Predictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndrome

Objectives: To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome. Methods: The predictive values for conversion to MS of clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) variables in 114 patients with acute partial myelitis confirmed by a spinal cord lesion on MRI were studied. Other causes of cord syndromes were excluded. Results: MS was diagnosed in 78 patients (86%) during 4.0 ± 1.9 years of follow-up. Some 67 of these patients had a second clinical episode. The diagnosis of isolated myelitis was maintained for 36 patients, 78% of whom (28 cases) were followed for at least 2 years, comparable to the MS patients. Age, bladder involvement, ≥2 cord lesions on MRI, ≥9 brain lesions, ≥3 periventricular lesions and intrathecal IgG synthesis predicted conversion to clinically definite MS. Multivariate logistic analysis identified three predictors of MS diagnosis: age ≤40 years, inflammatory CSF and ≥3 periventricular lesions on brain MRI. Conclusion: Two out of three baseline factors (age, periventricular lesions and inflammatory CSF) predicted conversion to MS with better accuracy than the revised McDonald criteria for dissemination in space.

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MRI of the Entire Spinal Cord—Worth the While or Waste of Time? A Retrospective Study of 74 Patients with Multiple Sclerosis

Diagnostics ◽

10.3390/diagnostics11081424 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1424

Author(s):

Esben Nyborg Poulsen ◽

Anna Olsson ◽

Stefan Gustavsen ◽

Annika Reynberg Langkilde ◽

Annette Bang Oturai ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Cervical Spinal Cord ◽

Brain Mri ◽

Anatomical Location ◽

Spinal Cord Lesions ◽

Chi Square ◽

Exact Test ◽

Mcdonald Criteria ◽

Chi Square Test

Spinal cord lesions are included in the diagnosis of multiple sclerosis (MS), yet spinal cord MRI is not mandatory for diagnosis according to the latest revisions of the McDonald Criteria. We investigated the distribution of spinal cord lesions in MS patients and examined how it influences the fulfillment of the 2017 McDonald Criteria. Seventy-four patients with relapsing-remitting MS were examined with brain and entire spinal cord MRI. Sixty-five patients received contrast. The number and anatomical location of MS lesions were assessed along with the Expanded Disability Status Scale (EDSS). A Chi-square test, Fischer’s exact test, and one-sided McNemar’s test were used to test distributions. MS lesions were distributed throughout the spinal cord. Diagnosis of dissemination in space (DIS) was increased from 58/74 (78.4%) to 67/74 (90.5%) when adding cervical spinal cord MRI to brain MRI alone (p = 0.004). Diagnosis of dissemination in time (DIT) was not significantly increased when adding entire spinal cord MRI to brain MRI alone (p = 0.04). There was no association between the number of spinal cord lesions and the EDSS score (p = 0.71). MS lesions are present throughout the spinal cord, and spinal cord MRI may play an important role in the diagnosis and follow-up of MS patients.

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Three-Tesla MRI does not improve the diagnosis of multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000005825 ◽

2018 ◽

Vol 91 (3) ◽

pp. e249-e257 ◽

Cited By ~ 11

Author(s):

Marloes H.J. Hagens ◽

Jessica Burggraaff ◽

Iris D. Kilsdonk ◽

Marlieke L. de Vos ◽

Niamh Cawley ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Diagnostic Criteria ◽

Brain Mri ◽

White Matter Lesions ◽

Lesion Detection ◽

Mcdonald Criteria ◽

Number Of Patients ◽

Work Up ◽

Three Tesla

ObjectiveIn the work-up of patients presenting with a clinically isolated syndrome (CIS), 3T MRI might offer a higher lesion detection than 1.5T, but it remains unclear whether this affects the fulfilment of the diagnostic criteria for multiple sclerosis (MS).MethodsWe recruited 66 patients with CIS within 6 months from symptom onset and 26 healthy controls in 6 MS centers. All participants underwent 1.5T and 3T brain and spinal cord MRI at baseline according to local optimized protocols and the MAGNIMS guidelines. Patients who had not converted to MS during follow-up received repeat brain MRI at 3–6 months and 12–15 months. The number of lesions per anatomical region was scored by 3 raters in consensus. Criteria for dissemination in space (DIS) and dissemination in time (DIT) were determined according to the 2017 revisions of the McDonald criteria.ResultsThree-Tesla MRI detected 15% more T2 brain lesions compared to 1.5T (p < 0.001), which was driven by an increase in baseline detection of periventricular (12%, p = 0.015), (juxta)cortical (21%, p = 0.005), and deep white matter lesions (21%, p < 0.001). The detection rate of spinal cord lesions and gadolinium-enhancing lesions did not differ between field strengths. Three-Tesla MRI did not lead to a higher number of patients fulfilling the criteria for DIS or DIT, or subsequent diagnosis of MS, at any of the 3 time points.ConclusionScanning at 3T does not influence the diagnosis of MS according to McDonald diagnostic criteria.

