Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.

This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the preentry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708).Methods: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with i nsertable cardiac monitors.Results: T he 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting 2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation c ohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). Conclusions:In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.term "embolic stroke of undetermined source (ESUS)" has been proposed as a new clinical entity to refine its definition,. Covert atrial fibrillation (AF) is thought to be relatively common among potential embolic sources of ESUS.

Background and Purpose— This study’s objective is to determine if nonstenotic carotid plaque of <50% luminal narrowing predominantly develops ipsilateral rather than contralateral to the stroke site. Methods— This was a cross-sectional observational study. We identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS), excluding stroke in multiple vascular territories. Using ultrasonography, we measured the internal carotid plaque size and stenosis for each patient. We dichotomized the plaque size at several predefined thresholds and calculated the frequency of the plaque size and morphology above each threshold ipsilateral versus contralateral to the stroke site. Results— We included 53 patients with unilateral anterior circulation ESUS. Initially, we found that plaque with a thickness ≥1.5 mm was present ipsilateral to the stroke site in 59% of the patients, and present contralateral to the stroke site in 42% of the patients (31/53 versus 22/53 patients; P =0.049). Plaque with low echo likewise had a similar prevalence when present ipsilateral (9%) and contralateral (4%) to the stroke site (5/53 versus 2/53; P =0.25). Conclusions— Internal carotid artery plaque with a thickness ≥1.5 mm but that is nonstenotic (<50%) is considerably more common when ipsilateral to the ESUS site than when contralateral to the ESUS site, especially in plaque with a thickness ≥2.6 mm. Large but nonstenotic carotid artery plaque is associated with anterior circulation ESUS.

Sequential computed tomography (CT) scans were obtained in 30 patients with acute cerebral infarction. In some cases, infarction was seen on the scans as early as three to six hours after onset of symptoms. Although small areas of petechial hemorrhagic infarction are not easily detected by currently available equipment, positive contrast enhancement helps locate petechial hemorrhagic infarction, which is usually in the cortical gray matter of the cerebral mantle and the central gray matter of the deep central gray matter. Contrast-enhanced CT scans are a useful method for detecting small infarctions. However, when a CT scan is performed within five days of ictus, contrast enhancement is usually not required.

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