Abstract
Neuroimaging is a key instrument for determining structural and in vivo functional
status of the brain, non-invasively. Multiple approaches can now determine aspects
of anatomic and neurochemical changes in brain, and have been utilized effectively
in Rett Syndrome patients to understand the biological basis of this neurodevelopmental
disorder. Studies performed at our institute include volumetric analyses of MRI, magnetic
resonance spectroscopy (MRS), diffusion tensor imaging (DTI), cerebral blood flow
measurements with MRI, and positron emission tomography scans (PET). These studies
have provided considerable insight into mechanisms underlying the clinical features
of this disease. Volumetric analyses suggest that decreased brain volume in RS results
from global reductions in both gray and white matter of the brain. A selective vulnerability
of the frontal lobes is evidenced by the preferential reduction of blood flow, increased
choline and reduced n-acetyl aspartate (NAA) by MRS, and increased glucose uptake
in these same regions as shown by (18F)-fluorodeoxyglucose (FDG) PET scans. We hypothesize that the increased glucose uptake
relates to increased glutamate cycling in synapses. The resulting neuroexcitotoxic
injury to the developing brain contributes to the seizures, behavioral disturbance
and respiratory irregularities commonly seen in phases 1 and 2 of this disorder.
Keywords
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References
- Rett syndrome is caused by mutations in X-linked MeCP2, encoding methyl-CpG-binding protein 2.Nat Genet. 1999; 23: 185-188
- Neuroanatomy of Rett syndrome: a volumetric imaging study.Ann Neurol. 1993; 34: 227-234
- Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa.Neurology. 1997; 48: 399-407
- The neuroanatomy of Rett syndrome: neuropathological and neuroimaging studies.Rivista Medica. 1998; 4: 187-199
- Rett syndrome: a disorder affecting early brain growth.Ann Neurol. 1997; 42: 3-10
- Brain development during childhood and adolescence: a longitudinal MRI study.Nat Neurosci. 1999; 2: 861-863
- Co-planar stereotaxic atlas of the human brain. Thieme, New York1988
- Application of an automated parcellation method to the analysis of pediatric brain volumes.Psychiatry Res: Neuroimaging. 1997; 76: 15-27
- Automated Talairach atlas-based parcellation measurement of cerebral lobes in children.Psychiatry Res: Neuroimaging. 1999; 91: 11-30
- Cortical development in Rett syndrome: molecular, neurochemical, and anatomical aspects.in: Kerr A. Engerstrom I.W. The Rett disorder and the developing brain. Oxford University Press, Oxford2000: 85-110
- Specificity of the neurodevelopmental effects of Turner syndrome.Arch Clin Neuropsych. 1999; 14: 677
- Brain MRI changes in Rett syndrome: cross-sectional and serial data.Soc Neurosci. 1999; 25: 488a
- Selective dendritic alterations in the cortex of Rett syndrome.J Neuropathol Exp Neurol. 1995; 54: 195-201
- Neuropathology of Rett syndrome.Acta Neuropathol. 1988; 76: 142-158
- Quantitative proton 1H MR spectroscopic imaging in early Rett syndrome.Neurology. 2000; 54: 715-722
- MR diffusion tensor spectroscopy and imaging.J Biophys. 1994; 66: 259-267
- Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain.Magn Reson Med. 1999; 42: 526-540
- In vivo visualization of human neural pathways by MRI.Ann Neurol. 2000; 47: 412-414
- Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging.J Neurol Neurosurg Psychiatry. 2000; 69: 528-530
- In vivo fiber tractography using DT-MRI data.Magn Reson Med. 2000; 44: 625-632
- Development of amino acid receptors in frontal cortex from girls with Rett syndrome.Ann Neurol. 1999; 45: 541-545
- Cerebral blood flow and oxygen metabolism in the Rett syndrome.Brain Dev. 1992; 14: S69-S74
- Cerebral magnetic resonance spectroscopy in Rett syndrome.Brain Dev. 1993; 15: 107-112
- Immature pattern of brain activity in Rett syndrome.Arch Neurol. 1990; 47: 982-986
- Brain perfusion SPECT and EEG findings in Rett syndrome.Acta Neurol Scand. 1997; 95: 44-50
- Regional cerebral blood flow: SPECT as a tool for localization of brain dysfunction.in: Hagberg B. Rett syndrome: clinical and biological aspects. MacKeith Press, London1993: 80-85
- Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD.Nucl Med Commun. 1997; 18: 527-534
- Transfer insensitive labeling technique (TILT): Application to multislice functional perfusion imaging.J Magn Reson Imaging. 1999; 9: 454-461
- Magnetic resonance imaging of perfusion using spin inversion of arterial water.Proc Natl Acad Sci. 1992; 89: 212-216
- Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates.Brain Dev. 1992; 14: S75-S79
- Dopaminergic D2 receptor SPECT imaging in Rett syndrome: increase of specific binding in striatum.J Nucl Med. 1993; 34: 1717-1721
- Decrease in benzodiazepine receptor binding in the brains of adult patients with Rett syndrome.J Neurol Sci. 1998; 154: 146-150
- In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428.Synapse. 1993; 15: 130-142
- Altered development of glutamate and GABA receptors in the basal ganglia of girls with Rett syndrome.Exp Neurol. 1999; 156: 345-352
- Dopamine transporters are markedly reduced in Lesch–Nyhan disease in vivo.Proc Natl Acad Sci USA. 1996; 93: 5539-5543
- Positron emission tomography study of human brain function and development.Ann Neurol. 1987; 22: 487-497
- The development of synapses in striate cortex of man.Hum Neurobiol. 1987; 6: 1-9
- The contribution of astrocytes to the 18F-2-deoxyglucose signal PET activation studies.Mol Psychiatry. 1996; 1: 445-452
- Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K+ ATPase.Dev Neurosci. 1996; 18: 336-342
- Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia.Proc Natl Acad Sci USA. 1995; 92: 4616-4620
- Functional energy metabolism: in vivo 13C-NMR spectroscopy evidence for coupling of cerebral glucose consumption and glutamatergic neuronal activity.Dev Neurosci. 1998; 20: 321-330
- Energy on demand.Science. 1999; 283: 496-497
- Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.Proc Natl Acad Sci USA. 1998; 95: 316-321
- In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics.Philos Trans R Soc Lond B Biol Sci. 1999; 354: 1165-1177
- Rett syndrome: 1H spectroscopic imaging at 4.1 Tesla.J Child Neurol. 1999; 14: 524-528
- Elevated CSF glutamate in Rett syndrome.Neuropediatrics. 1992; 23: 212-213
- High levels of cerebrospinal fluid glutamate in Rett syndrome.Pediatr Neurol. 1996; 15: 213-216
- Cerebral proton magnetic resonance spectroscopy in Rett syndrome.Neuropediatrics. 1995; 26: 126-127
- Physiological and pathological roles of excitatory amino acids during central nervous system development.Brain Res. 1990; 15: 41-70
Article info
Footnotes
☆Presented at the World Congress on Rett Syndrome 2000, Karuizawa, Japan, July, 2000.
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
