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. (J Child Neurol 2006;21:99—105; DOI 10.2310/7010.2006.00027).

Get full access to this article

View all access options for this article.

References

Gomez MR : Tuberous Sclerosis, 2nd ed. New York, Raven Press, 1998.

Curatolo P. , Verdecchia M. , Bombardieri R. : Tuberous sclerosis complex: A review of neurological aspects. Eur J Pediatr Neurol 2002;6:15—23.

Kuhlendahl HD , Gross-Selbeck G. , Doose H. , et al: Cranial computed tomography in children with tuberous sclerosis. Neuropadiatrie 1977 ;8:325—332.

Kingsley Dpe , Kendall BE , Fitz CR : Tuberous sclerosis: A clinicoradiological evaluation of 110 cases with particular reference to atypical presentation . Neuroradiology 1986;28:38—46.

Roach ES , Williams DP , Laster DW : Magnetic resonance imaging in tuberous sclerosis. Arch Neurol 1987;44:301—303.

Martin N. , De Broucker T. , Cambier J. , et al: MRI evaluation of tuberous sclerosis. Neuroradiology 1987;29:437—443.

Terwey B. , Doose H. : Tuberous sclerosis: Magnetic imaging of the brain. Neuropediatrics 1987;18:67—69.

Inoue Y. , Nakajima S. , Fukuda T. , et al: Magnetic resonance images of tuberous sclerosis. Further observations and clinical correlations. Neuroradiology 1988;30:379—384.

Iwasaki S. , Nakagawa H. , Kichikawa K. , et al: MR and CT of tuberous sclerosis: Linear abnormalities in the cerebral white matter. AJNR Am J Neuroradiol 1990;11:1029—1034.

10.

Tamaki K. , Okuno T. , Ito M. , et al: Magnetic resonance imaging in relation to EEG epileptic foci in tuberous sclerosis. Brain Dev 1990;12:316—320.

11.

Martin N. , Debussche C. , De Broucker T. , et al: Gadolinium-DTPA enhanced MR imaging in tuberous sclerosis. Neuroradiology 1990;31:492—497.

12.

Houser OW , Shepherd CW , Gomez MR : Imaging of intracranial tuberous sclerosis. Ann N Y Acad Sci 1991;615:81—93.

13.

Webb DW , Thomson Jlg , Osborne JP : Cranial magnetic resonance imaging in patients with tuberous sclerosis and normal intellect. Arch Dis Child 1991;66:1375—1377.

14.

Jambaqué I. , Cusmai R. , Curatolo P. , et al: Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings. Dev Med Child Neurol 1991;33:698—705.

15.

Houser OW , Gomez MR : CT and MR imaging of intracranial tuberous sclerosis. J Dermatol 1992;19:904—908.

16.

Menor F. , Martí-Bonmatí L. , Mulas F. , et al: Neuroimaging in tuberous sclerosis: A clinicoradiological evaluation in pediatric patients. Pediatr Radiol 1992 ;22:485—489.

17.

Shepherd CW , Stephenson Jbp : Seizures and intellectual disability associated with tuberous sclerosis complex in the west of Scotland. Dev Med Child Neurol 1992;34:766—774.

18.

Maeda M. , Tartaro A. , Matsuda T. , Ishii Y. : Cortical and subcortical tubers in tuberous sclerosis and FLAIR sequence . J Comput Assist Tomogr 1995;19:660—667.

19.

Shepherd CW , Houser OW , Gomez MR : MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment . AJNR Am J Neuroradiol 1995;16:149—155.

20.

Canapicchi R. , Abbruzzese A. , Guerrini R. , et al: Neuroimaging of tuberous sclerosis , in Guerrini R , Andermann F , Canapicchi R , et al (eds): Dysplasias of Cerebral Cortex. Philadelphia, Lippincott Raven, 1996, 151—162.

21.

Goodman M. , Lamm ST , Engel A. , et al: Cortical tuber count: A bio-marker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol 1997;12:85—90.

22.

Bolton PF , Griffiths PD : Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 1997;349:392—395.

23.

Hosoya M. , Naito H. , Nihei K. : Neurological prognosis correlated with variations over time in the number of subependymal nodules in tuberous sclerosis. Brain Dev 1999;21:544—547.

24.

