Brain lesion location and clinical status 20 years after a diagnosis of clinically isolated syndrome suggestive of multiple sclerosis

Background/Objectives: The objective of this study was to investigate associations between the spatial distribution of brain lesions and clinical outcomes in a cohort of people followed up 20 years after presentation with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: Brain lesion probability maps (LPMs) of T1 and T2 lesions were generated from 74 people who underwent magnetic resonance imaging (MRI) and clinical assessment a mean of 19.9 years following a CIS. One-tailed t-test statistics were used to compare LPMs between the following groups: clinically definite (CD) MS and those who remained with CIS, with an abnormal MRI; people with MS and an Expanded Disability Status Scale (EDSS) ≤3 and >3; people with relapsing–remitting (RR) and secondary progressive (SP) MS. The probability of each voxel being lesional was analysed adjusting for age and gender using a multiple linear regression model. Results: People with CDMS were significantly more likely than those with CIS and abnormal scan 20 years after onset to have T1 and T2 lesions in the corona radiata, optic radiation, and splenium of the corpus callosum (periventricularly) and T2 lesions in the right fronto-occipital fasciculus. People with MS EDSS >3, compared with those with EDSS ≤3, were more likely to have optic radiation and left internal capsule T2 lesions. No significant difference in lesion distribution was noted between RRMS and SPMS. Conclusion: This work demonstrates that lesion location characteristics are associated with CDMS and disability after long-term follow-up following a CIS. The lack of lesion spatial distribution differences between RRMS and SPMS suggests focal pathology affects similar regions in both subgroups.

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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Multiple Sclerosis Journal ◽

10.1177/1352458514568827 ◽

2015 ◽

Vol 21 (8) ◽

pp. 1013-1024 ◽

Cited By ~ 143

Author(s):

J Kuhle ◽

G Disanto ◽

R Dobson ◽

R Adiutori ◽

L Bianchi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinically Isolated Syndrome ◽

Nuclear Antigen ◽

Oligoclonal Bands ◽

Serum Samples ◽

T2 Lesions ◽

Definite Multiple Sclerosis ◽

Epstein Barr ◽

Csf Oligoclonal Bands

Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

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Cognitive impairment at the onset of multiple sclerosis: relationship to lesion location

Multiple Sclerosis Journal ◽

10.1177/1352458511398265 ◽

2011 ◽

Vol 17 (6) ◽

pp. 755-758 ◽

Cited By ~ 17

Author(s):

Françoise Reuter ◽

Wafaa Zaaraoui ◽

Lydie Crespy ◽

Anthony Faivre ◽

Audrey Rico ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Verbal Learning ◽

Clinically Isolated Syndrome ◽

Deep White Matter ◽

Lesion Location ◽

And Performance ◽

The Right ◽

The Impact ◽

Learning Performances

The impact of lesion location on cognitive functioning was assessed in a group of 97 patients with a clinically isolated syndrome. Using the Brief Repeatable Battery, we evidenced that 24% of patients showed at least one abnormal test, 20% at least two and 15% at least three. Verbal learning performances were inversely associated with presence of lesions in Broca’s area, in the right frontal lobe and in the splenium while spatial learning performances were inversely correlated to the presence of lesions in the deep white matter. No associations were evidenced between lesion location and performance of tasks exploring attention and executive functions.

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Clinical Correlations of Brain Lesion Location in Multiple Sclerosis: Voxel-Based Analysis of a Large Clinical Trial Dataset

Brain Topography ◽

10.1007/s10548-018-0652-9 ◽

2018 ◽

Vol 31 (5) ◽

pp. 886-894 ◽

Cited By ~ 8

Author(s):

Anna Altermatt ◽

Laura Gaetano ◽

Stefano Magon ◽

Dieter A. Häring ◽

Davorka Tomic ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Brain Lesion ◽

Large Clinical Trial ◽

Lesion Location ◽

Clinical Correlations

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Relevance of Brain Lesion Distribution and Frequency for Short-Term Conversion of Patients with Clinically Isolated Syndrome to Multiple Sclerosis (P03.033)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.p03.033 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. P03.033-P03.033

Author(s):

A. Giorgio ◽

M. Battaglini ◽

M. Rocca ◽

M. Absinta ◽

F. Barkhof ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Lesion ◽

Clinically Isolated Syndrome ◽

Short Term

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Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/135248506ms1263oa ◽

2006 ◽

Vol 12 (2) ◽

pp. 143-148 ◽

Cited By ~ 72

Author(s):

J Brettschneider ◽

A Petzold ◽

A Junker ◽

H Tumani

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Clinically Isolated Syndrome ◽

