Neurotherapeutics最新文献

{"title":"First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis","authors":"Simona Toscano ,&nbsp;Tim Spelman ,&nbsp;Serkan Ozakbas ,&nbsp;Raed Alroughani ,&nbsp;Clara G. Chisari ,&nbsp;Salvatore Lo Fermo ,&nbsp;Alexandre Prat ,&nbsp;Marc Girard ,&nbsp;Pierre Duquette ,&nbsp;Guillermo Izquierdo ,&nbsp;Sara Eichau ,&nbsp;Pierre Grammond ,&nbsp;Cavit Boz ,&nbsp;Tomas Kalincik ,&nbsp;Yolanda Blanco ,&nbsp;Katherine Buzzard ,&nbsp;Olga Skibina ,&nbsp;Maria Jose Sa ,&nbsp;Anneke van der Walt ,&nbsp;Helmut Butzkueven ,&nbsp;Francesco Patti","doi":"10.1016/j.neurot.2025.e00552","DOIUrl":"10.1016/j.neurot.2025.e00552","url":null,"abstract":"<div><div>Predicting long-term prognosis and choosing the appropriate therapeutic approach in patients with Multiple Sclerosis (MS) at the time of diagnosis is crucial in view of a personalized medicine. We investigated the impact of early therapeutic response on the 5-year prognosis of patients with relapsing-remitting MS (RRMS). We recruited patients from MSBase Registry covering the period between 1996 and 2022. All patients were diagnosed with RRMS and actively followed-up for at least 5 years to explore the following outcomes: clinical relapses, confirmed disability worsening (CDW) and improvement (CDI), EDSS 3.0, EDSS 6.0, conversion to secondary progressive MS (SPMS), new MRI lesions, Progression Independent of Relapse Activity (PIRA). Predictors included demographic, clinical and radiological data, and sub-optimal response (SR) within the first year of treatment. Female sex (HR 1.27; 95 ​% CI 1.16–1.40) and EDSS at baseline (HR 1.19; 95 ​% CI 1.15–1.24) were independent risk factors for the occurrence of relapses during the first 5 years after diagnosis, while high-efficacy treatment (HR 0.78; 95 ​% CI 0.67–0.91) and age at diagnosis (HR 0.83; 95 ​% CI 0.79–0.86) significantly reduced the risk. SR predicted clinical relapses (HR ​= ​3.84; 95 ​% CI 3.51–4.19), CDW (HR ​= ​1.74; 95 ​% CI 1.56–1.93), EDSS 3.0 (HR ​= ​3.01; 95 ​% CI 2.58–3.51), EDSS 6.0 (HR ​= ​1.77; 95 ​% CI 1.43–2.20) and new brain (HR ​= ​2.33; 95 ​% CI 2.04–2.66) and spinal (HR 1.65; 95 ​% CI 1.29–2.09) MRI lesions. This study highlights the importance of selecting the appropriate DMT for each patient soon after MS diagnosis, also providing clinicians with a practical tool able to calculate personalized risk estimates for different outcomes.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 2","pages":"Article e00552"},"PeriodicalIF":5.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The epidemiology, pathology and pathogenesis of MS: Therapeutic implications.","authors":"Douglas S Goodin","doi":"10.1016/j.neurot.2025.e00539","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00539","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic, and potentially disabling, inflammatory disease of the central nervous system (CNS). MS is generally characterized by recurrent, and self-limited, episodes of neurological dysfunction, which occur unpredictably and often result in multifocal tissue injury within the CNS. Currently, women are affected two to three times as often as men although this may not have been the case during earlier Time-Periods. The pathogenesis of MS is known to involve both critical genetic and environmental mechanisms. Nevertheless, in addition to these two mechanisms, disease-pathogenesis also involves a \"truly\" random event. Indeed, it is this random mechanism, which is responsible for the currently-observed (and increasing) excess of women among patients with MS. This review summarizes the current state of knowledge regarding the pathogenesis of MS (includong its epidemiology, pathology, and genetics) and considers the therapeutic implications that these pathogenetic mechanisms have both for our currently available therapies as well as for the possible therapeutic approaches to the management of this potentially disabling condition in the future.</p>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00539"},"PeriodicalIF":5.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic advances in multiple sclerosis: Novel therapies (immune checkpoint inhibitors, CAR-T, Anti-CD40L).","authors":"Sarah E Conway, Kristin Galetta","doi":"10.1016/j.neurot.2025.e00558","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00558","url":null,"abstract":"<p><p>As patients with multiple sclerosis (MS) age, the risk of cancer also increases. Immune checkpoint inhibitors (ICIs) are novel monoclonal antibodies that have revolutionized cancer treatment. However, their use is limited by immune related adverse events. In patients with MS and pre-existing autoimmune disease there is concern that use of ICIs could worsen disease outcome. In the first part of this review we discuss the current data on ICIs and MS which overall suggest that they are well tolerated from the standpoint of MS disease activity. We recommend that MS not be a strict contraindication to ICI use which should depend on an individualized risk benefit discussion. In the second part, we focus on novel therapies for MS including CAR-T cell and anti-CD40L treatments. These newer therapies have the potential to address an unmet need in MS as they can cross the blood-brain and have the potential to target compartmentalized central nervous inflammation that may underly the pathophysiology of progressive MS.