Non-lesional white matter in relapsing-remitting multiple sclerosis assessed by multicomponent T2 relaxation.

INTRODUCTION: The purpose of the study is to investigate, by T2 relaxation, non-lesional white matter (WM) in relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Twenty stable RR MS patients underwent 1.5T Magnetic Resonance Imaging (MRI) with 3D Fluid-Attenuated Inversion-Recovery (FLAIR), 3D-T1-weighted, and T2-relaxation multi-echo sequences. The Lesion Segmentation Tool processed FLAIR images to identify focal lesions (FLs), whereas T1 images were segmented to identify WM and FL sub-volumes with T1 hypo-intensity. Non-lesional WM was obtained as the segmented WM, excluding FL volumes. The multi-echo sequence allowed decomposition into myelin water, intra-extracellular water, and free water (Fw), which were evaluated on the segmented non-lesional WM. Correlation analysis was performed between the non-lesional WM relaxation parameters and Expanded Disability Status Scale (EDSS), disease duration, patient age, and T1 hypo-intense FL volumes. RESULTS: The T1 hypo-intense FL volumes correlated with EDSS. On the non-lesional WM, the median Fw correlated with EDSS, disease duration, age, and T1 hypo-intense FL volumes. Bivariate EDSS correlation of FL volumes and WM T2-relaxation parameters did not improve significance. CONCLUSION: T2 relaxation allowed identifying subtle WM alterations, which significantly correlated with EDSS, disease duration, and age but do not seem to be EDSS-predictors independent from FL sub-volumes in stable RR patients. Particularly, the increase in the Fw component is suggestive of an uninvestigated prodromal phenomenon in brain degeneration.

Sars-CoV2 infection in pregnant women with multiple sclerosis.

BACKGROUND: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. OBJECTIVE: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. METHODS: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). RESULTS: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. CONCLUSION: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

Epidemiology of neuronal surface antibody-mediated autoimmune encephalitis and antibody-based diagnostics.

Epidemiologic data on neuronal surface antibody (NSAb)-associated autoimmune encephalitides (NSAE) are scarce and heterogeneous. We review our 13-year-long biobank-data collection and provide the incidence of NSAE in two Italian provinces (approx. Population of 1,400,000) over a 5-year period (July 2013-June 2018). NSAbs were diagnosed in 75 out of 1179 tested patients (6.4%). The most common NSAbs were anti-LGI1 (30 cases), followed by NMDAR (24). Eleven cases of NSAE were diagnosed in Treviso and Trento provinces with an estimated incidence of 1.54 per 1,000,000 population (LGI1-encephalitis 0.84; C.I. 0.38-1.88). LGI1-E is the most frequent NSAE among adults.

Leptomeningeal metastasis from solid tumors: a diagnostic and therapeutic challenge.

Leptomeningeal metastasis (LM) is a severe complication in the natural history of malignancies that occurs in 4-15 % of patients (pts) with solid tumors. Clinical presentation, cerebrospinal fluid cytology (CSF), and gadolinium magnetic resonance imaging (gdMRI) of the brain and spine are the methods routinely used to diagnose LM. Treatment encompasses involved-field radiotherapy of bulky or symptomatic disease sites and chemotherapy; however, no standard therapy has been established yet. We collected and reviewed retrospectively the clinical, pathological, radiological findings as well as the outcomes of 50 consecutive patients with LM from solid tumors to determine whether the diagnostic modalities and therapeutic procedures affected the outcomes. The results of this study confirm the role of gdMRI in the diagnosis of LM in clinical practice and suggest that an aggressive treatment may improve survival in patients with this debilitating and increasingly frequent neurological complication.

Pachymeningeal involvement in POEMS syndrome: MRI and histopathological study.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare plasma cell disease. Vascular endothelial growth factor (VEGF) seems to play a pathogenic role. Peripheral neuropathy is the main neurological feature. Cranial pachymeningitis has occasionally been reported, but no histopathological studies have been performed. The authors extensively evaluated the central nervous system MRI in 11 patients (seven men, four women; mean age at diagnosis 54.45 years) with POEMS syndrome. In two patients, meningeal histopathology with staining for VEGF and VEGF receptor was performed, and pachymeningeal involvement characterised at histopathological, immunohistochemical and confocal microscopy levels. Nine patients presented with cranial pachymeningitis. One patient suffered from migraine, and none complained of cranial nerve palsies or visual loss. None showed any MRI signs of spinal pachymeningitis. No correlation was found with disease duration and VEGF serum level. Histopathology showed hyperplasia of meningothelial cells, neovascularisation and obstructive vessel remodelling, without inflammation. VEGF and VEGF receptor were strongly coexpressed on endothelium, smooth-muscle cells of arterioles and meningothelial cells. In conclusion, POEMS patients present a high prevalence of meningeal involvement. The histological changes, different from those present in chronic pachymeningitis of other aetiology, suggest a possible VEGF role in the pathogenesis of the meningeal remodelling.

Neurosarcoidosis. Clinical description of 7 cases with a proposal for a new diagnostic strategy.

OBJECTIVE: Chronic involvement of the nervous system is relatively rare in sarcoidosis. We describe 7 cases that fulfil Zajicek's criteria for neurosarcoidosis (NS) and propose some modifications to such criteria. MATERIALS AND METHODS: The patients were admitted for various neurological syndromes: 2 cases presented with chronic lymphocytic meningitis, 4 with spinal cord symptoms, one case was initially confused with multiple sclerosis. Serological tests, immunological screening, cerebrospinal fluid (CSF) analysis, bacteriological and viral testing were performed in all patients. Spinal and cerebral MRI, gallium scan, bronchoscopy with biopsy and bronchoalveolar-lavage fluid analysis, high-resolution computed tomography (HRCT) of the chest, biopsy of the lungs, skin, mediastinal lymph-node and meninges, were useful in diagnosing NS. RESULTS AND DISCUSSION: Laboratory tests showed serum inflammatory abnormalities, but were negative for infectious diseases, while CSF showed inflammatory signs in all patients. MRI revealed meningeal enhancement or hypertrophic pachymeningeal lesions in 4 patients, white matter abnormalities and mass lesions in 2 patients, and a spinal mass lesion in 1 patient. Gallium scan, HRCT, bronchoscopy were positive in most cases. Patients were treated with steroid and immunosuppressive therapy, with improvement in six cases. One patient died from infectious complications. CONCLUSION: A definite diagnosis of NS requires demonstration of non-caseating granulomas affecting nervous tissues. In most cases, histological evidence of systemic disease (probable NS) is sufficient in the presence of compatible alterations in the CNS. In our patients the bronchoalveolarlavage fluid analysis, gallium scan, and chest HRCT were important for diagnosis, while serum ACE was always normal and chest radiographs were not suggestive of sarcoidosis.