Abstracts

RATIONALE: The aetiology of the learning difficulty in tuberous sclerosis (TSC) is still debated. Some believe that it is related to the amount of tubers in the brain and others think it is caused by the infantile spasms that occur in the first year of life. We set out to examine the relative contributions to final intelligence (IQ) made by both cerebral tubers and infantile spasms.
METHODS: We recruited patients who were able to undergo magnetic resonance imaging (MRI) without the need for an anaesthetic. Epilepsy history was determined by interview and review of clinical records. IQ was assessed using either Wechsler intelligence scales or Raven[ssquote]s matrices. MRI scans were taken in 3 planes using T1,T2 and FLAIR sequences.
RESULTS: 41 patients consented to have an MRI scan. There were 24 females and 17 males. Ages ranged from 9 to 75 (median = 25, interquartile range 17 to 46). The IQ scores for this sub-set of patients were normally distributed about a mean of 91 (range 52 to 130, standard deviation = 18.8). Twenty- five patients (63%) had a positive history of epilepsy, and ten (25%) had suffered from infantile spasms. The basic regression model showed that there was a significant relationship between the number of tubers and IQ ( slope = -7.8; 95% CI, -12 to -3.7; t = - 3.8, p = 0.001; y = 116.3 - 7.8x; r2 = 0.28). Neither age nor sex was significantly related to IQ or tuber count. Patients with a positive history of infantile spasms had a mean IQ score of 72.5 compared to 96.9 in the other patients (p = 0.002, Wilcoxon ranksum test). Mean tuber count was also higher in those patients with infantile spasms (20.6) than without (9.4, p = 0.005 Wilcoxon ranksum test). The inclusion of infantile spasm status into the regression model partly confounded the relationship between tubers and IQ, but did not render the relationship statistically insignificant ( slope = - 4.9; 95%CI, -9.2 to -0.48; t = -2.25, p = 0.031; y = 75.7 - 4.9x1 + 17.7x2; r2 = 0.41). Similarly the relationship between infantile spasms and learning difficulty remained strong even when controlling for the number of tubers in the patients brains ( slope = 17.7; 95% CI, 5.1 to 30.2; t = 2.85, p = 0.007; y = 75.7 - 4.9x1 + 17.7x2; r2 = 0.41).
CONCLUSIONS: This is the first study that demonstrates that both tubers and infantile spasms are associated with cognitive performance in tuberous sclerosis patients independently of each other. This finding has important implications for clinicians treating these patients. It implies that prevention or rapid treatment of infantile spasms might result in the prevention of some of the intellectual deficits in TSC.
Support: The Wellcome Trust