</p>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00558"},"PeriodicalIF":5.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perivascular brain clearance as a therapeutic target in cerebral amyloid angiopathy and Alzheimer's disease","authors":"Orla Bonnar ,&nbsp;Beth Eyre ,&nbsp;Susanne J. van Veluw","doi":"10.1016/j.neurot.2025.e00535","DOIUrl":"10.1016/j.neurot.2025.e00535","url":null,"abstract":"<div><div>Although distinct diseases, both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) are characterized by the aggregation and accumulation of amyloid-β (Aβ). This is thought to be due, in part, to impaired perivascular Aβ clearance from the brain. This shared failure in both diseases presents a common opportunity for therapeutic intervention. In this review we discuss the idea that promoting perivascular brain clearance could be an effective strategy for safely reducing Aβ levels in CAA and AD thereby improving clinical outcomes, most notably hemorrhagic stroke and cognitive decline. We will explore the evidence for the different forces that are thought to drive perivascular brain clearance, review the literature on potential strategies for potentiating these driving forces, and finally we will discuss the substantial translational challenges and considerations that would accompany such an intervention.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 3","pages":"Article e00535"},"PeriodicalIF":5.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Gut microbiota dysbiosis and neurologic diseases: New Horizon with potential diagnostic and therapeutic impact’","authors":"Ali Keshavarzian ,&nbsp;Sangram S. Sisodia","doi":"10.1016/j.neurot.2024.e00502","DOIUrl":"10.1016/j.neurot.2024.e00502","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00502"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increase in beta frequency phase synchronization and power after a session of high frequency repetitive transcranial magnetic stimulation to the primary motor cortex","authors":"Enrico De Martino ,&nbsp;Adenauer Girardi Casali ,&nbsp;Bruno Andry Nascimento Couto ,&nbsp;Thomas Graven-Nielsen ,&nbsp;Daniel Ciampi de Andrade","doi":"10.1016/j.neurot.2024.e00497","DOIUrl":"10.1016/j.neurot.2024.e00497","url":null,"abstract":"<div><div>High-frequency repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) is used to treat several neuropsychiatric disorders, but the detailed temporal dynamics of its effects on cortical connectivity remain unclear. Here, we stimulated four cortical targets used for rTMS (M1; dorsolateral-prefrontal cortex, DLPFC; anterior cingulate cortex, ACC; posterosuperior insula, PSI) with TMS coupled with high-density electroencephalography (TMS-EEG) to measure cortical excitability and oscillatory dynamics before and after active- and sham-M1-rTMS. Before and immediately after active or sham M1-rTMS (15 ​min, 3000 pulses at 10 ​Hz), single-pulse TMS-evoked EEG was recorded at the four targets in 20 healthy individuals. Cortical excitability and oscillatory measures were extracted at the main frequency bands (α [8–13 ​Hz], low-β [14–24 ​Hz], high-β [25–35 ​Hz]). Active-M1-rTMS increased high-β synchronization in electrodes near the stimulation area and remotely, in the contralateral hemisphere (p ​= ​0.026). Increased high-β synchronization (48–83 ​ms after TMS-EEG stimulation) was succeeded by enhancement in low-β power (86–144 ​ms after TMS-EEG stimulation) both locally and in the contralateral hemisphere (p ​= ​0.006). No significant differences were observed in stimulating the DLPFC, ACC, or PSI by TMS-EEG. M1-rTMS engaged a sequence of enhanced phase synchronization, followed by an increase in power occurring within M1, which spread to remote areas and persisted after the end of the stimulation session. These results are relevant to understanding the M1 neuroplastic effects of rTMS in health and may help in the development of informed rTMS therapies in disease.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00497"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using artificial intelligence to optimize anti-seizure treatment and EEG-guided decisions in severe brain injury","authors":"Zade Akras ,&nbsp;Jin Jing ,&nbsp;M. Brandon Westover ,&nbsp;Sahar F. Zafar","doi":"10.1016/j.neurot.2025.e00524","DOIUrl":"10.1016/j.neurot.2025.e00524","url":null,"abstract":"<div><div>Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit. Artificial intelligence (AI) has already demonstrated clinical success in guiding cEEG allocation for patients at risk for seizures, and its potential uses in neurocritical care are expanding alongside improvements in AI itself. We review both current clinical uses of AI for EEG-guided management as well as ongoing research directions in automated seizure and ischemia detection, neurologic prognostication, and guidance of medical and surgical treatment.