Adaptive metabolic changes in CADASIL white matter
- 141 Downloads
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an important genetic cause of stroke, but pathogenic mechanisms and functional alterations remain poorly characterized. The purpose of this study was to investigate adaptive metabolic and functional changes in white matter hyperintensities and normal-appearing white matter in CADASIL patients using 1H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. 1H-MRSI data were acquired on a 3T scanner using high-resolution multi-spin echo spectroscopic imaging (T E = 288 ms) and non-accelerated medium-resolution MRSI (T E = 35 ms). MRI of all CADASIL patients demonstrated characteristic white matter hyper-intensities (WMH) in the subcortical periventricular white matter. Cre/Cho, Glx/Cho and Glx/Cre ratios were significantly decreased in WMH compared to normal-appearing white matter (NAWM) in patients, while Glx/Cre and mI/Cho ratios in NAWM showed a significant increase compared to healthy controls. In severely affected patients derived spectra reflected a decrease of NAA concentrations inside WMH when compared to healthy white matter. Metabolic abnormalities in WMH of CADASIL patients are compatible with axonal loss due to chronic micro-infarctions. Increased Glx/Cre and mI/Cho ratios in NAWM indicate an augmented glial cell density and decreased neuronal cell density. This altered tissue composition might be interpreted as adaptation to hypoperfusion and impaired vasoreactivity in NAWM of CADASIL patients. Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemia.
KeywordsCADASIL Magnetic resonance spectroscopy fMRI MRSI
T.A. received a fellowship of the European Neurological Society (ENS). The study was supported by the CADASIL Foundation of America. We thank Thomas Lange and Ulrike Dydak for providing SIview and their advice on the protocol optimization for the lactate detection and the Department of Statistics, Faculty of Medicine, University of Zurich, for statistical support.
Conflicts of interest statement
- 7.De Graaf RG (2007) In vivo NMR spectroscopy—principles and techniques, 2nd edn. Wiley, West SussexGoogle Scholar
- 14.Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cécillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 24:707–710CrossRefGoogle Scholar
- 15.Jouvent E, Viswanathan A, Mangin JF, O’Sullivan M, Guichard JP, Gschwendtner A, Cumurciuc R, Buffon F, Peters N, Pachaï C, Bousser MG, Dichgans M, Chabriat H (2007) Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL. Stroke 38:1786–1790CrossRefPubMedGoogle Scholar
- 16.Jung HH, Bassetti C, Tournier-Lasserve E, Vahedi K, Arnaboldi M, Arifi VB, Burgunder JM (1995) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a clinicopathological and genetic study of a Swiss family. J Neurol Neurosurg Psychiatry 59:138–143CrossRefPubMedGoogle Scholar
- 22.Oliveri RL, Mazzei R, Gabriele AL, Gambardella A (2001) A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy—genetic and magnetic resonance spectroscopic findings. Arch Neurol 58:1418–1422CrossRefPubMedGoogle Scholar
- 29.Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, Mas JL, Cabanis EA, Baudrimont M, Maciazek J, Bach MA, Bousser MG (1993) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 3:256–259CrossRefPubMedGoogle Scholar
- 30.Walter M, Henning A, Grimm S, Schulte RF, Beck J, Dydak U, Schnepf B, Boeker H, Boesiger P, Northoff G (2009) The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Arch Gen Psychiatry 66(5):478–486CrossRefPubMedGoogle Scholar