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Lesion topographies in multiple sclerosis diagnosis

Neurology ◽

10.1212/wnl.0000000000004715 ◽

2017 ◽

Vol 89 (23) ◽

pp. 2351-2356 ◽

Cited By ~ 18

Author(s):

Georgina Arrambide ◽

Mar Tintore ◽

Cristina Auger ◽

Jordi Río ◽

Joaquín Castilló ◽

...

Keyword(s):

Multiple Sclerosis ◽

Optic Neuritis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Consensus Recommendation ◽

Mcdonald Criteria ◽

Lesion Topography ◽

Periventricular Lesions ◽

Periventricular Lesion ◽

Multiple Sclerosis Diagnosis

Objectives:To assess the contributions of cortico-juxtacortical and corpus callosum lesions to multiple sclerosis diagnosis and to compare the value of ≥1 vs ≥3 periventricular lesions in clinically isolated syndromes (CIS).Methods:Step 1: We evaluated lesion topography classifications in 657 patients with CIS with stepwise Cox proportional hazards regression models considering second attack as the outcome. Step 2: We established 2 dissemination in space (DIS) versions according to the periventricular lesion cutoffs of ≥1 and ≥3 and assessed their performance at 10 years with second attack as the outcome, first individually and then combined with dissemination in time (DIT) in all cases (n = 326), by age, and by CIS topography.Results:Step 1: The models (hazard ratios [95% confidence interval]) favored ≥1 over ≥3 periventricular lesions (2.5 [1.7–3.6]) and cortico-juxtacortical over juxtacortical lesions (1.4 [1.0–1.8]). Callosal lesions were not selected. Step 2: DIS specificity with ≥1 periventricular lesions was slightly lower than with ≥3 (59.1 vs 61.4) and the same after adding DIT (88.6). Regarding age, ≥3 periventricular lesions improved DIS specificity over ≥1 lesions in the 40–49 years of age bracket (66.7 vs 58.3). This difference disappeared when adding DIT (83.3). Optic neuritis had a similar pattern when evaluating CIS topographies.Conclusions:Our results comply with the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) consensus recommendation of combining cortical and juxtacortical lesions into a single term when possible. Concerning periventricular lesions, maintaining the current ≥1 cutoff in the McDonald criteria does not compromise specificity in typical CIS cases, but attention should be paid to older patients or optic neuritis cases.

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Early predictors of multiple sclerosis after a typical clinically isolated syndrome

Multiple Sclerosis Journal ◽

10.1177/1352458514533397 ◽

2014 ◽

Vol 20 (13) ◽

pp. 1721-1726 ◽

Cited By ~ 24

Author(s):

Aurélie Ruet ◽

Georgina Arrambide ◽

Bruno Brochet ◽

Cristina Auger ◽

Eva Simon ◽

...

Keyword(s):

