BACKGROUND: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis. METHODS: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab. RESULTS: Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches. CONCLUSIONS: In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.).

• MeSH
• CD40 Antigens * antagonists & inhibitors   immunology   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Gadolinium MeSH
• Injections, Subcutaneous MeSH
• Administration, Intravenous MeSH
• Humans MeSH
• CD40 Ligand * antagonists & inhibitors   immunology   MeSH
• Magnetic Resonance Imaging MeSH
• Antibodies, Monoclonal * immunology   therapeutic use   MeSH
• Multiple Sclerosis, Relapsing-Remitting * diagnostic imaging   drug therapy   immunology   MeSH
• Multiple Sclerosis diagnostic imaging   drug therapy   immunology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

To improve quality and to overcome the wide discrepancies in stroke care both within- and between European countries, the European Stroke Organisation Executive Committee initiated in 2007 activities to establish certification processes for stroke units and stroke centres. The rapidly expanding evidence base in stroke care provided the mandate for the European Stroke Organisation Stroke Unit-Committee to develop certification procedures for stroke units and stroke centres with the goals of setting standards for stroke treatment in Europe, improving quality and minimising variation. The purpose of this article is to present the certification criteria and the auditing process for stroke units and stroke centres that aim to standardise and harmonise care for stroke patients, and hence become members of the European Stroke Organisation Stroke Unit and Stroke Centre network. Standardised application forms and guidelines for national and international auditors have been developed and updated by members of the European Stroke Organisation Stroke Unit-Committee. Key features are availability of trained personnel, diagnostic equipment, acute treatment and collaboration with other stroke-caregivers. After submission, the application is reviewed by one national and two international auditors. Based on their reports, the Stroke Unit-Committee will make a final decision. Validating on-site visits for a subset of stroke units and stroke centres are planned. We herein describe a novel, European Stroke Organisation-based online certification process of stroke units and stroke centres. This is a major step forward towards high-quality stroke care across Europe. The additional value by connecting high-quality European Stroke Organisation Stroke Unit and Stroke Centre is facilitation of future collaboration and research activities, enabling building and maintenance of a high-quality stroke care network in Europe.

• Publication type
• Journal Article MeSH

Willisův okruh (circle of Willis, CoW) tvoří hlavní oběhový systém v lidském mozku. Byla popsána dlouhá řada variací CoW i jejich souvislost s ischemickou cévní mozkovou příhodou (iCMP). Popisujeme tři případy mladých pacientů s kombinací iCMP a anomáliemi CoW, u nichž srovnáme hodnotu barevně kódované duplexní sonografie (color-coded duplex sonography, CCDS) s dalšími diagnostickými zobrazovacími metodami, jako jsou magnetická rezonanční angiografie (MRA) a digitální subtrakční angiografie (DSA). U uvedených pacientů byla zjištěna řada rizikových faktorů jako stenóza nebo trombóza nitrolebních mozkových cév, mechanická komprese cév, genetická mutace spojená s významným rizikem trombózy a užívání perorálních kontraceptiv. U pacientů byla nejdříve sepsána jejich anamnéza, následně byli vyšetřeni neurologem, byla provedena laboratorní vyšetření (celkový krevní obraz, lipidový profil, vyšetření na HIV1/2, syfilis RPR), následoval screening zaměřený na markery spojené se zvýšeným rizikem trombózy, rentgen srdce a plic, vyšetření likvoru, CCDS, DSA, MRA. Výsledky CCDS a ostatních zobrazovacích metod byly naprosto shodné. V článku autoři pojednávají o patogenní úloze vrozených anomálií CoW, incidenci ischemických cévních mozkových příhod a vysoké diagnostické hodnotě CCDS při vyhledávání uvedených anomálií.

The circle of Willis (CoW) forms the main circulatory system in the human brain. A large number of variations of the CoW is known, and also their association with ischemic stroke. Three cases of young patients with combination of ischemic stroke and anomalies in the CoW are presented, and the value of the color-coded duplex sonography (CCDS) is compared to other imaging diagnostics such as magnetic resonance angiography (MRA) and digital subtraction angiography (DSA). In these patients we found multiple risk factors such as: stenosis or thrombosis of intracranial brain vessels, mechanical compression of vessels, a genetic mutation associated with an increased risk of thrombosis, intake of oral contraceptives. For clinical evaluation several methods were used: detailed medical history, neurological status, laboratory examinations (complete blood count, biochemistry, lipid profile, HIV1/2, Syphilis RPR test), screening for markers associated with an increased risk of thrombosis, chest X-ray, spinal fluid study, CCDS, DSA, MRA. A full conformity in the data from CCDS and other imaging methods was found. The authors discuss the pathogenetic role of congenital anomalies of CoW, incidence of ischemic stroke and the high diagnostic value of CCDS for finding such anomalies.

• MeSH
• Cerebrovascular Disorders congenital   MeSH
• Circle of Willis * abnormalities   diagnostic imaging   pathology   MeSH
• Adult MeSH
• Brain Ischemia * diagnostic imaging   etiology   MeSH
• Collateral Circulation MeSH
• Humans MeSH
• Young Adult MeSH
• Risk Factors MeSH
• Ultrasonography, Doppler, Color MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Female MeSH
• Publication type
• Case Reports MeSH