Top

Published in:

01-02-2010 | Original Communication

Adaptive metabolic changes in CADASIL white matter

Authors: Tamar Akhvlediani, Anke Henning, Peter S. Sándor, Peter Boesiger, Hans H. Jung

Published in: Journal of Neurology | Issue 2/2010

Abstract

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.

Angelie E, Bonmartin A, Boudraa A, Gonnaud PM, Mallet JJ, Sappey-Marinier D (2001) Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study. Am J Neuroradiol 22:119–127PubMed

Auer DP, Schirmer T, Heidenreich JO, Herzog J, Puetz B, Dichgans M (2001) Altered white, grey matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study. Neurology 56:635–642PubMed

Barkhof F, van Walderveen M (1999) Characterization of tissue damage in multiple sclerosis by nuclear magnetic resonance. Philos Trans R Soc Lond B Biol Sci 354:1675–1686CrossRefPubMed

Brooks WM, Wesley MH, Kodituwakku PW, Garry PJ, Rosenberg GA (1997) 1H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly. Stroke 28:1940–1943PubMed

Chabriat H, Bousser MG, Pappata S (1995) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a positron emission tomography study in two affected family members. Stroke 26:1729–1730PubMed

Chabriat H, Pappata S, Poupon C, Clark CA, Vahedi K, Poupon F, Mangin JF, Pachot-Clouard M, Jobert A, Le Bihan D, Bousser MG (1999) Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI. Stroke 30:2637–2643PubMed

De Graaf RG (2007) In vivo NMR spectroscopy—principles and techniques, 2nd edn. Wiley, West Sussex

Dichgans M (2002) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: phenotypic and mutational spectrum. J Neurological Sci 203–204:77–80CrossRef

Dichgans M (2007) Genetics of ischemic stroke. Lancet Neurol 6:149–161CrossRefPubMed

10.

Dichgans M, Mayer M, Uttner I, Bruening R, Mueller-Hoecker J, Rungger G, Ebke M, Klockgether T, Gasser T (1998) The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol 44:731–739CrossRefPubMed

11.

Gray F, Polivka M, Viswanathan A, Baudrimont M, Bousser MG, Chabriat H (2007) Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol 66:597–607CrossRefPubMed

12.

Haase A, Frahm J, Hanicke W, Matthaei D (1985) 1H NMR chemical shift selective (CHESS) imaging. Phys Med Biol 30(4):341–344CrossRefPubMed

13.

Henning A, Schär M, Schulte RF, Wilm B, Pruessmann KP, Boesiger P (2008) SELOVS: brain MRSI localization based on highly selective T₁- and B₁-insensitive outer-volume suppression at 3T. Magn Reson Med 59:40–51CrossRefPubMed

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 24:707–710CrossRef

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 38:1786–1790CrossRefPubMed

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 59:138–143CrossRefPubMed

17.

Kemp GJ (2000) Non-invasive methods for studying brain energy metabolism: what they show and what it means. Dev Neurosci 22:418–428CrossRefPubMed

18.

Lacombe P, Oligo C, Domenga V, Tournier-Lasserve E, Joutel A (2005) Impaired cerebral vasoreactivity in a transgenic mouse model of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy arteriopathy. Stroke 36:1053–1058CrossRefPubMed

19.

Macri MA, Colonnese C, Garreffa G, Fattapposta F, Restuccia R, Bianco F, Labruna L, Maraviglia B (2006) A chemical shift imaging study on regional metabolite distribution in a CADASIL family. Magn Reson Imaging 24:443–447CrossRefPubMed

20.

Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, Powell JF (2002) Diagnostic strategies in CADASIL. Neurology 59:1134–1138PubMed

21.

Mellies JK, Bäumer T, Müller JA, Tournier-Lasserve E, Chabriat H, Knobloch O, Hackelöer HJ, Goebel HH, Wetzig L, Haller P (1998) SPECT study of a German CADASIL family: a phenotype with migraine and progressive dementia only. Neurology 50:1715–1721PubMed

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 58:1418–1422CrossRefPubMed

23.

Pfefferkorn T, von Stuckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M (2001) Reduced cerebrovascular CO(2) reactivity in CADASIL: a transcranial Doppler sonography study. Stroke 32:17–21PubMed

24.

Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679CrossRefPubMed

25.

Reddy H, De Stefano N, Mortilla M, Federico A, Matthews PM (2002) Functional reorganization of motor cortex increases with greater axonal injury from CADASIL. Stroke 33:502–508CrossRefPubMed

26.

Rubio A, Rifkin D, Powers JM, Patel U, Stewart J, Faust P, Goldman JE, Mohr JP, Numaguchi Y, Jensen K (1997) Phenotypic variability of CADASIL and novel morphologic findings. Acta Neuropathol 94:247–254CrossRefPubMed

27.

Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, Tournier-Lasserve E (1994) Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 25:2291–2292PubMed

28.

Ruchoux MM, Guerouaou D, Vandenhaute B, Pruvo JP, Vermersch P, Leys D (1995) Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol 89:500–512CrossRefPubMed

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 3:256–259CrossRefPubMed

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):478–486CrossRefPubMed

Title: Adaptive metabolic changes in CADASIL white matter
Authors: Tamar Akhvlediani
Anke Henning
Peter S. Sándor
Peter Boesiger
Hans H. Jung
Publication date: 01-02-2010
Publisher: D. Steinkopff-Verlag
Published in: Journal of Neurology / Issue 2/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-009-5281-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Adaptive metabolic changes in CADASIL white matter

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2010

A clinical, radiological and outcome study of status epilepticus from India

Bilateral brainstem activation by thermal stimulation of the face in healthy volunteers

Alaska, multiple sclerosis, and the vitamin D hypothesis

Albert Gombault (1844–1904)

Demographic and clinic characteristics of French patients treated with natalizumab in clinical practice

Apathy in drug-naïve patients with incident Parkinson’s disease: the Norwegian ParkWest study