenter une comorbidité est élevé. Les TND sont ainsi fréquemment associés à d’autres troubles, au premier rang desquels les troubles psychiatriques ou encore l’épilepsie.

Parfois diagnostiquées dès la petite enfance, parfois survenant plus tard, les épilepsies sont une maladie neurologique fréquente qui demeure particulièrement stigmatisée, du fait du caractère brutal, imprévisible et parfois spectaculaire des crises et de leurs répercussions sur la vie quotidienne. Lorsque épilepsie et TND coexistent, les risques de retards de diagnostic, de ruptures de parcours, de difficultés scolaires et de vulnérabilités sociales sont accrus.

Face à ce constat, ce livret, réalisé avec l’appui de nombreux experts, a pour ambition de fournir des clés de compréhension aux professionnels, aux personnes concernées, à leurs proches et au grand public.

Document pratique et accessible, il présente les différentes formes d’épilepsies, les différents signes d’alerte, les liens possibles avec les TND et la conduite à tenir en cas de crise.

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L'épilepsie et les troubles du neuro-développement : quel est le lien ? IMIND, non daté

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L'épilepsie et les troubles du neuro-développement : quel est le lien ? IMIND, non daté

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L’épilepsie peut avoir un impact considérable sur la vie quotidienne d’une personne en termes d’indépendance, de sécurité, de bien-être mental et d’inclusion sociale. C’est une population hétérogène et assez mal connue; par exemple, on manque de chiffres sur ceux qui sont en situation de handicap à cause de leur épilepsie et/ou de troubles ou déficiences associés. Cet article vise donc à donner un large aperçu des particularités de la vie avec l’épilepsie et à expliquer pourquoi nous en parlons dans le domaine des troubles du neuro-développement.

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L'épilepsie peut avoir un impact considérable sur la vie quotidienne d'une personne en termes d'indépendance, de sécurité, de bien-être mental et d'inclusion sociale. C'est une population hétérogène et assez mal connue; par exemple, on manque de chiffres sur ceux qui sont en situation de handicap à cause de leur épilepsie et/ou de troubles ou déficiences associés. Cet article vise donc à donner un large aperçu des particularités de la vie avec l'épilepsie et à expliquer pourquoi nous en parlons dans le domaine des troubles du neuro-développement.
Qu'est-ce que l'épilepsie ?

L'épilepsie est une condition neurologique reliée à un déséquilibre dans les réseaux du cerveau. Elle se caractérise par la présence de crises épileptiques récurrentes et par des conséquences psychologiques, sociales et cognitives. Une crise d'épilepsie est une manifestation clinique transitoire, liée à une activité électrique, neuronale anormale des cellules du cortex cérébral. Durant la crise, les neurones s'activent, pouvant générer jusqu'à 6 fois plus d'impulsions par seconde qu'en temps normal.

La prévalence de l'épilepsie, comme celle des TSA, est d'environ 1% de la population générale en France. Il s'agit d'une condition qui peut être efficacement prise en charge avec un traitement médicamenteux : 70% des enfants et adultes épileptiques sont libres de crise avec un traitement adapté. Cependant 30% des cas sont pharmaco-résistants. Ces personnes ont au moins une crise par an, alors qu'elles ont un traitement adapté.

L'épilepsie sévère est définie comme un handicap depuis 2011. On l'appelle " sévère " en raison de son impact sur la capacité à mobiliser ses compétences et du danger qu'elle représente (blessure, état de mal, SUDEP - " Mort subite inattendue en épilepsie ") contre lequel la personne ne peut ni s'autoprotéger ni prévenir un aidant...! Même non sévère, elle peut être source de handicap en raison de l'imprévisibilité des crises, des effets secondaires des traitements, d'un manque d'autonomie, d'un manque de confiance ou de séquelles neuro-développementales.

Différents types d'épilepsie

Les origines et les pronostics de l'épilepsie sont très divers comme mentionné ci-dessus (ex. génétique, maladie rare), ainsi que les types de crises. Des crises peuvent prendre différentes formes et avoir différentes intensités. En raison de ces nombreuses manifestations, on dit parfois qu'il y a des épilepsies.

Les crises tonico cloniques sont les plus connues du public parce que ce sont les plus 'spectaculaires' avec perte de conscience, raideur brutale entraînant une chute, secousses convulsives, parfois apnée, cri, bave, perte d'urine ou morsure de langue. La personne perd immédiatement conscience et ne se rappelle de rien.

Les absences entraînent une suspension de conscience pouvant durer quelques secondes voire plus et se répètent souvent plusieurs fois dans la journée.

Les crises myocloniques qui sont des secousses musculaires brèves peuvent survenir en pleine conscience.

Les crises atoniques sont caractérisées par une brusque perte musculaire qui provoque une chute soudaine.

