Dissemination In Space Criteria Research Articles

Improving criteria for dissemination in space in multiple sclerosis by including additional regions.

We investigated the effects of adding regions to current dissemination in space (DIS) criteria for multiple sclerosis (MS). Participants underwent brain, optic nerve, and spinal cord MRI. Baseline DIS was assessed by 2017 McDonald criteria and versions including optic nerve, temporal lobe, or corpus callosum as a fifth region (requiring 2/5), a version with all regions (requiring 3/7) and optic nerve variations requiring 3/5 and 4/5 regions. Performance was evaluated against MS diagnosis (2017 McDonald criteria) during follow-up. Eighty-four participants were recruited (53F, 32.8 ± 7.1 years). 2017 McDonald DIS criteria were 87% sensitive (95% CI: 76-94), 73% specific (50-89), and 83% accurate (74-91) in identifying MS. Modified criteria with optic nerve improved sensitivity to 98% (91-100), with specificity 33% (13-59) and accuracy 84% (74-91). Criteria including temporal lobe showed sensitivity 94% (84-98), specificity 50% (28-72), and accuracy 82% (72-90); criteria including corpus callosum showed sensitivity 90% (80-96), specificity 68% (45-86), and accuracy 85% (75-91). Criteria adding all three regions (3/7 required) had sensitivity 95% (87-99), specificity 55% (32-76), and accuracy 85% (75-91). When requiring 3/5 regions (optic nerve as the fifth), sensitivity was 82% (70-91), specificity 77% (55-92), and accuracy 81% (71-89); with 4/5 regions, sensitivity was 56% (43-69), specificity 95% (77-100), and accuracy 67% (56-77). Optic nerve inclusion increased sensitivity while lowering specificity. Increasing required regions in optic nerve criteria increased specificity and decreased sensitivity. Results suggest considering the optic nerve for DIS. An option of 3/5 or 4/5 regions preserved specificity, and criteria adding all three regions had highest accuracy.

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. We analyzed children (≤ 18y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). We included 103 children with RIS (67% girls, median age = 14.9y). Children ≥ 12y were more likely than children < 12y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12y (median 11d vs. 159d, p = 0.03). Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.

Optic nerve topography in multiple sclerosis diagnostic criteria: Existing knowledge and future directions.

Current diagnostic criteria for multiple sclerosis (MS) do not consider the optic nerve as a typical topography for establishing the diagnosis. Recent studies have proved the utility of optic nerve magnetic resonance imaging, optical coherence tomography and visual evoked potentials in detecting optic nerve lesions during the early stages of MS. In addition, emerging evidence supports the inclusion of optic nerve topography as a fifth region to fulfil the dissemination in space criteria. Anticipating a modification in the McDonald criteria, it is crucial for neurologists to familiarize with the diagnostic properties of each test in detecting optic nerve lesions and understand how to incorporate them into the MS diagnostic process. Therefore, the objective of this article is to review the existing evidence supporting the use of these tests in the diagnostic process of MS and provide a practical algorithm that can serve as a valuable guide for clinical practice.

Identification of demyelinating lesions and application of McDonald criteria when confronted with white matter lesions on brain MRI

