Abstract
The cerebellum plays an important role in motor learning and cognition, and structural
cerebellar abnormalities have been associated with cognitive impairment. In tuberous
sclerosis complex, neurologic outcome is highly variable, and no consistent imaging
or pathologic determinant of cognition has been firmly established. The cerebellum
calls for specific attention because mouse models of tuberous sclerosis complex have
demonstrated a loss of cerebellar Purkinje cells, and cases of human histologic data
have demonstrated a similar loss in patients. We hypothesized that there might be
a common cerebellar finding in tuberous sclerosis complex that could be measured as
morphometric changes with magnetic resonance imaging. Using a robust, automated image
analysis procedure, we studied 36 patients with tuberous sclerosis complex and age-matched
control subjects and observed significant volume loss among patients in the cerebellar
cortices and vermis. Furthermore, this effect was strongest in a subgroup of 19 patients
with a known, pathogenic mutation of the tuberous sclerosis 2 gene and impacted all
cerebellar structures. We conclude that patients with tuberous sclerosis complex exhibit
volume loss in the cerebellum, and this loss is larger and more widespread in patients
with a tuberous sclerosis 2 mutation.
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References
- National Institutes of Health consensus conference: tuberous sclerosis complex.Arch Neurol. 2000; 57: 662-665
- Tuberous sclerosis.Lancet. 2008; 372: 657-668
- Cognitive prognosis of patients with tuberous sclerosis complex.Neurology. 2007; 68: 62-64
- Characterization of autism in young children with tuberous sclerosis complex.J Child Neurol. 2008; 23: 520-525
- Autism in tuberous sclerosis.Eur J Paediatr Neurol. 2004; 8: 327-332
- The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management.Arch Dis Child. 2011; 96: 1020-1025
- Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex.Acad Radiol. 2012; 19: 17-25
- Loss of the tuberous sclerosis complex protein tuberin causes Purkinje cell degeneration.Neurobiol Dis. 2011; 43: 113-122
- Clinicopathological and immunohistochemical findings in an autopsy case of tuberous sclerosis complex.Neuropathology. 2008; 28: 577-590
- The cerebellum and neuropsychological functioning: a critical review.J Clin Exp Neuropsychol. 2012; 34: 35-56
- The cerebellum and cognition.Eur J Paediatr Neurol. 2007; 11: 232-234
- Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria.J Child Neurol. 1998; 13: 624-628
- Automatic segmentation of newborn brain MRI.Neuroimage. 2009; 47: 564-572
- Learning likelihoods for labeling (L3): a general multi-classifier segmentation algorithm.Med Image Comput Comput Assist Interv. 2011; 14: 322-329
- A reproducible evaluation of ANTs similarity metric performance in brain image registration.Neuroimage. 2011; 54: 2033-2044
- Performance-based classifier combination in atlas-based image segmentation using expectation-maximization parameter estimation.IEEE Trans Med Imaging. 2004; 23: 983-994
- Incorporating priors on expert performance parameters for segmentation validation and label fusion: a maximum a posteriori STAPLE.Med Image Comput Comput Assist Interv. 2010; 13: 25-32
- Simultaneous truth and performance level estimation (STAPLE): an algorithm for the validation of image segmentation.IEEE Trans Med Imaging. 2004; 23: 903-921
- Normalization of cerebral volumes by use of intracranial volume: implications for longitudinal quantitative MR imaging.AJNR Am J Neuroradiol. 2001; 22: 1483-1489
- Patterns of cerebellar atrophy in patients with chronic epilepsy: a quantitative neuropathological study.Epilepsy Res. 2000; 41: 63-73
- Controlling the false discovery rate: a practical and powerful approach to multiple testing.J Roy Statist Soc Ser B. 1995; 57: 289-300
- Brain abnormalities in tuberous sclerosis complex.J Child Neurol. 2004; 19: 650-657
- Standardized whole brain mapping of tubers and subependymal nodules in tuberous sclerosis complex.J Child Neurol. 2004; 19: 658-665
- Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex.Neurology. 2011; 76: 981-987
- Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex.Brain. 2002; 125: 1247-1255
- Autism and the cerebellum: evidence from tuberous sclerosis.J Autism Dev Disord. 2000; 30: 511-517
- Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis.Psychol Med. 2001; 31: 1437-1446
- Neuroanatomical correlates of memory deficits in tuberous sclerosis complex.Cereb Cortex. 2007; 17: 261-271
- Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR-dependent manner.J Neurosci. 2009; 29: 5926-5937
- Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death.Cell Death Differ. 2008; 15: 1582-1592
- Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis.Neurobiol Dis. 2011; 43: 356-363
- Cerebellar abnormality in children and young adults with tuberous sclerosis complex: MR and diffusion weighted imaging findings.J Neuroradiol. 2010; 37: 231-238
- Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates.J Child Neurol. 2006; 21: 846-851
- Mechanisms of neurocognitive dysfunction and therapeutic considerations in tuberous sclerosis complex.Curr Opin Neurol. 2011; 24: 106-113
- Expression of the tuberous sclerosis complex gene products, hamartin and tuberin, in central nervous system tissues.Acta Neuropathol. 2000; 99: 223-230
- The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination.Oncogene. 2000; 19: 6306-6316
- Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.Am J Hum Genet. 2001; 68: 64-80
- Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex.Hum Mol Genet. 2011; 20: 445-454
- TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/TSC2 frequency ratios.Eur J Pediatr. 2002; 161: 393-402
- Genotype and psychological phenotype in tuberous sclerosis.J Med Genet. 2004; 41: 203-207
- Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.Genet Med. 2007; 9: 88-100
- Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype–phenotype correlations and comparison of diagnostic DNA techniques in tuberous sclerosis complex.Eur J Hum Genet. 2005; 13: 731-741
- Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.Am J Hum Genet. 1999; 64: 1305-1315
- Regional cerebellar volumes predict functional outcome in children with cerebellar malformations.Cerebellum. 2012; 11: 531-542
- Cerebellar hypoplasia and hyperplasia in infantile autism.Lancet. 1994; 343: 63-64
- Cerebellum, language, and cognition in autism and specific language impairment.J Autism Dev Disord. 2010; 40: 300-316
- Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice.Nature. 2012; 488: 647-651
Article info
Publication history
Accepted:
October 29,
2012
Received:
May 22,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
