Gray matter damage in multiple sclerosis: Impact on clinical symptoms

Munster, Caspar E.P. van; Jonkman, Laura E.; Weinstein, Henry C.; Uitdehaag, Bernard M. J.; Geurts, Jeroen J. G.

doi:10.1016/j.neuroscience.2015.07.006

Cited by 68 publications

(42 citation statements)

References 223 publications

(399 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, early cerebellar involvement is a predictor for disability progression in MS, given the abundant connections between the cerebellum and many cerebral cortical areas [28]. Additionally, the parietal lobe was reported to be associated with both physical disability and cognitive decline in MS [29, 30]. …”

Section: Discussionmentioning

confidence: 99%

A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression

Nakamura

Gaetano

Matsushita

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundWe compared the magnetic resonance imaging (MRI) features between Japanese and Caucasian patients with multiple sclerosis (MS), and identified the relationships between MRI features and disability.MethodsFrom the baseline data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing-remitting MS patients were enrolled. The number, volume, and distribution of brain MRI lesions were evaluated using T2-weighted (T2W) images. Cross-sectional total normalized brain volume (NBV), normalized cortical gray matter volume, normalized deep gray matter volume (NDGMV), normalized white matter volume (NWMV), and normalized thalamic volume were measured.ResultsJapanese patients had significantly lower Expanded Disability Status Scale (EDSS) scores than Caucasian patients (mean 2.0 vs. 2.3, p = 0.008), despite a similar disease duration. Japanese patients showed a trend towards fewer T2W-lesions (median 50 vs. 65, p = 0.08) and significantly lower frequencies of cerebellar and parietal lobe lesions (p = 0.02 for both) than Caucasian patients. There were no differences in T2W-lesion volume between races, whereas Japanese patients had a significantly larger T2W-lesion volume per lesion compared with Caucasian patients (median 140 mm3 vs. 85 mm3, p < 0.0001). T2W-lesion volumes were positively correlated with EDSS scores in Japanese patients (p < 0.0001). In both races, NBV, normalized cortical gray matter volume, NDGMV, and thalamic volume were negatively correlated with disease duration and EDSS scores (p < 0.01 for all). NWMV was negatively correlated with disease duration and EDSS scores only in Caucasian patients (p = 0.03 and p = 0.004, respectively). NBV, NDGMV, NWMV, and thalamic volume were consistently smaller in Japanese compared with Caucasian patients throughout the entire examined disease duration (p = 0.046, p = 0.01, p = 0.005, and p = 0.04, respectively). Japanese patients had a significantly faster reduction in NDGMV (p = 0.001), particularly for thalamic volume (p = 0.001), with disease duration compared with Caucasian patients.ConclusionsGray matter atrophy is a common denominator for disability in Japanese and Caucasian patients. Additional contributory factors for disability include T2W-lesion volume in Japanese patients and white matter atrophy in Caucasian patients. Less frequent parietal and cerebellar involvement with fewer T2W-lesions may underlie milder disability in Japanese patients.

show abstract

Section: Discussionmentioning

confidence: 99%

A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression

Nakamura

Gaetano

Matsushita

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Recently, MRI studies further broadened our knowledge about the prevalence of cortical lesions in various subtypes of MS and at different stages of the disease (50). Cortical lesions are clearly linked to cognitive impairment and disability progression (51). In this context, it is interesting that several studies suggested a correlation between the occurrence of meningeal inflammation and cortical demyelination (11, 20–22, 52, 53).…”

Section: Occurrence and Significance In Msmentioning

confidence: 99%

Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

Mitsdoerffer

Peters

2016

Front. Immunol.

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS), which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease; however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines, and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs) were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function, and clinical significance. Mechanistic studies in patients are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE) recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation, and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs.

show abstract

“…Possible mechanisms are retrospective degenerative changes, inflammatory infiltrate in the meninges, MiA, iron accumulation, and primary oligodendrocytic degeneration (51). GM atrophy correlate better with the long-term disability than WMLs (52). …”

Section: Pathological Changesmentioning

confidence: 99%

Primary Progressive Multiple Sclerosis: Putting Together the Puzzle

2017

View full text Add to dashboard Cite

The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein–Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation. Histological studies revealed diffuse infiltration of the gray and white matter as well as of the meninges with inflammatory cells such as B-, T-, natural killer, and plasma cells. While numerous anti-inflammatory agents effective in relapsing remitting multiple sclerosis basically failed in treatment of PPMS, the B-cell-depleting monoclonal antibody ocrelizumab recently broke the dogma that PPMS cannot be treated by an anti-inflammatory approach by demonstrating efficacy in a phase 3 PPMS trial. Other treatments aiming at enhancing remyelination (MD1003) as well as EBV-directed treatment strategies may be promising agents on the horizon. In this article, we aim to summarize new advances in the understanding of risk factors, pathophysiology, and treatment of PPMS. Moreover, we introduce a novel concept to understand the nature of the disease and possible treatment strategies in the near future.

show abstract

Gray matter damage in multiple sclerosis: Impact on clinical symptoms

Cited by 68 publications

References 223 publications

A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression

A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression

Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

Primary Progressive Multiple Sclerosis: Putting Together the Puzzle

Contact Info

Product

Resources

About