MOG and AQP4 Antibodies among Children with Multiple Sclerosis and Controls.

OBJECTIVE: The purpose of this study was to determine the frequency of myelin oligodendrocyte glycoprotein (MOG)-IgG and aquaporin-4 (AQP4)-IgG among patients with pediatric-onset multiple sclerosis (POMS) and healthy controls, to determine whether seropositive cases fulfilled their respective diagnostic criteria, to compare characteristics and outcomes in children with POMS versus MOG-IgG-associated disease (MOGAD), and identify clinical features associated with final diagnosis. METHODS: Patients with POMS and healthy controls were enrolled at 14 US sites through a prospective case-control study on POMS risk factors. Serum AQP4-IgG and MOG-IgG were assessed using live cell-based assays. RESULTS: AQP4-IgG was negative among all 1,196 participants, 493 with POMS and 703 healthy controls. MOG-IgG was positive in 30 of 493 cases (6%) and zero controls. Twenty-five of 30 patients positive with MOG-IgG (83%) had MOGAD, whereas 5 of 30 (17%) maintained a diagnosis of multiple sclerosis (MS) on re-review of records. MOGAD cases were more commonly in female patients (21/25 [84%] vs 301/468 [64%]; p = 0.044), younger age (mean = 8.2 ± 4.2 vs 14.7 ± 2.6 years; p < 0.001), more commonly had initial optic nerve symptoms (16/25 [64%] vs 129/391 [33%]; p = 0.002), or acute disseminated encephalomyelitis (ADEM; 8/25 [32%] vs 9/468 [2%]; p < 0.001), and less commonly had initial spinal cord symptoms (3/20 [15%] vs 194/381 [51%]; p = 0.002), serum Epstein-Barr virus (EBV) positivity (11/25 [44%] vs 445/468 [95%]; p < 0.001), or cerebrospinal fluid oligoclonal bands (5/25 [20%] vs 243/352 [69%]; p < 0.001). INTERPRETATION: MOG-IgG and AQP4-IgG were not identified among healthy controls confirming their high specificity for pediatric central nervous system (CNS) demyelinating disease. Five percent of those with prior POMS diagnoses ultimately had MOGAD; and none had AQP4-IgG positivity. Clinical features associated with a final diagnosis of MOGAD in those with suspected MS included initial ADEM phenotype, younger age at disease onset, and lack of EBV exposure. ANN NEUROL 2023;93:271-284.

The Multiple Sclerosis Prodrome in a Retrospective Pediatric Cohort.

BACKGROUND: Evidence suggests a prodromal phase in multiple sclerosis (MS), with increased health care use preceding the first demyelinating event (FDE). Although prior studies have explored this in adults, limited data exist for pediatric cases. We aimed to analyze health care utilization and prodromal symptoms in the two years before FDE in patients with pediatric-onset MS (POMS). METHODS: From 122 patients at the Pediatric Multiple Sclerosis & Demyelinating Diseases Center at Washington University School of Medicine from 2011 to 2021, 37 POMS cases were identified. Of these, 21 with at least two years of records preceding FDE were included. Retrospective analysis covered symptoms and health care utilization in the two-year period before FDE, including ambulatory visits, hospital admissions, and office calls. RESULTS: Patients showed increased health care utilization in the year preceding FDE (period B; 96 interactions) compared with the prior year (period A; 77 interactions) and an increase in the percentage of neurology-related encounters (P < 0.001). There was an increase in all office calls from period A to period B (P = 0.01). Neurological complaints included headaches (28.6%), visual (19.0%), sensory (14.3%), and balance (14.3%) in the two years before FDE, and 28.6% of patients presented for psychiatric complaints. Common non-neurological complaints included infection, dermatologic, and musculoskeletal issues and injury. CONCLUSIONS: Our POMS cohort showed increased health care use before FDE, consistent with population-based data. This study emphasizes diverse symptoms in prodromal POMS, with headaches being the most common neurological symptom in the two-year period before FDE.

Clinical Reasoning: A 6-Year-Old Girl With Right-Sided Pain and Weakness.

We outline the case of a 6-year-old girl presenting with a 2-week course of waxing and waning neurologic symptoms, including right-sided pain, weakness, dizziness, and difficulty walking. Her examination was notable for right-sided weakness, hyperreflexia, and dysmetria. Diagnostic evaluation was significant for MRI with numerous T2 hyperintense, T1 hypointense, and T1-enhancing lesions located in the juxtacortical and periventricular regions, corpus callosum, brainstem, and spinal cord; positive CSF oligoclonal bands; negative serum aquaporin-4 immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein IgG; and positive serum Epstein-Barr viral capsid antigen IgG.

Pearls & Oy-sters: MOG-AD Meningoencephalitis With Holocord Gray Matter Predominant Myelitis.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been implicated in a wide range of CNS encephalitis and myelitis presentations. We present a previously healthy 16-year-old girl who presented with acute onset headaches that rapidly progressed to encephalopathy, flaccid paraparesis, lower extremity hyperreflexia, and urinary retention. Serial MRI brain and total spine imaging demonstrated evolving diffuse supratentorial leptomeningeal enhancement and holocord gray matter restricted T2 bright lesion without enhancement. CSF was markedly inflammatory with MOG antibody positive >1:10,000. The patient improved after empiric steroids, plasma exchange, and IVIG.