Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis.

OBJECTIVE: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. METHODS: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported. RESULTS: We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. INTERPRETATION: GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024.

Real-world application of the 2022 diagnostic criteria for first-ever episode of optic neuritis.

Optic neuritis (ON) admits diverse differential diagnoses. Petzold proposed diagnostic criteria for ON in 2022, although real-world application of these criteria is missing. We conducted a retrospective review of patients with ON. We classified patients into definite or possible ON, and into groups A (typical neuritis), B (painless), or C (binocular) and estimated the frequency of etiologies for each group. We included 77 patients, with 62% definite and 38% possible ON. CRION and NMOSD-AQP4 negative-ON were less commonly seen in definite ON. Application of the 2022 criteria revealed a lower-than-expected frequency of definite ON, particularly for seronegative non-MS causes.

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

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 aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease 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; and Expanded Disability Status Scale (EDSS) score 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 and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) 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, the 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 is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease 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 further analyses towards the diagnosis of MOG-antibody disease in clinical practice.

Primary angiitis of the central nervous system as a mimic of multiple sclerosis: A case report.

BACKGROUND: Primary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. CASE PRESENTATION: A 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. DISCUSSION: Our patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. CONCLUSION: The presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis.

White matter microstructural damage in chronic ischemic stroke affecting the left inferior frontal gyrus: Association with cognitive functions.

Brain ischemia affects the integrity of local white matter and regions that are distant to the primary lesion location. In this study, we analyzed the patterns of white matter microstructural damage and the cognitive performance of 22 patients with left hemisphere stroke. Patients were divided in two groups: one with target lesion affecting the left inferior frontal gyrus (left inferior frontal gyrus, LIFG, n = 11) and the other without ischemic lesion in this region (non-left inferior frontal gyrus, NLIFG, n = 11). Each group was compared with 11 matched healthy controls. Tract-Based Spatial Statistics was used to assess differences in diffusion tensor indices between the groups and for the association of white matter structure with cognitive performance. When compared to Controls, the LIFG showed extensive intra- and interhemispheric disconnection, with surrogate markers for tissue loss with demyelination in the corpus callosum, and microstructural changes that are independent of gross tissue loss in the contralateral hemisphere. The NLIFG group presented discrete alterations in white matter from the ipsilateral hemisphere, with surrogate markers for tissue loss with axonal injury. When LIFG is compared to NLIFG, white matter abnormalities with no gross tissue loss were observed in the corpus callosum and in the contralateral hemisphere. In addition LIFG had worse performance on cognitive functions. In conclusion, our results identify different diffusion profiles for LIFG and NLIFG groups, suggesting more extensive and pronounced white matter damage in the commissural and interhemispheric connections in the LIFG group, in addition to more pronounced cognitive impairment.

Treatment and outcome of aquaporin-4 antibody-positive NMOSD: A multinational pediatric study.

OBJECTIVE: To describe the clinical phenotypes, treatment response, and outcome of children with antibodies against aquaporin-4 (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD). METHODS: Retrospective, multicenter, and multinational study of patients with AQP4-Ab NMOSD aged <18 years at disease onset from a center in Brazil and 13 European centers. Data on demographics, clinical findings, and laboratory results were analyzed; calculation of annualized relapse rates (ARRs) pre- and on-treatment with disease-modifying therapies (DMTs) and of ORs for predictors of poor outcome was performed. RESULTS: A total of 67 children were identified. At last follow-up (median 4 years, interquartile range 2-10 years), 37/67(57.8%) were found to have permanent disability. A more severe disease course was seen in the non-White ethnicity with both a shorter time to first relapse (p = 0.049) and a worse Expanded Disability Status Scale score at last follow-up (p = 0.008). The median ARR on treatment was 0.18 on azathioprine (n = 39, range 0-4), 0 on mycophenolate mofetil (n = 18, range 0-3), and 0 on rituximab (n = 29, range 0-2). No patient treated with rituximab as first-line therapy relapsed. Optic neuritis at onset was associated with a poor visual outcome below 20/200 (OR 8.669, 95% CI 1.764-42.616, p = 0.008), and a younger age at onset was associated with cognitive impairment (OR 0.786, 95% CI 0.644-0.959, p = 0.018). CONCLUSIONS: AQP4-Ab NMOSD in children is an aggressive disease with permanent disabilities observed in over half the cohort. All DMTs were associated with a reduction of ARR. First-line rituximab prevented further clinical relapses. International consensus on treatment protocols for children is required to reduce heterogeneity of treatment regimens used worldwide. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.