Cortical tubers, cognition, and epilepsy in tuberous sclerosis.
ABSTRACT Tuberous sclerosis complex is an autosomal-dominant genetic disorder characterized by hamartomatous growth in various organs. Patients who have this disorder exhibit a high rate of epilepsy and cognitive problems. We investigated number of tubers, location, seizure types, and cognitive outcome, and we analyzed the relationships among them in our tuberous sclerosis patients in the Comprehensive Epilepsy Program at the University of Alberta. We also examined the seizure outcome after tuber resection. Our study cohort included 24 patients with tuberous sclerosis complex. We obtained seizure history, electroencephalogram, and neuropsychologic parameters. Magnetic resonance imaging was used to examine tuber numbers and locations. Ten patients underwent surgical removal of tubers responsible for intractable epilepsy. A negative correlation was found between the number of tubers and intelligent quotient score. Epilepsy surgery led to freedom from seizures in this patient group. We demonstrated that the total number and location of cortical tubers play a significant role in the extent of mental retardation in patients with tuberous sclerosis complex. In addition, patients with intractable seizures and well-defined epileptic focus had excellent surgical outcome.
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ABSTRACT: Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0-16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans. TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity. The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.Psychological Medicine 04/2015; DOI:10.1017/S0033291715000264 · 5.43 Impact Factor
Society for Neuroscience, New Orleans, LA; 01/2012
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ABSTRACT: Neurobehavioral impairments such as learning difficulty, autism, attention deficit hyperactivity disorder (ADHD) and mood or behavioural problems are known to be increased in children with epilepsy; however, they remain under-recognised and often cause considerable morbidity. Quantitative neuroimaging techniques offer a potential avenue to improving our understanding of the underlying pathological basis for these disorders, aiding with diagnosis and risk stratification. A systematic review was undertaken for original research articles involving magnetic resonance imaging in children with epilepsy and one or more neurobehavioural impairments. Studies were reviewed with respect to patient population, methodology and magnetic resonance imaging (MRI) findings. A total of 25 studies were identified and included in this review. The majority of studies looked at single impairments, commonly cognitive impairment or ADHD, with few studies reporting on other impairments. Reductions in cortical grey matter and disruptions of functional and structural brain networks were associated with poorer cognitive performance and disruptions of grey and white matter within a fronto-striatal-cerebellar network associated with ADHD. Insufficient studies were available to report on other impairments. Relatively few studies exist in this field and those that do are methodologically diverse. Further investigation is required to determine if the changes reported to date are epilepsy syndrome specific or have broader applicability.04/2015; 5(2):225-37. DOI:10.3978/j.issn.2223-4292.2015.01.06