Slowly Expanding Lesions Differentiate Pediatric Multiple Sclerosis from Myelin Oligodendrocyte Glycoprotein Antibody Disease.

Slowly expanding lesions (SELs) in adults with multiple sclerosis (MS) indicate a progressive pathological process. Whether SELs are present in pediatric-onset MS (POMS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. We studied 19 children with POMS and 14 with MOGAD (median age 14.3 and 9.4 years, respectively) recruited to the Canadian Pediatric Demyelinating Disease Study with: (1) ≥3 research scans 12 months apart; and (2) ≥1 T2-lesions on the earliest scan. A total of 70 SELs from 16 POMS participants and 1 SEL in the MOGAD group were detected. SELs are an early feature of POMS and essentially not a feature of MOGAD. ANN NEUROL 2024.

Fadda G ，Banwell B ，Elliott C ，Fetco D ，Arnold DL ，Waters P ，Yeh EA ，Marrie RA ，Bar-Or A ，Narayanan S ，Canadian Pediatric Demyelinating Disease Network ... -  《-》

Cognitive function in pediatric-onset relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Myelin oligodendrocyte glycoprotein antibodies are identified in approximately 30-50% of youth with pediatric-onset acquired demyelinating syndromes. Little is known about the cognitive sequelae of relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with onset in childhood or adolescence.Overall, adults had 41% more risk than children to relapse over the whole disease course Overall, adults had 41% more risk than children to relapse over the whole disease course OBJECTIVE: To compare cognitive performance in participants with pediatric-onset relapsing MOGAD, pediatric-onset multiple sclerosis (POMS), and age-matched healthy controls. The Penn Computerized Neurocognitive Battery (PCNB) was administered to 12 individuals with relapsing MOGAD (age = 16.3 ± 4.8 years; 75% female; disease duration = 8.1 ± 2.7 years), 68 individuals with POMS (age = 18.3 ± 4.0 years; 72% female; disease duration = 3.8 ± 3.9 years), and 108 healthy controls (age = 17.0 ± 4.9 years; 68.5% female). Accuracy was assessed on four domains: Executive Function, Episodic Memory, Complex Cognition, Social Cognition; and overall response time (RT) and RT across three factors (i.e., Time Constrained, Open-Window, Memory). Global performance was determined by a composite score. Multiple linear regression was used to examine group differences on PCNB domain and factor z-scores, controlling for age and sex. We also covaried disease duration for relapsing MOGAD vs. POMS analyses. Relative to healthy controls, relapsing MOGAD participants were less accurate on the Complex Cognition domain (B=-0.28, SE=0.11, p=.02), and had slower overall response time (B=-0.16, SE=0.07, p=.02). Relative to POMS, relapsing MOGAD participants were more accurate on the Executive Function domain (B = 0.70, SE=0.30, p=.02) and on the battery overall (B = 0.41, SE=0.18, p=.02). Relative to controls, overall PCNB score was significantly lower in the POMS group (B=-0.28, SE=0.06, p<.001) whereas the relapsing MOGAD participants did not differ from controls (p=.06) on the overall PCNB score. The relapsing MOGAD group demonstrated reduced reasoning skills and slower overall response time, relative to controls. A broad pattern of deficits was observed among POMS participants relative to controls. Overall, cognitive difficulties in the MOGAD group were milder relative to the POMS group.

Fabri TL ，O'Mahony J ，Fadda G ，Gur RE ，Gur RC ，Yeh EA ，Banwell BL ，Till C ... -  《-》

Assessment of international MOGAD diagnostic criteria in patients with overlapping MOG-associated disease and multiple sclerosis phenotypes.

The clinical spectrum and diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has evolved in the setting of an optimized anti-MOG-IgG cell-based assay and expert consensus. The McDonald criteria for MS have been revised multiple times to improve the accuracy and specificity of diagnosis on a framework based on clinical presentation, MRI findings, and CSF results. While the uses of MS and MOGAD diagnostic criteria are helpful for typical cases, such utility for patients with overlapping clinical, laboratorial, and imaging features is unknown, posing diagnostic and management uncertainties. To report a multicenter cohort of patients with overlapping phenotypic features of MOGAD and MS and evaluate the application of new MOGAD diagnostic criteria. A collaborative retrospective cohort study was performed to identify patients with both positive serum anti-MOG-IgG and fulfillment of the MS revised 2017 McDonald criteria. Clinical and radiographic features of patients fulfilling inclusion criteria were reviewed longitudinally, including relapses, repeated MRI, and MOG-IgG testing in detail to allow the panel of expert opinion to assign to each case. The International MOGAD Panel proposed criteria were applied at onset and last follow-up to each case and compared to the expert author diagnosis assignment based on presentation, clinical and imaging features, and response to treatment. Ten of 225 (4%) MOG-IgG seropositive cases met study inclusion criteria [seven of 10 were female; age at initial event: eight adults (mean age 26.8 years), two adolescents (mean age 14.5 years)]. AQP4-IgG was negative for all. Apart from serum titers of MOG-IgG, distinguishing clinical and radiographic features [i.e., clinical severity of the initial demyelinating event, radiographic features (optic nerve/spine/brain), and presence/absence of lesion normalization on serial scans] led to consensus of three separate classifications differing by degrees of shared features of MOGAD and MS. Patients were classified by expert panel into (1) Classic MOGAD even with MS-like, well-defined brain lesions, when severe events and most T2 lesions normalized (n = 5; MOG-IgG titers 1:100, 1:20, 1:160, 1:40, 1:200); (2) Classic RRMS included cases thought to have likely false positive or clinically irrelevant MOG-IgG, due to mild clinical events and no radiographic normalization of well-defined MS-like lesions (n = 3; MOG titers 1:20, 1:100, 1:40); (3) MOGAD and MS overlapping phenotype was defined by those with a combination of mild and severe clinical events, partial T2 lesion normalization, both well- and ill-defined lesions (n = 2; MOG titers 1:20, 1:100). The application of the International MOGAD Panel criteria categorized five patients (50%) in agreement with expert assignment. One additional patient was classified in agreement to assignment when MOGAD criteria were applied after serial MOG-IgG titers testing. While the International MOGAD Panel diagnostic criteria have helped with accuracy for the diagnosis of this condition, in a group of patients seropositive for MOG-IgG with overlapping clinical and imaging features of RRMS criteria review may lead to increased accuracy. Serial serologies, repeated imaging, close attention to clinical course, and response to therapy are possible variables to consider for further refinement of MOGAD diagnostic criteria.