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00524"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO","authors":"Sue J. Hong ,&nbsp;Bradley J. De Souza ,&nbsp;Kristen K. Penberthy ,&nbsp;Lisa Hwang ,&nbsp;David E. Procaccini ,&nbsp;John N. Kheir ,&nbsp;Melania M. Bembea","doi":"10.1016/j.neurot.2024.e00521","DOIUrl":"10.1016/j.neurot.2024.e00521","url":null,"abstract":"<div><div>Extracorporeal membrane oxygenation (ECMO) is a technique used to support severe cardiopulmonary failure. Its potential life-saving benefits are tempered by the significant risk for acute brain injury (ABI), from both primary pathophysiologic factors and ECMO-related complications through central nervous system cellular injury, blood-brain barrier dysfunction (BBB), systemic inflammation and neuroinflammation, and coagulopathy. Plasma biomarkers are an emerging tool used to stratify risk for and diagnose ABI, and prognosticate neurofunctional outcomes. Components of the neurovascular unit have been rational targets for this inquiry in ECMO. Central nervous system (CNS) neuronal and astroglial cellular-derived neuron-specific enolase (NSE), tau, glial fibrillary acidic protein (GFAP) and S100β elevations have been detected in ABI and are associated with poorer outcomes. Evidence of BBB breakdown through peripheral blood detection of CNS cellular components NSE, GFAP, and S100β, as well as evidence of elevated BBB components vWF and PDGFRβ are associated with higher mortality and worse neurofunctional outcomes. Higher concentrations of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) are associated with abnormal neuroimaging, and proteomic expression panels reveal different coagulation and inflammatory responses. Abnormal coagulation profiles are common in ECMO with ongoing studies attempting to describe specific abnormalities either being causal or associated with neurologic outcomes; vWF has shown some promise. Understanding these mechanisms of injury through biomarker analysis supports potential neuroprotective strategies such as individualized blood pressure targets, judicious hypercarbia and hypoxemia correction, and immunomodulation (inhaled hydrogen and N-acetylcysteine). Further research continues to elucidate the role of biomarkers as predictors, prognosticators, and therapeutic targets.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00521"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of astrocytes connexins - pannexins in acute brain injury","authors":"Juan E. Tichauer,&nbsp;Maximiliano Rovegno","doi":"10.1016/j.neurot.2025.e00523","DOIUrl":"10.1016/j.neurot.2025.e00523","url":null,"abstract":"<div><div>Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs). In astrocytes, GJs and HCs enable intercellular communication and have active participation in normal brain physiological processes, such as calcium waves, synapsis modulation, regional blood flow regulation, and homeostatic control of the extracellular environment, among others. However, after acute brain injury, astrocytes can change their phenotype and modify the activity of both channels and hemichannels, which can result in the amplification of danger signals, increased mediators of inflammation, and neuronal death, contributing to the expansion of brain damage and neurological deterioration. This is known as secondary brain damage. In this review, we discussed the main biological mechanism of secondary brain damage with a particular focus on astroglial connexin and pannexin participation during acute brain injuries.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00523"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving concepts in intracranial pressure monitoring - from traditional monitoring to precision medicine","authors":"Rohan Mathur ,&nbsp;Lin Cheng ,&nbsp;Josiah Lim ,&nbsp;Tej D. Azad ,&nbsp;Peter Dziedzic ,&nbsp;Eleanor Belkin ,&nbsp;Ivanna Joseph ,&nbsp;Bhagyashri Bhende ,&nbsp;Sudha Yellapantula ,&nbsp;Niteesh Potu ,&nbsp;Austen Lefebvre ,&nbsp;Vishank Shah ,&nbsp;Susanne Muehlschlegel ,&nbsp;Julian Bosel ,&nbsp;Tamas Budavari ,&nbsp;Jose I. Suarez","doi":"10.1016/j.neurot.2024.e00507","DOIUrl":"10.1016/j.neurot.2024.e00507","url":null,"abstract":"<div><div>A wide range of acute brain injuries, including both traumatic and non-traumatic causes, can result in elevated intracranial pressure (ICP), which in turn can cause further secondary injury to the brain, initiating a vicious cascade of propagating injury. Elevated ICP is therefore a neurological injury that requires intensive monitoring and time-sensitive interventions. Patients at high risk for developing elevated ICP undergo placement of invasive ICP monitors including external ventricular drains, intraparenchymal ICP monitors, and lumbar drains. These monitors all generate an ICP waveform, but each has its own unique caveats in monitoring and accuracy. Current ICP monitoring and management clinical guidelines focus on the mean ICP derived from the ICP waveform, with standard thresholds of treating ICP greater than 20 ​mmHg or 22 ​mmHg applied broadly to a wide range of patients. However, this one-size fits all approach has been criticized and there is a need to develop personalized, evidence-based and possibly multi-factorial precision-medicine based approaches to the problem. This paper provides historical and physiological context to the problem of elevated ICP, provides an overview of the challenges of the current paradigm of ICP management strategies, and discusses advances in ICP waveform analysis, emerging non-invasive ICP monitoring techniques, and applications of machine learning to create predictive algorithms.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00507"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}