Intrathecal B cell activation and memory impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. METHODS: A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. RESULTS: κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5-195.2 vs. median 37.2, range 2.3-396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. CONCLUSION: Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans.

Impact of post-contrast MRI in the definition of active multiple sclerosis.

BACKGROUND: For multiple sclerosis (MS) phenotypes classification, the presence of "disease activity" can be defined by clinical relapses and/or by magnetic resonance imaging (MRI) through gadolinium-enhancing (Gd+) lesions or new/enlarged T2 lesions. Recent MRI and pathology findings have demonstrated Gd deposition in the brain, suggesting to avoid Gd administration when dispensable. In this scenario, we aimed to evaluate the contribution of post-contrast MRIs to the definition of "active" MS phenotype. METHODS: We retrospectively selected 84 "active" relapsing-remitting MS (RRMS) patients according to Lublin 2013, calculating both the number of Gd+ lesions not detectable as new/unequivocally enlarged on T2 images and the proportion of patients who would be still correctly classified as "active" without Gd administration. RESULTS: 13 out of 164 (7.9%) Gd+ lesions did not correspond to a new/enlarged T2 lesion. Gd administration did not modify the classification of MS as "active" in 83 out of 84 subjects (98.8%). CONCLUSION: The contribution of Gd+ lesions to the correct classification of RRMS patients as "active" is marginal, thus limiting the need of routine Gd administration for this scope. Further studies are warranted to support these conclusions.

The no evidence of disease activity (NEDA) concept in MS: impact of spinal cord MRI.

BACKGROUND: Measures to define treatment response, such as no evidence of disease activity (NEDA), are routinely used in multiple sclerosis (MS) clinical practice. Although spinal cord involvement is a frequent feature of MS, its magnetic resonance imaging (MRI) monitoring is not routinely performed. OBJECTIVE: To assess the impact of spinal cord MRI in the definition of NEDA in a cohort of people with MS (pwMS) with available spinal cord imaging performed as for routine monitoring. METHODS: We included 115 pwMS undergoing treatment with first-line disease-modifying therapies (DMTs) and retrospectively analyzed the presence of NEDA in the whole cohort, either considering or not spinal cord imaging. RESULTS: When considering only clinical and brain MRI measures, 97 out of 115 pwMS (84.3%) satisfied the criteria for NEDA. In the same cohort, the number of pwMS with NEDA significantly decreased to 88 (76.5%) (p < 0.01) when considering also spinal cord imaging. CONCLUSION: These findings suggest that, in routine clinical practice, spinal cord MRI monitoring in pwMS under first-line DMTs leads to a slight but significant change in the proportion of subjects classified as clinically and radiologically stable according to the NEDA definition.

Hyperdense middle cerebral and/or internal carotid arteries in acute ischemic stroke: rate, predictive factors and influence on clinical outcome.

BACKGROUND: In patients with acute stroke, the hyperdense middle cerebral artery (MCA) and internal carotid artery (ICA) signs on CT scans are markers of early ischemia, but their prognostic implications remain unclear.The aims of this prospective study were to assess: (1) the occurrence rate of hyperdense MCA and/or ICA in patients admitted for acute ischemic stroke; (2) the risk factors for hyperdense MCA and/or ICA; (3) the correlation between hyperdense MCA and/or ICA and functional outcome at 3 months. METHODS: Consecutive patients admitted with ischemic stroke between 1 January 2006 and 30 June 2010 were included in this prospective single-centre cohort study. RESULTS: 1,010 patients (mean age 71.9 years; 56.7% males) were included in the study. Among these patients, 148 (14.7%; mean age 71.2 years; 52% males) had hyperdense MCA and/or ICA. Overall, 163 patients (16.1%) had a final infarct covering more than one third of the MCA territory. Seventy-eight of 148 patients (52.7%) with hyperdense MCA and/or ICA had an infarct involving more than one third of the MCA territory compared to 85 of the 862 patients without artery hyperdensity (9.9%). At 3 months, 18 patients were lost to follow-up, 325 patients (32.8%) were disabled and 165 died (16.5%). Age (OR 1.06 for 1 added year; 95% CI 1.04-1.08), National Institute of Health Stroke Scale score for 1 added point on admission (OR 1.2; 95% CI 1.2-1.3), stroke due to atherosclerosis (OR 2.3; 95% CI 1.0-5.4), hemorrhagic transformation of the ischemic lesion (OR 2.2; 95% CI 1.0-4.9), and hyperdense MCA and/or ICA (OR 2.0; 95% CI 1.0-4.0) were associated with adverse outcome. CONCLUSIONS: In this prospective cohort of patients with acute ischemic stroke, we observed an incidence of hyperdense MCA and/or ICA arteries of about 15%; hyperdense MCA and/or ICA were associated with a final infarct involving more than one third of the MCA territory and poor functional outcome at 3 months.