Inflammation and atrophy in multiple sclerosis: MRI associations with disease course

Author(s): Lin X, Blumhardt LD


Brain atrophy may be a useful surrogate marker of axonal loss and disease progression in multiple sclerosis (MS). Several studies have suggested that inflammatory disease activity is a risk factor for atrophy in the early stages of the disease, but may become less important later in the disease course. We aimed to investigate the relationships between atrophy and active inflammation at different stages of the disease course using brain volume measurements from magnetic resonance imaging (MRI) in patients with both relapsing-remitting (RR) (n=95) and secondary progressive (SP) (n=76) MS. Conventional dual echo and three-dimensional magnetization-prepared rapid-acquisition gradient echo imaging were performed in all patients and in 31 healthy controls. Supratentorial and infratentorial brain, and lateral ventricular volumes were determined using modern design stereology. Patients with SP MS had smaller supratentorial (p=0.003) and infratentorial brain volumes (p=0.0003), and larger lateral ventricles (p=0.02) than patients with RR MS. RR MS patients with T(1)-enhancing lesions had smaller supratentorial (p=0.02) and infratentorial (p=0.002) brain volumes and larger ventricles (p=0.002) than those without enhancing lesions. SP MS patients with enhancing lesions also had significantly larger lateral ventricles (p=0.03). Categorical analysis showed that more RR MS patients with enhancing lesions had smaller supratentorial brain (p=0.005), or larger lateral ventricular (p=0.028) volumes, and more SP MS patients with enhancing lesions had increased lateral ventricle volumes (p=0.013), than patients without enhancements. The number of enhancing lesions was significantly correlated with lateral ventricular volumes in both RR MS (r=0.39, p=0.0001) and SP MS (r=0.46, p<0.0001). Our data shows that the presence of active inflammation on a single MRI in the course of RR and SP MS, is associated with a higher risk and higher level of brain atrophy. These findings emphasise the important long-term relationship between inflammation and atrophy in MS and provide additional support for the strategy of early anti-inflammatory treatment to protect tissue integrity.

Similar Articles

Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a longitudinal perfusion MRI study

Author(s): Wuerfel J, Bellmann-Strobl J, Brunecker P, Aktas O, McFarland H, et al.

Axonal transection in the lesions of multiple sclerosis

Author(s): Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, et al.

Magnetic resonance frequency shifts during acute MS lesion formation

Author(s): Wiggermann V, Hernández Torres E, Vavasour IM, Moore GR, Laule C, et al.

Weekly diffusion-weighted imaging of normal-appearing white matter in MS

Author(s): Rocca MA, Cercignani M, Iannucci G, Comi G, Filippi M

Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis

Author(s): van Walderveen MA, Kamphorst W, Scheltens P, van Waesberghe JH, Ravid R, et al.

MRI in multiple sclerosis: current status and future prospects

Author(s): Bakshi R, Thompson AJ, Rocca MA, Pelletier D, Dousset V, et al.

Quantification of perfusion and permeability in multiple sclerosis: dynamic contrast-enhanced MRI in 3D at 3T

Author(s): Ingrisch M, Sourbron S, Morhard D, Ertl-Wagner B, Kümpfel T, et al.

Diffusion tensor magnetic resonance imaging in multiple sclerosis

Author(s): Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G

Hypoperfusion and T1-hypointense lesions in white matter in multiple sclerosis

Author(s): Narayana PA, Zhou Y, Hasan KM, Datta S, Sun X, et al.

White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis

Author(s): Varga AW, Johnson G, Babb JS, Herbert J, Grossman RI, et al.

Brain atrophy: an in-vivo measure of disease activity in multiple sclerosis

Author(s): Radü EW, Bendfeldt K, Mueller-Lenke N, Magon S, Sprenger T

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria"

Author(s): Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, et al.

Clinical correlations of brain lesion distribution in multiple sclerosis

Author(s): Vellinga MM, Geurts JJ, Rostrup E, Uitdehaag BM, Polman CH, et al.

Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR

Author(s): van Waesberghe JH, van Walderveen MA, Castelijns JA, Scheltens P, Lycklama à Nijeholt GJ, et al.

Measuring myelin repair and axonal loss with diffusion tensor imaging

Author(s): Fox RJ, Cronin T, Lin J, Wang X, Sakaie K, et al.

Imaging axonal damage of normal-appearing white matter in multiple sclerosis

Author(s): Fu L, Matthews PM, De Stefano N, Worsley KJ, Narayanan S, et al.

T1 lesion load and cerebral atrophy as a marker for clinical progression in patients with multiple sclerosis

Author(s): Sailer M, Losseff NA, Wang L, Gawne-Cain ML, Thompson AJ, et al.

Secondary progressive multiple sclerosis: the relationship between short-term MRI activity and clinical features

Author(s): Tubridy N, Coles AJ, Molyneux P, Compston DA, Barkhof F, et al.

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials

Author(s): Barkhof F, Held U, Simon JH, Daumer M, Fazekas F, et al.

Poor PASAT performance correlates with MRI contrast enhancement in multiple sclerosis

Author(s): Bellmann-Strobl J, Wuerfel J, Aktas O, Dörr J, Wernecke KD, et al.