Quantitative MR Imaging and Spectroscopy in Congenital Cytomegalovirus Infection and Periventricular Leukomalacia Suggests a Comparable Neuropathological Substrate of the Cerebral White Matter Lesions

Abstract

Congenital cytomegalovirus (CMV) infection and periventricular leukomalacia (PVL) both lead to static cerebral white matter lesions. In contrast to PVL, the neuropathologicAL substrate of these lesions in congenital CMV is not clear. By comparing changes in quantitative magnetic resonance (MR) parameters and MR spectroscopy metabolite concentrations we wanted to determine whether the nature of the white matter pathology in congenital CMV infection could be similar to the known pathology of PVL. Diffusion parameters, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), magnetization transfer ratio (MTR) and MR spectroscopy concentrations were studied in white matter lesions in five patients with a congenital CMV infection and six patients with PVL. In both groups ADC values were increased, FA and MTR values were reduced, concentrations of total N-acetylaspartate and choline-containing compounds were reduced; and myo-inositol concentrations were slightly increased. No differences were found between the two groups, suggesting that the pathology of the white matter lesions in congenital CMV infections is similar to that of PVL and also characterized by axonal losses, lack of myelin deposition due to oligodendrocytic losses, and astrogliosis. Congenital CMV infection and PVL affect the cerebral white matter in the same developmental period when immature oligodendrocytes are particularly vulnerable.

Key words

white matter - periventricular leukomalacia - congenital cytomegalovirus infection

References

• 1 Barkovich AJ, Lindan CE. Congenital cytomegalovirus infection of the brain: imaging analysis and embryologic considerations.  Am J Neuroradiol. 1994;  15 703-715
• 2 Cady EB. Magnetic resonance spectroscopy in neonatal hypoxic-ischaemic insults.  Child's Nerv Syst. 2001;  17 145-149
• 3 Deng W, Pleasure J, Pleasure D. Progress in periventricular leukomalacia.  Arch Neurol. 2008;  65 1291-1295
• 4 Fan GG, Yu B, Quan SM. et al . Potential of diffusion tensor MRI in the assessment of periventricular leukomalacia.  Clinical Radiology. 2006;  61 358-364
• 5 Folkerth RD. Neuropathologic substrate of cerebral palsy.  J Child Neurol. 2005;  20 940-949
• 6 Horsfield MA, Jones DK. Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases-a review.  NMR Biomed. 2002;  15 570-577
• 7 Imamura K. Proton MR spectroscopy of the brain with a focus on chemical issues.  Magn Res Med Sciences. 2003;  3 117-132
• 8 Jones DK, Horsfield MA, Simmons A. Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging.  Magn Reson Med. 1999;  42 515-525
• 9 Khwaja O, Volpe JJ. Pathogenesis of cerebral white matter injury of prematurity.  Arch Dis Child Fetal Neonatal Ed. 2008;  93 F153-F161
• 10 Kim MJ, Provenzale JM, Law M. Magnetic resonance and diffusion tensor imaging in pediatric white matter disease.  Top Magn Reson Imaging. 2006;  17 265-274
• 11 Luo MH, Schwartz PH, Fortunado EA. Neonatal neural progenitor cells and their neuronal and glial cell derivatives are fully permissive for human cytomegalovirus infection.  J Virol. 2008;  20 9994-10007
• 12 Maxim CJ, Lokensgard JR, Schleis MR. Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention.  Clin Microbiol Rev. 2009;  99-126
• 13 Mejaski-Bosnjak V . Congenital CMV infection: a common cause of childhood disability.  Dev Med Child Neurol. 2008;  50 403
• 14 Nagea LM, Hoon AH, Stashinko E. et al . Diffusion tensor imaging in children with periventricular leukomalacia: variability of injuries to white matter tracts.  AJNR. 2007;  28 1213-1222
• 15 Odeberg J, Wolmer N, Falci S. et al . Human cytomegalovirus inhibits neuronal differential and induces apoptosis in human neural precursor cells.  J Virol. 2006;  80 8929-8939
• 16 Pouwels PJW, Brockmann K, Kruse B. et al . Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS.  Pediatr Res. 1999;  46 474-485
• 17 Provencher SW. Estimation of metabolite concentrations from localized in vivo proton MR spectra.  Magn Reson Med. 1993;  30 672-679
• 18 Rezaie P, Dean A. Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system.  Neuropathology. 2002;  22 106-132
• 19 Soares DP, Law M. Magnetic resonance spectroscopy of the brain: review of metabolites and clinical applications.  Clinical Radiology. 2009;  64 12-21
• 20 Steinlin MI, Nadal D, Eich GF. et al . Late intrauterine cytomegalovirus infection: clinical and neuroimaging findings.  Pediatr Neurol. 1996;  15 249-253
• 21 Symms M, Jager HR, Schmierer K. et al . A review of structural magnetic resonance neuroimaging.  J Neurol Neurosurg Psychiatry. 2004;  75 1235-1244
• 22 Van der Voorn JP, Pouwels PJ, Hart AA. et al . Childhood white matter disorders: quantitative MR imaging and spectroscopy.  Radiology. 2006;  241 510-517
• 23 Van der Knaap MS, Vermeulen G, Barkhof F. et al . Pattern of white matter abnormalities at MR imaging: use of polymerase chain reaction testing of guthrie cards to link pattern with congenital cytomegalovirus infection.  Radiology. 2004;  230 529-536
• 24 Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances.  Lancet Neurol. 2009;  8 110-124

Notice

This article was changed according to the following erratum on March 01, 2010:

Some of the authors' names of this article were incorrect. The names of the authors should be as follows: van der Voorn JP, Pouwels PJ, Vermeulen RJ, Barkhof F, van der Knaap MS.

Correspondence