Few individuals with Lennox-Gastaut syndrome have autism spectrum disorder: a comparison with Dravet syndrome

Abstract

BackgroundAutism spectrum disorder (ASD) in epilepsy has been a topic of increasing interest, which in general occurs in 15–35% of the patients with epilepsy, more frequently in those with intellectual disability (ID). Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are two typical forms of intractable epileptic encephalopathy associated with ID. We previously reported that ASD was diagnosed in 24.3% of patients with DS, higher in those with profound ID. Given the severe epilepsy and high frequency of ID in LGS, it is necessary to know whether ASD is a common psychomotor co-morbidity of LGS. This study evaluated the autistic behaviors and intelligence in patients with LGS and further compared that between LGS and DS, aiming to understand the complex pathogenesis of epilepsy-ASD-ID triad.MethodsA total of 50 patients with LGS and 45 patients with DS were enrolled and followed up for at least 3 years. The clinical characteristics were analyzed, and evaluations of ASD and ID were performed.ResultsNo patients with LGS fully met the diagnostic criteria for ASD, but three of them exhibited more or less autistic behaviors. Majority (86%) of LGS patients presented ID, among which moderate to severe ID was the most common. Early onset age and symptomatic etiology were risk predictors for ID. The prevalence of ASD in LGS was significantly lower than that in DS (0/50 vs. 10/45, p < 0.001), while the prevalence and severity of ID showed no significant difference between the two forms of epileptic encephalopathy.ConclusionsThis study demonstrated a significant difference in the co-morbidity of ASD between LGS and DS, although they had a similar prevalence and severity of ID, refuting the proposal that the prevalence of ASD in epilepsy is accounted for by ID. These findings suggest that the co-morbidity of ASD, ID, and epilepsy may result from multifaceted pathogenic mechanisms.

Lennox-Gastaut Syndrome: In a Nutshell

“…The prevalence of Lennox-Gastaut syndrome is 1%-2% of the epileptic patients and 1%-10% (mean 4%) of the childhood epilepsies [ 3 ]. The age of onset ranged from the tenth day of life to nine years of age, with the mean age of onset of 35.3 months [ 5 ]. The peak age of the onset in patients with the cryptogenic Lennox-Gastaut syndrome is lower than in those with a disease due to some identifiable etiology [ 1 ].…”

“…Almost all the patients are on two to six antiepileptic drugs (mean 3.4). Of the patients, 28% have been found to be seizure-free after using these drugs for at least 1.5 years [ 5 ].…”

“…The mutation of other genes involved in human brain development (e.g., the forkhead box G1 (FOXG1), chromodomain-helicase-DNA-binding protein 2 (CHD2) genes) and the gene for presynaptic protein dynamin 1 (DNM 1) have also been found to be associated with this syndrome. The genetic heterogeneity of this syndrome identifies it to be one of the manifestations of other genetic disorders, rather being an independent entity [ 3 , 5 ].…”

“…The epileptiform abnormalities contribute to gradual-onset intellectual disabilities along with psychiatric comorbidities like anxiety, depression, and behavioral abnormalities. All the three criteria must not be present at the time of the onset of seizure and diagnosis is established after following up with the patient for several years [ 5 ].…”

“…The specific electroencephalographic pattern varies from either bursts of slow spike-wave complexes or generalized paroxysmal fast activity. Slow spike-wave complexes (<2.5 Hz) are not considered to be pathognomonic for Lenox-Gastaut syndrome, but some experts have found generalized paroxysmal fast activity on electroencephalogram to be an essential criterion for diagnosing Lennox-Gastaut syndrome [ 5 ].…”