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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    • "(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.
    Clinical neuroimaging 12/2014; 6. DOI:10.1016/j.nicl.2014.09.015 · 2.53 Impact Factor
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    • "Based on the location in the cortex, GM lesions are classified as type I (mixed GM/WM lesions-leukocortical); type II (intracortical); type III/IV (subpial) (Peterson et al., 2001). The GM regions more often affected by demyelination are the cingulate gyrus, frontal, temporal, insular and cerebellar cortices, the hippocampus, and deep GM nuclei (Popescu and Lucchinetti, 2012). Whether neuronal loss is independent or secondary to axonal injury it is still unknown. "
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    ABSTRACT: Multiple sclerosis is the leading nontraumatic cause of neurologic disability in young adults. The need to prevent neurodegeneration and promote repair in multiple sclerosis (MS) has gained increasing interest in the last decade leading to the search and development of pharmacological agents and non-pharmacologic strategies able to target not only the inflammatory but also the neurodegenerative component of the disease. This paper will provide an overview of the therapeutics currently employed in MS, with a focus on their potential neuroprotective effects and on the MRI methods employed to detect and monitor in-vivo neuroprotection and repair and the relevance of this information to schizophrenia investigation and treatment.
    Schizophrenia Research 05/2014; 161(1). DOI:10.1016/j.schres.2014.04.040 · 3.92 Impact Factor
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    • "Neurodegeneration in multiple sclerosis (MS) is a multifactorial process manifesting from the very onset of the disease [1] [2]. While, in the early stages of MS, neurodegeneration is mainly driven by inflammation [3], later in the course of the disease several interacting factors are involved. "
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    ABSTRACT: Background: Oxidative stress is well documented in multiple sclerosis (MS) lesions, but its correspondence at peripheral level is still controversial. Objective. To evaluate peripheral oxidative stress markers in MS patients. Methods: We studied total blood levels of Coenzyme Q10 (CoQ10), oxidized and reduced forms of glutathione, malondialdehyde, reactive oxygen species (ROS), anti-oxidized-low-density lipoproteins (anti-oxLDL) antibodies, and antioxidant power (PAO) in 87 patients with different MS clinical phenotypes and in 77 controls. Results: CoQ10 was lower whereas anti-oxLDL antibodies titer was higher in MS patients than in controls. The benign variant of MS displayed both higher CoQ10 and higher anti-oxLDL than other MS clinical variants. Female patients had lower CoQ10 and PAO and higher ROS than male patients. Differences were greater in younger patients with shorter disease duration. Surprisingly, there was no difference for these markers between treated and untreated patients. Conclusion: We found lower antioxidant agents and higher anti-oxLDL antibodies in MS, and the highest antibody titers occurred in the benign form. We suggest that natural anti-oxLDL antibodies can be protective against MS, saving blood brain barrier integrity. Our findings also suggest that milder MS is associated with a distinct oxidative stress pattern, which may provide a useful biomarker of disease prognosis.
    Journal of Immunology Research 03/2014; 2014:961863. DOI:10.1155/2014/961863 · 2.93 Impact Factor
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