Neurología

Rationale, design and baseline characteristics of participants in the OCEANIC-STROKE trial of FXIa inhibition for secondary stroke prevention

2026-05-27T17:38:06Z

Rationale, design and baseline characteristics of participants in the OCEANIC-STROKE trial of FXIa inhibition for secondary stroke prevention Sharma, Mukul; Dong, Qiang; Hirano, Teruyuki; Kasner, Scott E.; Saver, Jeffrey; Masjuan, Jaime; Demchuk, Andrew M.; Cordonnier, Charlotte; Bereczki, Daniel; Tsivgoulis, Georgios; Veltkamp, Roland; Staikov, Ivan; Bae, Hee-Joon; Campbell, Bruce C. V.; Zini, Andrea; Lee, I-Hui; Ameriso, Sebastián Francisco; Kovar, Martin; Mikulik, Robert; Lemmens, Robin Introduction: Genetic deficiency of factor XI is associated with a reduced risk of ischemic stroke. Asundexian is a direct inhibitor of activated factor XIa (FXIa) with a low risk of bleeding in early trials. We seek to determine its efficacy and safety combined with antiplatelet therapy for prevention of ischemic stroke. Patients and methods: Oral faCtor Eleven A iNhibitor asundexian as novel antithrombotiC (OCEANIC-STROKE) is a placebo-controlled, double-blind, event-driven randomised trial including participants with stroke (NIHSS ≤ 15) or high-risk TIA (ABCD2 6 or 7) within 72 h of onset. Participants had at least one of the following: atherosclerosis of extra- or intracranial vessels, a medical history of atherosclerosis or an imaged acute non-lacunar infarct. We excluded sources of stroke requiring anticoagulation and active non-trivial bleeding other than hemorrhagic infarction (HI 1 or 2). Participants received asundexian 50 mg daily or placebo stratified by planned concurrent antiplatelet therapy (single vs dual). The primary endpoint is time to ischemic stroke. We present baseline characteristics as of 5 June 2025. Results: Between January 2023 and February 2025, we randomised 12,327 participants. Participants were 67% male with a mean (SD) age of 68 (11) years. Ischemic stroke was the index event for 95% of whom 27.4% had thrombolysis and/or mechanical thrombectomy. By TOAST classification, 43% of index strokes were LAA, 22% small vessel disease, 30% undetermined and 2% cardioembolic. Dual antiplatelets were planned in 63% as standard initial treatment. Trial completion is anticipated in October 2025. Conclusion: OCEANIC-STROKE will be the first completed trial of FXIa inhibition for prevention of stroke after non-cardioembolic stroke or TIA.

Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?

2026-05-19T18:18:20Z

Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum? Piedrabuena, María Agustina; Marrodán, Mariano; Zárate, María Agustina; Fiol, Marcela; Ysrraelit, María Célica; Correale, Jorge Background: Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory demyelinating CNS conditions. Patients negative for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies are classified as double seronegative (DN). Objective: To characterize and compare the clinical, radiological, and therapeutic profiles of DN, AQP4-IgG+, and MOG-IgG+ patients. Methods: Retrospective analysis of patients meeting 2015 NMOSD criteria, grouped by serostatus (AQP4-IgG+, MOG-IgG+, and DN). Demographic, clinical, and imaging data were compared. Results: We analyzed 111 patients: 64 AQP4-IgG+, 31 DN, and 16 MOG-IgG+. At onset, AQP4-IgG+ patients were older than DN and MOG-IgG+ (49 ± 14 vs 41 ± 12 vs 35 ± 12 years, p < 0.0001). DN had more relapses in the first two years (p = 0.02) and higher EDSS (p < 0.001). Myelitis was common in DN and AQP4-IgG+, while optic neuritis in MOG-IgG+. Relapse rates were highest in AQP4-IgG+ (p < 0.001). Oligoclonal bands were more common in DN (39 %) than in AQP4-IgG+ (27.7 %) and MOG-IgG+ (25 %)(p < 0.0001). Area postrema lesions were more frequent in DN (p = 0.02). Rituximab was mainly used in AQP4-IgG+ and DN (p < 0.001), with lower failure in DN (4.8 % vs 18 %). Conclusion: DN NMOSD shows distinct features but comparable disability to AQP4-IgG+ individuals. Conventional immunosuppressants seem effective, though further research is needed to clarify mechanisms and optimize treatment strategies.

