Standardized Whole Brain Mapping of Tubers and Subependymal Nodules in Tuberous Sclerosis Complex

Abstract

Tuberous sclerosis complex is associated with radiologically visible abnormalities of brain structure, principally tubers and subependymal nodules. We reviewed the literature on neuroimaging of tubers and subependymal nodules and found qualitative evidence of bilateral, predominantly frontal distribution of tubers and bilateral, predominantly subcortical distribution of subependymal nodules in prior studies of pediatric samples. We studied 25 high-functioning adults with tuberous sclerosis complex and normal IQ, acquiring both dual spin-echo and fluid-attenuated inversion recovery magnetic resonance imaging sequences to optimize radiologic diagnosis of tubers and nodules. Individual lesion maps were then coregistered in a standard stereotactic space to facilitate construction of lesion density maps and estimation of lesion density in cortical and subcortical regions reliably defined by a parcellated template image. We found the highest frequency of tubers in frontal lobes and the highest density of tubers in parietal regions. There was significant regional variation in tuber density but no significant lateralization of frequently bilateral tubers. Nodules were located predominantly in the caudate nucleus and were not significantly lateralized. Tuber and nodule volumes were significantly positively correlated. Tuber volume was larger, on average, in patients with a lifetime history of epilepsy, but there was no correlation between IQ and these measures of lesion load. Contemporary image processing tools can be used to enhance quantitative, whole brain analysis of lesion load in patients with tuberous sclerosis complex. (J Child Neurol 2004; 19:658-665).

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References

Braffman BH , Bilaniuk LT , Naidich TP , et al: MR imaging of tuberous sclerosis: Pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review. Radiology 1992; 183:227—238.

Griffiths PD , Martland TR : Tuberous sclerosis complex: The role of neuroradiology . Neuropediatrics 1997;28:244—252.

Cusmai R. , Chiron C. , Curatolo P. , et al: Topographic comparative study of magnetic resonance imaging and electroencephalography in 34 children with tuberous sclerosis. Epilepsia 1990; 31:747—755.

Jambaque 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.

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

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.

Takanashi J. , Sugita K. , Fujii K. , Niimi H. : MR evaluation of tuberous sclerosis: Increased sensitivity with fluid-attenuated inversion recovery and relation to severity of seizures and mental retardation. AJNR Am J Neuroradiol 1995;16:1923—1928.

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

Griffiths PD , Bolton P. , Verity C. : White matter abnormalities in tuberous sclerosis complex. Acta Radiol 1998;39:482—486.

10.

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

11.

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.

12.

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.

13.

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

14.

Walz NC , Byars AW , Egelhoff JC , Franz DN : Supratentorial tuber location and autism in tuberous sclerosis complex. J Child Neurol 2002;17:830—832.

15.

Bolton PF , Park RJ , Higgins JN , et al: Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 2002;125:1247—1255.

16.

Asano E. , Chugani DC , Muzik O. , et al: Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex. Neurology 2000;54:1976—1984.

17.

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—661.

18.

Roach ES , Gomez MR , Northrup H. : Tuberous sclerosis complex consensus conference: Revised clinical diagnostic criteria. J Child Neurol 1998;13:624—628.

19.

Wechsler D. : Wechsler Abbreviated Scale of Intelligence (WASI). San Antonio, USA, Psychological Corporation, 1999.

20.

Van Tassel P , Cure JK , Holden KR : Cystlike white matter lesions in tuberous sclerosis. AJNR Am J Neuroradiol 1997;18:1367—1373.

21.

Talairach J. , Tournoux P. : Co-planar Stereotaxic Atlas of the Human Brain. New York , Thieme Medical Publishers, 1988 .

22.

Press WH , Teukolsky SA , Vetterling WT , Flannery BP : Numeric Recipes in C: The Art of Scientific Computing, vol 2. Cambridge: UK, Cambridge University Press, 1992.

23.

Brammer MJ , Bullmore ET , Simmons A. , et al: Generic brain activation mapping in functional magnetic resonance imaging: A non-parametric approach. Magn Reson Imaging 1997;15:763—770.

24.

Tzourio-Mazoyer N. , Landeau B. , Papathanassiou D. , et al: Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 2002;15:273—289.

25.

Ridler K. , Bullmore ET , De Vries PJ , et al: Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis. Psychol Med 2001;31:1437—1446.