Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With Imaging

Cortese, Rosa; Carrasco, Ferran Prados; Tur, Carmen; Bianchi, Alessia; Brownlee, Wallace; Angelis, Floriana De; Paz, Isabel De La; Grussu, Francesco; Haider, Lukas; Jacob, Anu; Kanber, Baris; Magnollay, Lise; Nicholas, Richard; Trip, Anand; Yiannakas, Marios C.; Toosy, Ahmed; Hacohen, Yael; Barkhof, Frederik; Ciccarelli, Olga

doi:10.1212/wnl.0000000000201465

Cited by 43 publications

(56 citation statements)

References 51 publications

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“…disease phenotypes at onset were optic neuritis and/or transverse myelitis for the majority of patients. 20 . Imaging characteristics are age-dependent in MOGAD, with the highest frequency of brain involvement in children, ranging from poorly demarcated and widespread lesions in the childhood to small nonspecific cerebral lesions in older children and adults.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, only few and relatively small studies have assessed MOGAD patients in the non-acute phases. 16,[18][19][20] Against this background, we carried out a study aiming at identifying key features able to distinguish non-acute adult MOGAD from AQP4-NMOSD and RRMS. Our ultimate goal was to provide advice on how to identify MOGAD patients in clinical practice, by suggesting sequential tests and supporting features beyond or in addition to serological testing.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Clinical and MRI measures to identify non-acute MOG-antibody disease in adults

Cortese

Battaglini

Carrasco

et al. 2022

Brain

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MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG-antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of MOG-antibody disease patients in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease, AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis, brain and cord MRI at least 6 months from relapse, EDSS on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random-forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred sixty-two patients with MOG-antibody disease (99F, mean age: 41 [±14] years, median EDSS: 2 [0-7.5]), 162 with AQP4-neuromyelitis optica spectrum disorder (132F, mean age: 51 [±14] years, median EDSS: 3.5 [0-8]), 189 with multiple sclerosis (132F, mean age: 40 [±10] years, median EDSS: 2 [0-8]) and 152 healthy controls (91F) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson’s fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, p < 0.001). In these non-acute patients, a number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, p < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, p < 0.001). A workflow with sequential tests and supporting features has been proposed to guide a better identification of MOG-antibody disease patients. Adult non-acute MOG-antibody disease patients showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information, can guide for further analyses towards diagnosis of MOG-antibody disease in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Clinical and MRI measures to identify non-acute MOG-antibody disease in adults

Cortese

Battaglini

Carrasco

et al. 2022

Brain

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“…When Select6* and Select3* algorithms were used, they were not superior to the cutoff calculated when all lesions were considered. 3 In conclusion, CVS remains mainly a research biomarker, which is both personnel and time-intensive and requires optimal pulse sequences that are not widely available on clinical scanners. 6 Given that the 2017 McDonald criteria can accurately diagnose paediatric MS (with the inclusion of intrathecal oligoclonal bands and serum myelin oligodendrocyte glycoprotein, MOG, antibody testing), we would suggest that CVS is used as an additive metric for selected cases, in whom the diagnosis may be challenging, for MS confirmation, rather than part of recommended imaging protocols.…”

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confidence: 99%

“… 2 A recent two-centre prospective study of 91 adult patients with acquired demyelinating disorders demonstrated that CVS was one of the most accurate measures differentiating MS from seropositive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) (84% vs 33%, accuracy/specificity/sensitivity: 91/88/93%, p < 0.001). 3 To date, few studies have looked at the diagnostic accuracy of CVS in paediatric-onset MS.…”

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Is the central vein sign a useful diagnostic marker for paediatric-onset multiple sclerosis?

Abdel‐Mannan

Ciccarelli

2022

Mult Scler

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Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis

Cagol,

Cortese,

Barakovic

et al. 2024

JAMA Neurol

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ImportanceMultiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice.ObjectiveTo quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI).Design, Setting, and ParticipantsThis was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants’ diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2).ExposuresMS/CIS vs non-MS conditions.Main Outcomes and MeasuresArea under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model.ResultsThe presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P &lt; .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis.Conclusions and RelevanceThe findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

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Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With Imaging

Cited by 43 publications

References 51 publications

Clinical and MRI measures to identify non-acute MOG-antibody disease in adults

Clinical and MRI measures to identify non-acute MOG-antibody disease in adults

Is the central vein sign a useful diagnostic marker for paediatric-onset multiple sclerosis?

Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis

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