Headache articles within Nature Reviews Neurology

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  • Review Article |

    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.

    • Håkan Ashina
    • , Rune H. Christensen
    •  & Messoud Ashina

  • News & Views |

    New guidelines for designing controlled clinical trials for idiopathic intracranial hypertension (IIH) have been published. The design of such trials remains a challenge, as the heterogeneity of IIH necessitates different outcome measures for specific clinical presentations.

    • Valérie Biousse
    •  & Nancy J. Newman

  • News & Views |

    Results from a phase III trial have set zavegepant as the first intranasal gepant to be approved by the FDA for the acute treatment of migraine. The therapeutic benefits were modest, however, and more work is needed to address unmet treatment needs.

    • Håkan Ashina
    •  & Peer Tfelt-Hansen

  • News & Views |

    A new paper published in Neuron presents an analysis of mRNA expression in human and mouse trigeminal ganglia at single-nucleus resolution. The resulting resource is thought-provoking and suggests new targets for pain therapies; however, the findings should be interpreted in the context of the available protein data and warrant functional verification.

    • Lars Edvinsson
    • , Jacob C. A. Edvinsson
    •  & Kristian A. Haanes

  • Review Article |

    Headaches and epilepsy frequently co-exist in the same individual, but the pathophysiological mechanisms underlying this relationship are not yet clear. Here, the authors discuss the epidemiological and pathophysiological links between epilepsy and headache, and apply this knowledge to the clinical management of the two disorders.

    • Prisca R. Bauer
    • , Else A. Tolner
    •  & Josemir W. Sander

  • News & Views |

    Results of two recent studies by Messoud Ashina and colleagues demonstrate that infusion of two different potassium channel openers can trigger migraine in humans; one of the compounds also triggered aura in patients diagnosed with migraine with aura. The findings highlight the importance of human experimental models in migraine research.

    • Alan M. Rapoport
    •  & Richard B. Lipton

  • Perspective |

    Several childhood disorders, including infantile colic and cyclical vomiting syndrome, are thought to be related to migraine. In this Perspective, Gelfand and Abu-Arafeh present evidence for each of these disorders to be considered as part of a ‘childhood migraine syndrome’.

    • Ishaq Abu-Arafeh
    •  & Amy A. Gelfand

  • Review Article |

    In this Review, Wei and Goadsby discuss the pathophysiology of cluster headache, the treatments available and their mechanisms, and the insights being provided by results from trials of emerging treatments, which indicate mechanistic differences between episodic and chronic cluster headache.

    • Diana Y. Wei
    •  & Peter J. Goadsby

  • News & Views |

    A recent study reports an improvement in migraine symptoms during a COVID-19 lockdown in the Netherlands. The findings suggest that lifestyle changes can substantially alter the course of migraine, opening the door for greater use of behavioural interventions alongside existing pharmacological therapies.

    • Licia Grazzi
    •  & Paul Rizzoli

  • News & Views |

    Although common, post-traumatic headache remains poorly understood and poorly treated. New data have implicated calcitonin gene-related peptide and the trigeminovascular system in this disorder, opening up new avenues for research into its pathophysiology and treatment.

    • Dimos D. Mitsikostas
    •  & Michael A. Moskowitz

  • News & Views |

    A new study shows that the monoclonal antibody fremanezumab is effective for migraine prophylaxis, even in patients who have failed to respond to multiple preventive treatments. However, not all patients benefit from this treatment, and detailed investigation of non-responders could help to identify additional pharmacological targets and increase the number of responders.

    • Tessa de Vries
    •  & Antoinette MaassenVanDenBrink

  • Review Article |

    In this Review, the authors describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, consider the potential mechanisms and highlight treatments that affect metabolism. They conclude that migraine is a conserved adaptive response that helps to restore brain energy homeostasis.

    • Elena C. Gross
    • , Marco Lisicki
    •  & Jean Schoenen

  • Review Article |

    Post-traumatic headache (PTH) is a common disabling consequence of mild traumatic brain injury. In this Review, Ashina et al. discuss possible pathogenic mechanisms of PTH, the research needed to improve our understanding, and drugs for prevention and treatment of persistent PTH.