Axonal Damage ◽

T2 Lesions ◽

Definite Multiple Sclerosis ◽

Relapsing Remitting ◽

Csf Levels ◽

Magnetic Resonance Imaging Mri ◽

In Cis

Clinically isolated syndrome (CIS) represents the earliest phase of multiple sclerosis (MS). This study tested whether biomarkers for axonal degeneration can improve upon sensitivity and specificity of magnetic resonance imaging (MRI) parameters in predicting conversion from CIS to MS. Patients with CIS ( n=52), relapsing-remitting MS (RRMS, n=38) and age-matched controls ( n=25) were included. Cerebrospinal fluid (CSF) levels of tau and neurofilaments (NfHSMI35) were measured using ELISA. The MRI T2-lesion load and the Expanded Disability Status Scale (EDSS) were recorded. CSF tau and NfHSMI35 were elevated in CIS compared to controls (p<0.05). RRMS patients with acute relapse had higher NfHSMI35 levels than stable patients. Tau and NfHSMI35 levels correlated with EDSS in CIS and RRMS. In RRMS, the number of T2-lesions correlated with tau levels ( R=0.53, P=0.01). The sensitivity predicting the conversion from CIS to MS was higher for the combination of CSF markers (either tau or NfHSMI35 elevated) than for MRI (40 versus 34%), but could be further increased to 60% if CSF and MRI criteria were combined. Similarly, the combination of tau and NfHSMI35 showed higher specificity (94%) than MRI (82%). Tau and NfHSMI35 are valuable biomarkers for axonal damage in the CIS patients. Predicting conversion from CIS to MS can be improved if CSF markers are combined with MRI.

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Very early scans for demonstrating dissemination in time in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458507087327 ◽

2008 ◽

Vol 14 (5) ◽

pp. 631-635 ◽

Cited By ~ 13

Author(s):

C Tur ◽

M Tintoré ◽

Á Rovira ◽

C Nos ◽

J Río ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Symptom Onset ◽

Clinical Syndrome ◽

Clinically Isolated Syndrome ◽

Lesion Effect ◽

T2 Lesions ◽

Central Nervous System Demyelination ◽

Time To Relapse

Objective To evaluate the clinical significance of the 2005 modified imaging criteria for dissemination in time in multiple sclerosis stating that detection of a new T2 lesion appearing at any time compared with a reference scan done at least 30 days after the onset of a clinically isolated syndrome implies dissemination in time. Methods We included consecutive patients younger than 50 years examined at our center within 3 months of a clinical syndrome suggestive of central nervous system demyelination of the type seen in multiple sclerosis and followed for at least 3 years. We classified patients into one of two groups, according to the timing when reference scan was performed: less than 30 days and at least 30 days after symptom onset. We analyzed the interaction in time to relapse between timing of reference scan and new T2 lesion effect. Results A total of 218 patients were included. The hazard ratio (95% confidence interval) of this interaction was 0.90 (0.31–2.62) (or 1.02 (0.27–3.91) in patients with dissemination in space). Conclusions We conclude that new T2 lesions increased relapse risk regardless of timing of the reference scan, supporting the use of scans performed at any time within 30 days of symptom onset for dissemination in time demonstration.

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Internal jugular and vertebral vein volume flow in patients with clinically isolated syndrome or mild multiple sclerosis and healthy controls: results from a prospective sonographer-blinded study

Phlebology The Journal of Venous Disease ◽

10.1177/0268355513505505 ◽

2013 ◽

Vol 29 (8) ◽

pp. 528-535 ◽

Cited By ~ 16

Author(s):

Brian Chambers ◽

Jayne Chambers ◽

Leonid Churilov ◽

Heather Cameron ◽

Richard Macdonell

Keyword(s):

Multiple Sclerosis ◽

Internal Jugular Vein ◽

Jugular Vein ◽

Control Volume ◽

Clinically Isolated Syndrome ◽

Volume Flow ◽

Cube Root ◽

Flow Data ◽

Sitting Posture ◽

Significant Difference

Objectives & Methods: We evaluated internal jugular vein and vertebral vein volume flow using ultrasound, in patients with clinically isolated syndrome or mild multiple sclerosis and controls, to determine whether volume flow was different between the two groups. Results: In patients and controls, internal jugular vein volume flow increased from superior to inferior segments, consistent with recruitment from collateral veins. Internal jugular vein and vertebral vein volume flow were greater on the right in supine and sitting positions. Internal jugular vein volume flow was higher in the supine posture. Vertebral vein volume flow was higher in the sitting posture. Regression analyses of cube root transformed volume flow data, adjusted for supine/sitting, right/left and internal jugular vein/vertebral vein, revealed no significant difference in volume flow in patients compared to controls. Conclusions: Our findings further refute the concept of venous obstruction as a causal factor in the pathogenesis of multiple sclerosis. Control volume flow data may provide useful normative reference values.

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Deep learning of brain lesion patterns and user-defined clinical and MRI features for predicting conversion to multiple sclerosis from clinically isolated syndrome

Computer Methods in Biomechanics and Biomedical Engineering Imaging & Visualization ◽

10.1080/21681163.2017.1356750 ◽

2017 ◽

Vol 7 (3) ◽

pp. 250-259 ◽

Cited By ~ 3

Author(s):

Youngjin Yoo ◽

Lisa Y. W. Tang ◽

David K. B. Li ◽

Luanne Metz ◽

Shannon Kolind ◽

...

Keyword(s):

Multiple Sclerosis ◽

Deep Learning ◽

Brain Lesion ◽

Clinically Isolated Syndrome ◽

Mri Features

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Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/13524585211053001 ◽

2021 ◽

pp. 135245852110530

Author(s):

Susana Otero-Romero ◽

Pere Carbonell-Mirabent ◽

Luciana Midaglia ◽

María Zuluaga ◽

Ingrid Galán ◽

...

Keyword(s):

Multiple Sclerosis ◽

Prospective Cohort ◽

Cox Regression ◽

Clinically Isolated Syndrome ◽

Sensitivity Analyses ◽

Oligoclonal Bands ◽

Cross Sectional Survey ◽

Cross Sectional ◽

T2 Lesions ◽

Disease Modifying Treatment

Objective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.

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