scholarly journals 7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (10) ◽  
pp. 2973-2987 ◽  
Author(s):  
Russell Ouellette ◽  
Constantina A Treaba ◽  
Tobias Granberg ◽  
Elena Herranz ◽  
Valeria Barletta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
White Matter ◽  
Cervical Spinal Cord ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Spinal Cord Lesions ◽  
Secondary Progressive ◽  
Relapsing Remitting

Abstract We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein. Brain imaging at 7 T was used to segment cortical and white matter lesions and 3 T imaging for cortical thickness estimation. Cervical spinal cord lesions were mapped voxel-wise as a function of distance from the inner central canal CSF pool to the outer subpial surface. Similarly, brain white matter lesions were mapped voxel-wise as a function of distance from the ventricular system. Subjects with relapsing-remitting multiple sclerosis showed a greater predominance of spinal cord lesions nearer the outer subpial surface compared to secondary progressive cases. Inversely, secondary progressive participants presented with more centrally located lesions. Within the brain, there was a strong gradient of lesion formation nearest the ventricular system that was most evident in participants with secondary progressive multiple sclerosis. Lesion fractions within the spinal cord grey and white matter were related to the lesion fraction in cerebral white matter. Cortical thinning was the primary determinant of the Expanded Disability Status Scale, white matter lesion fractions in the spinal cord and brain of the 9-Hole Peg Test and cortical thickness and spinal cord grey matter cross-sectional area of the Timed 25-Foot Walk. Spinal cord lesions were localized nearest the subpial surfaces for those with relapsing-remitting and the central canal CSF surface in progressive disease, possibly implying CSF-mediated pathogenic mechanisms in lesion development that may differ between multiple sclerosis subtypes. These findings show that spinal cord lesions involve both grey and white matter from the early multiple sclerosis stages and occur mostly independent from brain pathology. Despite the prevalence of cervical spinal cord lesions and atrophy, brain pathology seems more strongly related to physical disability as measured by the Expanded Disability Status Scale.

White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis

2016 ◽  
Vol 22 (11) ◽  
pp. 1429-1437 ◽  
Author(s):  
Kim A Meijer ◽  
Nils Muhlert ◽  
Mara Cercignani ◽  
Varun Sethi ◽  
Maria A Ron ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Cognitive Domains ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Tract Damage

Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.

scholarly journals Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2276-2287 ◽  
Author(s):  
Wallace J Brownlee ◽  
Dan R Altmann ◽  
Ferran Prados ◽  
Katherine A Miszkiel ◽  
Arman Eshaghi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Spinal Cord Lesions ◽  
Secondary Progressive ◽  
Disability Status ◽  
Serial Addition

Abstract The clinical course of relapse-onset multiple sclerosis is highly variable. Demographic factors, clinical features and global brain T2 lesion load have limited value in counselling individual patients. We investigated early MRI predictors of key long-term outcomes including secondary progressive multiple sclerosis, physical disability and cognitive performance, 15 years after a clinically isolated syndrome. A cohort of patients with clinically isolated syndrome (n = 178) was prospectively recruited within 3 months of clinical disease onset and studied with MRI scans of the brain and spinal cord at study entry (baseline) and after 1 and 3 years. MRI measures at each time point included: supratentorial, infratentorial, spinal cord and gadolinium-enhancing lesion number, brain and spinal cord volumetric measures. The patients were followed-up clinically after ∼15 years to determine disease course, and disability was assessed using the Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test. Multivariable logistic regression and multivariable linear regression models identified independent MRI predictors of secondary progressive multiple sclerosis and Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test, respectively. After 15 years, 166 (93%) patients were assessed clinically: 119 (72%) had multiple sclerosis [94 (57%) relapsing-remitting, 25 (15%) secondary progressive], 45 (27%) remained clinically isolated syndrome and two (1%) developed other disorders. Physical disability was overall low in the multiple sclerosis patients (median Expanded Disability Status Scale 2, range 0–10); 71% were untreated. Baseline gadolinium-enhancing (odds ratio 3.16, P < 0.01) and spinal cord lesions (odds ratio 4.71, P < 0.01) were independently associated with secondary progressive multiple sclerosis at 15 years. When considering 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant and new spinal cord lesions over time were associated with secondary progressive multiple sclerosis. Baseline gadolinium-enhancing (β = 1.32, P < 0.01) and spinal cord lesions (β = 1.53, P < 0.01) showed a consistent association with Expanded Disability Status Scale at 15 years. Baseline gadolinium-enhancing lesions was also associated with performance on the Paced Auditory Serial Addition Test (β = − 0.79, P < 0.01) and Symbol Digit Modalities Test (β = −0.70, P = 0.02) at 15 years. Our findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset multiple sclerosis. Established MRI measures, available in routine clinical practice, may be useful in counselling patients with early multiple sclerosis about long-term prognosis, and personalizing treatment plans.

