Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study.

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.

Are natalizumab and fingolimod analogous second-line options for the treatment of relapsing-remitting multiple sclerosis? A clinical practice observational study.

BACKGROUND: It is unclear whether natalizumab and fingolimod have analogous efficacy for relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: To compare the outcome of RRMS patients treated with either therapy. METHODS: RRMS patients treated with natalizumab or fingolimod at Verona Hospital, Italy, were included. The study design was retrospective, based on prospectively collected clinical and MRI data. As efficacy outcomes, time to relapse, relapse rate, expanded disability status scale (EDSS) score change, and new T2/gadolinium-enhancing lesions on brain MRI were compared over treatment period between the two groups. Multivariate Cox and logistic regression models were used to control for potential confounders. RESULTS: Fifty-seven subjects receiving natalizumab and 30 receiving fingolimod for a median duration of 23 (1-63) and 22 (2-35) months, respectively (p = 0.22) were included. Patients treated with natalizumab had a more active pre-treatment disease course compared to those treated with fingolimod. In multivariate analysis, the relapse risk was reduced in patients on natalizumab (Hazard Ratio = 0.33; 95% CI = 0.11-1.03; p = 0.056) compared to those on fingolimod. There was no significant difference in EDSS and MRI outcomes. No relevant unexpected adverse events occurred. One patient discontinued natalizumab for progressive multifocal leukoencephalopathy. CONCLUSIONS: RRMS patients receiving natalizumab had higher baseline disease activity and lower relapse risk over 20 months of treatment compared to those receiving fingolimod. Head-to-head randomized clinical trials are needed.

Benign course of tumour-like multiple sclerosis. Report of five cases and literature review.

BACKGROUND: Multiple sclerosis (MS) with initial neuroradiological features suggestive of brain tumour (tumour-like MS) may represent a challenging diagnosis. METHODS: Among the patients seen at the MS centre of our Institution between 2000 and 2010, we identified cases presenting with a large (diameter>2 cm), well-defined lesion, suggestive of brain tumour on initial brain magnetic resonance imaging (MRI). Only patients with at least 10 years follow-up were included. RESULTS: Five young women with MS who presented with a tumour-like lesion on initial brain MRI are described. All cases presented with sudden-onset neurological deficits due to a single large brain lesion compatible with neoplasm at MRI. Two cases underwent brain stereotactic biopsy, both misdiagnosed as astrocytoma. However, the subsequent clinical and MRI follow-up was consistent with MS in all cases. Unnecessary surgery and radiotherapy were responsible for disability in two cases. In three cases, the course of the disease remains benign after more than 13 years from symptoms onset. CONCLUSIONS: Our report of clinical, radiological and pathological features of five tumour-like MS cases confirms that it is mandatory to consider a demyelinating process in the differential diagnosis of tumour-like brain lesions. Many tumour-like MS cases may have a favourable long term prognosis.

Prognostic value of multimodal evoked potentials in multiple sclerosis: the EP score.

Evoked potentials (EPs) have long been used as diagnostic tools in multiple sclerosis (MS), although their importance decreased as magnetic resonance imaging (MRI) became available. However, the prognostic value of EPs in MS has not been completely established. The aim of the study was to analyze the prognostic significance of EPs in a cohort of MS cases. From the Verona University Hospital MS Clinic database we retrospectively identified 80 MS patients who underwent a complete neurophysiological evaluation, including visual, brain stem, somatosensory and motor EPs and who were followed for at least 5 years after the study. EPs abnormalities were quantified through an index of global EPs alteration (EP score). The relationship between EP score and disability in terms of Expanded Disability Status Scale (EDSS) was analyzed by the Kaplan-Meier survival method and Spearman ρ correlation coefficient. ROC curves were used to determine the best EP score cut off to predict different EDSS endpoints. For each endpoint, sensitivity, specificity, positive and negative predictive value of EP score were calculated. We found a significant correlation (p < 0.001) between EP score and EDSS score at the time of neurophysiological study and at 1, 3 and 5 years of follow-up, particularly for motor and somatosensory EPs. Kaplan-Meier curves confirmed an increased risk of disability in those patients with EP score higher than the median value. EP score of 8 or 9 showed the highest sensitivity and specificity in predicting EDSS 4.0 and 6.0. EPs are reliable procedures to predict disability in MS patients. The correlation between EPs abnormalities and EDSS is higher than between conventional MRI and EDSS.