Multiple Sclerosis ◽

At Risk ◽

High Specificity ◽

Clinically Isolated Syndrome ◽

Oligoclonal Bands ◽

Mcdonald Criteria ◽

Early Predictors ◽

Patients At Risk ◽

Magnetic Resonance Imaging Mri ◽

Periventricular Lesions

Background: The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance imaging (MRI) scan. Nevertheless, not all patients at risk fulfil criteria at baseline. Other predictive factors (PFs) are: age ≤40 years, positive oligoclonal bands (OBs), and ≥3 periventricular lesions. Objective: The purpose of this study was to evaluate the 2010 McDonald criteria performance and to assess other PFs in patients without dissemination in space (DIS). Methods: Patients with clinically isolated syndrome (CIS) underwent baseline MRI and OB determination with clinical and radiological follow-up. Adjusted hazard ratios (aHRs) for clinically definite MS were estimated for DIS, dissemination in time (DIT), and DIS+DIT. Diagnostic properties at two years were calculated. In cases without DIS, combinations of ≥2 PFs were assessed. Results: A total of 652 patients were recruited; aHRs were 3.8 (2.5–5.8) for DIS, 4.2 (1.9–9.2) for DIT, and 8.6 (5.4–13.8) for DIS+DIT. Sensitivities were 69.6%, 42.3%, and 36.4%, and specificities were 67.3%, 87.9%, and 90.2%, respectively. In patients without DIS, aHRs varied between 2.7–5.5 and specificities ranged from 73.5–89.7% for PF combinations. Conclusion: The high specificity of the 2010 McDonald criteria is confirmed. In patients without DIS, PF combinations could be helpful in identifying those at risk for MS.

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What do we currently know about the clinically isolated syndrome suggestive of multiple sclerosis? An update

Reviews in the Neurosciences ◽

10.1515/revneuro-2019-0084 ◽

2020 ◽

Vol 31 (3) ◽

pp. 335-349

Author(s):

Tomasz Grzegorski ◽

Jacek Losy

Keyword(s):

Multiple Sclerosis ◽

Predictive Factors ◽

Clinically Isolated Syndrome ◽

Clinical Image ◽

Double Blind ◽

Beneficial Effects ◽

Mcdonald Criteria ◽

Clinical Episode ◽

The Central Nervous System ◽

Large Groups

AbstractMultiple sclerosis (MS) is a chronic, demyelinating, not fully understood disease of the central nervous system. The first demyelinating clinical episode is called clinically isolated syndrome (CIS) suggestive of MS. Although the most common manifestations of CIS are long tracts dysfunction and unilateral optic neuritis, it can also include isolated brainstem syndromes, cerebellar involvement, and polysymptomatic clinical image. Recently, the frequency of CIS diagnosis has decreased due to the more sensitive and less specific 2017 McDonald criteria compared with the revisions from 2010. Not all patients with CIS develop MS. The risk of conversion can be estimated based on many predictive factors including epidemiological, ethnical, clinical, biochemical, radiological, immunogenetic, and other markers. The management of CIS is nowadays widely discussed among clinicians and neuroscientists. To date, interferons, glatiramer acetate, teriflunomide, cladribine, and some other agents have been evaluated in randomized, placebo-controlled, double-blind studies relying on large groups of patients with the first demyelinating event. All of these drugs were shown to have beneficial effects in patients with CIS and might be used routinely in the future. The goal of this article is to explore the most relevant topics regarding CIS as well as to provide the most recent information in the field. The review presents CIS definition, classification, clinical image, predictive factors, and management. What is more, this is one of very few reviews summarizing the topic in the light of the 2017 McDonald criteria.

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Leber’s hereditary optic neuropathy associated with a multiple-sclerosis-like picture in a man

Multiple Sclerosis Journal ◽

10.1177/1352458511404033 ◽

2011 ◽

Vol 17 (6) ◽

pp. 763-766 ◽

Cited By ~ 10

Author(s):

Antonella La Russa ◽

Rita Cittadella ◽

Virginia Andreoli ◽

Paola Valentino ◽

Francesca Trecroci ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Optic Neuropathy ◽

Brain Mri ◽

Resonance Imaging ◽

Gadolinium Enhancement ◽

Demyelinating Lesions ◽

Male Patients ◽

Magnetic Resonance Imaging Mri ◽

Symptoms And Signs

A 35-year-old young man displayed Leber’s optic neuropathy (LHON) due to T14484C and multiple sclerosis (MS) phenotype that was dominated by symptoms and signs of spinal cord impairment. Magnetic resonance imaging (MRI) revealed demyelinating lesions extending from D6 to D11 in the spinal cord with gadolinium enhancement, while only three linear demyelinating lesions were seen on brain MRI. In the literature, a major involvement of the spinal cord was already reported in three of four male patients with the 14484 LHON mutation who developed MS, but the reasons of this peculiar association remain unknown, and further research in this area is needed.

