Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis

Abstract

Wallerian degeneration measured by the NAA concentration at pons and cerebellar peduncles is present early in the disease and correlates with the number of relapses and disease duration.

1H MR spectroscopy of the brain in multiple sclerosis subtypes with analysis of the metabolite concentrations in gray and white matter: initial findings

“…The NAA concentrations in all PPMS/SPMS patients compared with controls are reduced significantly in GM and NAWM (P<0.01, both) although further and even more significantly so in GM. Our finding of NAA reduction in NAWM is in agreement with numerous studies focussing on NAWM [3][4][5][6][7][8][9]. Cho and Cr are decreased in the GM of PPMS/SPMS patients and Cr also in PPMS/ SPMS patients' NAWM.…”

“…This, while in agreement with observations that NAA levels are reduced in WMLs and in NAWM of patients with MS [3][4][5][6][7][8][9], contrasts sharply with the Cr [5,6,9,10] and/or Cho [4,6,9,11,12] increases reported in WML compared with controls. A complication in our WML data is that we arbitrarily included all lesions filling more than 50% of voxel volume.…”

“…Nevertheless, several issues remain unresolved. The prevailing point of view appears to be that (1) white matter (WM) metabolism is more seriously affected by MS than gray matter (GM) metabolism in analogy to what is observed on MRI [1,2], (2) N-acetylaspartate (NAA) levels are reduced in white matter lesions (WML) and in normal-appearing white matter (NAWM) of patients with MS [3][4][5][6][7][8][9], and (3) creatine (Cr; 5, 6, 9, 10) and/or choline (Cho; 4,6,9,11,12) are increased by MS, especially so in WML. However, GM involvement in relapsing remitting MS (RRMS) has been proposed recently [13], and others showed Cho as well as NAA decreases in cortical GM rather than in NAWM [14].…”

MR Spectroscopy in Multiple Sclerosis - A New Piece of the Puzzle or Just a New Puzzle

“…However, following characteristics of the NAWM of CIS and R R M S p a t i e n t s c o u l d b e i d e n t i f i e d ( t a b l e 2 , r e f e r e n c e s a r e l i s t e d c h r o n o l o g i c a l l y b y publication date). Twenty-four MRS studies were published with decreased ratios of NAA to Cr or Cho, or decreased NAA absolute concentrations in the NAWM in a total of 56 CIS or 418 RRMS patients (Davie et al, 1994;Husted et al, 1994;Peters et al, 1995;Fu et al, 1998;Schiepers et al, 1997;Foong J et al, 1999;Sarchielli et al, 1999;van Walderveen et al, 1999;Suhy et al, 2000;de Stefano et al, 2001;Tedeschi et al, 2001;Kapeller et al, 2001;Chard et al, 2002;de Stefano et al, 2002;Casanova et al 2003;Inglese et al, 2004;Adalsteinsson et al, 2004;He et al, 2005;Staffen et al, 2005;Tiberio et al, 2006;Sijens et al, 2006;Pascual et al, 2007;.…”

“…Twenty-nine MRS studies were published with no significant Cho changes in the NAWM in a total of 190 CIS or 513 RRMS patients (Husted et al, 1994;Peters et al, 1995;Schiepers et al, 1997;Davie et al, 1997;Sarchielli et al, 1999;Foong J et al, 1999;Sarchielli et al, 1999;Brex et al, 1999;van Walderveen et al, 1999;Suhy et al, 2000;de Stefano et al, 2001;Kapeller et al, 2001;Chard et al, 2002;de Stefano et al, 2002;Kapeller et al, 2002;Casanova et al 2003;Inglese et al, 2004;Adalsteinsson et al, 2004;Fernando et al, 2004;Ruiz-Pena et al, 2004;Vrenken et al, 2005;Mathiesen et al, 2005;Khan et al, 2005;Sijens et al, 2006;Khan et al, 2008;Bellmann-Strobl et al, 2009;AboulEnein et al, 2010).…”