Focal thinning of the cerebral cortex in multiple sclerosis

Abstract

Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo, the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper-intense and T1 hypo-intense lesion volumes. High-resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age-matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject's entire brain and computed cross-subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression.

Focal cortical atrophy in multiple sclerosis: Relation to lesion load and disability

“…However, this is unlikely since the correlation between cortical thickness and age, in our patient sample, revealed statistically significant areas bilaterally in premotor and primary sensorimotor and visual cortices, confirming previous findings in normal aging (Salat et al, 2004). The low degree of cortical thinning per either TWMLL or disability score in primary sensorimotor areas in our relatively mildly impaired patients suggests that atrophy of primary motor cortex preferentially appears later in the disease course (Sailer et al, 2003).…”

“…Total brain atrophy can be viewed as a surrogate marker of the destructive pathological processes taking place in MS and can be observed with magnetic resonance imaging (MRI) by measuring the brain parenchymal fraction, a normalized measure that represents the sum of both gray matter (GM) and WM atrophy (Chard et al, 2002). In addition to establishing global brain atrophy as a pathological feature of the disease, studies have focused separately on the atrophy of cortical GM by measuring decreases in normalized cortical volumes (De Stefano et al, 2003), by means of an ordinal visual scale (Bakshi et al, 2001), or by directly measuring cortical thickness in vivo (Sailer et al, 2003;Chen et al, 2004). MS-related cerebral atrophy appears to be clinically relevant as it correlates with measures of both disability (Bakshi et al, 2001;De Stefano et al, 2003) and disease progression (Hardmeier et al, 2003;Kalkers et al, 2002).…”

Classifying minimally disabled multiple sclerosis patients from resting state functional connectivity

“…Likewise, some temporal regions (with high regional discriminative weights in our data) have also been found to show a particularly early occurrence of grey matter atrophy and cortical thinning, even after less than 3 years disease duration (Sailer et al, 2003). Recent multivariate predictive modelling results on structural images also report the relative high importance of the superior temporal gyrus and middle temporal gyrus (among others) in distinguishing early from late MS patients (Bendfeldt et al, 2012).…”

A comparison of voxel and surface based cortical thickness estimation methods

“…The thickness of the cortex is of interest as it develops, follows the normal ageing process and changes under a wide variety of neurodegenerative diseases. Recently, imaging studies of cortical thickness have compared the group-wise differences between healthy control subjects and patients with conditions such as sporadic and familial Alzheimer's disease (AD) Gutierrez-Galve et al, 2009;Knight et al, 2009), fronto-temporal lobar degeneration (FTLD) (Du et al, 2007;Rohrer et al, 2009), posterior cortical atrophy , multiple sclerosis (Sailer et al, 2003), Huntington's disease (Rosas et al, 2008), and the changes that occur in healthy controls under normal ageing (Salat et al, 2004).…”