IntroductionWhite matter lesions (WML) on magnetic resonance imaging (MRI) are common in clinical practice. When analyzing WML, radiologists sometimes propose a pathophysiological mechanism to explain the observed MRI abnormalities, which can be a source of anxiety for patients. In some cases, discordance may appear between the patient's clinical symptoms and the identification of the MRI-appearing WML, leading to extensive diagnostic work-up. To avoid misdiagnosis, the analysis of WML should be standardized, and a consensual MRI reading approach is needed. ObjectiveTo analyze the MRI WML identification process, associated diagnosis approach, and misinterpretations in physicians involved in WML routine practice. MethodsThrough a survey distributed online to practitioners involved in WML diagnostic work-up, we described the leading causes of MRI expertise misdiagnosis and associated factors: clinical experience, physicians’ subspecialty and location of practice, and type of device used to complete the survey. The survey consisted of sixteen T2-weighted images MRI analysis, from which ten were guided (binary response to lesion location identification), four were not shown (multiple possible answers), and two were associated with dissemination in space (DIS) McDonald criteria application. Two independent, experienced practitioners determined the correct answers before the participants’ completion. ResultsIn total, 364 participants from the French Neuro Radiological (SFNR), French Neurological (SFN), and French Multiple Sclerosis (SFSEP) societies completed the survey entirely. According to lesion identification, 34.3% and 16.9% of the participants correctly identified juxtacortical and periventricular lesions, respectively, whereas 56.3% correctly identified non-guided lesions. Application of the 2017 McDonald's DIS criteria was correct for 35.3% of the participants. According to the global survey scoring, factors independently associated with correct answers in multivariate analysis were MS-expert subspecialty (P<0.001), young clinical practitioners (P=0.02), and the use of a computer instead of a smartphone to perform WML analysis (P=0.03). ConclusionOur results highlight the difficulties regarding WML analysis in clinical practice and suggest that radiologists and neurologists should rely on each other to ensure the diagnosis of multiple sclerosis and related disorders and limit misdiagnoses.

A multicenter study of radiologically isolated syndrome in children and adolescents: Can we predict the course?

ObjectivesTo evaluate clinical characteristics, imaging features and etiological profile of Radiologically Isolated Syndrome (RIS) along with clinical and radiological follow-up. MethodsDemographic, clinical and radiological data of patients younger than 18 years fulfilling the criteria for RIS were retrospectively analyzed. RIS was defined by the detection of lesions meeting the revised 2010 McDonald Criteria for dissemination in space on magnetic resonance imaging (MRI) in the absence of any symptoms of demyelinating disease or an alternative cause for the MRI findings. ResultsThere were total 69 patients (38 girls, 31 boys). The median age at index MRI was 15.7 years, and median follow-up time was 28 months. The most common reason for neuroimaging was headache (60.9%). A first clinical event occurred with median 11 months in 14/69 (20%) of cases. Those with oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and follow-up longer than 3 years were more likely to experience a clinical event (p<0.05): 25% of those with OCB manifested clinical symptoms within the first year and 33.3% within the first two years compared to 6.3% and 9.4%, respectively in those without OCB. Radiological evolution was not associated with any variables: age, sex, reason for neuroimaging, serum 25-hydroxyvitamin D level, elevated IgG index, OCB positivity, total number and localization of lesions, presence of gadolinium enhancement, achievement of 2005 criteria for DIS and duration of follow-up. ConclusionChildren and adolescents with RIS and CSF OCB should be followed-up for at least 3 years in order to detect any clinical symptoms suggestive of a demyelinating event. Because disease-modifying treatments are not approved in RIS and no consensus report justifies their use especially in pediatric RIS, close follow-up of OCB-positive patients is needed for early recognition of any clinical event and timely initiation of specific treatment.

Defining the natural history of tumefactive demyelination: A retrospective cohort of 257 patients.

To describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes. Retrospective review of TD cases seen at Mayo Clinic, 1990-2021. Of 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow-up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), 0 had aquaporin-4-IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic. Onset before age 18 was present in 18/257 (7%). Female to male ratio was 1.3:1. Cerebrospinal fluid oligoclonal (CSF) bands were present in 95/153 (62%). TD was the first demyelinating attack in 176/257 (69%). At presentation, 59/126 (47%) fulfilled Barkhof criteria for dissemination in space, 59/100 (59%) had apparent diffusion coefficient (ADC) restriction, and 57/126 (45%) had mass effect. Despite aggressive clinical presentation at onset, 181/257 (70%) of patients remained fully ambulatory (Expanded Disability Status Scale [EDSS] ≤4) after a 3.0-year median follow-up duration. Severe initial attack-related disability (EDSS ≥4) was more common in patients with motor symptoms (81/143 vs. 35/106, p < 0.0001), encephalopathy (20/143 vs. 2/106, p < 0.0001) and ADC restriction on initial MRI (42/63 vs. 15/33, p = 0.04). Poor long-term outcome (EDSS ≥4) was more common in patients with older onset age (41.9 ± 15 vs. 36.8 ± 15.6, p = 0.02) and motor symptoms at onset (49/76 vs. 66/171, p < 0.0001). Most TD patients should be considered part of the MS spectrum after excluding MOGAD and NMOSD. Motor symptoms and older age at presentation portend a poor outcome.

