Early predictors of clinical and mental outcome in tuberous sclerosis complex: A prospective study

Abstract

Aim: We aimed to identify early predictors of intractable epilepsy, intellectual disability (ID) and autism spectrum disorders (ASD) in the cohort of TSC patients initially diagnosed with cardiac rhabdomyomas (CR).

Method: Over the period of twelve years we prospectively obtained clinical, neuropsychological, electrophysiological and neuroimaging data in a group of 22 TSC patients (9 females, 13 males) with the pre/perinatal diagnosis of CR, included to the study at the time of diagnosis. Afterwards, we statistically determined variables associated with ID, ASD and intractable epilepsy.

Results: Development of ID was predicted by severe epilepsy (a higher number of anti-epileptic drugs used), a higher number of dysplastic lesions on MRI, and abnormal background activity on EEG (p < 0.05). Predictors of ASD included early developmental delay, abnormal background activity on EEG at the end of follow-up and a higher number of areas with dysplastic features on MRI (p < 0.05). Intractable epilepsy was associated with a higher number of areas with dysplastic features on MRI, ID and with TSC2 genotype.

Conclusion: Adverse mental and clinical outcome was associated with intractable epilepsy and the severe anatomical brain involvement; therefore, our centre developed a tailored protocol for early identification of TSC patients at a higher risk of developing intractable epilepsy with its deleterious effect on cognitive outcome.

Keywords: Autism spectrum disorder; Epilepsy; Intellectual disability; Prospective follow-up; Tuberous sclerosis complex.