The relation of focal white matter signal abnormality and focal volume loss                 in multiple sclerosis

There were two aims to this study. First, to explore how the reduction in the volume of abnormal T2-signal intensity associated with white matter (WM) lesions in multiple sclerosis (MS) relates to tissue loss resulting from focal pathology inside lesions. Second, to demonstrate that this volume of abnormal T2-signal intensity underestimates the actual size of the region to which the direct effects of lesion activity extend. For these purposes, we used deformation field analysis to quantify the evolution of local atrophy associated with a chronic peri-ventricular lesion in a patient with secondary progressive MS. This subject had particular features that may not necessarily co-exist in a group of unselected patients, which enabled interesting observations to be made. We show, quantitatively, that the focal WM lesion was associated with adjacent regional WM volume loss, which was disproportionate to concurrent diffuse atrophy in the rest of the normal appearing brain tissue, and that the loss of volume associated with the lesion was partially reciprocated by local ventricular expansion. Our observations re-emphasise the complex relationship between the change in the volume of abnormal signal intensity on magnetic resonance images and the tissue volume change directly related to lesion pathology. Multiple Sclerosis 2007; 13: 809-813. http:// msj.sagepub.com

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Plasma Exchange in a Patient with Tumefactive, Corticosteroid-Resistant Multiple Sclerosis

International Journal of MS Care ◽

10.7224/1537-2073.2014-078 ◽

2015 ◽

Vol 17 (5) ◽

pp. 231-235 ◽

Cited By ~ 6

Author(s):

Kristin M. Ikeda ◽

Donald H. Lee ◽

J. Alexander Fraser ◽

Seyed Mirsattari ◽

Sarah A. Morrow

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Plasma Exchange ◽

Magnetic Resonance Images ◽

Periventricular White Matter ◽

Disease Modifying Therapy ◽

Natalizumab Treatment ◽

Demyelinating Lesions ◽

Recent Diagnosis ◽

Tumefactive Multiple Sclerosis

Tumefactive multiple sclerosis (MS) is an aggressive form of MS that can be difficult to treat with standard therapies. In severe MS relapses, plasma exchange (PLEX) has shown some benefit, but reports of its use in patients with tumefactive MS are limited. This article describes the successful use of PLEX in a patient with tumefactive MS. A 46-year-old right-handed woman with a recent diagnosis of MS presented with drowsiness, dysarthria, horizontal nystagmus, and quadriparesis. Her brain magnetic resonance images demonstrated multiple tumefactive demyelinating lesions in the medulla, bilateral periventricular white matter, and corona radiata white matter. She was initially treated with a 10-day course of intravenous methylprednisolone without benefit; therefore, PLEX was initiated. After the second exchange, the patient started to improve and was discharged initially to rehabilitation and then home. She was started on disease-modifying therapy with natalizumab and did not experience further relapses but had slow clinical decline during the next year, which led to discontinuation of natalizumab treatment. PLEX may be used as second-line treatment in corticosteroid-resistant MS relapses, but there are limited reports of its use in patients with tumefactive MS. This patient presented with aggressive disease with multiple tumefactive lesions and did not respond to standard treatment with corticosteroids. PLEX was successful in improving her symptoms, allowing her to return home, although the disease progressed during the next year.

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Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513515084 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1066-1073 ◽

Cited By ~ 19

Author(s):

Silvia Mangia ◽

Adam F Carpenter ◽

Andy E Tyan ◽

Lynn E Eberly ◽

Michael Garwood ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Magnetization Transfer ◽

Magnetic Resonance Images ◽

Relaxation Methods ◽

Normal Appearing White Matter ◽

Relaxation Parameters ◽

Relapsing Remitting ◽

Cortical Gray Matter ◽

The Brain

Background: Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that is “normal appearing” on T1-weighted and T2-weighted magnetic resonance images. Objectives: With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods: Nine relapsing–remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to the AC-PC line. Results: The MT ratio of regions encompassing the normal-appearing white matter (NAWM) was different in MS patients as compared with controls ( p = 0.043); however, the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups ( p = 0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p = 0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical gray matter for any relaxation parameter. Conclusions: The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

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Thalamic Injury and Cognition in Multiple Sclerosis

Frontiers in Neurology ◽

10.3389/fneur.2020.623914 ◽

2021 ◽

Vol 11 ◽

Author(s):

Moein Amin ◽

Daniel Ontaneda

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Diffusion Tensor ◽

Clinical Manifestations ◽

White Matter Injury ◽

Volume Loss ◽

Thalamic Nuclei ◽

Dorsomedial Nucleus ◽

Deep Gray Matter

Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.

