Whose International Law?: Sovereignty and Non-State Groups

This is the first of three keynote panels at this 88th Annual Meeting, under the overarching theme of The Transformation of Sovereignty

The burden of history: the constraints and challenges of the democratization process in Ethiopia

Paper presented at the Wits History Workshop: Democracy, Popular Precedents, Practice and Culture, 13-15 July, 1994

UA12/2/1 College Heights Herald, Vol. 57, No. 36, Magazine

Magazine feature of WKU campus newspaper. This issue contains articles: Pillow, Robert. Tradition Amid Noise and Chaos Wood, Michele. Shipley’s – J.E. Shipley Battles, Jim. Fraternizin

MOG CNS Autoimmunity and MOGAD.

At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Whereas Abs targeting aquaporin-4 (AQP4) in NMO are pathogenic, the extent that anti-MOG Abs contribute to CNS damage in MOGAD is unclear. Both AQP4-specific Abs in NMO and MOG-specific Abs in MOGAD are predominantly IgG1, a T cell-dependent immunoglobulin (Ig) subclass. Key insights in neuroimmunology and MOGAD pathogenesis have been learned from MOG experimental autoimmune encephalomyelitis (EAE), described 2 decades before the term MOGAD was introduced. MOG-specific T cells are required in MOG EAE, and while anti-MOG Abs can exacerbate EAE and CNS demyelination, those Abs are neither necessary nor sufficient to cause EAE. Knowledge regarding the spectrum of MOGAD clinical and radiologic presentations is advancing rapidly, yet our grasp of MOGAD pathogenesis is incomplete. Understanding both the humoral and cellular immunology of MOGAD has implications for diagnosis, treatment, and prognosis

Plasma <i>N</i>-Glycan Profiling Enhances Diagnostic Precision in Multiple Sclerosis, AQP4-Ab NMOSD, and MOGAD

Background and objectivesDifferentiating multiple sclerosis (MS) from antibody (Ab)-defined diseases, such as neuromyelitis optica spectrum disorders (NMOSDs), remains challenging, particularly as Ab levels decline. N-glycans play a key role in immunity, with changes in branching and fucosylation linked to T/B-cell function and MS onset while increased N-acetylglucosamine residues correlate with disease progression. Despite growing recognition of glycosylation in neuroinflammation, direct comparisons of the N-glycome between MS and Ab-defined diseases are lacking. This study aims to assess whether plasma N-glycome profiling can effectively differentiate these conditions and their subtypes.MethodsThis cohort study included 120 participants: 30 with relapsing-remitting MS (RRMS), 30 with secondary progressive MS (SPMS), 30 with myelin oligodendrocyte glycoprotein Ab-associated disease (MOGAD), and 30 with aquaporin-4 (AQP4)-Ab NMOSD, recruited from the John Radcliffe Hospital, Oxford University Hospitals National Health System (NHS) Trust. Plasma N-glycans were analyzed using ultra-high-performance (UHPLC) hydrophilic interaction liquid chromatography (HILIC) coupled with high-resolution mass spectrometry. Orthogonal partial least-squares discriminant analysis was applied to identify disease-specific glycomic patterns.ResultsDistinct N-glycome profiles were identified across diseases and phenotypes. Plasma N-glycans differentiated MS from Ab-defined diseases with 80.5% accuracy (±1.5%), MOGAD from AQP4-Ab NMOSD with 77.8% accuracy (±3.1%), and RRMS from SPMS with 75.2% accuracy (±3.6%). Key discriminatory features included increased monosialylation (S1; odds ratio [OR] = 2.57, p < 0.0001), trigalactosylation (G3; OR = 2.70, p < 0.0001), highly branched N-glycans (OR = 2.32, p = 0.0002), and antennary fucosylation (OR = 2.89, p < 0.0001), effectively distinguishing Ab-defined diseases from MS, independent of Ab serostatus at the time of sampling.DiscussionThese findings underscore the potential of plasma N-glycomics as a diagnostic tool for neuroinflammatory diseases. While further research is needed to clarify the mechanistic links between glycomic alterations and disease pathology, our results suggest that plasma N-glycan profiling could improve disease classification. Given its noninvasive and cost-effective nature, this approach holds promise as a complementary diagnostic tool for CNS demyelinating diseases in clinical practice

Intravenous immunoglobulin treatment for acute attacks in myelin oligodendrocyte glycoprotein antibody disease

BACKGROUND: The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. OBJECTIVE: The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks. METHODS: A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients' demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment. RESULTS: Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5-74 years), and the median disease duration was 4 months (range 0-93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral n = 14, bilateral n = 5, associated with transverse myelitis (TM), n = 1), followed by acute disseminated encephalomyelitis (ADEM) (n = 8), multifocal (n = 7), TM (n = 3), brainstem (n = 1), and other encephalitis (n = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation (p < 0.0001 for both outcome measures). CONCLUSION: IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results

