Direct neuronal activation by IBS mucosal biopsy supernatants is primarily a feature of submucous rather than myenteric neurons. This is associated with a stronger excitation of submucous neurons by serotonin. The plexus-specific effects support the concept that altered mucosa-nerve signaling underlies disturbances in IBS.

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Background:The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS).Objective:To investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria.Methods:From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral-domain OCT scan obtained within 180 days. Modified DIS criteria (DIS+OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT inter-eye differences. Time to second clinical attack was the primary endpoint.Results:We analyzed 267 MS patients (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13 - 98).Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS+OCT 81.2% vs. DIS 65.6%,) and sensitivity (DIS+OCT 84.2% vs. DIS 77.9%) without lowering specificity (DIS+OCT 52.2% vs. DIS 52.2%).Fulfilling DIS+OCT criteria (≥2 of 5 DIS+OCT regions involved) indicated a similar risk of a second clinical attack (HR 3.6, CI 1.4 – 14.5) compared to a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2 – 11.8).When the analysis was conducted according to topography of the first demyelinating event, DIS+OCT criteria performed similarly in both optic neuritis and non–optic neuritis.Conclusions:Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity.Classification of Evidence:This study provides Class II evidence that adding the optic nerve as determined by optical coherence tomography (OCT) as a fifth dissemination in space (DIS) criterion to the 2017 McDonald criteria improves diagnostic accuracy.

Background: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. Methods: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. Results: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic–ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). Conclusions: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.