Long‐term cognitive outcomes in tuberous sclerosis complex

• Published in: Developmental medicine and child neurology Vol. 62; no. 3; pp. 322 - 329
• Main Authors: Tye, Charlotte, Mcewen, Fiona S, Liang, Holan, Underwood, Lisa, Woodhouse, Emma, Barker, Edward D, Sheerin, Fintan, Yates, John R W, Bolton, Patrick F, Higgins, N, Attard, V, Clarke, A, Elmslie, FV, Saggar, AK, Baines, D, Kerr, BA, Brayne, C, Carcani‐Rathwell, I, Connolly, C, Clifford, M, Lydon, A, Oluwo, F, Rogers, H, Srivastava, C, Steenbruggen, J, Cook, JA, Falconer, C, Davies, DM, Sampson, JR, Fryer, AE, Haslop, M, Granader, Y, Griffiths, PD, Hunt, A, Lam, WWK, Kingswood, JC, Miedzybrodzka, ZH, Crawford, H, Morrison, PJ, O'Callaghan, FJK, Philip, SG, Seri, S, Sheehan‐Dare, R, Shepherd, CH
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01-03-2020
• Subjects: Adolescent; Child; Child, Preschool; Cognition - physiology; Female; Humans; Infant; Intellectual Disability - etiology; Intellectual Disability - psychology; Longitudinal Studies; Male; Neuropsychological Tests; Original; Prospective Studies; Tuberous Sclerosis - complications; Tuberous Sclerosis - psychology
• ISSN: 0012-1622; 1469-8749
• DOI: 10.1111/dmcn.14356

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.
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.
This article is commented on by Curatolo on page 269 of this issue.