Background: Axonal and neuronal damage are widely accepted as key events in the disease course of multiple sclerosis. However, it has been unclear to date at which stage in disease evolution neurodegeneration begins and whether neuronal damage can occur even in the absence of acute inflammatory attacks. Objective: To characterize inner retinal layer changes in patients with clinically isolated syndrome (CIS). Method: 45 patients with CIS and age-and sex-matched healthy controls were investigated using spectral domain optical coherence tomography. Patients' eyes were stratified into the following categories according to history of optic neuritis (ON): eyes with clinically-diagnosed ON (CIS-ON), eyes with suspected subclinical ON (CIS-SON) as indicated by a visual evoked potential latency of >115ms and eyes unaffected by ON (CIS-NON).Results: CIS-NON eyes showed significant reduction of ganglion cell-and inner plexiform layer and a topography similar to that of CIS-ON eyes. Seven eyes were characterized as CIS-SON and likewise showed significant retinal layer thinning. The most pronounced thinning was present in CIS-ON eyes. Conclusion: Our findings indicate that retinal pathology does occur already in CIS. Intraretinal layer segmentation may be an easily applicable, non-invasive method for early detection of retinal pathology in patients unaffected by ON.

No abstract

ObjectiveTo examine whether treatment with epigallocatechin gallate (EGCG) influences progression of brain atrophy, reduces clinical and further radiologic disease activity markers, and is safe in patients with progressive multiple sclerosis (PMS).MethodsWe enrolled 61 patients with primary or secondary PMS in a randomized double-blind, parallel-group, phase II trial on oral EGCG (up to 1,200 mg daily) or placebo for 36 months with an optional open-label EGCG treatment extension (OE) of 12-month duration. The primary end point was the rate of brain atrophy, quantified as brain parenchymal fraction (BPF). The secondary end points were radiologic and clinical disease parameters and safety assessments.ResultsIn our cohort, 30 patients were randomized to EGCG treatment and 31 to placebo. Thirty-eight patients (19 from each group) completed the study. The primary endpoint was not met, as in 36 months the rate of decrease in BPF was 0.0092 ± 0.0152 in the treatment group and −0.0078 ± 0.0159 in placebo-treated patients. None of the secondary MRI and clinical end points revealed group differences. Adverse events of EGCG were mostly mild and occurred with a similar incidence in the placebo group. One patient in the EGCG group had to stop treatment due to elevated aminotransferases (>3.5 times above normal limit).ConclusionsIn a phase II trial including patients with multiple sclerosis (MS) with progressive disease course, we were unable to demonstrate a treatment effect of EGCG on the primary and secondary radiologic and clinical disease parameters while confirming on overall beneficial safety profile.Clinicaltrial.gov IdentifierNCT00799890.Classification of EvidenceThis phase II trial provides Class II evidence that for patients with PMS, EGCG was safe, well tolerated, and did not significantly reduce the rate of brain atrophy.

Background: Epigallocatechin gallate (EGCG) is an anti-inflammatory agent and has proven neuroprotective properties in animal models of multiple sclerosis (MS). Optical coherence tomography (OCT) assessed retinal thickness analysis can reflect treatment responses in MS.Objective: To analyze the influence of EGCG treatment on retinal thickness analysis as secondary and exploratory outcomes of the randomized controlled Sunphenon in Progressive Forms of MS trial (SUPREMES, NCT00799890).Methods: SUPREMES patients underwent OCT with the Heidelberg Spectralis device at a subset of visits. We determined peripapillary retinal nerve fiber layer (pRNFL) thickness from a 12° ring scan around the optic nerve head and thickness of the ganglion cell/inner plexiform layer (GCIP) and inner nuclear layer (INL) within a 6 mm diameter grid centered on the fovea from a macular volume scan. Longitudinal OCT data were available for exploratory analysis from 31 SUPREMES participants (12/19 primary/secondary progressive MS (PPMS/SPMS); mean age 51 ± 7 years; 12 female; mean time since disease onset 16 ± 11 years). We tested the null hypothesis of no treatment*time interaction using nonparametric analysis of longitudinal data in factorial experiments.Results: After 2 years, there were no significant differences in longitudinal retinal thickness changes between EGCG treated and placebo arms in any OCT parameter (Mean change [confidence interval] ECGC vs. Placebo: pRNFL: −0.83 [1.29] μm vs. −0.64 [1.56] μm, p = 0.156; GCIP: −0.67 [0.67] μm vs. −0.14 [0.47] μm, p = 0.476; INL: −0.06 [0.58] μm vs. 0.22 [0.41] μm, p = 0.455).Conclusion: Retinal thickness analysis did not reveal a neuroprotective effect of EGCG. While this is in line with the results of the main SUPREMES trial, our study was probably underpowered to detect an effect.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT00799890.

Introduction The severe acute respiratory syndrome-coronavirus-2 (SARS-Cov2) pandemic has been overcome after more than 3 years1. Several patients were affected by neurosurgery-related complications during SARS-CoV-2 infection 2,3. The aim of the present study was to assess the incidence of SARS-Cov2-associated intracranial hemorrhage (ICH), the reasons therefore and to identify predictors of outcome. Methods We retrospectively analyzed data of patients with SARS-CoV-2 infection admitted to the intensive care unit (ICU) of our hospital in the period of 2 years. We included all patients who acquired a SARS-CoV-2 infection and required intensive care treatment. All patients were followed up until death or discharge from ICU. The primary outcome was the incidence of mortality during ICU stay and occurrence of ICH. We compared survivors and non-survivors with ICH during their ICU stay and patients who developed intracerebral hemorrhage with those who did not. Results Four hundred and sixty-seven patients with a mean age of 64.33 (± 14.76) years with confirmed SARS-CoV2-infection were registered. The mortality rate during ICU stay was 32.11%. Within the two years period, 18 out of 467 patients (3,85%) with spontaneous SARS-Cov2-associated ICH were treated in our department. In the multivariate analysis, ICH was not identified as an independent risk factor for mortality. ECMO treatment (OR 5.130, 95%: 1.739-15.133, p=0.003) was the only independent risk factor of the occurrence of ICH. Conclusion SARS-Cov2-associated ICH itself did not result in increased mortality in patients with SARS-CoV-2 infection treated on the ICU. We hypothesize, that increased mortality in patients with ICH is caused by other comorbidities such as renal failure requiring dialysis, age over 65, the use of ECMO and mechanical ventilation. The use of ECMO was found to be the strongest independent risk factor associated with the occurrence of ICH.