**6. Epilepsy syndromes with ASD as frequent neurodevelopmental sequelae**

Several specific epilepsy syndromes with early onset epilepsy show an autistic behavior, some also appear to be the risk factor for later diagnosis of ASD. If they are identified appropriately and treated, behavioral improvement which is radical in some of the cases can be seen. In these cases, epilepsy originates in the brain networks responsible for communication and interactions. These include infantile spasms and Lennox–Gastaut syndrome. More recently, clinical overlap has been observed in cases with continuous slow waves during sleep (CSWS) and Landau– Kleffner syndrome and ASD [82].

#### **6.1 West syndrome (WS)**

WS is an epileptic encephalopathy characterized by infantile spasm/epileptic spasms, an EEG pattern of hypsarrhythmia and cognitive stagnation or regression. They usually occur before 2 years of age. Genetic causes are present in many of them and abnormalities in several brain developmental pathways are noted.

ASD may develop in a few of them. However, an association between TSC and duplications of FOXG1 have been reported consistently.

### **6.2 Lennox–Gastaut syndrome (LGS)**

LGS is a childhood-onset epilepsy, which is characterized by constellation of several distinct types of seizures and electroclinical features of diffuse slow spike waves and generalized paroxysmal fast activity in sleep. Prevalence of ASD in LGS is rare, although ASD has been reported in patient with LGS resulting from duplications of maternal 15q11q13 [83].

### **6.3 Landau–Kleffner syndrome (LKS)/continuous spikes and slow waves during slow sleep (CSWS)**

LKS is an epilepsy-aphasia syndrome that is characterized by regression in language and characteristic CSWS on EEG-termed as electrical status epilepticus of slow sleep (ESES). Several children who had been diagnosed with ASD were noted to have a predominant language deficit. Stereotypies and withdrawal are also common in LKS, but whether these children also have deficits in social reciprocity is not clear. The association may be more related to severe receptive language deficit. Copy number variants have been detected in patients with LKS who also have associated ASD [84], and, most recently, GRIN2A mutation have been identified in patients with epilepsy-aphasia phenotypes [85].

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*Epilepsy: A Common Co-Morbidity in ASD DOI: http://dx.doi.org/10.5772/intechopen.96484*

Developmental regression is present in approximately one-third of children with ASD [86] and is believed to have an association with epilepsy. The relationship between regression and epilepsy in ASD has therefore long been of interest because of the hope that some developmental regression in idiopathic ASD could be caused

The overlap of language and autistic regression to epilepsy, EEG epileptiform

LKS or acquired epileptic aphasia may present as a developmental language regression followed by autistic-like social-communicative phenotype. LKS usually presents between 3 and 7 years of age with loss of language skill in children who were previously normal and most but not all affected children have convulsive seizures. In case on early LKS, it becomes difficult to differentiate it from ASD clinically and the diagnosis is done mainly on EEG finding and response to antiseizure treatment. The EEG in the awakened state often has a normal background with seizures of various types in LKS. During sleep, it is characterized by epileptic discharges throughout the sleep-electrical status epilepticus (ESES) on EEG that may affect cognitive processing. In children with autistic regression, both language and behavior in association with significant social deficits occur between 18 and 24 months compared to usually only language regression in LKS, which is more dramatic and the social deficits are less severe than those with autism [88]. McVicar et al. in their study reported that children with isolated language regression have a higher frequency of epileptiform discharges and seizures than children with both

An extensive review, in 2002 on epileptiform neurocognitive disorders linked with speech/language deterioration concluded that "acquired epileptiform aphasia (AEA) can be conceptualized on a spectrum with other epileptiform neurocognitive disorders that may share pathophysiological features". They also added that "without better documentation of potential factors around the time of the regression, it will be difficult to identify the fundamental factors that differentiate these condi-

CSWS, an epileptic syndrome of that is associated with EEG pattern of ESES may present with regression in global skills that overlaps with autism [91]. However, the differences in age of regression, type of regression, frequency of epilepsy and

Nonconvulsive status epilepticus (NCSE) may also have features that have a strong similarity to autism. The child may exhibit poor reciprocal social interaction, poor verbal and nonverbal communication. But with effective treatment, the

Magnetoencephalography has identified precise location of the source of these epileptic EEG discharges. The finding from this investigation shows that focal spike waves (FSW) in the perisylvian region and located in the superior temporal gyrus may cause auditory and verbal agnosia (LKS). When FSW predominate in the prefrontal regions, a cognitive regression with features of CSWS, when in cortical areas like the superior temporal sulcus or the fusiform gyrus involving the networks relating emotions to higher-level visual representations could interfere with the developing capacity to recognize the emotional signals of faces, that are typically

Other epileptic disorders, like refractory partial epilepsies of frontal or temporal origin like the Benign epilepsy with centrotemporal spikes (BECTS)also interfere

by epilepsy and be reversible through using anti-seizure therapies [87].

language and autistic (i.e., social and behavioral) regression [89].

tions, their response to treatment and long-term prognosis" [90].

EEG abnormalities suggest that these are distinct phenotypes.

features of autism disappear.

deficient in autism.

activity, sleep, and to epileptic encephalopathies such as LKS continue to be controversial areas of research and of clinical interest because of the close clinical

**7. Regression in Autism**

resemblance to autism.
