Tuberous Sclerosis Complex: Correlation of Magnetic Resonance Imaging (MRI) Findings With Comorbidities

Abstract

We studied the magnetic resonance imaging (MRI) findings in a cohort of Chinese children with tuberous sclerosis complex to determine the relationship between age, sex, mental retardation, autism, epilepsy, infantile spasm, and early age at onset of seizures and the numbers and locations of tubers detected. We searched our tuberous sclerosis registry, established in 1985 (N = 44), and performed an analysis of children who had MRIs of the brain performed (n = 22). A neuroradiologist blinded to the clinical findings scored the MRIs according to the total number and site of the tubers. The following factors were analyzed: age, sex, presence of autism (n = 7), presence (n = 19) and severity of mental retardation (mild [n = 12], moderate to severe [n = 7]), presence of epilepsy (n = 21) or infantile spasm (n = 8), and age at onset of seizures less than 1 year (n = 10). There was no significant relationship between the number and site of tubers and the following factors: sex, autism, mental retardation, degree of mental retardation, epilepsy, history of infantile spasm, or age at onset of seizures less than 1 year. Only the presence of cortical tubers in the parietal regions had a significant relationship with the history of infantile spasm (P = .012). Using multiple regression analysis of all of the risk factors, only age is related to the number of tubers in the MRI (P = .047), and a history of infantile spasm is related to the presence of tubers in the parietal (P = .009) and occipital (P = .031) lobes. The associated comorbidities in tuberous sclerosis complex might be explained by more complex underlying genetic or pathologic issues rather than purely by the site of the cortical tubers. We suggest that a developmental approach, by analyzing the age at the appearance of tubers in both symptomatic and asymptomatic cases with the development of other neuropsychiatric comorbidities, should be undertaken to assess the causal relationship.

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

“…Thus, the ratio of cerebellar tubers was 3:1for ASD and non-ASD cases in the study by Bolton and Griffiths (1997). Consistent with this interpretation a study found no significant correlation between number and site of tubers and factors including autism (Wong and Khong 2006). Two other studies, however did reveal an association between cerebellar tubers and autistic symptomatology even after controlling for number and location of cortical tubers (Eluvathingal et al 2006;Weber et al 2000).…”

Pulsed Arterial Spin-Labeled MR Imaging Evaluation of Tuberous Sclerosis

“…25 Cortical tuber burden has been correlated with seizure onset and frequency, with mixed results. [26][27][28] Our study showed no statistically significant correlation between total cortical tuber count and seizure frequency. The phenotype and mutational analysis of the patients in our study are unknown.…”

Cytoarchitectural alterations are widespread in cerebral cortex in tuberous sclerosis complex

“…Indeed, recent studies have suggested that higher cortical tuber count is associated with lower intelligence and increased incidence of infantile spasms [8]. One issue that complicates our clinical view of TSC is that there may be a disparity between the number, size, or morphology [12,21,25] of cortical tubers and the severity of neurological phenotype, e.g., lack of solid correlation between tuber burden and severity of seizures, cognitive disability, or autism [24]. These observations have raised the possibility that histopathological features of TSC may not be confined to cortical tubers and may include distinct or more subtle morphological changes.…”