Radiologically Isolated Syndrome and the Multiple Sclerosis Prodrome in Pediatrics: Early Features of the Spectrum of Demyelination

Radiologically isolated syndrome refers to the clinical scenario in which individuals have imaging concerning for multiple sclerosis and would otherwise satisfy radiographic dissemination in space criteria, but do not have any attributable signs or symptoms. Radiologically isolated syndrome has been increasingly recognized in the pediatric population and it is understood certain individuals will transition to a formal diagnosis of multiple sclerosis over time. This review aims to outline the available data within this unique population including the diagnostic criteria, epidemiology, risk factors associated with transitioning to multiple sclerosis, and the current therapeutic landscape. Radiologically isolated syndrome will also be positioned within a broader spectrum of demyelinating disease as recent data has pointed towards a likely prodromal phase that precedes a first clinical event and diagnosis of multiple sclerosis. Characterizing the radiographic features, clinical symptoms, and biomarkers that constitute this prodromal phase of multiple sclerosis would help identify patients who may most benefit from early intervention in the future.

Addition of optic nerve involvement to dissemination in space criteria for multiple sclerosis – the value of optical coherence tomography (S46.009)

Addition of optic nerve involvement to dissemination in space criteria for multiple sclerosis – the value of optical coherence tomography (S46.009)

The radiologically isolated syndrome: revised diagnostic criteria.

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.

Disease Characteristics of Seropositive Neuromyelitis Optica Spectrum Disorder in a Turkish Cohort

Objective To determine the clinical, demographic and imaging characteristics of a Turkish cohort with aquaporin-4-antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) from a single center. Background NA. Design/Methods 35 patients seen between January-2008 and December-2020 with a diagnosis of AQP4-IgG+NMOSD who could be studied in detail were included in the study. Inclusion criteria for patients with NMOSD diagnosis was defined according to International Consensus Diagnostic Criteria (Wingerchuk et al.2015) and all patients were confirmed for AQP4-IgG positive serology at least once by Euroimmune transfected cells assay (EU90). Demographic, clinical and MRI data were obtained retrospectively. Results The female-to-male ratio was 16.5: 1. The mean age of disease onset was 26,16±10,96 years for patients with optic neuritis onset (n:12), and 43.17±11,95 for the subgroup that started with transverse myelitis (TM) (n:16), confirming a significant difference of age at onset according to the first attack type (p &lt; 0.001). The mean age at onset in 5 patients with area postrema syndrome was 35,74±16,83. Half of the total attacks occurred within the first year of disease onset (98/196). The mean time to diagnosis was 2,98±5,78 years after the initial attack. Disease duration was 10,06±9,76 years. Cerebrospinal fluid oligoclonal bands were studied in 24 and were positive in 25%. An autoimmune rheumatologic disease comorbidity was present in 34.5% of the patients. In patients with MRI disclosing = 2 McDonald dissemination in space criteria (spinal included) was more common in TM group and correlated with a higher disability (EDSS) score. Conclusions Turkish AQP4-IgG+NMOSD patients whose disease start with optic neuritis have an earlier age of onset compared to the ones with TM onset. Half of the total attacks occur within the first year of disease onset. Patients with = 2 McDonald MRI dissemination in space criteria were more common in the TM group and had a higher disability (EDSS) score.

