Determinants of Disability in Multiple Sclerosis: An Immunological and MRI Study

Multiple sclerosis (MS) is characterized by a wide interpatient clinical variability and available biomarkers of disease severity still have suboptimal reliability. We aimed to assess immunological and MRI-derived measures of brain tissue damage in patients with different motor impairment degrees, forin vivoinvestigating the pathogenesis of MS-related disability. Twenty-two benign (B), 26 secondary progressive (SP), and 11 early, nondisabled relapsing-remitting (RR) MS patients and 37 healthy controls (HC) underwent conventional and diffusion tensor brain MRI and, as regards MS patients, immunophenotypic and functional analysis of stimulated peripheral blood mononuclear cells (PBMC). Corticospinal tract (CST) fractional anisotropy and grey matter volume were lower and CST diffusivity was higher in SPMS compared to RRMS and BMS patients. CD14+IL6+ and CD4+IL25+ cell percentages were higher in BMS than in SPMS patients. A multivariable model having EDSS as the dependent variable retained the following independent predictors: grey matter volume, CD14+IL6+ and CD4+IL25+ cell percentages. In patients without motor impairment after long-lasting MS, the grey matter and CST damage degree seem to remain as low as in the earlier disease stages and an immunological pattern suggestive of balanced pro- and anti-inflammatory activity is observed. MRI-derived and immunological measures might be used as complementary biomarkers of MS severity.

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FP14-TU-03 The effect of disease duration on grey matter volume and cognitive performance in relapsing-remitting multiple sclerosis patients

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(09)70337-5 ◽

2009 ◽

Vol 285 ◽

pp. S79 ◽

Cited By ~ 1

Author(s):

A.A. Achiron ◽

S. Tal ◽

D. Magalashvili ◽

A. Achiron

Keyword(s):

Multiple Sclerosis ◽

Cognitive Performance ◽

Grey Matter ◽

Disease Duration ◽

Grey Matter Volume ◽

Matter Volume ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

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Serum neurofilament light is a sensitive biomarker that reflects grey matter volume in Japanese patients with multiple sclerosis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.117528 ◽

2021 ◽

pp. 117528

Author(s):

Juichi Fujimori ◽

Ichiro Nakashima

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Japanese Patients ◽

Grey Matter Volume ◽

Neurofilament Light ◽

Matter Volume

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Imaging Cerebral Grey Matter Volume in Multiple Sclerosis

Normal-appearing White and Grey Matter Damage in Multiple Sclerosis ◽

10.1007/978-88-470-2127-3_10 ◽

2004 ◽

pp. 111-120

Author(s):

N. De Stefano

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Grey Matter Volume ◽

Matter Volume ◽

Cerebral Grey Matter

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Altered brainstem anatomy in migraine

Cephalalgia ◽

10.1177/0333102417694884 ◽

2017 ◽

Vol 38 (3) ◽

pp. 476-486 ◽

Cited By ~ 16

Author(s):

Kasia K Marciszewski ◽

Noemi Meylakh ◽

Flavia Di Pietro ◽

Vaughan G Macefield ◽

Paul M Macey ◽

...

Keyword(s):

Grey Matter ◽

Diffusion Tensor ◽

Free Water ◽

Trigeminal System ◽

Grey Matter Volume ◽

Matter Volume ◽

Diffusion Weighted Images ◽

Diffusion Tensor Images ◽

And Diffusion ◽

Brainstem Anatomy

Background The exact mechanisms responsible for migraine remain unknown, although it has been proposed that changes in brainstem anatomy and function, even between attacks, may contribute to the initiation and maintenance of headache during migraine attacks. The aim of this investigation is to use brainstem-specific analyses of anatomical and diffusion weighted images to determine if the trigeminal system displays altered structure in individuals with migraine. Methods Voxel-based morphometry of T1-weighted anatomical images (57 controls, 24 migraineurs) and diffusion tensor images (22 controls, 24 migraineurs) were used to assess brainstem anatomy in individuals with migraine compared with controls. Results We found grey matter volume decreases in migraineurs in the spinal trigeminal nucleus and dorsomedial pons. In addition, reduced grey matter volume and increased free water diffusivity occurred in areas of the descending pain modulatory system, including midbrain periaqueductal gray matter, dorsolateral pons, and medullary raphe. These changes were not correlated to migraine frequency, duration, intensity or time to next migraine. Conclusion Brainstem anatomy changes may underlie changes in activity that result in activation of the ascending trigeminal pathway and the perception of head pain during a migraine attack.

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In vivo Effects of Mitoxantrone on the Production of Pro- and Anti-Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Secondary Progressive Multiple Sclerosis Patients

NeuroImmunoModulation ◽

10.1159/000095762 ◽

2006 ◽

Vol 13 (2) ◽

pp. 76-81 ◽

Cited By ~ 4

Author(s):

Francesco Angelucci ◽

Anna Paola Batocchi ◽

Marcella Caggiula ◽

Giovanni Frisullo ◽

Katia Patanella ◽

...

