Prognostic factors for disease activity in newly diagnosed teriflunomide-treated patients with multiple sclerosis: a nationwide Danish study.

BACKGROUND: Clinicians frequently rely on relapse counts, T2 MRI lesion load (T2L) and Expanded Disability Status Scale (EDSS) scores to guide treatment decisions for individuals diagnosed with multiple sclerosis (MS). This study evaluates how these factors, along with age and sex, influence prognosis during treatment with teriflunomide (TFL). METHODS: We conducted a nationwide cohort study using data from the Danish Multiple Sclerosis Registry.Eligible participants had relapsing-remitting MS or clinically isolated syndrome and initiated TFL as their first treatment between 2013 and 2019. The effect of age, pretreatment relapses, T2L and EDSS scores on the risk of disease activity on TFL were stratified by sex. RESULTS: In total, 784 individuals were included (57.4% females). A high number of pretreatment relapses (≥2) was associated with an increased risk of disease activity in females only (OR and (95% CI): 1.76 (1.11 to 2.81)). Age group 50+ was associated with a lower risk of disease activity in both sexes (OR females=0.28 (0.14 to 0.56); OR males=0.22 (0.09 to 0.55)), while age 35-49 showed a different impact in males and females (OR females=0.79 (0.50 to 1.23); OR males=0.42 (0.24 to 0.72)). EDSS scores and T2L did not show any consistent associations. CONCLUSION: A high number of pretreatment relapses was only associated with an increased risk of disease activity in females, while age had a differential impact on the risk of disease activity according to sex. Clinicians may consider age, sex and relapses when deciding on TFL treatment.

Acute disseminated encephalomyelitis following the COVID-19 vaccine Ad26.COV2.S, a case report.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has been leading to dramatic health, social and economic problems around the world. It was necessary to introduce worldwide vaccination program against SARS-CoV-2 virus. Vaccination of billions of people around the world leads to many questions about risk of vaccines and possible side effects. It is well known that acute disseminated encephalomyelitis (ADEM) is a rare, but possible complication of vaccines. Previously, cases of ADEM following various COVID-19 vaccines, including the vaccines from AstraZenica, Pfizer, Sputnik V, SinoVac, Moderna, Sinopharm, have been described. In this case report, we present the first documented case of ADEM following the COVID-19 vaccine Ad26.COV2.S from Johnson & Johnson. Case presentation: We present the case of a 31-year-old female with gradually progression of right-sided weakness and numbness during a three-week period. Four weeks prior to symptom onset, the patient received the single-dose SARS-CoV-2 vaccine Ad26.COV2.S. Neuroimaging revealed five large juxtacortical T2 FLAIR hyperintense lesions with incomplete contrast enhancement on post-contrast T1 images located supratentorial: one in the right cerebral hemisphere and four in left cerebral hemisphere. The patient was followed up for four months. Symptom debut, clinical picture and MRI were typical for ADEM and the patient completely recovered after high dose intravenous methylprednisolone treatment. Conclusions: This is, to the best of our knowledge, the first case report of ADEM following the COVID-19 vaccine Ad26.COV2.S. This case illustrates, although ADEM is a rare complication following SARS-CoV-2 vaccines, the necessity of maintaining a vaccine safety monitoring system to identify patients at high risk from developing severe complications from the vaccines.

Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis.