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Preferential spinal cord volume loss in primary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458518775006 ◽

2018 ◽

Vol 25 (7) ◽

pp. 947-957 ◽

Cited By ~ 15

Author(s):

Charidimos Tsagkas ◽

Stefano Magon ◽

Laura Gaetano ◽

Simon Pezold ◽

Yvonne Naegelin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Clinical Outcomes ◽

Brain Mri ◽

Progressive Multiple Sclerosis ◽

Lesion Volume ◽

Primary Progressive Multiple Sclerosis ◽

Primary Progressive ◽

Over Time ◽

Spinal Cord Volume

Background: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). Objective: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. Methods: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). Results: PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS. Conclusion: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

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ANALYSIS OF THE TOPIC STUDY USING 2010 MCDONALD CRITERIA

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2015-312379.122 ◽

2015 ◽

Vol 86 (11) ◽

pp. e4.27-e4

Author(s):

David Rog ◽

Jerry Wolinsky ◽

Philippe Truffinet ◽

Karthinathan Thangavelu ◽

Aaron Miller

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Resonance Imaging ◽

Mcdonald Criteria ◽

Clinical Episode ◽

Magnetic Resonance Imaging Lesion ◽

Consistent Treatment ◽

Post Hoc ◽

Reduced Risk ◽

Risk Of Relapse

IntroductionTOPIC (NCT00622700) was designed to evaluate teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis (MS). Teriflunomide 14 mg reduced risk of relapse determining conversion to clinically definite MS by 42.6%, and of new relapse or magnetic resonance imaging lesion by 34.9% vs placebo. After study initiation, the 2005 McDonald criteria were revised, potentially allowing earlier MS diagnosis.MethodsThe 2010 McDonald criteria were applied retrospectively. Patients who received teriflunomide 14 mg or placebo for ≤108 weeks were grouped according to fulfilment of 2010 criteria at baseline. Time to MS was analysed for those not fulfilling the 2010 criteria at baseline. Additional post hoc analyses will evaluate differences in outcomes based on baseline radiological characteristics of reclassified patients.ResultsPatients receiving teriflunomide 14mg (n=214) or placebo (n=197) were analysed. For those not meeting the 2010 criteria (n=163), probability of conversion to MS was 54.1% (14 mg) and 74.4% (placebo). Teriflunomide 14mg reduced the probability of conversion to MS by 39.1% vs placebo. Data regarding time to MS based upon baseline radiological characteristics will be presented.ConclusionsTeriflunomide demonstrates a consistent treatment effect in patients with MS diagnosed according to differing diagnostic criteria. (Study supported by Genzyme, a Sanofi company).

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Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519900971 ◽

2020 ◽

Vol 27 (1) ◽

pp. 28-38 ◽

Cited By ~ 1

Author(s):

Rosa Cortese ◽

Carmen Tur ◽

Ferran Prados ◽

Torben Schneider ◽

Baris Kanber ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Brain Mri ◽

Progressive Multiple Sclerosis ◽

Cervical Cord ◽

Primary Progressive Multiple Sclerosis ◽

Disability Progression ◽

Mixed Effect ◽

Primary Progressive ◽

Over Time

Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. Methods: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. Results: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years. Conclusion: Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.

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Imaging of the Spinal Cord in Multiple Sclerosis: Past, Present, Future

Brain Sciences ◽

10.3390/brainsci10110857 ◽

2020 ◽

Vol 10 (11) ◽

pp. 857

Author(s):

Yongsheng Chen ◽

Ewart Mark Haacke ◽

Evanthia Bernitsas

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Disease Progression ◽

White Matter Lesions ◽

Quantitative Mri ◽

Axonal Loss ◽

Spinal Cord Atrophy ◽

Diagnosis And Prognosis ◽

Mcdonald Criteria ◽

Spinal Cord Imaging

Spinal cord imaging in multiple sclerosis (MS) plays a significant role in diagnosing and tracking disease progression. The spinal cord is one of four key areas of the central nervous system where documenting the dissemination in space in the McDonald criteria for diagnosing MS. Spinal cord lesion load and the severity of cord atrophy are believed to be more relevant to disability than white matter lesions in the brain in different phenotypes of MS. Axonal loss contributes to spinal cord atrophy in MS and its degree correlates with disease severity and prognosis. Therefore, measures of axonal loss are often reliable biomarkers for monitoring disease progression. With recent technical advances, more and more qualitative and quantitative MRI techniques have been investigated in an attempt to provide objective and reliable diagnostic and monitoring biomarkers in MS. In this article, we discuss the role of spinal cord imaging in the diagnosis and prognosis of MS and, additionally, we review various techniques that may improve our understanding of the disease.

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