White matter disruption is associated with persistent seizures in tuberous sclerosis complex

Moavero, Romina; Napolitano, Antonio; Cusmai, Raffaella; Vigevano, Federico; Figà-Talamanca, Lorenzo; Calbi, G; Curatolo, Paolo; Bernardi, Bruno

doi:10.1016/j.yebeh.2016.04.026

Cited by 25 publications

(24 citation statements)

References 24 publications

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“…33 Refractory epilepsy with persistent seizures may aggravate the neurodevelopmental phenotype, disrupting white matter connectivity, especially in brain circuits involved in social behavior and cognition. 34 Therefore, seizures may represent a superimposed injury to an already abnormal myelogenic process. 35 In the Tuberous Sclerosis 2000 Study, a prospective longitudinal study in 125 children (age 0-16 years), the authors found that severe early onset epilepsy appeared to be strictly associated with intellectual disability.…”

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

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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.

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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

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“…However, infants with earlier age of seizure onset, higher seizure frequency, and more EEG abnormalities proposed to be particularly in the temporal lobes, are at higher risk for ASD, with all these factors acting as adjunctive risk factors (Bolton et al, 2002; Numis et al, 2011). Recent evidence also showed that in subjects with early onset and refractory seizures, there is a significant alteration of white matter connectivity in areas playing a role in ASD, such as the cingulate cortex (Moavero et al, 2016). This makes early and prompt antiepilepsy treatment necessary to minimize the long-term sequelae of early-onset seizures.…”

Section: The Psychiatric Levelmentioning

confidence: 99%

A clinical update on tuberous sclerosis complex‐associated neuropsychiatric disorders (TAND)

Vries

Wilde

Vries

et al. 2018

American J of Med Genetics Pt C

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Tuberous sclerosis complex (TSC) is associated with a wide range of behavioral, psychiatric, intellectual, academic, neuropsychological, and psychosocial difficulties, which are often underdiagnosed and undertreated. Here, we present a clinical update on TSC-associated neuropsychiatric disorders, abbreviated as "TAND," to guide screening, diagnosis, and treatment in practice. The review is aimed at clinical geneticists, genetic counselors, pediatricians, and all generalists involved in the assessment and treatment of children, adolescents and adults with TSC, and related disorders. The review starts with a summary of the construct and levels of TAND, before presenting up-to-date information about each level of investigation. The review concludes with a synopsis of current and future TAND research.

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“…From a neuropathologic point of view, the early dysregulation of the mTOR pathway, causing altered migration and cell morphology, leads to the formation of tubers including different abnormal cells, such as dysplastic neurons and giant cells. Furthermore, white matter abnormalities appear to be more evident in children with early onset and refractory epilepsy with persistent seizures seeming to determine extensive connectivity alterations in areas of the brain that are crucial for language, social development, and global intellectual functioning (Moavero et al, 2016). They are dynamic lesions, and changes within tubers, through pre-and postnatal life, may contribute to the establishment of extensive epileptogenic networks (Curatolo, Moavero, Van Scheppingen, & Aronica, 2018).…”

Section: Pathogenesis Of Epilepsy In Tscmentioning

confidence: 99%

“…However, also normal appearing white matter can be interested by microstructural changes that are visible when diffusion tensor imaging is performed, and can be linked to epileptogenesis (Widjaja et al, 2010). Furthermore, white matter abnormalities appear to be more evident in children with early onset and refractory epilepsy with persistent seizures seeming to determine extensive connectivity alterations in areas of the brain that are crucial for language, social development, and global intellectual functioning (Moavero et al, 2016).…”

Section: Pathogenesis Of Epilepsy In Tscmentioning

confidence: 99%

Current concepts on epilepsy management in tuberous sclerosis complex

Canevini

Curatolo

Briola

et al. 2018

American J of Med Genetics Pt C

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Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease affecting approximately 1 in 6,000 people, and represents one of the most common genetic causes of epilepsy. Epilepsy affects 90% of the patients and appears in the first 2 years of life in the majority of them. Early onset of epilepsy in the first 12 months of life is associated with high risk of cognitive decline and neuropsychiatric problems including autism. Prenatal or early infantile diagnosis of TSC, before the onset of epilepsy, provides a unique opportunity to monitor EEG before the onset of clinical seizures, thus enabling early intervention in the process of epileptogenesis. In this review, we discuss the current status of knowledge on epileptogenesis in TSC, and present recommendations of American and European experts in the field of epilepsy.

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White matter disruption is associated with persistent seizures in tuberous sclerosis complex

Cited by 25 publications

References 24 publications

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

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

A clinical update on tuberous sclerosis complex‐associated neuropsychiatric disorders (TAND)

Current concepts on epilepsy management in tuberous sclerosis complex

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