Importance: Ocrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrelizumab. Objective: To evaluate whether the effectiveness of rituximab is noninferior to ocrelizumab in relapsing-remitting MS. Design, Setting, and Participants: This was an observational cohort study conducted between January 2015 and March 2021. Patients were included in the treatment group for the duration of study therapy and were recruited from the MSBase registry and Danish MS Registry (DMSR). Included patients had a history of relapsing-remitting MS treated with ocrelizumab or rituximab, a minimum 6 months of follow-up, and sufficient data to calculate the propensity score. Patients with comparable baseline characteristics were 1:6 matched with propensity score on age, sex, MS duration, disability (Expanded Disability Status Scale), prior relapse rate, prior therapy, disease activity (relapses, disability accumulation, or both), magnetic resonance imaging lesion burden (missing values imputed), and country. Exposure: Treatment with ocrelizumab or rituximab after 2015. Main outcomes and Measures: Noninferiority comparison of annualized rate of relapses (ARRs), with a prespecified noninferiority margin of 1.63 rate ratio. Secondary end points were relapse and 6-month confirmed disability accumulation in pairwise-censored groups. Results: Of the 6027 patients with MS who were treated with ocrelizumab or rituximab, a total of 1613 (mean [SD] age; 42.0 [10.8] years; 1089 female [68%]) fulfilled the inclusion criteria and were included in the analysis (898 MSBase, 715 DMSR). A total of 710 patients treated with ocrelizumab (414 MSBase, 296 DMSR) were matched with 186 patients treated with rituximab (110 MSBase, 76 DMSR). Over a pairwise censored mean (SD) follow-up of 1.4 (0.7) years, the ARR ratio was higher in patients treated with rituximab than in those treated with ocrelizumab (rate ratio, 1.8; 95% CI, 1.4-2.4; ARR, 0.20 vs 0.09; P < .001). The cumulative hazard of relapses was higher among patients treated with rituximab than those treated with ocrelizumab (hazard ratio, 2.1; 95% CI, 1.5-3.0). No difference in the risk of disability accumulation was observed between groups. Results were confirmed in sensitivity analyses. Conclusion: In this noninferiority comparative effectiveness observational cohort study, results did not show noninferiority of treatment with rituximab compared with ocrelizumab. As administered in everyday practice, rituximab was associated with a higher risk of relapses than ocrelizumab. The efficacy of rituximab and ocrelizumab administered at uniform doses and intervals is being further evaluated in randomized noninferiority clinical trials.

Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry.

OBJECTIVE: Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019. METHODS: This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits. RESULTS: A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up. CONCLUSIONS: Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.

[Carbon monoxide poisoning and development of delayed neuropsychiatric syndrome in a 77-year-old woman].

This case report describes carbon monoxide (CO) poisoning in a woman. CO is a toxic, odourless and colourless gas. Delayed cognitive sequelae have been described in up to 40% of patients with significant CO poisoning. A 77-year-old woman suffered from severe smoke- and CO poisoning and received hyperbaric O2 therapy, but she continued to have memory impairment and unsteady gait at day 26. Brain MRI showed diffuse white matter lesions in both hemispheres with increased signal on diffusion-weighted imaging. Diagnosis, pathogenesis and treatment of CO poisoning are discussed.

Initial high-efficacy disease-modifying therapy in multiple sclerosis: A nationwide cohort study.

OBJECTIVE: To determine the effectiveness of high-efficacy disease-modifying therapies (heDMTs) vs medium-efficacy disease-modifying therapies (meDMT) as the first treatment choice in treatment-naive patients with multiple sclerosis (MS) on disability worsening and relapses. We assessed this using a nationwide population-based MS registry. METHODS: We identified all patients starting a heDMT as first-time treatment from the Danish Multiple Sclerosis Registry and compared treatment outcomes with a propensity score matched sample of patients starting meDMT. RESULTS: We included 388 patients in the study: 194 starting initial therapy with heDMT matched to 194 patients starting meDMT. At 4 years of follow-up, the probabilities of a 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening were 16.7% (95% confidence interval [CI] 10.4%-23.0%) and 30.1% (95% CI 23.1%-37.1%) for heDMT and meDMT initiators, respectively (hazard ratio [HR] 0.53, 95% CI 0.33-0.83, p = 0.006). Patients initiating heDMT also had a lower probability of a first relapse (HR 0.50, 95% CI 0.37-0.67). Results were similar after pairwise censoring and in subgroups with high baseline activity, diagnosis after 2006, or information on baseline T2 lesion load. CONCLUSION: We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting meDMT.

Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study.