scholarly journals Conversion of diffusely abnormal white matter to focal lesions is linked to progression in secondary progressive multiple sclerosis

2020 ◽  
pp. 135245852091217
Author(s):  
Mahsa Dadar ◽  
Sridar Narayanan ◽  
Douglas L Arnold ◽  
D Louis Collins ◽  
Josefina Maranzano
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Magnetic Resonance Images ◽  
Secondary Progressive Multiple Sclerosis ◽  
Clinical Progression ◽  
Focal Lesions ◽  
Secondary Progressive ◽  
Over Time

Background: Diffusely abnormal white matter (DAWM) regions are observed in magnetic resonance images of secondary progressive multiple sclerosis (SPMS) patients. However, their role in clinical progression is still not established. Objectives: To characterize the longitudinal volumetric and intensity evolution of DAWM and focal white matter lesions (FWML) and assess their associations with clinical outcomes and progression in SPMS. Methods: Data include 589 SPMS participants followed up for 3 years (3951 time points). FWML and DAWM were automatically segmented. Screening DAWM volumes that transformed into FWML at the last visit (DAWM-to-FWML) and normalized T1-weighted intensities (indicating severity of damage) in those voxels were calculated. Results: FWML volume increased and DAWM volume decreased with an increase in disease duration ( p < 0.001). The Expanded Disability Status Scale (EDSS) was positively associated with FWML volumes ( p = 0.002), but not with DAWM. DAWM-to-FWML volume was higher in patients who progressed (2.75 cm3 vs. 1.70 cm3; p < 0.0001). Normalized T1-weighted intensity of DAWM-to-FWML was negatively associated with progression ( p < 0.00001). Conclusion: DAWM transformed into FWML over time, and this transformation was associated with clinical progression. DAWM-to-FWML voxels had greater normalized T1-weighted intensity decrease over time, in keeping with relatively greater tissue damage. Evaluation of DAWM in progressive multiple sclerosis provides a useful measure for therapies aiming to protect this at-risk tissue with the potential to slow progression.

scholarly journals Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731878334 ◽  
Author(s):  
Francisco Coret ◽  
Francisco C Pérez-Miralles ◽  
Francisco Gascón ◽  
Carmen Alcalá ◽  
Arantxa Navarré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

T1 relaxation maps allow differentiation between pathologic tissue subsets in relapsing-remitting and secondary progressive multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 556-561 ◽  
Author(s):  
A Castriota-Scanderbeg ◽  
F Fasano ◽  
M Filippi ◽  
C Caltagirone
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Relaxation Times ◽  
Brain Regions ◽  
Progressive Multiple Sclerosis ◽  
Clinical Group ◽  
Secondary Progressive ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Normal White Matter

In an attempt to clarify whether T1 relaxation time mapping may assist in characterizing the pathological brain tissue substrate of multiple sclerosis (MS), we compared the T1 relaxation times of lesions, areas of normal-appearing white matter (NAWM) located proximal to lesions, and areas of NAWM located distant from lesions in 12 patients with the relapsing-remitting and 12 with the secondary progressive (SP) subtype of disease. Nine healthy volunteers served as controls. Calculated mean T1 values were averaged across all patients within each clinical group, and comparisons were made by means of the Mann-Whitney U-test. Significant differences were found between all investigated brain regions within each clinical subgroup. Significant differences were also detected for each investigated brain region among clinical subgroups. While T1 values of NAWM were significantly higher in patients with SP disease than in normal white matter (NWM) of controls, no differences were detected when corresponding brain areas of patients with RR MS were compared with NWM of controls. T1 maps identify areas of the brain that are damaged to a different extent in patients with MS, and may be of help in monitoring disease progression.

