Risk and outcomes of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. METHODS: A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. RESULTS: Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70-0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76-6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. CONCLUSIONS: Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk-benefit assessment.

Successful Isavuconazole Salvage Therapy for a Cryptococcus deuterogattii (AFLP6/VGII) Disseminated Infection in a European Immunocompetent Patient.

Members of the Cryptococcus gattii species complex are notorious causes of cryptococcosis as they often cause severe, life-threatening infections. Here we describe a case of a severe disseminated C. deuterogattii infection in a previously healthy patient who was initially treated with amphotericin B, 5-fluorocytosine and fluconazole, which led to a good neurological response, but the infection in the lungs remained unaltered and was not completely resolved until switching the antifungal therapy to isavuconazole. The infection was likely acquired during a one-month stay at the Azores Islands, Portugal. Environmental sampling did not yield any cryptococcal isolate; therefore, the source of this apparent autochthonous case could not be determined. Molecular typing showed that the cultured C. deuterogattii isolates were closely related to the Vancouver Island outbreak-genotype.

Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study.

BACKGROUND: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. OBJECTIVE: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. METHODS: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. RESULTS: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. CONCLUSIONS: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.

Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population.

BACKGROUND: Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population. OBJECTIVE: To evaluate DMF tolerability, safety and persistence in MS in a real-world setting. METHODS: We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation. RESULTS: We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p < 0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported. CONCLUSIONS: Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation.

Effects of Oral Supplementation with Docosahexaenoic Acid (DHA) plus Antioxidants in Pseudoexfoliative Glaucoma: A 6-Month Open-Label Randomized Trial.

PURPOSE: To assess the effects of antioxidant oral supplementation based on docosahexaenoic acid (DHA) in pseudoexfoliative (PEX) glaucoma. PATIENTS AND METHODS: A prospective 6-month open-label randomized controlled trial was conducted in patients with PEX glaucoma and adequate intraocular pressure (IOP) control. Patients in the DHA group received a high-rich DHA (1 g) nutraceutical formulation. Ophthalmological examination, DHA erythrocyte membrane content (% total fatty acids), plasma total antioxidant capacity (TAC), plasma malondialdehyde (MDA), and plasma IL-6 levels were assessed. RESULTS: Forty-seven patients (DHA group 23, controls 24; mean age 70.3 years) were included. In the DHA group, the mean IOP in the right eye decreased from 14.7 [3.3] mmHg at baseline to 12.1 [1.5] mmHg at 6 months (P=0.01). In the left eye, IOP decreased from 15.1 [3.3] mmHg at baseline to 12.2 [2.4] mmHg at 6 months (P=0.007). DHA erythrocyte content increased in the DHA group, with significant differences versus controls at 3 months and 6 months (8.1% [0.9] vs. 4.4% [0.7]; P < 0.0001). At 6 months and in the DHA group only, TAC levels as compared with baseline increased significantly (919.7 [117.9] vs. 856.9 [180.3] µM copper-reducing equivalents; P=0.01), and both MDA (4.4 [0.8] vs. 5.2 [1.1] nmol/mL; P = 0.02) and IL-6 (2.8 [1.3] vs. 4.7 [2.3] pg/mL; P=0.006) levels were lower than in controls. CONCLUSIONS: Targeting pathophysiology mechanisms of PEX glaucoma by reducing oxidative stress and inflammation with a high-rich DHA supplement might be an attractive therapeutic approach. Despite the short duration of treatment, decrease in IOP supports the clinical significance of DHA supplementation.

Anti-JC virus seroprevalence in a Spanish multiple sclerosis cohort: JC virus seroprevalence in Spain.

OBJECTIVE: To estimate the seroprevalence of anti-JCV antibodies, seroconverting rates and evolution of antibody levels in a multiple sclerosis (MS) Spanish cohort. METHODS: Multicenter, retrospective cross-sectional and longitudinal study. The JCV seroprevalence was analyzed in 711 MS patients by using 1st (STRATIFY-1) and 2nd generation (STRATIFY-2) two-step ELISA over 2.65 (±0.97) years. Seroconversion rate was obtained over 2 samples from 314 patients, and index stability from 301 patients with 3 or more samples available. The effect of each ELISA generation, demographics, clinical characteristics and therapy on seroprevalence was assessed by logistic regression. RESULTS: The overall anti-JCV seroprevalence was 55.3% (51.6-58.9), similar across regions (p=0.073). It increased with age (p<0.000) and when STRATIFY-2 was used (60.5%, p=0.001). Neither sex nor immunosuppressive therapy had any influence. Yearly seroconversion rate was 7% (considering only STRATIFY-2). Serological changes were observed in 24/301 patients, 5.7% initially seropositive reverted to seronegative and 7% initially seronegative changed to seropositive and again to seronegative, all these cases had initial index values around the assay's cut-off. CONCLUSIONS: JCV seroprevalence in Spanish MS patients was similar to that reported in other European populations. Changes in serostatus are not infrequent and should be considered in clinical decisions.

Frequency of cognitive impairment without dementia in patients with stroke: a two-year follow-up study.

BACKGROUND AND PURPOSE: Studies on cognitive impairment without dementia (CIND) after stroke are scarce and there are no widely accepted diagnostic criteria for this condition. The purpose of this study was to determine the frequency of CIND in a hospital cohort before and after stroke during a 2-year follow up according to two alternative operational criteria. METHODS: Three hundred twenty-seven consecutive stroke inpatients were prospectively evaluated with an extensive neuropsychological battery and the Informant Questionnaire of Cognitive Decline in the Elderly (IQCODE) on admission and then at 3, 12, and 24 months after discharge. CIND was established according to two alternative operational criteria: proxy information (a cutoff score of 3.35 in the IQCODE: IQ-c) or to neuropsychologic examination (a score below the sixth percentile in >/=50% of the tests exploring one cognitive domain: NPE-c). RESULTS: A total of 12.6% patients had CIND (IQ-c) before stroke. After 3 months, the CIND frequency was 26.9% (IQ-c) or 19.6% (NPE-c); after 12 months, 39.5% or 26.8%; and after 24 months, 36.6% or 21%. The risk for developing delayed dementia was significantly higher for poststroke patients with CIND diagnosed by IQ-c (OR 8.8), NPE-c (OR 10.3), or both criteria (OR 20.8). CONCLUSIONS: Patients with CIND are frequent before and after stroke and prone to delayed dementia. Both criteria are valid for identifying CIND cases and predicting long-term conversion to dementia, but NPE-c may be more adequate for the long-term follow up and IQ-c for detecting changes from prestroke status.