Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers

Vignoli, Aglaia; Briola, Francesca La; Peron, Angela; Turner, Katherine; Vannicola, Chiara; Saccani, Monica; Magnaghi, Elisabetta; Scornavacca, Giulia Federica; Canevini, Maria Paola

doi:10.1186/s13023-015-0371-1

Cited by 78 publications

(60 citation statements)

References 29 publications

(40 reference statements)

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“…In other words, although the seizure type most likely to occur at seizure onset in our population was infantile spasms, we found that age at seizure onset exhibited greater impact on predicting developmental outcome. Our finding that timing of seizure onset is more significant than the presence or absence of infantile spasms differs from conclusions drawn by others [2, 10, 11, 15, 28]. For example, Jozwiak et al found that the presence of infantile spasms was associated with 3–4 times higher risk of moderate to profound delays independent of age of seizure onset [11].…”

Section: Discussioncontrasting

confidence: 95%

“…Type and severity of seizures, especially infantile spasms, along with early age of seizure onset also appear to be associated with increased likelihood of cognitive and behavioral difficulties particularly if seizures are not controlled [8–12]. Similar associations have been reported for higher risk for ASD in TSC [9, 13–15], and it has been suggested that epilepsy may be an independent predictor of intellectual ability in TSC [7, 10, 16]. At this time, it is unclear as to whether neurodevelopmental disorders are caused by the underlying brain abnormalities seen in TSC, subsequent development of epilepsy, or both [17].…”

Section: Introductionmentioning

confidence: 83%

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Influence of seizures on early development in tuberous sclerosis complex

Capal

Bernardino-Cuesta

Horn

et al. 2017

Epilepsy & Behavior

144

141

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Objective Epilepsy is commonly seen in Tuberous Sclerosis Complex (TSC). The relationship between seizures and developmental outcomes has been reported, but few studies have examined this relationship in a prospective, longitudinal manner. The objective of the study was to evaluate the relationship between seizures and early development in TSC. Methods Analysis of 130 patients ages 0–36 months with TSC participating in the TSC Autism Center of Excellence Network, a large multicenter, prospective observational study evaluating biomarkers predictive of autism spectrum disorder (ASD), was performed. Infants were evaluated longitudinally with standardized evaluations, including cognitive, adaptive, and autism-specific measures. Seizure history was collected continuously throughout, including seizure type and frequency. Results Data were analyzed at 6, 12, 18, and 24 months of age. Patients without a history of seizures performed better on all developmental assessments at all time points compared to patients with a history of seizures and exhibited normal development at 24 months. Patients with a history of seizures not only performed worse, but developmental progress lagged the non-seizing group. All patients with a history of infantile spasms performed worse on all developmental assessments at 12, 18, and 24 months. Higher seizure frequency correlated with poorer outcomes on developmental testing at all time points, but particularly at 12 months and beyond. Patients with higher seizure frequency during infancy continued to perform worse developmentally through 24 months. A logistic model looking at the individual impact of infantile spasms, seizure frequency, and age of seizure onset as predictors of developmental delay revealed that age of seizure onset was the most important factor in determining developmental outcome. Conclusions Results of this study further define the relationship between seizures and developmental outcomes in young children with TSC. Early seizure onset in infants with TSC negatively impacts very early neurodevelopment, which persists through 24 months of age.

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Section: Discussioncontrasting

confidence: 95%

Section: Introductionmentioning

confidence: 83%

Influence of seizures on early development in tuberous sclerosis complex

Capal

Bernardino-Cuesta

Horn

et al. 2017

Epilepsy & Behavior

144

141

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“…This equal gender distribution has also been reported in previous studies assessing the prevalence of ASD in TSC 24,25 .…”

Section: Discussionsupporting

confidence: 86%

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex

Capal

Horn

Murray

et al. 2017

Pediatric Neurology

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Background Tuberous Sclerosis Complex (TSC) is a genetic disorder with high prevalence of associated autism spectrum disorder (ASD). Primary objectives were to determine early predictors of autism risk to identify children with TSC in most need of early interventions. The Autism Observation Scale for Infants (AOSI) was evaluated as a measure of ASD-associated behaviors in infants with TSC at age 12 months and its ability to predict ASD at 24 months. Methods Children ages 0 to 36 months with TSC were enrolled in the TSC Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study to identify biomarkers of ASD. The AOSI was administered at age 12 months and the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R) at 24 months. Developmental functioning was assessed using the Mullen Scales of Early Learning. Children were classified as ASD or non-ASD according to the ADOS-2. Results Analysis included 79 children who had been administered the AOSI at 12 months and ADOS-2 and ADI-R at 24 months. The ASD group had a mean AOSI total score at 12 months significantly higher than the non-ASD group (11.8 ± 7.4 vs. 6.3 ± 4.7; p<0.001). An AOSI total score cut-off of 13 provided a specificity of 0.89 to detect ASD with the ADOS-2. AOSI total score at 12 months was similarly associated with exceeding cut-off scores on the ADI-R. Conclusions The AOSI is a useful clinical tool in determining which infants with TSC are at increased risk for developing ASD.

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“…Neurodevelopmental or neuropsychiatric disorders (referred to as TSC‐associated neuropsychiatric disorders); [de Vries et al, ; Leclezio, Jansen, Whittemore, & de Vries, ] are common. About 25–60% of children with TSC will receive a diagnosis of Autism Spectrum Disorder (ASD) [Capal et al, ; Granader et al, ; Jeste, Sahin, Bolton, Ploubidis, & Humphrey, ; Vignoli et al, ], and more than 50% have some degree of cognitive impairment [Curatolo, Moavero, & de Vries, ; Joinson et al, ].…”

Section: Introductionmentioning

confidence: 99%

Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex

Dickinson¹,

Varcin

Şahin

et al. 2019

Autism Research

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Tuberous sclerosis complex (TSC) is a rare genetic disorder that confers a high risk for autism spectrum disorders (ASD), with behavioral predictors of ASD emerging early in life. Deviations in structural and functional neural connectivity are highly implicated in both TSC and ASD. For the first time, we explore whether electroencephalographic (EEG) measures of neural network function precede or predict the emergence of ASD in TSC. We determine whether altered brain function (a) is present in infancy in TSC, (b) differentiates infants with TSC based on ASD diagnostic status, and (c) is associated with later cognitive function. We studied 35 infants with TSC (N = 35), and a group of typically developing infants (N = 20) at 12 and 24 months of age. Infants with TSC were later subdivided into ASD and non-ASD groups based on clinical evaluation. We measured features of spontaneous alpha oscillations (6–12 Hz) that are closely associated with neural network development: alpha power, alpha phase coherence (APC), and peak alpha frequency (PAF). Infants with TSC demonstrated reduced interhemispheric APC compared to controls at 12 months of age, and these differences were found to be most pronounced at 24 months in the infants who later developed ASD. Across all infants, PAF at 24 months was associated with verbal and nonverbal cognition at 36 months. Associations between early network function and later neurodevelopmental and cognitive outcomes highlight the potential utility of early scalable EEG markers to identify infants with TSC requiring additional targeted intervention initiated very early in life.

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Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers

Cited by 78 publications

References 29 publications

Influence of seizures on early development in tuberous sclerosis complex

Influence of seizures on early development in tuberous sclerosis complex

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex

Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex

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