Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study

Moavero, Romina; Benvenuto, Arianna; Gialloreti, Leonardo Emberti; Siracusano, Martina; Kotulska, Katarzyna; Weschke, Bernhard; Riney, Kate; Jansen, Floor E.; Feucht, Martha; Kršek, Pavel; Nabbout, Rima; Jansen, Anna; Wojdan, Konrad; Borkowska, Julita; Sadowski, Krzystof; Hertzberg, Christoph; Hulshof, Hanna M.; Samueli, Sharon; Beňová, Barbora; Aronica, Eleonora; Kwiatkowski, David J.; Lagae, Lieven; Jóźwiak, Sergiusz; Curatolo, Paolo

doi:10.3390/jcm8060788

Cited by 50 publications

(77 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24 Early identification of an abnormal trajectory in social communication skills and a global developmental impairment is usually present by the age of 9 months. [30][31][32] However, TAND in infancy and childhood are often underdiagnosed and undertreated, 2 and most previous studies aiming to investigate the relationship between epilepsy and early development in TSC lack accurate and objective phenotypic characterization of neurodevelopment in infancy at seizure onset. In our cohort, we identified a clear decline of DQ in some children identified with risk of ASD at 2 years of age.…”

Section: Discussionmentioning

confidence: 99%

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

Moavero

Kotulska

Lagae

et al. 2020

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

Objective To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80–150 mg/kg/day). Methods Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). Results Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD (P = 0.02) and DD (P = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient < 55). In 20% of children abnormal developmental trajectories were detected before the onset of seizures. Furthermore, 21% of all children with risk of ASD at 24 months had not developed seizures at that timepoint. There was no significant difference between early and conventional treatment with respect to rate of risk of ASD (P = 0.8) or DD (P = 0.9) at 24 months. Interpretation This study confirms a relationship between epilepsy and risk of ASD/DD. However, in this combined randomized/open label study, early treatment with vigabatrin did not alter the risk of ASD or DD at age 2 years.

show abstract

Section: Discussionmentioning

confidence: 99%

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

Moavero

Kotulska

Lagae

et al. 2020

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Besides clinical and quantitative EEG features, other characteristics, such as the pathogenic TSC variant, the epilepsy course (including the development of refractory epilepsy or epileptic spasms), MRI features and early development, can help to identify young infants with TSC at risk of developmental comorbidities (6,12,16,(42)(43)(44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Prediction of Neurodevelopment in Infants With Tuberous Sclerosis Complex Using Early EEG Characteristics

Ridder¹,

Lavanga²,

Verhelle³

et al. 2020

Front. Neurol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on the Quality in Prognosis Strategy (QUIPS) tool, the most commonly found risk factors for bias in the studies reviewed included study participation, ASD measure, and study confounders. Many [14] of the reviewed articles included participants drawn from one clinic or hospital (18,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32); others [5] had a specific age range (12,13,(33)(34)(35) or a particular subset of the TSC population (18, 35-47, 49, 50). Only 18 of the included articles reported the diagnostic criteria for ASD ( Table 1).…”

Section: Search Strategy and Article Selectionmentioning

confidence: 99%

“…Early identifiers of autism or autistic-like features in patients with TSC include early DD or a slowing in nonverbal cognition (13,38). Studies of very young infants with TSC suggest early delay in visual reception (12) and under-developed fine-motor skills to be markers of the development of autism traits (12,34). Deficits across all domains of the Bayley Scales of Infant Development (BSDI) at 1 year of age were predictive of higher autism traits on the Autism Diagnostic Observation Schedule (ADOS) at 2 years within a prospective study of infants with TSC (n = 82) in 10 sites across Europe and Australia (34).…”

Section: Phenotype/behaviormentioning

confidence: 99%

Autism and Epilepsy in Patients With Tuberous Sclerosis Complex

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction: Individuals with Tuberous Sclerosis Complex (TSC) are at increased risk of developing both epilepsy and autism spectrum disorder (ASD), but the relationship between these conditions is little understood. We reviewed published reports to elucidate the relationship between ASD, epilepsy, and TSC, and to define the genetic and neurological risk factors. Methods: Articles (January 2004-May 2019) were identified via PubMed, EMBASE, and CENTRAL databases. Article inclusion required report on individuals with TSC-associated ASD and epilepsy with prevalence, odds ratio, or rate report on the comorbidity of ASD in epileptic patients due to TSC. Results: A total of 841 abstracts were identified in the original search. Thirty-six articles were included, which identified study populations, ASD measures used, and study confounders as bias factors. This review included 2,666 TSC patients, with a mean age of 15.9 years (range 1.94-30.3 years). The percentage of TSC patients with epilepsy and autism was 33.7%. Patients with TSC and autism showed more frequent seizures and earlier epilepsy onset than TSC patients without autism. ASD and intractable epilepsy were both predicted by a higher number of areas with dysplastic features revealed in brain MR scans. ASD, the onset of seizures in children <2 years of age, and >3 tubers have all been associated with an increased risk of refractory epilepsy in TSC patients. However, the direction of the relationship is not clear because a history of epilepsy, or infantile spasms in patients with TSC is also associated with an increased likelihood of ASD. Overall, 73.2% of patients carried TSC2 genetic variant and, among patients with TSC and autism, the percentage of TSC2 individuals was 85.6%. Conclusions: The complex interrelationship between TSC, autism, and epilepsy, coupled with limited knowledge on the neurobiological basis for the interrelationship, limits overall understanding and opportunities for management. The results of this review highlight the need for early identification and management to optimize favorable outcomes in the most vulnerable individuals with TSC. Regardless of whether studies are considered individually or collectively, interpretation is made difficult due to the differences between the studies, most notably between methods and diagnostic criteria used to assess intellectual ability.

show abstract

Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study

Cited by 50 publications

References 44 publications

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

Prediction of Neurodevelopment in Infants With Tuberous Sclerosis Complex Using Early EEG Characteristics

Autism and Epilepsy in Patients With Tuberous Sclerosis Complex

Contact Info

Product

Resources

About