Épilepsie et troubles du neuro-développement

Alors pourquoi parler de l'épilepsie en relation avec les troubles du neuro-développement ?

Car les épilepsies de la petite enfance sont souvent sources de troubles du neuro-développement (TND), soit que la maladie génétique ou la lésion du cerveau à l'origine des crises soit aussi cause de TND, soit que la répétition des crises perturbe le neurodéveloppement. On sait aussi que les enfants atteints de TND ont davantage de risque d'être épileptiques que la population générale.

Des enfants atteints de TND peuvent développer une épilepsie soit dès l'enfance soit plus tardivement. Par exemple, 8% des enfants porteurs de Trisomie 21 ont une épilepsie, 28% des plus de 45 ans ; 18% des enfants TSA sont épileptiques, 28% des adultes. Ainsi, l'épilepsie est souvent une condition qui se chevauche avec d'autres troubles neurodéveloppementaux (ex. TDAH, DYS etc) et psychiatriques (ex. anxiété et dépression) et troubles de comportement.

Il est donc important de tenir compte des conditions coexistantes afin de mieux comprendre les besoins uniques de chaque personne.

Repérage des TNDs chez une personne épileptique

Aujourd'hui nous avons une meilleure connaissance des TND chez les personnes épileptiques grâce à :

La systématisation des bilans neuropsychologiques dans les centres de référence épilepsies rares

De gros progrès dans le traitement des encéphalopathies épileptiques (épilepsies graves de la petite enfance)

La volonté des familles soutenue par les neuropédiatres de favoriser le développement de l'enfant

✔ Oui, il faut faire une recherche de TND dès que l'on a un doute, lorsqu'il y a une épilepsie précoce, même si elle a pu être stabilisée.

✔ Oui il faut faire une recherche d'épilepsie chez un enfant ou adulte atteint de TND, dès qu'on a un doute. Soigner l'épilepsie a un impact positif sur le développement de l'enfant et sur les troubles de l'enfant ou l'adulte.

✔ Oui, il n'est jamais trop tard : même chez un adulte épileptique depuis l'enfance, il est utile de comprendre et prendre en charge ses TND (et vice-versa).

Obtenir un diagnostic peut aider à identifier et mieux comprendre les besoins d'une personne. Cette vidéo donne un aperçu du déroulement du diagnostic de l'épilepsie. Le processus peut être complexe en raison du chevauchement des troubles. Par exemple, une épilepsie peut passer inaperçue car certaines crises d'épilepsies peuvent être confondues avec d'autres troubles moteurs. Aussi parce que rechercher une épilepsie chez un enfant ou un adulte atteint de TSA ou déficience intellectuelle sévère peut être complexe. L'EEG ou l'IRM demandent que la personne accepte l'examen et reste tranquille le temps nécessaire. Il existe pourtant des moyens pour l'aider à comprendre et accepter l'examen. Par exemple les fiches santeBD.org sont d'excellents outils pédagogiques pour expliquer le processus de manière visuelle. C'est important aussi de prévenir l'équipe qui doit réaliser l'examen afin d'en faciliter le déroulement en tenant compte des besoins de la personne.

Prises en charge adaptées

À quoi ressemble l'inclusion pour les personnes épileptiques ?

Tout d'abord c'est considérer la personne dans sa globalité et tous les troubles qui lui sont associés. L'inclusion c'est:

se sentir en sécurité vis à vis de l'imprévisibilité de ses crises d'épilepsie (aménagements matériels, présence humaine)

mobiliser ses compétences

être soutenu dans un environnement adapté à ses troubles du neurodéveloppement.

Depuis la petite enfance (crèche, école maternelle) jusqu'à l'âge adulte, il faut penser l'inclusion des personnes épileptiques dans un milieu aussi ordinaire que possible et aussi dans les établissements et services médico-sociaux. Pour cela une bonne connaissance de l'ensemble des difficultés de la personne, et aussi de ses compétences est indispensable pour l'aider à bâtir un projet de vie épanouissant.

Les recherches nous permettent de mieux connaître la population, les troubles associés et les impacts sur la santé mentale, la famille et la vie sociale et est donc une facette essentielle dans la quête pour l'inclusion.

RESSOURCES

Les Centres de référence des épilepsies rares - CARTE DES CENTRES

Dans la région nous avons : HFME et Hôpital neurologique Pierre Wertheimer qui est aussi un des 8 sites constitutifs du centre de référence épilepsies rares.

Il y a aussi des centres de compétence épilepsies rares dans les CHU de Grenoble, St Etienne et Clermont-Ferrand.

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L'épilepsie et les troubles du neuro-développement : quel est le lien ? - IMIND

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Cet article vise à donner un large aperçu des particularités de la vie avec l'épilepsie et à expliquer pourquoi nous en parlons dans le domaine des troubles du neuro-développement.