{"title":"Tau phosphorylation correlates with multiple sclerosis disease course","authors":"Heather Wood","doi":"10.1038/s41582-024-01017-y","DOIUrl":"10.1038/s41582-024-01017-y","url":null,"abstract":"New research adds to growing evidence of altered tau phosphorylation in multiple sclerosis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"569-569"},"PeriodicalIF":28.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Håkan Ashina, Rune H. Christensen, Debbie L. Hay, Amynah A. Pradhan, Jan Hoffmann, Dora Reglodi, Andrew F. Russo, Messoud Ashina
{"title":"Pituitary adenylate cyclase-activating polypeptide signalling as a therapeutic target in migraine","authors":"Håkan Ashina, Rune H. Christensen, Debbie L. Hay, Amynah A. Pradhan, Jan Hoffmann, Dora Reglodi, Andrew F. Russo, Messoud Ashina","doi":"10.1038/s41582-024-01011-4","DOIUrl":"10.1038/s41582-024-01011-4","url":null,"abstract":"Migraine is a disabling neurological disorder that affects more than one billion people worldwide. The clinical presentation is characterized by recurrent headache attacks, which are often accompanied by photophobia, phonophobia, nausea and vomiting. Although the pathogenesis of migraine remains incompletely understood, mounting evidence suggests that specific signalling molecules are involved in the initiation and modulation of migraine attacks. These signalling molecules include pituitary adenylate cyclase-activating polypeptide (PACAP), a vasoactive peptide that is known to induce migraine attacks when administered by intravenous infusion to people with migraine. Discoveries linking PACAP to migraine pathogenesis have led to the development of drugs that target PACAP signalling, and a phase II trial has provided evidence that a monoclonal antibody against PACAP is effective for migraine prevention. In this Review, we explore the molecular and cellular mechanisms of PACAP signalling, shedding light on its role in the trigeminovascular system and migraine pathogenesis. We then discuss emerging therapeutic strategies that target PACAP signalling for the treatment of migraine and consider the research needed to translate the current knowledge into a treatment for migraine in the clinic. Pituitary adenylate cyclase-activating polypeptide signalling has been linked to migraine pathogenesis. In this Review, Ashina and co-workers explore the molecular and cellular mechanisms of pituitary adenylate cyclase-activating polypeptide signalling and discuss emerging therapeutic strategies to target this pathway for migraine treatment.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"660-670"},"PeriodicalIF":28.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giancarlo Comi, Gloria Dalla Costa, Bruno Stankoff, Hans-Peter Hartung, Per Soelberg Sørensen, Patrick Vermersch, Letizia Leocani
{"title":"Assessing disease progression and treatment response in progressive multiple sclerosis","authors":"Giancarlo Comi, Gloria Dalla Costa, Bruno Stankoff, Hans-Peter Hartung, Per Soelberg Sørensen, Patrick Vermersch, Letizia Leocani","doi":"10.1038/s41582-024-01006-1","DOIUrl":"10.1038/s41582-024-01006-1","url":null,"abstract":"Progressive multiple sclerosis poses a considerable challenge in the evaluation of disease progression and treatment response owing to its multifaceted pathophysiology. Traditional clinical measures such as the Expanded Disability Status Scale are limited in capturing the full scope of disease and treatment effects. Advanced imaging techniques, including MRI and PET scans, have emerged as valuable tools for the assessment of neurodegenerative processes, including the respective role of adaptive and innate immunity, detailed insights into brain and spinal cord atrophy, lesion dynamics and grey matter damage. The potential of cerebrospinal fluid and blood biomarkers is increasingly recognized, with neurofilament light chain levels being a notable indicator of neuro-axonal damage. Moreover, patient-reported outcomes are crucial for reflecting the subjective experience of disease progression and treatment efficacy, covering aspects such as fatigue, cognitive function and overall quality of life. The future incorporation of digital technologies and wearable devices in research and clinical practice promises to enhance our understanding of functional impairments and disease progression. This Review offers a comprehensive examination of these diverse evaluation tools, highlighting their combined use in accurately assessing disease progression and treatment efficacy in progressive multiple sclerosis, thereby guiding more effective therapeutic strategies. The approval of therapies for progressive multiple sclerosis has heightened the need for thorough assessment of disease progression and treatment response. This Review provides a comprehensive summary of available and emerging techniques, including advanced imaging, fluid biomarkers and patient-reported outcomes, highlighting their combined use for the accurate assessment of disease.