Enlarged perivascular spaces are associated with brain microangiopathy and aging in multiple sclerosis.

BACKGROUND: Growing evidence links brain-MRI enlarged perivascular spaces (EPVS) and multiple sclerosis (MS), but their role remains unclear. OBJECTIVE: This study aimed to investigate the cross-sectional associations of EPVS with several neuroinflammatory and neurodegenerative features in a large multicentric-MS cohort. METHODS: In total, 207 patients underwent 3T axial-T2-weighted brain-MRI for EPVS assessment (EPVS dichotomized into high/low according to ⩾ 2/< 2 rating categories). MRI biomarkers included brain-predicted age and brain-predicted age difference (brain-PAD), central vein sign (CVS)-positive lesion percentage (CVS%), paramagnetic rim and cortical lesions, T2-lesion load, and brain volumetry. The variable relative importance for EPVS-category prediction was explored using a classification random forest approach. RESULTS: High EPVS patients were older (49 vs 44 years, p = 0.003), had ⩾ 1 vascular risk factors (VRFs; p = 0.005), lower CVS% (67% vs 78%, p < 0.001), reduced brain volumes (whole brain: 0.63 vs 0.73, p = 0.01; gray matter: 0.36 vs 0.40; p = 0.002), and older brain-predicted age (58 vs 50 years, p < 0.001). No differences were found for neuroinflammatory markers. After adjusting for age and VFRs (multivariate analyses), the high EPVS category correlated with lower CVS% (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96-0.99; p = 0.02), lower whole brain (OR = 0.01, 95% CI = 0.0003-0.5; p = 0.02), gray matter (OR = 0.0004, 95% CI = 0.0000004-0.4; p = 0.03) volumes, and higher brain-PAD (OR = 1.05, 95% CI = 1.01-1.09; p = 0.02). Random forest identified brain-PAD as the most important predictor of high EPVS. CONCLUSION: EPVS in MS likely reflect microangiopathic disease rather than neuroinflammation, potentially contributing to accelerated neurodegeneration.

The central vein sign in multiple sclerosis patients with vascular comorbidities.

BACKGROUND: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. OBJECTIVE: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. METHODS: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. RESULTS: The median frequency of CVS+ lesions was 71% (range: 35%-100%). In univariate analysis, age (p < 0.0001), hypertension (p < 0.001), diabetes (p < 0.01), obesity (p < 0.01), smoking (p < 0.05), and the presence of enlarged-perivascular-spaces on MRI (p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). CONCLUSION: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. METHODS: In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. RESULTS: The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. DISCUSSION: The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.

Esophagitis dissecans superficialis : a case series of 7 patients and review of the literature.

INTRODUCTION: Esophagitis dissecans superficialis (EDS) is a rare desquamative disorder of the eso-phagus, characterized by sloughing of the superficial mucosa. It is a benign entity of uncertain etiology. Most cases of EDS are idiopathic but can be caused by medications, hot beverages, chemical irritants, celiac disease and many skin conditions. AIM: Knowing that few case series have described this entity, we decided to review all the cases diagnosed in our center to characterize them. METHODS: The pathological institutional database of Erasme University Hospital (Brussels, Belgium) was searched for the diagnosis of EDS. We reviewed retrospectively the clinical and endoscopic findings as well as histological features of all cases of EDS (Table 1). During this period of time, 21497 upper gastrointestinal endoscopies have been performed in our institution. RESULTS: From January 2010 to September 2016, we identified 7 cases of EDS diagnosed in our institution in this time period. During the same period, 21497 upper gastrointestinal endoscopies were performed (incidence 0.03%). Endoscopic findings evoked in 2 patients a suspicion of an esophageal tumor; the first one was described as a raised detached lesion of the distal third of the esophagus with suspicion of squamous cell carcinoma (Fig. 1) and the second as a suspected tumor of the proximal third of the esophagus (Fig. 2). For other patients, EDS was misdiagnosed as unspecific esophagitis in 2, reflux or mycotic esophagitis in 2. Only one patient was suspected to have sloughing esophagitis.Histologic features present in all of those cases were characterized by the presence of a sloughing and necrosis of the superficial layer of the esophageal squamous epithelium with negative anti HSV and anti CMV antibodies, negative periodic acid Schiff stain for fungal infections as well as absence of signs of dysplasia or signs of malignancy. In 2 patients, there was a presence of multiple bacterial colonies on the superficial epithelium. Acute inflammation was reported in 4 of the patients with the presence of eosinophils in the superficial epithelium described in 2 of these patients and of polymorphonuclear leukocytes in 2 other patients (Fig. 3).An endoscopic follow up 2 months after PPI treatment performed in 3 patients, 2 of them had an atypical endoscopic presentation with suspicion of a tumor on endoscopic examination showed a complete resolution of the esophageal lesions was observed in these patients. CONCLUSION: EDS is a rare benign entity that endoscopists must be aware of in order not to mistake it for other entities such as esophagitis or squamous cell carcinoma. The diagnosis is based on biopsies. The prognosis is good after stopping the causative agent.