O'Callaghan Fjk , Renowden S. , Needham C. , et al: Cerebral pathology and cognitive function in individuals with normal intellect with tuberous sclerosis. Dev Med Child Neurol 1999;41(Suppl 82):22.

25.

Marti-Bonmati L. , Menor F. , Dosda R. : Tuberous sclerosis: Differences between cerebral and cerebellar cortical tubers in a pediatric population. AJNR Am J Neuroradiol 2000;21:557—560.

26.

Mizuno S. , Takahashi Y. , Kato Z. , et al: Magnetic resonance spectroscopy of tubers in patients with tuberous sclerosis. Acta Neurol Scand 2000;102:175—178.

27.

Weber AM , Egelhoff JC , McKellop JM , Franz DN : Autism and the cerebellum: Evidence from tuberous sclerosis. J Autism Dev Disord 2000;30:511—517.

28.

O'Callaghan FJ K , Osborne JP : Advances in the understanding of tuberous sclerosis. Arch Dis Child 2000 ;83:140—142.

29.

O'Callaghan Fjk , Osborne JP : The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex. Arch Dis Child 2004;89:530—533.

30.

Baron Y. , Barkovich AJ : MR imaging of tuberous sclerosis in neonates and young infants. AJNR Am J Neuroradiol 1999; 20:907—916.

31.

American Psychiatric Association : Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC , American Psychiatric Association, 1994.

32.

Lord C. , Rutter M. , Le Couteur A. : Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for care-givers of individuals with possible pervasive developmental disorders . J Autism Dev Disord 1994;24:659—685.

33.

Hunt A. , Shepherd C. : A prevalence study of autism in tuberous sclerosis. J Autism Dev Disord 1993;23:323—339.

34.

Curatolo P. , Cusmai R. : Autism and infantile spasms in children with tuberous sclerosis. Dev Med Child Neurol 1987 ;29:550—551.

35.

Hunt A. , Dennis J. : Psychiatric disorder among children with tuberous sclerosis. Dev Med Child Neurol 1987;29:190—198.

36.

Olsson I. , Steffenburg S. , Gillberg C. : Epilepsy in autism and autistic like conditions. A population-based study . Arch Neurol 1988;45:666—668.

37.

Riikonen R. , Simell O. : Tuberous sclerosis and infantile spasms. Dev Med Child Neurol 1990;32:203—209.

38.

Curatolo P. , Cusmai R. , Cortesi F. , et al: Neuropsychiatric aspects of tuberous sclerosis. Ann N Y Acad Sci 1991;615:8—16.

39.

Wong V. : Epilepsy in children with autistic spectrum disorder. J Child Neurol 1993;8:316—322.

40.

Baker P. , Piven J. , Sato Y. : Medical temporal lobe structures and autism: A review of clinical and experimental findings. Neuropsychologia 1994;32:627—648.

41.

Gillberg IC , Gillberg C. , Ahlsen G. : Autistic behaviour and attention deficits in tuberous sclerosis: A population based study. Dev Med Child Neurol 1994;36:50—56.

42.

Tuchman RF , Rapin I. : Regression in pervasive developmental disorders: Seizures and epileptiform electroencephalogram correlates. Pediatrics 1997;99:560—566.

43.

Gutierrez GC , Smalley SL , Tanguay PE : Autism in tuberous sclerosis complex. J Autism Dev Disord 1998 ;28:97—103.

44.

Jóźwiak S. , Goodman M. , Lamm SH : Poor mental development in patients with tuberous sclerosis complex. Arch Neurol 1998 ;55:379—384.

45.

Gomez MR : Neurologic and psychiatric features, in Gomez MR (ed): Tuberous Sclerosis. New York , Raven Press, 1998, 21—36.

46.

van Slegtenhorst M. , Nellist M. , Nagelkerken B. , et al: Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 1998; 7:1053-1057.

47.

Wienecke R. , Konig A. , DeClue JE : Identification of tuberin, the tuberous sclerosis-2 product—Tuberin possesses specific rap1GAP activity. J Biol Chem 1995;270:16409—16414.

48.

Seri S. , Cerquiglini A. , Pisani F. , Curatolo P. : Autism in tuberous sclerosis: Evoked potential evidence for a deficit in auditory sensory processing. Clin Neurophysiol 1999 ; 110: 1825—1830.