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"573-586"},"PeriodicalIF":28.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stiff-person syndrome and related disorders — diagnosis, mechanisms and therapies","authors":"Marinos C. Dalakas","doi":"10.1038/s41582-024-01012-3","DOIUrl":"10.1038/s41582-024-01012-3","url":null,"abstract":"Stiff-person syndrome (SPS) is the prototypical and most common autoimmune neuronal hyperexcitability disorder. It presents with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias and startle responses, collectively leading to disability. Increased awareness of SPS among patients and physicians has created concerns about diagnosis, misdiagnosis and treatment. This Review addresses the evolving diagnostic challenges in SPS and overlapping glutamic acid decarboxylase (GAD) antibody spectrum disorders, highlighting the growing number of overdiagnoses and focusing on the progress made in our understanding of SPS pathophysiology, antibodies against GAD and other inhibitory synaptic antigens, and the fundamentals of neuronal hyperexcitability. It considers the role of impaired GABAergic or glycinergic inhibition in the cortex and at multiple levels in the neuraxis; the underlying autoimmunity and involvement of GAD antibodies; immunopathogenic mechanisms beyond antibodies, including environmental triggers; familial and immunogenetic susceptibility; and potential T cell cytotoxicity. Finally, the mechanistic rationale for target-specific therapeutic interventions is presented along with the available therapeutic approaches, including enhancers of GABA signalling drugs and immunotherapies. Stiff-person syndrome is an autoimmune neuronal hyperexcitability disorder that causes limb stiffness, painful spasms and falls, and increased awareness of the disease is creating diagnostic and management challenges. In this Review, Dalakas provides an overview of the current clinical and mechanistic understanding of stiff-person syndrome and related disorders and discusses current and emerging therapeutic interventions.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"587-601"},"PeriodicalIF":28.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruth Geraldes, Georgina Arrambide, Brenda Banwell, Àlex Rovira, Rosa Cortese, Hans Lassmann, Silvia Messina, Mara Assunta Rocca, Patrick Waters, Declan Chard, Claudio Gasperini, Yael Hacohen, Romina Mariano, Friedemann Paul, Gabriele C. DeLuca, Christian Enzinger, Ludwig Kappos, M. Isabel Leite, Jaume Sastre-Garriga, Tarek Yousry, Olga Ciccarelli, Massimo Filippi, Frederik Barkhof, Jacqueline Palace, MAGNIMS Study Group
{"title":"The influence of MOGAD on diagnosis of multiple sclerosis using MRI","authors":"Ruth Geraldes, Georgina Arrambide, Brenda Banwell, Àlex Rovira, Rosa Cortese, Hans Lassmann, Silvia Messina, Mara Assunta Rocca, Patrick Waters, Declan Chard, Claudio Gasperini, Yael Hacohen, Romina Mariano, Friedemann Paul, Gabriele C. DeLuca, Christian Enzinger, Ludwig Kappos, M. Isabel Leite, Jaume Sastre-Garriga, Tarek Yousry, Olga Ciccarelli, Massimo Filippi, Frederik Barkhof, Jacqueline Palace, MAGNIMS Study Group","doi":"10.1038/s41582-024-01005-2","DOIUrl":"10.1038/s41582-024-01005-2","url":null,"abstract":"Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders. Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease that is distinct from multiple sclerosis but shares some of its characteristics. This Expert Recommendation, based on a Magnetic Resonance Imaging in MS workshop, proposes a diagnostic algorithm for the differential diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease and multiple sclerosis, using serological, imaging and clinical features.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"620-635"},"PeriodicalIF":28.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}