scholarly journals Adenosine A2A Receptors in Secondary Progressive Multiple Sclerosis: A [11C]TMSX Brain PET Study

2013 ◽  
Vol 33 (9) ◽  
pp. 1394-1401 ◽  
Author(s):  
Eero Rissanen ◽  
Jere R Virta ◽  
Teemu Paavilainen ◽  
Jouni Tuisku ◽  
Semi Helin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Pet Imaging ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Adenosine A2a Receptors ◽  
A2a Receptors ◽  
Secondary Progressive ◽  
Normal Appearing White Matter ◽  
Adenosine A2a

In this study, positron emission tomography (PET) imaging with a radioligand to adenosine A2A receptors (A2AR)—a potent regulator of inflammation—was used to gain insight into the molecular alterations in normal-appearing white matter (NAWM) and gray matter (GM) in secondary progressive multiple sclerosis (SPMS). Normal-appearing white matter and GM, despite seeming normal in conventional mangnetic resonance imaging (MRI), are important loci of widespread inflammation, neuronal damage, and source of progressive disability in multiple sclerosis (MS). Dynamic PET imaging using A2AR-specific [ 11 C]TMSX and brain MRI with diffusion tensor imaging were performed to eight SPMS patients and seven healthy controls. Distribution volumes ( VT) of [ 11 C]TMSX were analyzed from 13 regions of interest using Logan plot with arterial plasma input. The SPMS patients had significantly increased [ 11 C]TMSX- VT in NAWM compared with controls (mean (s.d.): 0.55 (± 0.08) vs. 0.45 (± 0.05); P = 0.036). Both the increased VT and the decreased fractional anisotropy (FA) in NAWM were associated with higher expanded disability status scale (EDSS) scores ( P = 0.030 and P = 0.012, respectively), whereas the T2-lesion load of SPMS patients did not correlate with EDSS. This study shows, that A2ARs are increased in the brain of SPMS patients, and that [ 11 C]TMSX-PET provides a novel approach to learn about central nervous system pathology in SPMS in vivo.

Different white matter lesion characteristics correlate with distinct grey matter abnormalities on magnetic resonance imaging in secondary progressive multiple sclerosis

2009 ◽  
Vol 15 (6) ◽  
pp. 687-694 ◽  
Author(s):  
J Furby ◽  
T Hayton ◽  
D Altmann ◽  
R Brenner ◽  
J Chataway ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Secondary Degeneration ◽  
Secondary Progressive ◽  
Demyelinating Lesions ◽  
The Relationship

Background Although MRI measures of grey matter abnormality correlate with clinical disability in multiple sclerosis, it is uncertain whether grey matter abnormality measured on MRI is entirely due to a primary grey matter process or whether it is partly related to disease in the white matter. Methods To explore potential mechanisms of grey matter damage we assessed the relationship of white matter T2 lesion volume, T1 lesion volume, and mean lesion magnetisation transfer ratio (MTR), with MRI measures of tissue atrophy and MTR in the grey matter in 117 subjects with secondary progressive multiple sclerosis. Results Grey matter fraction and mean grey matter MTR were strongly associated with lesion volumes and lesion MTR mean ( r = ±0.63–0.72). In contrast, only weak to moderate correlations existed between white matter and lesion measures. In a stepwise regression model, T1 lesion volume was the only independent lesion correlate of grey matter fraction and accounted for 52% of the variance. Lesion MTR mean and T2 lesion volume were independent correlates of mean grey matter MTR, accounting for 57% of the variance. Conclusions Axonal transection within lesions with secondary degeneration into the grey matter may explain the relationship between T1 lesions and grey matter fraction. A parallel accumulation of demyelinating lesions in white and grey matter may contribute to the association of T2 lesion volume and lesion MTR with grey matter MTR.

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