Clinical correlates of grey matter pathology in multiple sclerosis (original) (raw)
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Grey matter atrophy in patients suffering from multiple sclerosis
Ideggyógyászati szemle, 2014
White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.
DIR-visible grey matter lesions and atrophy in multiple sclerosis: partners in crime?
Journal of neurology, neurosurgery, and psychiatry, 2015
The extent and clinical relevance of grey matter (GM) pathology in multiple sclerosis (MS) are increasingly recognised. GM pathology may present as focal lesions, which can be visualised using double inversion recovery (DIR) MRI, or as diffuse pathology, which can manifest as atrophy. It is, however, unclear whether the diffuse atrophy centres on focal lesions. This study aimed to determine if GM lesions and GM atrophy colocalise, and to assess their independent relationship with motor and cognitive deficits in MS. Eighty people with MS and 30 healthy controls underwent brain volumetric T1-weighted and DIR MRI at 3 T, and had a comprehensive neurological and cognitive assessment. Probability mapping of GM lesions marked on the DIR scans and voxel- based morphometry (assessing GM atrophy) were carried out. The associations of GM lesion load and GM volume with clinical scores were tested. DIR-visible GM lesions were most commonly found in the right cerebellum and most apparent in pati...
Journal of Neuroimaging, 2007
Magnetic resonance imaging (MRI) has emerged as a powerful noninvasive tool to assist in the diagnosis and monitoring of multiple sclerosis (MS). In addition, investigators have used MRI metrics as supportive outcome measures to explore drug efficacy in clinical trials. Conventional MRI surrogates provide information at the macroscopic level but lack sensitivity and specificity in identifying the full extent of underlying MS pathology. They also show relatively weak relationships to clinical status such as predictive strength for clinical change. Advanced MRI techniques involving quantitative measures of diffuse damage in normal appearing (NA) white matter (WM) and gray matter (GM) may help in resolving this apparent clinical MRI paradox. T2 hypointensity has been described in the GM of patients with MS and has been linked to physical disability, cognitive dysfunction, and brain atrophy. While this T2 hypointensity is thought to represent iron deposition, this awaits pathologic confirmation. Advanced MRI measures of iron deposition such as R2, R2 * , R2' relaxometry, 3T imaging and other new approaches are beginning to be applied to studies of MS and should yield interesting information. Both T1 and T2 relaxometry have a role in detecting damage in NA brain tissue that escapes detection by conventional MRI lesion measures. For example, T2 mapping may allow an assessment of myelin content in NAWM. In this review, we will focus on MRI advances in the last 10 years pertaining to T1 and T2 measures of diffuse GM and WM damage. . T1-and T2-based MRI measures of diffuse gray matter and white matter damage in patients with multiple sclerosis.
PLOS ONE, 2015
Background Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients. Methods We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration <5 years), 29 with late RRMS (disease duration ! 5 years) and 20 with secondary-progressive MS (SPMS). The distribution and evolution of regional cortical thickness and GM lesions were assessed during 5-year follow-up. Results The results showed that new lesions appeared more frequently in hippocampus and parahippocampal gyri (9.1%), insula (8.9%), cingulate cortex (8.3%), superior frontal gyrus (8.1%), and cerebellum (6.5%). The aforementioned regions showed the greatest reduction in thickness/volume, although (several) differences were observed across subgroups. The correlation between the appearance of new cortical lesions and cortical thinning was stronger in CIS (r 2 = 50.0, p<0.001
Gray Matter Involvement in Multiple Sclerosis: A New Window into Pathogenesis
Journal of Neuroimaging, 2003
Gray matter (GM) involvement is detected even in the earliest stages of multiple sclerosis (MS), and GM atrophy occurs at a faster rate than white matter (WM) atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression. It remains likely that GM damage is related to WM damage. However, continued studies of GM pathology as well as neuronal and axonal involvement in MS and related experimental models are necessary to better understand the etiology and pathogenesis of the degenerative components.
Gray matter pathology in (chronic) MS: Modern views on an early observation
Journal of the Neurological Sciences, 2009
Involvement of the gray matter (GM) in the pathology of multiple sclerosis (MS) was already recognized in the early days of MS research, but the detection of (cortical) GM lesions under the microscope and with magnetic resonance imaging (MRI) techniques was initially suboptimal and could only recently be enhanced. The visualization of GM lesions in vivo opens new doors for studies focusing on clinical, especially cognitive, effects of GM pathology, as well as for monitoring of neuroprotective treatment. However, so far little is known about what causes GM pathology. In this review, several pathogenetic mechanisms will be discussed, affecting the MS brain both from the 'outside-in' and from the 'inside-out'. Also, the use and reliability of MRI atrophy measures as a monitoring tool for GM damage in the therapeutic setting will be reviewed.
Exploring the origins of grey matter damage in multiple sclerosis
Nature reviews. Neuroscience, 2015
Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage.