Adaptive metabolic changes in CADASIL white matter.
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 (1)H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. (1)H-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.
Akhvlediani
Tamar
T
Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
Henning
Anke
A
Sándor
Peter S
PS
Boesiger
Peter
P
Jung
Hans H
HH
D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D046589:CADASIL / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D011522:Protons; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics; D012720:Severity of Illness Index
C499374:NOTCH3 protein, human; D011522:Protons; D000071656:Receptor, Notch3; D051880:Receptors, Notch
Nat Genet. 1993 Mar;3(3):256-9
8485581
Stroke. 1997 Oct;28(10):1940-3
9341699
Acta Neuropathol. 1995;89(6):500-12
7676806
Stroke. 2007 Jun;38(6):1786-90
17446424
J Neurol Neurosurg Psychiatry. 1995 Aug;59(2):138-43
7629527
Phys Med Biol. 1985 Apr;30(4):341-4
4001160
Neurology. 1998 Jun;50(6):1715-21
9633716
Stroke. 1999 Dec;30(12):2637-43
10582990
J Neurol Sci. 2002 Nov 15;203-204:77-80
12417361
Neurology. 2002 Oct 22;59(8):1134-8
12395806
Magn Reson Med. 2008 Jan;59(1):40-51
18050349
Magn Reson Imaging. 2006 May;24(4):443-7
16677951
Stroke. 2001 Jan;32(1):17-21
11136908
Arch Gen Psychiatry. 2009 May;66(5):478-86
19414707
Nature. 1996 Oct 24;383(6602):707-10
8878478
Stroke. 1995 Sep;26(9):1729-30
7660422
Stroke. 2005 May;36(5):1053-8
15817893
Arch Neurol. 2001 Sep;58(9):1418-22
11559313
AJNR Am J Neuroradiol. 2001 Jan;22(1):119-27
11158897
Stroke. 2002 Feb;33(2):502-8
11823660
Magn Reson Med. 1993 Dec;30(6):672-9
8139448
J Neuropathol Exp Neurol. 2007 Jul;66(7):597-607
17620985
Stroke. 1994 Nov;25(11):2291-2
7974561
Dev Neurosci. 2000 Sep-Dec;22(5-6):418-28
11111158
Lancet Neurol. 2007 Feb;6(2):149-61
17239802
Philos Trans R Soc Lond B Biol Sci. 1999 Oct 29;354(1390):1675-86
10603619
Acta Neuropathol. 1997 Sep;94(3):247-54
9292694
Neurology. 2001 Mar 13;56(5):635-42
11245716
Ann Neurol. 1998 Nov;44(5):731-9
9818928