Manzano GS ，Levy M ，Salky R ，Mateen FJ ，Klawiter EC ，Chitnis T ，Vasileiou ES ，Sotirchos ES ，Gibbons E ，Huda S ，Jacob A ，Matiello M ... -  《-》

Classification of Myelin Oligodendrocyte Glycoprotein Antibody-Related Disease and Its Mimicking Acute Demyelinating Syndromes in Children Using MRI-Based Radiomics: From Lesion to Subject.

To develop MRI-based radiomics models from the lesion level to the subject level and assess their value for differentiating myelin oligodendrocyte glycoprotein antibody-related disease (MOGAD) from non-MOGAD acute demyelinating syndromes in pediatrics. 66 MOGAD and 66 non-MOGAD children were assigned to the training set (36/35), internal test set (14/16), and external test set (16/15), respectively. At the lesion level, five single-sequence models were developed alongside a fusion model (combining these five sequences). The radiomics features of each lesion were quantified as the lesion-level radscore (LRS) using the best-performing model. Subsequently, a lesion-typing function was employed to classify lesions into two types (MOGAD-like or non-MOGAD-like), and the average LRS of the predominant type lesions in each subject was considered as the subject-level radscore (SRS). Based on SRS, a subject-level model was established and compared to both clinical models and radiologists' assessments. At the lesion level, the fusion model outperformed the five single-sequence models in distinguishing MOGAD and non-MOGAD lesions (0.867 and 0.810 of area under the curve [AUC] in internal and external testing, respectively). At the subject level, the SRS model showed superior performance (0.844 and 0.846 of AUC in internal and external testing, respectively) compared to clinical models and radiologists' assessments for distinguishing MOGAD and non-MOGAD. MRI-based radiomics models have potential clinical value for identifying MOGAD from non-MOGAD. The fusion model and SRS model can distinguish between MOGAD and non-MOGAD at the lesion level and subject level, respectively, providing a differential diagnosis method for these two diseases.

Ding S ，Zheng H ，Wang L ，Fan X ，Yang X ，Huang Z ，Zhang X ，Yan Z ，Li X ，Cai J ... -  《-》

Central Vein Sign in Pediatric Multiple Sclerosis and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

The central vein sign (CVS) on brain magnetic resonance imaging (MRI) is a promising diagnostic marker for distinguishing adult multiple sclerosis (MS) from other demyelinating conditions, but its prevalence is not well-established in pediatric-onset multiple sclerosis (POMS) versus myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD can mimic MS radiologically. This study seeks to determine the utility of CVS, together with other radiological findings, in distinguishing POMS from MOGAD in children. Children with POMS or MOGAD were identified in a pediatric demyelinating database. Two reviewers, blinded to diagnosis, fused fluid-attenuated inversion recovery sequences and susceptibility-weighted imaging from clinical imaging to identify CVS. Agreement in CVS number was reported using intraclass correlation coefficients (ICC). We performed topographic analyses as well as characterization of the clinical information and lesions on brain, spinal cord, and orbital MRI when available. Twenty children, 10 with POMS and 10 with MOGAD, were assessed. The median lesion percentage of CVS was higher in POMS versus MOGAD for both raters (rater 1: 80% vs 9.8%; rater 2: 22.7% vs 7.5%). Inter-rater reliability for identifying total white matter lesions was strong (ICC 0.94 [95% confidence interval [CI] 0.84, 0.97]); however, it was poor for detecting CVS lesions (ICC -0.17 [95% CI: -0.37, 0.58]). The CVS can be a useful diagnostic tool for differentiating POMS from MOGAD. However, advanced clinical imaging tools that can better detect CVS are needed to increase inter-rater reliability before clinical application.

Harrison KL ，Gaudioso C ，Levasseur VA ，Dunham SR ，Schanzer N ，Keuchel C ，Salter A ，Goyal MS ，Mar S ... -  《-》