OBJECTIVE: To compare on-treatment efficacy and discontinuation outcomes in teriflunomide (TFL) and dimethyl fumarate (DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in a real-world setting. METHODS: We identified all patients starting TFL or DMF from the Danish Multiple Sclerosis Registry and compared on-treatment efficacy outcomes between DMF using TFL, adjusted for clinical baseline variables and propensity score-based methods. RESULTS: We included 2,236 patients in the study: 1,469 patients on TFL and 767 on DMF. Annualized relapse rates (ARRs) in TFL and DMF were 0.16 (95% confidence interval [CI] 0.13-0.20) and 0.09 (95% CI 0.07-0.12), respectively. Relapse rate ratio for DMF/TFL was 0.58 (95% CI 0.46-0.73, p < 0.001). DMF had a higher relapse-free survival proportion at 48 months of follow-up (p < 0.05). We observed no difference in Expanded Disability Status Scale score worsening. Discontinuations due to disease breakthrough were 10.2% (95% CI 7.6%-12.8%) and 22.1% (95% CI 19.2%-25.0%) for DMF and TFL, respectively. A subgroup analysis of ARRs in 708 patients with available baseline MRI T2 lesion amount reported similar results after adjustment. CONCLUSION: We found lower ARR, higher relapse-free survival, and lower incidence of discontinuation due to disease breakthrough on treatment with DMF compared with TFL. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS, DMF is more effective in preventing relapses and has lower discontinuation due to disease breakthrough compared with TFL.

[Changes of protein S100B serum concentration during ischemic and hemorrhagic stroke in relation to the volume of stroke lesion]. / Zmiany stezenia bialka S100B w surowicy krwi w udarze niedokrwiennym i krwotocznym mózgu w zaleznosci od wielkosci ogniska udarowego.

BACKGROUND AND PURPOSE: Biochemical markers offer a new strategy in the diagnosis, estimation of clinical prognosis and monitoring of treatment in patients with brain damage. At present, two specific brain originated proteins play a major role: S100B protein and neuron-specific enolase (NSE). S100B comes from astrocytes and NSE has been found in neuronal cytoplasm. The aim of this study was to evaluate dynamics of protein S100B level changes in blood in stroke patients. MATERIAL AND METHODS: The material consisted of 67 patients, 53 with ischemic stroke (mean age 67.7) and 14 with hemorrhagic stroke (mean age 66.7). The diagnosis of stroke was made on the basis of clinical symptoms and computed tomography (CT). Plasma concentration of S100B was measured using the immunoluminometric test (Lia-Mat Sangtec 100(R)) on the 1st, 3rd, 7th and 14th day after stroke onset. RESULTS: The highest levels of protein S100B were found in ischemic stroke predominantly on the 3rd day and in hemorrhagic stroke on the 1st day. The concentrations of protein S100B were similar in ischemic and hemorrhagic stroke on the 3rd, 7th and 14th day but they were significantly higher on the 1st day in hemorrhagic stroke. Serum levels of protein S100B after stroke onset have shown a correlation with infarct volume, especially in patients with large or medium stroke. In small stroke lesions, concentrations of protein S100B were under the cut-off level. In hemorrhagic stroke protein S100B levels were higher in patients with midline shift visible in brain CT, but the differences were not significant. CONCLUSIONS: Ischemic and hemorrhagic strokes lead to release of protein S100B into the blood. A good correlation between the release pattern of S100B and volume of vascular lesion has been found. S100B protein is the marker of brain damage during stroke. It is possible to use protein S100B measurements in monitoring the stroke treatment.

[Primary leptomeningeal sarcomatosis. Case report]. / Przypadek pierwotnej miesakowatosci opon mózgowo-rdzeniowych.

Primary intracranial sarcomas are very rare and aggressive tumors. A case of a 40-year-old woman with primary leptomeningeal sarcomatosis is presented. Initially her clinical symptoms resembled those of a pseudo tumor cerebri. Neuroimaging did not allow establishing a diagnosis of leptomeninges neoplastic infiltration. The patient died 8 months since the onset of symptoms. A neuropathological examination revealed diffuse thickening of leptomeninges. Microscopically a widespread sarcomatous infiltration of the subarachnoid space was shown, as well as a neoplastic infiltration of the choroid plexus and of some perivascular spaces in the cerebral cortex. On the grounds of a review of the literature diagnostic problems, differential diagnosis and clinical course of primary leptomeningeal sarcomatosis are discussed.