The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome

BackgroundPatients with radiologically isolated syndrome (RIS) exhibit CNS lesions suggestive of multiple sclerosis (MS) in the absence of overt neurological symptoms characteristic of the disease. They may have concurrent brain atrophy, subtle cognitive impairment, and intrathecal inflammation. At least half ultimately develop MS, cementing RIS as preclinical MS for many. However, high-quality data, including immunologic biomarkers, to guide treatment decisions in this population are lacking. Early intervention with ocrelizumab, a humanized monoclonal antibody approved for relapsing and primary progressive MS that targets CD20+ B-cells, may affect disease course and improve long-term outcomes. The objective of this study is to describe the protocol for CELLO, a clinical trial assessing the effect of ocrelizumab on RIS. MethodsThe CELLO clinical trial, a phase 4, multicenter, randomized, double-blind, placebo-controlled study conducted as an academic-industry collaboration, aims to (1) assess the efficacy of ocrelizumab in patients with RIS and (2) identify biomarkers indicative of emerging autoimmunity as well as immune recovery after transient B-cell depletion. The study will enroll 100 participants across ≥15 sites. Participants will be aged 18 to 40 years, have RIS (defined as meeting 2017 revised McDonald criteria for dissemination in space), and have either been diagnosed with RIS within the last 5 years or have had new brain lesions identified within 5 years of study entry. A screening program of first-degree relatives of patients with MS will be used to boost recruitment. Eligible patients will be randomized 1:1 to receive 3 courses of ocrelizumab or placebo at baseline, week 24, and week 48. Patients will subsequently be followed up for ≥3 years. The primary outcome is time to development of new radiological or clinical evidence of MS. Secondary and exploratory objectives will investigate neuroimaging, serological and immunologic biomarkers, cognitive function, and patient-reported outcomes. A substudy using single-cell RNA sequencing to characterize blood and CSF immune cells will assess markers associated with conversion to clinical MS. ConclusionThe CELLO study will improve the understanding of B-cell biology in early MS disease pathophysiology, characterize the emergence of CNS autoimmunity, and provide evidence to inform treatment decision-making for individuals with RIS. ClinicalTrials.govNCT04877457

Population-based incidence and clinico-radiological characteristics of tumefactive demyelination in Olmsted County, Minnesota, United States.

Tumefactive demyelination (TD) presents with large inflammatory lesions mimicking tumors or other space-occupying lesions. Limited epidemiological, clinical and radiological data exist for TD. We aimed to report the incidence rate, and clinical and radiological features of TD in Olmsted County, Minnesota. We retrospectively reviewed patients with central nervous system inflammatory demyelination-related diagnostic codes (January 1, 1998 to December 31, 2018) in the Rochester Epidemiology Project database, and adjusted incidence rates by age and sex to the 2010 US total population. We used the Expanded Disability Status Scale (EDSS) to assess outcomes (index attack and last follow-up). Of 792 multiple sclerosis (MS) patients, 15 (eight males, seven females) had tumefactive MS, representing 1.9% of the MS population. The median (range) age at attack onset was 34.2(2-61) years. Tumefactive lesion was the first clinical MS attack in 8/16 patients. Cerebrospinal fluid oligoclonal bands (OCBs) were present in 8/12 patients and 11/16 patients met the Barkhof criteria for dissemination in space. Most patients remained fully ambulatory (EDSS score ≤4 in 13/16 patients [81%]) after a median (range) follow-up duration of 10.5(1-20.5) years. Age-adjusted annual incidence rates were 0.46/100,000 (95% confidence interval [CI] 0.12-0.81) for female patients, 0.66/100,000 (95% CI 0.23-1.02) for male patients, and 0.56/100,000 [95% CI 0.28-0.83] overall. When age- and sex-adjusted to the 2010 US total population, the overall annual incidence rate was 0.57 (95% CI 0.28-0.84). Despite aggressive clinical presentation at disease onset, most patients remained fully ambulatory (EDSS score ≤4 in 13/16 patients) with a relapsing-remitting course. Although incidence is rare, TD should be suspected in patients presenting with subacutely progressive neurological deficits associated with magnetic resonance imaging findings of ring enhancement, apparent diffusion coefficient restriction, and OCB on spinal fluid analysis.

Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome: A MAGNIMS Study.

To compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing multiple sclerosis (MS) diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of MS. CSF examination and brain and spinal cord MRI obtained ≤5 months from CIS onset and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 patients with CIS from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Scale score (EDSS) ≥3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), dissemination in time (DIT) (including oligoclonal bands assessment), and DIS plus DIT for predicting a second clinical attack (clinically definite MS [CDMS]) and EDSS ≥3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated. At follow-up (median 69.1 months), 406/785 patients with CIS developed CDMS. At 36 months, the 2017 DIS plus DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60), and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision, 3.2; 2010 revision, 13.0; CDMS, 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years. The 2017 McDonald criteria showed higher sensitivity, lower specificity, and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS. This study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria.

Radiologically isolated syndrome and clinically isolated syndrome

The incidental evidence of white matter (WM) T2-hyperintense lesions on brain magnetic resonance imaging (MRI) is a clinical challenge. In a small subset of asymptomatic patients (less than 1%), lesions morphology and distribution are highly suggestive of multiple sclerosis (MS), hence meeting the disease dissemination in space criteria for the diagnosis of radiologically isolated syndrome (RIS). Conversely, in patients at first neurological presentation (clinically isolated syndrome [CIS]), prompt recognition of typical MS features and a correct application of McDonald criteria is fundamental for early diagnosis, and consequent disease-modifying treatments start.

Characterization of alexithymia in clinically isolated syndrome

BackgroundIn multiple sclerosis (MS), the prevalence of alexithymia, defined as an inability to identify and describe emotions, is close to 50% but the prevalence of this symptom in clinically isolated syndrome (CIS) is unknown. Characterizing alexithymia at an early stage of the disease can help to clarify psychobehavioural disturbances in CIS patients. MethodsForty CIS patients, who fulfilled the MRI criteria for dissemination in space, were matched with 40 healthy subjects. They completed self-assessment scales for alexithymia, depression, anxiety, apathy and empathy. Cognitive functions were assessed using a battery of neuropsychological tests. ResultsThe mean delay (± standard deviation) between the occurrence of CIS and inclusion in the study was 3.9 (2.8) months. The frequency of alexithymia was higher in CIS patients than in controls, with a prevalence of 42% (P<0.0001). Alexithymia correlated with anxiety and depression but not with cognition. Alexithymia was dependent only on depression (P=0.003). ConclusionAlexithymia, characterized by difficulty identifying feelings, is present in patients in the early stage of MS, and seems to be strongly associated with depression. Difficulty in social interaction could be a risk of future affective disorders.

Editors' Note: Asymptomatic Optic Nerve Lesions: An Underestimated Cause of Silent Retinal Atrophy in MS

Editors' Note: Asymptomatic Optic Nerve Lesions: An Underestimated Cause of Silent Retinal Atrophy in MS

Editor Response: Asymptomatic Optic Nerve Lesions: An Underestimated Cause of Silent Retinal Atrophy in MS.