Understanding Mechanisms of Whole Brain and Regional Grey Matter Atrophy in Children With MOGAD

Objective: To investigate the mechanisms driving whole brain and regional grey matter (GM) volume changes along with their clinical correlates in paediatric myelin oligodendrocyte glycoprotein antibody (MOG-Ab)–associated disease (MOGAD). / / Methods: One-hundred-nine paediatric MOGAD patients from two UK centres underwent MRI at attack nadir and follow-up (at least 1) ≥ 6 weeks later. Normative trajectories from 317 typically developing children informed volumetric comparisons. MRI segmentation with SynthSeg+ enabled volumetric analysis. Linear mixed-effects models examined impact of brain lesions, disease course, MOG-Ab serostatus and age at onset on brain volumes and changes over time, along with clinical correlates. / / Results: Brain lesions were present in 71/109 patients, who were younger and more likely to present with acute disseminated encephalomyelitis. At onset, 79% showed reduced brain growth, particularly those with brain lesions. Over time, 46% developed atrophy, associated with lesion presence and relapsing disease. All patients exhibited cortical and deep GM growth reduction at onset, with brain lesions driving progressive atrophy. Brain lesion complete resolution mitigated atrophy in the left supramarginal and right inferior parietal gyri. Relapsing disease was linked to greater GM atrophy in the frontal, temporal and parietal lobes. Persistent MOG-Ab positivity correlated with GM atrophy in the cingulate and entorhinal cortices and temporal pole. Disability progression was linked to deep GM, temporal pole and lateral orbitofrontal atrophy, while learning difficulties were associated with lateral occipital and parietal atrophy. / / Interpretation: Brain lesions at onset and their persistence, relapsing disease and MOG-Ab positivity are key risk factors for GM atrophy and clinical impairment in paediatric MOGAD

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 202

E.U. paediatric MOG consortium consensus: Part 2 - Neuroimaging features of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

Imaging plays a crucial role in differentiating the spectrum of paediatric acquired demyelinating syndromes (ADS), which apart from myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) includes paediatric multiple sclerosis (MS), aquaporin-4 antibody neuromyelitis optica spectrum disorders (NMOSD) and unclassified patients with both monophasic and relapsing ADS. In contrast to the imaging characteristics of children with MS, children with MOGAD present with diverse imaging patterns which correlate with the main demyelinating phenotypes as well as age at presentation. In this review we describe the common neuroradiological features of children with MOGAD such as acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, AQP4 negative NMOSD. In addition, we report newly recognized presentations also associated with MOG-ab such as the 'leukodystophy-like' phenotype and autoimmune encephalitis with predominant involvement of cortical and deep grey matter structures. We further delineate the features, which may help to distinguish MOGAD from other ADS and discuss the future role of MR-imaging in regards to treatment decisions and prognosis in children with MOGAD. Finally, we propose an MRI protocol for routine examination and discuss new imaging techniques, which may help to better understand the neurobiology of MOGAD

Evolution of brain MRI lesions in paediatric myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and its relevance to disease course

BACKGROUND: Lesion resolution is often observed in children with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and asymptomatic lesions are less commonly reported in MOGAD than in multiple sclerosis (MS). OBJECTIVE: We aimed to evaluate brain MRI changes over time in paediatric MOGAD. METHODS: Retrospective study in eight UK paediatric neuroscience centres. Acute brain MRI and available follow-up MRIs were reviewed. Predictors for lesion dynamic were evaluated using multivariable regression and Kaplan-Meier survival analyses were used to predict risk of relapse, disability and MOG-Ab status. RESULTS: 200 children were included (MOGAD 97; MS 103). At first MRI post attack, new symptomatic and asymptomatic lesions were seen more often in MS versus MOGAD (52/103 vs 28/97; p=0.002 and 37/103 vs 11/97; p<0.001); 83% of patients with MOGAD showed at least one lesion's resolution at first follow-up scan, and 23% had normal MRI. Only 1 patient with MS had single lesion resolution; none had normal MRI. Disappearing lesions in MOGAD were seen in 40% after the second attack, 21% after third attack and none after the fourth attack.New lesions at first follow-up scan were associated with increased likelihood of relapse (p=0.02) and persistent MOG-Ab serostatus (p=0.0016) compared with those with no new lesions. Plasma exchange was associated with increased likelihood of lesion resolution (p=0.01). Longer time from symptom onset to steroids was associated with increased likelihood of new lesions; 50% increase at 20 days (p=0.01). CONCLUSIONS: These striking differences in lesion dynamics between MOGAD and MS suggest greater potential to repair. Early treatment with steroids and plasma exchange is associated with reduced likelihood of new lesions