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Purpose: We have developed the Early Childhood Epilepsy Severity Scale (E-Chess) to quantify the severity of epilepsy in infants and young children with tuberous sclerosis as an aid to the evaluation of treatment efficacy and the investigation of the influence of epilepsy severity on development., Methods: Twenty infants aged 11-36 months with a diagnosis of tuberous sclerosis participated in the study. From the literature, six potential measures of epilepsy severity were identified: time period over which seizures occurred; seizure frequency; number of seizure types; occurrence and duration of status epilepticus; number of anticonvulsant medications used; response to treatment. The variables were given a score, usually from 0 to 3, a higher score indicating greater severity. For each child, these variables were scored over consecutive 1 year time periods by three independent raters. We employed restricted and nonrestricted factor analytic models to identify the latent structure of the six items., Results: The six severity items had a unidimensional structure. All severity indicators loaded highly on the latent epilepsy severity factor (>0.77), with the exception of the status indicator which had a poor loading (<0.40) and was excluded from further analyses. Goodness of fit indices were all well within the acceptable criteria for model fit. The E-Chess score at 12 months was significantly predictive of scores at 24 and 36 months., Conclusions: A single continuous latent variable accounts for the variation in five of the six epilepsy severity indicators under study. These form the Early Childhood Epilepsy Severity Scale. The predictive validity of the E-Chess was satisfactory. The E-Chess provides an epilepsy severity score that can be easily used to assess epilepsy severity in tuberous sclerosis and would merit evaluation in other early onset childhood epilepsies.

Aim: To investigate the interdependence between risk factors associated with long-term intellectual development in individuals with tuberous sclerosis complex (TSC).Method: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with TSC. In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with TSC and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to IQ at phase 2.Results: Intellectual disability was present in 57% of individuals with TSC. Individuals without intellectual disability had significantly lower mean IQ compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with TSC who had a slower gain in IQ from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to IQ in middle childhood and adolescence.Interpretation: Early-onset and severe epilepsy in the first 2 years of life are associated with increased risk of long-term intellectual disability in individuals with TSC, emphasizing the importance of early and effective treatment or prevention of epilepsy.What This Paper Adds: Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC). Those with TSC without intellectual disability had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC. [ABSTRACT FROM AUTHOR]

Summary: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in TSC1 or TSC2. Epilepsy occurs in 80%‐90% of affected individuals during their lifetime, and up to one‐third of children with TSC will develop epileptic (infantile) spasms, for which vigabatrin has been shown to be particularly effective. Epilepsy severity and epileptic spasms are consistent markers of risk for the development of intellectual impairment in TSC. Although previous studies demonstrate a bimodal distribution of intellectual ability in TSC, recent findings suggest a unimodal distribution, which may reflect a change in IQ distribution over time. We compared 3 large historical UK cohorts of TSC (n = 331) that show varied distributions of intellectual ability, first ruling out differences in study methodology. Later‐born individuals had a higher frequency of reported spasms and higher likelihood of vigabatrin administration, but were less likely to have profound intellectual impairment, compared to the earlier‐born individuals. Our findings suggest that epileptic spasms went undetected in the older patients and therefore were not treated, leading to a higher occurrence of profound impairment, whereas the later born cohort had better access to treatment. These findings support the importance of early identification and treatment of seizures in TSC. [ABSTRACT FROM AUTHOR]

The article focuses on the tuberous sclerosis phenotype expansion, an autosomal dominant disorder that causes mental retardation and epilepsy. It references the case of a family with an unusually mild phenotype due to TSC1 splice site (SS) mutation wherein the proband had generalised tonic-clonic seizures when he was 11, his brother had nocturnal seizues, and his father has mild facial erythema with no definite angiofibromas. It adds the classification of the proband and father as possible TS.