Davion et al.1 examined the frequency of asymptomatic optic nerve MRI signal in patients with multiple sclerosis (MS) on natalizumab. All patients were seronegative or had low antibody titers for JC virus (<1.50). The authors found that 60 or 73 (82.2%) eyes with a history of symptomatic optic neuritis (ON) had high signal on MRI of the orbits using 3D double inversion recovery (DIR). There were 123 asymptomatic eyes with no history of ON; nearly 50% of these eyes also showed high signal using DIR MRI. The DIR MRI findings were examined in the context of optical coherence tomography (OCT) findings and low-contrast letter acuity (LCLA) performance. This publication is of significance for several reasons. First, it shows the rate of high signal abnormality in a chronic cohort of symptomatic optic neuritis eyes. The case series also demonstrates a high rate of DIR-identified high signal change in asymptomatic eyes; the association of this finding with reduced OCT-measured retinal thickness values and impaired monocular LCLA scores is also highlighted. Results from DIR imaging of the asymptomatic eyes are notable since the most recent 2017 McDonald Criteria for MS diagnosis do not include optic nerve lesions as part of the criteria for dissemination in space by MRI.2 Thus, OCT imaging and DIR MRI may be valuable to detect subtle symptomatic or asymptomatic optic nerve abnormalities.1,3 Ongoing investigations will need to confirm the value of DIR imaging to define potential false-positive rates for identifying optic nerve disease vs changes in imaging without functional impairment. This study and others that document OCT-measured intereye differences should lead to further investigation into the role of the optic nerve as a lesion site for MS diagnosis.

Optic Nerve Topography in Multiple Sclerosis Diagnosis: The Utility of Visual Evoked Potentials.

ObjectiveTo assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria.MethodsFrom the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non–optic neuritis).ResultsThe addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non–optic neuritis CIS.ConclusionThe addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity.

Improved performance of the 2017 McDonald criteria for diagnosis of multiple sclerosis in children in a real-life cohort

Objective: To compare the performance of the 2017 McDonald criteria with that of the 2010 criteria for the diagnosis of multiple sclerosis (MS) in children in the clinical setting. Methods: In this retrospective, multi-centre study, we identified children who presented with symptoms suggestive of a clinically isolated syndrome (CIS) and were followed up for at least 2 years or until their second attack. Results: Of 156 children with CIS followed up for a median of 4.17 years, 94 (60.3%) were diagnosed with MS. In all, 83 (88.3%) of these fulfilled the 2010 dissemination in space (DIS) criteria at onset. Three additional children fulfilled the 2017 DIS criteria because of the inclusion of symptomatic lesions. Of the 59 children with MS who underwent post-gadolinium magnetic resonance imaging (MRI), 44 (74.6%) fulfilled the 2010 dissemination in time (DIT) criteria at baseline. When the presence of oligoclonal bands (OCBs) was used to substitute DIT, an additional 35 children (79/94, 84.0%) were diagnosed with MS according to the 2017 criteria. The 2017 criteria had higher accuracy (87.2% vs 66.7%), higher sensitivity (84.0% vs 46.8%), but reduced specificity (91.9% vs 96.8%) when compared to the 2010 criteria. Conclusion: The improved performance of the 2017 criteria when compared to the 2010 criteria was predominantly due to the inclusion of intrathecal OCBs.

Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 - continuity and change.

The purpose of this review is to describe the new 2017 revisions of the McDonald diagnostic criteria for multiple sclerosis and review first experiences in their application to different patient populations. The 2017 revisions agreed on by an international expert panel, as the precursors, define criteria needed to fulfill dissemination in time and space in the clinically isolated syndrome after exclusion of alternative diagnoses. One major change is the inclusion of cerebrospinal fluid (CSF) oligoclonal bands as evidence of dissemination in time in a patient with dissemination in space gathered by clinical or magnetic resonance examination. The distinction between asymptomatic and symptomatic lesions in counting for evidence of dissemination in space or time in supra, infratentorial, and spinal cord syndrome has been abandoned. Finally, cortical lesions can be used to demonstrate dissemination in space. Major differential diagnoses, in particular, the still-evolving concept of neuromyelitis optica spectrum disorders and the myelin oligodendrocyte glycoprotein-IgG-related demyelinating central nervous system disorders. The new 2017 revisions will simplify the application of the MRI criteria for dissemination in space and include CSF findings as evidence for dissemination in time in clinically isolated syndrome.