Anti-GQ1b antibody syndrome presenting as acute isolated bilateral ophthalmoplegia: Report on two patients and review of the literature.

BACKGROUND: Miller Fisher syndrome (MFS) is an acute polyradiculoneuritis regarded as an uncommon clinical variant of Guillain-Barré syndrome (GBS). MFS is characterized by the acute onset of the clinical triad of ophthalmoplegia, cereballar ataxia and areflexia. Atypical forms of MFS presenting as isolated ophthalmoplegia without ataxia have been rarely described, mostly in adults. PATIENTS: We present two cases of acute isolated bilateral ophthalmoplegia in childhood, both occurring shortly after Campylobacter jejuni enteritis. Serum analysis of anti-ganglioside antibodies revealed elevated levels of anti-GQ1b IgG and IgM. We observed in both children complete spontaneous resolution several weeks after onset. CONCLUSION: The cases of the two patients confirm the rare but possible occurrence of atypical MFS in young children a few weeks after gastrointestinal infection. Identification of high levels of anti-GQ1b antibodies in the serum may help confirm the diagnosis of MFS even when its clinical presentation is incomplete.

Quantifying brain volumes for Multiple Sclerosis patients follow-up in clinical practice - comparison of 1.5 and 3 Tesla magnetic resonance imaging.

INTRODUCTION: There is emerging evidence that brain atrophy is a part of the pathophysiology of Multiple Sclerosis (MS) and correlates with several clinical outcomes of the disease, both physical and cognitive. Consequently, brain atrophy is becoming an important parameter in patients' follow-up. Since in clinical practice both 1.5Tesla (T) and 3T magnetic resonance imaging (MRI) systems are used for MS patients follow-up, questions arise regarding compatibility and a possible need for standardization. METHODS: Therefore, in this study 18 MS patients were scanned on the same day on a 1.5T and a 3T scanner. For each scanner, a 3D T1 and a 3D FLAIR were acquired. As no atrophy is expected within 1 day, these datasets can be used to evaluate the median percentage error of the brain volume measurement for gray matter (GM) volume and parenchymal volume (PV) between 1.5T and 3T scanners. The results are obtained with MSmetrix, which is developed especially for use in the MS clinical care path, and compared to Siena (FSL), a widely used software for research purposes. RESULTS: The MSmetrix median percentage error of the brain volume measurement between a 1.5T and a 3T scanner is 0.52% for GM and 0.35% for PV. For Siena this error equals 2.99%. When data of the same scanner are compared, the error is in the order of 0.06-0.08% for both MSmetrix and Siena. CONCLUSIONS: MSmetrix appears robust on both the 1.5T and 3T systems and the measurement error becomes an order of magnitude higher between scanners with different field strength.