Signal Intensity Evaluation in the Dentate Nucleus and Subcortical Gray Matter : Effect of Several Administrations of Gadoterate Meglumine in Multiple Sclerosis.

PURPOSE: Several studies reported gadolinium deposition in the dentate nuclei (DN) and the globus pallidus (GP) that was associated to linear GBCA administrations rather than macrocyclic. It is therefore imperative to evaluate and assess the safety of cumulative administration of gadoterate meglumine (macrocyclic). Thus, T1-weighted images (T1WI) of multiple sclerosis (MS) patients longitudinally followed for 4 years were retrospectively analyzed. METHODS: In this study 44 patients, 10 with clinically isolated syndrome (CIS), 24 relapsing-remitting MS (RRMS) and 10 primary-progressive MS (PPMS) were examined every 6 months (first four scans) and then with a 1-year interval (last two scans). Image processing consisted in reorienting unenhanced T1WI to standard space, followed by B1 inhomogeneity correction. A patient-specific template was then generated to normalize T1WI signal intensity (SI) and segment the DN and subcortical GM structures. All structures were then transformed to each patient space in order to measure the SI in each region. The cerebellar peduncles (CP) and semi-oval (SO) white matter were then manually delineated and used as reference to calculate SI ratios in the DN and subcortical GM structures. A linear mixed-effect model was finally applied to longitudinally analyze SI variations. RESULTS: The SI measurements performed in all structures showed no significant increases with the cumulative GBCA administration. CONCLUSION: This study showed no significant SI increases within the DN and subcortical GM structures of longitudinally followed MS patients even with the cumulative administration of the macrocyclic GBCA gadoterate meglumine.

Evaluation of CSF1R-related adult onset leukoencephalopathy with axonal spheroids and pigmented glia diagnostic criteria.

BACKGROUND AND PURPOSE: Diagnostic criteria for adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation have recently been proposed. Our objective was to assess their accuracy in an independent multicenter cohort. METHODS: We evaluated the sensitivity and specificity of the diagnostic criteria for ALSP (including the "probable" and "possible" definitions) in a national cohort of 22 patients with CSF1R mutation, and 59 patients with an alternative diagnosis of adult onset inherited leukoencephalopathy. RESULTS: Overall, the sensitivity of the diagnostic criteria for ALSP was 82%, including nine of 22 patients diagnosed as probable and nine of 22 diagnosed as possible. Twenty of the 59 CSF1R mutation-negative leukoencephalopathies fulfilled the diagnostic criteria, leading to a specificity of 66%. CONCLUSIONS: Diagnostic criteria for ALSP have an overall limited sensitivity along with a modest specificity. We suggest that in patients suspected of genetic leukoencephalopathy, a comprehensive magnetic resonance imaging pattern-based approach is warranted, together with white matter gene panel or whole exome sequencing.

T1/T2 ratio: A quantitative sensitive marker of brain tissue integrity in multiple sclerosis.

BACKGROUND AND PURPOSE: The aim of this study is to determine whether cerebral white matter (WM) microstructural damage, defined by decreased fractional anisotropy (FA) and increased axial (AD) and radial (RD) diffusivities, could be detected as accurately by measuring the T1/T2 ratio, in relapsing-remitting multiple sclerosis (RRMS) patients compared to healthy control (HC) subjects. METHODS: Twenty-eight RRMS patients and 24 HC subjects were included in this study. Region-based analysis based on the ICBM-81 diffusion tensor imaging (DTI) atlas WM labels was performed to compare T1/T2 ratio to DTI values in normal-appearing WM (NAWM) regions of interest. Lesions segmentation was also performed and compared to the HC global WM. RESULTS: A significant 19.65% decrease of T1/T2 ratio values was observed in NAWM regions of RRMS patients compared to HC. A significant 6.30% decrease of FA, as well as significant 4.76% and 10.27% increases of AD and RD, respectively, were observed in RRMS compared to the HC group in various NAWM regions. Compared to the global WM HC mask, lesions have significantly decreased T1/T2 ratio and FA and increased AD and RD (p < . 001). CONCLUSIONS: Results showed significant differences between RRMS and HC in both DTI and T1/T2 ratio measurements. T1/T2 ratio even demonstrated extensive WM abnormalities when compared to DTI, thereby highlighting the ratio's sensitivity to subtle differences in cerebral WM structural integrity using only conventional MRI sequences.

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Multiple sclerosis with atypical MRI presentation: Results of a nationwide multicenter study in 57 consecutive cases.

BACKGROUND: The recent 2017 modification have increased the sensitivity of McDonald criteria for MS. Nevertheless, some MS patients with atypical MRI findings have been identified, leading to prolonged delay to diagnosis and high costs to look for alternative diagnoses. OBJECTIVE: To describe a series of MS patients with atypical MRI presentation. MATERIAL AND METHODS: Patients with atypical MS were identified through a nationwide retrospective study. We established a five groups classification: tumefactive demyelinating lesion (TDL)-onset MS, acute disseminated encephalomyelitis (ADEM)-like MS, cavitary MS and leukodystrophy-like MS. All the patients meeting our radiological criteria for atypical MS were included. RESULTS: A total of 57 patients met the inclusion criteria. 7 cases were classified in the TDL-onset group, 10 in the ADEM-like group, 26 in the cavitary group and 14 in the leukodystrophy-like group. Overall risk of conversion to MS after an isolated TDL was around 30% at five years. Patients in the TDL-onset and ADEM-like groups globally presented an acute onset and a relapsing-remitting evolution. Conversely, patients in the cavitary and leukodystrophy- groups largely evolved with a progressive and severe course. CONCLUSION: A significant number of MS patients can have a striking atypical presentation and may be misdiagnosed. This preliminary analysis helps to refine the spectrum of atypical MS patients.