Keyword(s):

Multiple Sclerosis ◽

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Progressive Multiple Sclerosis ◽

Peripheral Blood Mononuclear ◽

Secondary Progressive ◽

Blood Mononuclear Cells ◽

Multiple Sclerosis Patients ◽

In Vivo Effects

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Whole brain and grey matter volume of Japanese patients with multiple sclerosis

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2017.03.009 ◽

2017 ◽

Vol 306 ◽

pp. 68-75 ◽

Cited By ~ 12

Author(s):

Tetsuya Akaishi ◽

Ichiro Nakashima ◽

Shunji Mugikura ◽

Masashi Aoki ◽

Kazuo Fujihara

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Japanese Patients ◽

Grey Matter Volume ◽

Whole Brain ◽

Matter Volume

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Multiple Sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001041 ◽

2021 ◽

Vol 8 (5) ◽

pp. e1041

Author(s):

Anna E. Zurawska ◽

Marcin P. Mycko ◽

Igor Selmaj ◽

Cedric S. Raine ◽

Krzysztof W. Selmaj

Keyword(s):

Multiple Sclerosis ◽

B Cell ◽

Mononuclear Cells ◽

Cell Function ◽

Brain Mri ◽

Cell Activity ◽

Bioinformatic Analysis ◽

Circular Rna ◽

Peripheral Blood Mononuclear ◽

Reverse Transcription Pcr

Background and ObjectivesTo investigate the total circular RNA (circRNA) profile in patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HCs).MethodsHybridization microarray was used to define the circRNA profile in peripheral blood mononuclear cells (PBMCs) from 20 untreated patients with RRMS (10 in relapse and 10 in remission) and 10 HCs. We analyzed close to 14,000 individual circRNAs per sample. The discovery set data were validated using quantitative reverse transcription-PCR with an independent cohort of 47 patients with RRMS (19 in relapse and 28 in remission) and 27 HCs.ResultsMicroarray analysis revealed 914 transcripts to be differentially expressed between patients with RRMS in relapse and HCs (p < 0.05). We validated 3 circRNAs from 5 showing highest levels of differential expression in the RRMS relapse vs HC group: hsa_circRNA_101348, hsa_circRNA_102611, and hsa_circRNA_104361. Their expression was significantly increased during relapse in RRMS (p = 0.0002, FC = 2.9; p = 0.01, FC = 1.6; and p = 0.001, FC = 1.5, respectively) and in patients showing gadolinium enhancement on brain MRI (hsa_circRNA_101348, p = 0.0039, FC = 2.4; hsa_circRNA_104361, p = 0.029, FC = 1.7). Bioinformatic analysis revealed 15 microRNAs interacting with these circRNAs in a complementary manner and led to the discovery and validation of 3 protein-coding RNAs upregulated in patients with RRMS during relapse. Two of these, AK2 and IKZF3, have previously been implicated in B-cell function.DiscussioncircRNAs display a distinct profile in PBMCs from patients with RRMS, and our results may implicate circRNA in the known disturbed B-cell activity in RRMS and thus represent a novel biomarker for monitoring relapse activity.

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Usefulness of two-dimensional measurements for the evaluation of brain volume and disability in multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/20552173211070749 ◽

2022 ◽

Vol 8 (1) ◽

pp. 205521732110707

Author(s):

Satori Ajitomi ◽

Juichi Fujimori ◽

Ichiro Nakashima

Keyword(s):

Multiple Sclerosis ◽

Processing Speed ◽

Lateral Ventricle ◽

Grey Matter ◽

Brain Volume ◽

Grey Matter Volume ◽

Two Dimensional ◽

Whole Brain ◽

Brain Volumes ◽

Matter Volume

Background Two-dimensional (2D) measures have been proposed as potential proxies for whole-brain volume in multiple sclerosis (MS). Objective To verify whether 2D measurements by routine MRI are useful in predicting brain volume or disability in MS. Methods In this cross-sectional analysis, eighty-five consecutive Japanese MS patients—relapsing-remitting MS (81%) and progressive MS (19%)—underwent 1.5 Tesla T1-weighted 3D MRI examinations to measure whole-brain and grey matter volume. 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), brain width, bicaudate ratio, and corpus callosum index (CCI), were obtained from each scan. Correlations between 2D measurements and 3D measurements, the Expanded Disability Status Scale (EDSS), or processing speed were analysed. Results The third and lateral ventricle widths were well-correlated with the whole-brain volume ( p < 0.0001), grey matter volume ( p < 0.0001), and EDSS scores ( p = 0.0001, p = .0004, respectively).The least squares regression model revealed that 78% of the variation in whole-brain volume could be explained using five explanatory variables, namely, LVW, CCI, age, sex, and disease duration. By contrast, the partial correlation coefficient excluding the effect of age showed that the CCI was significantly correlated with the EDSS and processing speed ( p < 0.0001). Conclusion Ventricle width correlated well with brain volumes, while the CCI correlated well with age-independent (i.e. disease-induced) disability.

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