The Neurochemical Landscape of Oligodendrocyte Physiology: From Myelination to Metabolic and Synaptic Modulation

2026-05-19T17:53:18Z

The Neurochemical Landscape of Oligodendrocyte Physiology: From Myelination to Metabolic and Synaptic Modulation Correale, Jorge Oligodendrocytes, traditionally recognized for their role in axonal myelination, are increasingly appreciated as metabolically dynamic and functionally diverse cells integral to central nervous system (CNS) homeostasis. This review delineates the evolving neurochemical landscape of oligodendrocyte physiology, emphasizing their roles beyond myelin production. We explore key processes including lipid metabolism, metabolic coupling with neurons, ion buffering, neurotransmitter signaling, and synaptic modulation. Oligodendrocytes preferentially utilize aerobic glycolysis and support axonal energy metabolism via the export of lactate and phosphocreatine, maintaining ATP levels even in the absence of mitochondria within the myelin sheath. Their capacity for regional and transcriptional heterogeneity allows adaptive responses to local microenvironments and neuronal activity. Lipid biosynthesis and storage mechanisms are intricately regulated through mTORC1, SREBPs, and lipophagy, enabling rapid membrane expansion, and structural integrity during myelination. Furthermore, oligodendrocytes modulate the periaxonal milieu via potassium buffering, pH regulation, and osmotic balance, primarily through Kir channels, carbonic anhydrases, and aquaporins. They also express a wide array of neurotransmitter receptors, enabling bidirectional communication with neurons and activity-dependent modulation of maturation and plasticity. Intracellular signaling pathways such as PI3K/Akt/mTOR, MAPK/ERK, and Wnt/β-catenin orchestrate the integration of metabolic and transcriptional programs. Collectively, these findings redefine oligodendrocytes as active participants in CNS physiology, contributing to neuronal health, circuit plasticity, and responses to injury or disease.

Diagnostic value of genetic testing, with focus on CACNA1A, in children with episodic neurologic disorders: a single-centre retrospective study

2026-05-19T17:45:26Z

Diagnostic value of genetic testing, with focus on CACNA1A, in children with episodic neurologic disorders: a single-centre retrospective study Chinigioli, Micaela; Martí-Sanchez, Laura; Yubero, Delia; Xiol, Clara; Olival, Jonathan; Alcalá San Martín, Adrián; Hernando-Davalillo, Cristina; Martorell, Loreto; Armstrong, Judith; Schteinschnaider, Ángeles; Ortigoza-Escobar, Juan Darío Background: Episodic neurologic disorders, such as paroxysmal torticollis, paroxysmal tonic upward gaze deviation, migraine, and episodic ataxia, represent a diagnostic challenge in paediatric patients. Variants in the CACNA1A and other genes such SCN8A and DEPDC5, have been implicated in episodic ataxia, hemiplegic migraine, and related conditions. However, the diagnostic yield of CACNA1A testing in paediatric populations with these symptoms remains uncertain. Methods: We conducted a retrospective study at Hospital Sant Joan de Déu, Barcelona, analysing 32 paediatric patients with episodic neurologic disorders. Clinical evaluation, neuroimaging, video EEG, and genetic testing were performed. Clinical and genetic data were correlated to identify predictors of pathogenic variants. Results: The cohort included 32 patients (21 females), with a mean age at symptom onset of 1.3 years. Paroxysmal torticollis (12/32) and paroxysmal tonic upgaze deviation (9/32) were the most frequent initial symptoms. Pathogenic variants were identified in 6/32 patients, of whom 2 carried CACNA1A variants. Positive genetic findings were significantly associated with developmental delay (p = 0.0056) and paroxysmal tonic upgaze deviation (p = 0.0185). Additional variants were identified in genes not classically linked to episodic disorders, including KAT6A, NFIX, and DEPDC5. Neuroimaging abnormalities were observed in 7/22 patients, and EEG abnormalities in 3/16. Conclusions: Genetic testing provides important insights in the evaluation of paediatric patients with episodic neurologic disorders, particularly in those with developmental delay, paroxysmal tonic upgaze, or episodic ataxia. Although the overall diagnostic yield remained low, consistent with other paroxysmal movement disorders, these findings support the integration of genetic testing into the diagnostic algorithm and underscore the need to consider broader genetic aetiologies. Larger studies are warranted to confirm these observations.