Meningeal and cortical grey matter pathology in multiple sclerosis

Department of Anatomy and Cell Biology, University of Saskatchewan, 107Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
BMC Neurology (Impact Factor: 2.04). 03/2012; 12(1):11. DOI: 10.1186/1471-2377-12-11
Source: PubMed


Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Subpial, intracortical and leukocortical lesions are the three cortical lesion types described in the cerebral and cerebellar cortices of patients with multiple sclerosis. Cortical demyelination may be the pathological substrate of progression, and an important pathologic correlate of irreversible disability, epilepsy and cognitive impairment. Cortical lesions of chronic progressive multiple sclerosis patients are characterized by a dominant effector cell population of microglia, by the absence of macrophagic and leukocytic inflammatory infiltrates, and may be driven in part by organized meningeal inflammatory infiltrates. Cortical demyelination is also present and common in early MS, is topographically associated with prominent meningeal inflammation and may even precede the appearance of classic white matter plaques in some MS patients. However, the pathology of early cortical lesions is different than that of chronic MS in the sense that early cortical lesions are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS.

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    • "The deterioration of whole brain gray matter (GM) and white matter (WM) volumes and volumes of deep GM structures (e.g., hippocampus, thalamus, caudate, putamen, and pallidum) occurs in people with multiple sclerosis (MS) [1] [2]. Such deterioration is associated with disability status [3] and cognitive dysfunction [4] [5] [6] in MS. "
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    ABSTRACT: Background. Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). Purpose. This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. Method. 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations () controlling for demographic and clinical variables. Results. Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (, ), NWMV (, ), hippocampus (, ), thalamus (, ), caudate (, ), putamen (, ), and pallidum (, ) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. Conclusion. Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS.
    Full-text · Article · Jul 2015 · Behavioural neurology
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    • "(Popescu and Lucchinetti, 2012) However, cortical lesions in early MS may also be associated with cortical oligodendrocyte degeneration, demyelination and neuronal damage. (Popescu and Lucchinetti, 2012, Zivadinov and Pirko, 2012) While cortical demyelination and neurodegeneration in the progressive stages of the disease are mainly driven by oxidative injury, it is not fully understood whether these mechanisms are also relevant to the early stages of the disease. (Fischer et al., 2013) However, it has been shown that excessive oxidative injury may be related to the MS-specific gene expression changes of molecular pathways associated with inflammation and oxidative stress that result in DNA damage and alterations of regenerative mechanisms affecting glial and A C C E P T E D M A N U S C R I P T "
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    ABSTRACT: Background Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS). Objectives To investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS). Methods This prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons. Results SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes. Conclusions Development of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression.
    Full-text · Article · Dec 2014 · Clinical neuroimaging
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    • "Systemic inflammation is also found to correlate with progression of MS, both PPMS and SPMS (Romme Christensen et al., 2013). Although treatment of progressive patients with Natalizumab leads to a decrease in biomarkers of neurodegeneration, suggesting ongoing contribution by the peripheral immune system on the neuroinflammation during SPMS (Romme Christensen et al., 2014 ), the vast majority of inflammation leading to continuous inflammation and neurodegeneration during SPMS and PPMS, in particular in the GM, resided from intrathecally driven immune cell activation (Serafini et al., 2004; Popescu and Lucchinetti, 2012). An increase in cortical atrophy and loss of neurons, astrocytes and oligodendrocytes in a gradient pattern from the meninges are also seen in FLS positive cases in both GM lesions and NAGM (Magliozzi et al., 2010 ). "
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    ABSTRACT: B lymphocytes play an important role in the pathogenesis of multiple sclerosis. Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive multiple sclerosis (SPMS). They contain proliferating B lymphocytes, plasma cells, helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death. In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13).
    Full-text · Article · Oct 2014 · Journal of Neuroimmunology
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