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Association of regional gray matter volume loss and progression of white matter lesions in multiple sclerosis — A longitudinal voxel-based morphometry study

NeuroImage ◽

10.1016/j.neuroimage.2008.10.006 ◽

2009 ◽

Vol 45 (1) ◽

pp. 60-67 ◽

Cited By ~ 68

Author(s):

Kerstin Bendfeldt ◽

Pascal Kuster ◽

Stefan Traud ◽

Hanspeter Egger ◽

Sebastian Winklhofer ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Gray Matter Volume ◽

White Matter Lesions ◽

Volume Loss ◽

Voxel Based Morphometry ◽

Matter Volume

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Spinal Cord Atrophy in Multiple Sclerosis Caused by White Matter Volume Loss

Archives of Neurology ◽

10.1001/archneur.62.12.1859 ◽

2005 ◽

Vol 62 (12) ◽

pp. 1859 ◽

Cited By ~ 37

Author(s):

Christopher P. Gilmore ◽

Gabriele C. DeLuca ◽

Lars Bö ◽

Trudy Owens ◽

James Lowe ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

White Matter ◽

Volume Loss ◽

White Matter Volume ◽

Spinal Cord Atrophy ◽

Matter Volume

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Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000005292 ◽

2018 ◽

Vol 90 (15) ◽

pp. e1324-e1332 ◽

Cited By ~ 23

Author(s):

Laura Gaetano ◽

Dieter A. Häring ◽

Ernst-Wilhelm Radue ◽

Nicole Mueller-Lenke ◽

Avinash Thakur ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Brain Volume ◽

Percentage Change ◽

Phase Iii ◽

Volume Loss ◽

Image Evaluation ◽

Long Term Outcome ◽

Structural Image

ObjectiveTo study the effect of fingolimod on deep gray matter (dGM), thalamus, cortical GM (cGM), white matter (WM), and ventricular volume (VV) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsData were pooled from 2 phase III studies. A total of 2,064 of 2,355 (88%) contributed to the analysis: fingolimod 0.5 mg n = 783, fingolimod 1.25 mg n = 799, or placebo n = 773. Percentage change from baseline in dGM and thalamic volumes was evaluated with FMRIB’s Integrated Registration & Segmentation Tool; WM, cGM, and VV were evaluated with structural image evaluation using normalization of atrophy cross-sectional version (SIENAX) at months 12 and 24.ResultsAt baseline, compound brain volume (brain volume in the z block [BVz] = cGM + dGM + WM) correlated with SIENAX-normalized brain volume (r = 0.938, p < 0.001); percentage change from baseline in BVz over 2 years correlated with structural image evaluation using normalization of atrophy percentage brain volume change (r = 0.713, p < 0.001). For placebo, volume reductions were most pronounced in cGM, and relative changes from baseline were strongest in dGM. Over 24 months, there were significant reductions with fingolimod vs placebo for dGM (0.5 mg −14.5%, p = 0.017; 1.25 mg −26.6%, p < 0.01) and thalamus (0.5 mg −26.1%, p = 0.006; 1.25 mg −49.7%, p < 0.001). Reduction of cGM volume loss was not significant. Significantly less WM loss and VV enlargement were seen with fingolimod vs placebo (all p < 0.001). A high T2 lesion volume at baseline predicted on-study cGM, dGM, and thalamic volume loss (p < 0.0001) but not WM loss. Patients taking placebo with high dGM (hazard ratio [HR] 0.54, p = 0.0323) or thalamic (HR 0.58, p = 0.0663) volume at baseline were less likely to show future disability worsening.ConclusionsFingolimod significantly reduced dGM volume loss (including thalamus) vs placebo in patients with RRMS. Reducing dGM and thalamic volume loss might improve long-term outcome.

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Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing−remitting multiple sclerosis: A retrospective analysis

Multiple Sclerosis Journal ◽

10.1177/1352458515599072 ◽

2015 ◽

Vol 22 (5) ◽

pp. 668-676 ◽

Cited By ~ 16

Author(s):

E Fisher ◽

K Nakamura ◽

J-C Lee ◽

X You ◽

B Sperling ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Gray Matter ◽

Interferon Beta ◽

Placebo Treatment ◽

Tissue Loss ◽

Volume Loss ◽

Disability Progression ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis

Background: Changes in gray matter (GM) volume may be a useful measure of tissue loss in multiple sclerosis (MS). Objectives: To investigate the rate, patterns, and disability correlates of GM volume change in an MS treatment clinical trial. Methods: Patients ( n=140) with relapsing−remitting MS were randomized to intramuscular (IM) interferon (IFN) beta-1a or placebo. Treatment effects on GM fraction (GMF) and white matter (WM) fraction (WMF) changes, differences in rates of GMF and WMF change in year one and two on treatment, and differences in atrophy rates by disease progression status were assessed retrospectively. Results: Significantly less GM atrophy (during year two), but not WM atrophy (at any point), was observed with IM IFN beta-1a compared with placebo. Pseudoatrophy effects were more apparent in WM than in GM; in year one, greater WM volume loss was observed with IM IFN beta-1a than with placebo, whereas GM volume loss was similar between groups. Risk of sustained disability progression was significantly associated with GM, but not WM, atrophy. Conclusions: These results suggest that GMF change is more meaningful than WMF as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials.

