Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis.

Background: Serum biomarkers as neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enabled early identification of multiple sclerosis (MS) patients at risk of relapse-associated worsening (RAW) or progression independent of relapses (PIRA). However, the immunological mechanisms underlying these clinical phenotypes remain unclear.

Methods: We conducted a cross-sectional study including 117 MS patients and 84 healthy controls (HC).

Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis.

The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset.

Double Stent Retriever Mechanical Thrombectomy for Distal Medium Vessel Clots in the Middle Cerebral Artery: Initial Experience.

Background And Purpose: Mechanical thrombectomy (MT) is increasingly performed for distal medium vessel occlusions (DMVOs) of the anterior circulation in acute stroke patients. Although trials have not shown superiority over usual care, selected patients may still benefit from MT. The ideal endovascular technique is debated.

Timing of starting anticoagulation following decompressive surgery for cerebral vein and sinus thrombosis: An observational study.

Background: Anticoagulation is the mainstay acute therapy for cerebral venous thrombosis (CVT). Decompressive surgery is required in a small minority of patients with large parenchymal lesions and impending herniation, which requires a temporary suspension of anticoagulation.

Aim: The objective of this study was to identify the optimal timing for starting or resuming anticoagulation following decompressive surgery.

Hemorrhagic Infarction Does Not Worsen Functional Outcomes in Noncardioembolic Ischemic Stroke: Secondary Analysis From PACIFIC-STROKE.

Background: Hemorrhagic infarction (HI) of acute ischemic stroke is frequent. Whether radiologically detected HI affects stroke outcomes has been less explored.

Methods: This was a secondary analysis of the PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), which enrolled patients with acute noncardioembolic ischemic stroke receiving either asundexian or placebo in addition to guideline-based antiplatelet therapy.

Grading Right-to-Left Shunt With Transforaminal Doppler: A Valid Approach in Patients With Cryptogenic Stroke.

Background And Purpose: Right-to-left shunt (RLS), usually related to a patent foramen ovale (PFO), is an important cause of cryptogenic stroke (CS) in young patients. Transcranial Doppler (TCD) with an agitated saline bubble study is a highly sensitive modality for RLS diagnosis using a transtemporal approach (TTD). However, a minority of patients have insufficient temporal bone windows.

Corrigendum: Biomarkers of response to ocrelizumab in relapsing-remitting multiple sclerosis.

[This corrects the article DOI: 10.3389/fimmu.2024.

Effect of Natalizumab on sNfL and sGFAP Levels in Multiple Sclerosis Patients.

Natalizumab is a highly effective therapy for multiple sclerosis (MS). The aim of this study was to evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS treated with Natalizumab. sNfL and sGFAP were analyzed at baseline, 6 and 12 months post treatment using the single-molecule array (SiMoA) technique.

Biomarkers of response to ocrelizumab in relapsing-remitting multiple sclerosis.

Objective: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response.

Methods: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology.

Progression independent of relapse activity can be predicted by passively acquired tapping speed through a smartphone for 1 month: A prospective study.

Background: Tapping speed (TS) correlates with baseline disability scales in people with multiple sclerosis (pwMS).

Objective: The study aimed to address if progression independent of relapse activity (PIRA) could be predicted by first-month measurement of TS.

Methods: Prospective study including pwMS in one referral MS center.

COVID-19 vaccines are not associated with axonal injury in patients with multiple sclerosis.

Objective: To evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage.

Methods: Single-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine.

Effect of alemtuzumab over sNfL and sGFAP levels in multiple sclerosis.

Introduction: Alemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS).

Aim: To evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years.

Methods: This prospective study involved MS patients treated with Alemtuzumab at a referral MS center.

Establishing Normal Serum Values of Neurofilament Light Chains and Glial Fibrillary Acidic Protein Considering the Effects of Age and Other Demographic Factors in Healthy Adults.

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers.

Clot migration in patients treated with tenecteplase versus alteplase before mechanical thrombectomy.

Introduction: This study aimed to describe and analyze the rate of clot migration of vessel thrombosis to distal segments in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis (IVT) with tenecteplase (TNK) and alteplase (ALT) before mechanical thrombectomy (MT). In addition, we aimed to determine the relationship between thrombus migration and functional prognosis.

Methods: This study followed the STROBE reporting guidelines.

Hemorrhagic Transformation in Noncardioembolic Acute Ischemic Stroke: MRI Analysis From PACIFIC-STROKE.

Background: In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT). In this secondary analysis, we aimed to investigate the frequency, types, and risk factors of HT on brain magnetic resonance imaging (MRI).

Methods: This was a secondary analysis of the PACIFIC-STROKE trial.

Passive assessment of tapping speed through smartphone is useful for monitoring multiple sclerosis.

Introduction: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS.

Methods: Single-center prospective study in patients with MS.

Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

Background: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort.

Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes.

Background: Exploratory analysis of the phase 2 PACIFIC-Stroke (Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-Non-Cardioembolic Stroke) randomized trial suggested that asundexian, an oral factor XIa inhibitor, prevents recurrent stroke and transient ischemic attacks in patients with atherosclerotic stroke. In this post hoc exploratory analysis, we hypothesized that asundexian would be more effective in patients enrolled with large, multiple, or cortical acute infarcts on magnetic resonance imaging than in patients enrolled with a single small subcortical acute infarct, and asundexian would prevent incident cortical covert infarcts.

Methods: In this placebo-controlled double-blinded randomized controlled trial, patients with mild-to-moderate noncardioembolic ischemic stroke were assigned to asundexian (10, 20, or 50 mg once daily) or placebo, in addition to antiplatelet therapy.

Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke.

Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented as a need. With this goal in mind, our research group's collaborative studies into cerebral ischemia and subsequent reperfusion concluded that there is a need to develop compounds with antioxidant and radical scavenger features.

Establishing the best combination of the kappa free light chain index and oligoclonal bands for an accurate diagnosis of multiple sclerosis.

Introduction: The immunoglobulin kappa free light chain (KFLC) index has been proposed as a potentially suitable alternative to oligoclonal IgG bands (OCGB) for diagnosing multiple sclerosis (MS), offering automation and reduced processing time. However, there is no consensus on the preferred approach or how to combine both techniques.

Methods: This prospective cohort study aimed to determine the best utilization of OCGB and KFLC index in patients with a clinically isolated syndrome (CIS) followed for at least two years.

Blood CD8+ Naïve T-Cells Identify MS Patients with High Probability of Optimal Cellular Response to SARS-CoV-2 Vaccine.

This single-center study included 68 multiple sclerosis (MS) patients who received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from one of several approved vaccine preparations in Spain. Blood samples were collected one to three months after the second dose of the vaccine had been administered. Cellular immune responses to the vaccine were assessed using QuantiFERON analysis, and peripheral blood mononuclear cell subsets were assayed using flow cytometry.

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial.

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers.

Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke.

Design, Setting, And Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022.

Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia.

Transient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the translation-regulation initiation step, the eukaryotic initiation factor (eIF) 4E is a key player regulated by its association with eIF4E-binding proteins (4E-BPs), mostly 4E-BP2 in brain tissue. In a previous work, we identified dihydropyrimidinase-related protein 2 (DRP2) as a 4E-BP2-interacting protein.