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Automated White Matter Hyperintensity Detection in Multiple Sclerosis Using 3D T2 FLAIR

International Journal of Biomedical Imaging ◽

10.1155/2014/239123 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Yi Zhong ◽

David Utriainen ◽

Ying Wang ◽

Yan Kang ◽

E. Mark Haacke

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Signal Intensity ◽

High Spatial Frequency ◽

Inversion Recovery ◽

White Matter Hyperintensity ◽

Mr Images ◽

Automated Algorithm ◽

Fluid Attenuated Inversion Recovery

White matter hyperintensities (WMH) seen on T2WI are a hallmark of multiple sclerosis (MS) as it indicates inflammation associated with the disease. Automatic detection of the WMH can be valuable in diagnosing and monitoring of treatment effectiveness. T2 fluid attenuated inversion recovery (FLAIR) MR images provided good contrast between the lesions and other tissue; however the signal intensity of gray matter tissue was close to the lesions in FLAIR images that may cause more false positives in the segment result. We developed and evaluated a tool for automated WMH detection only using high resolution 3D T2 fluid attenuated inversion recovery (FLAIR) MR images. We use a high spatial frequency suppression method to reduce the gray matter area signal intensity. We evaluate our method in 26 MS patients and 26 age matched health controls. The data from the automated algorithm showed good agreement with that from the manual segmentation. The linear correlation between these two approaches in comparing WMH volumes was found to beY=1.04X+1.74 (R2=0.96). The automated algorithm estimates the number, volume, and category of WMH.

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Multiple sclerosis: High prevalence of the ‘central vein’ sign in white matter lesions on susceptibility-weighted images

The Neuroradiology Journal ◽

10.1177/1971400918763577 ◽

2018 ◽

Vol 31 (4) ◽

pp. 356-361 ◽

Cited By ~ 13

Author(s):

Gianvincenzo Sparacia ◽

Francesco Agnello ◽

Angelo Gambino ◽

Martina Sciortino ◽

Massimo Midiri

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Magnetic Resonance ◽

Small Vessel Disease ◽

White Matter Lesions ◽

Magnetic Resonance Images ◽

Inversion Recovery ◽

Central Vein ◽

Fluid Attenuated Inversion Recovery ◽

The Difference

Purpose The aim of this study was to determine the occurrence and distribution of the ‘central vein’ sign in white matter lesions on susceptibility-weighted magnetic resonance images in patients with multiple sclerosis (MS) and cerebral small vessel disease (CSVD). Materials and methods T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of 19 MS patients and 19 patients affected by CSVD were analysed for the presence and localisation of focal hyperintense white matter lesions. Lesions were subdivided into periventricular or non-periventricular (juxtacortical, subcortical, deep white matter and cerebellar) distributed. The number and localisation of lesions presenting with the central vein sign were recorded and compared between MS and CSVD lesions. Results A total of 313 MS patients and 75 CSVD lesions were identified on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. The central vein sign was found in 128 MS lesions (40.9%), and the majority of them (71/128, 55.5%) had a periventricular distribution. The central vein sign was found in 22 out of 75 (29.3%) CSVD lesions, and periventricular distribution was seen in six out of 22 (27.2%) CSVD lesions. The difference in the proportion of white matter hyperintense lesions that presented with the central vein sign on susceptibility-weighted images in patients with MS and CSVD was statistically different, and a significantly higher number of MS patients presented with lesions with the central vein sign compared to CSVD patients. Conclusion The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the understanding of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease.

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Deep grey matter volume loss drives disability worsening in multiple sclerosis

10.1101/182006 ◽

2017 ◽

Author(s):

Arman Eshaghi ◽

Ferran Prados ◽

Wallace Brownlee ◽

Daniel R. Altmann ◽

Carmen Tur ◽

...

Keyword(s):

Multiple Sclerosis ◽

Standard Deviation ◽

Grey Matter ◽

Therapeutic Interventions ◽

Tissue Loss ◽

Cerebral White Matter ◽

Spatiotemporal Pattern ◽

Grey Matter Volume ◽

Volume Loss

AbstractObjectiveGrey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.MethodsWe analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsingremitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.ResultsSPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; p<0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%)[p<0.01]. The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%) (all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta=0.04, p<0.001).InterpretationThis large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions.

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