    • Håkan Ashina
    • , Frank Porreca
    •  & David W. Dodick

  • News & Views |

    The benefits of targeting calcitonin gene-related peptide (CGRP) could go beyond migraine prevention, and three new studies report success with a new small-molecule CGRP receptor antagonist in acute migraine and with a monoclonal antibody in cluster headache.

    • Jes Olesen
    •  & Messoud Ashina

  • Perspective |

    Migraine is one of the world’s most prevalent diseases, and approximately 2% of the general population experiences chronic migraine. Edvinsson and colleagues argue that inflammation could have an important role in migraine chronification, through a mechanism termed neurogenic neuroinflammation.

    • Lars Edvinsson
    • , Kristian Agmund Haanes
    •  & Karin Warfvinge

  • News & Views |

    In the past few years, a number of new migraine treatments have emerged, including monoclonal antibodies against calcitonin gene-related peptide (CGRP) and the CGRP receptor. Now, a position statement from the American Headache Society offers guidance on the integration of these agents into clinical practice in the prevention of migraine.

    • Hans-Christoph Diener

  • Year in Review |

    In the past few years the scientific community has witnessed a prodigious surge in research activity, publication of data and progress in understanding the mechanistic components of migraine. This renaissance is the result of efforts initiated decades ago that are finally being translated into benefits for individuals affected by this disease.

    • Cristina Tassorelli
    •  & Roberto De Icco

  • News & Views |

    Chronic migraine is a debilitating condition that arises from the worsening of episodic migraine. A large population-based questionnaire study showed that individuals with chronic migraine reported more sleep apnoea and worse sleep quality than individuals with episodic migraine. This finding provides important insights into the association between sleep disturbances and chronic migraine.

    • Min Kyung Chu

  • Review Article |

    Premonitory symptoms of migraine can start hours to days before the onset of headache. In this Review, Karsan and Goadsby discuss the phenotypes of these premonitory symptoms and the insights that they provide into the neurobiology of migraine.

    • Nazia Karsan
    •  & Peter J. Goadsby

  • News & Views |

    During cluster headache attacks, plasma levels of calcitonin gene-related peptide (CGRP) increase, and trigeminal nerve activation leads to pain. A new study shows that CGRP infusion can induce cluster headache attacks in some patients, with important implications for the investigation of CGRP-targeted therapies in cluster headache.

    • Massimo Leone

  • Review Article |

    Migraine is prevalent in the paediatric population and represents a major cause of disability. This Review outlines the epidemiology and natural history of paediatric migraine, discusses the recent landmark clinical trials of treatments for paediatric migraine and examines the best evidence-based interventions for this population in light of these new findings.

    • Serena L. Orr
    • , Marielle A. Kabbouche
    •  & Andrew D. Hershey

  • Review Article |

    The causes of migraine remain unknown despite the high prevalence and societal burden of this disorder. Here, the authors highlight how advances in imaging and genetic studies of migraine provide insights into the underlying mechanisms of this disorder; furthermore, they discuss the potential for genetic and imaging biomarkers to improve our ability to prevent and treat migraine attacks.

    • Dale R. Nyholt
    • , David Borsook
    •  & Lyn R. Griffiths

  • Review Article |

    In the ongoing search for new and better migraine treatments, human models have a key role in the discovery of novel targets for antimigraine drugs. This Review summarizes existing experimental models of migraine in humans, and describes the development and use of these models in the identification of key molecular pathways, biomarkers and drug targets.

    • Messoud Ashina
    • , Jakob Møller Hansen
    •  & Jes Olesen

  • News & Views |

    A growing body of evidence indicates that people with migraine have an increased risk of cervical artery dissection (CeAD). A new study in young patients with ischaemic stroke has identified a specific link between CeAD and migraine without aura.

    • Caspar Grond-Ginsbach
    •  & Manja Kloss

  • Review Article |

    The primary headache disorders are among the most common diseases worldwide. Nathaniel Schuster and Alan Rapoport discuss new and emerging preventive and acute treatments that have the potential to address unmet needs of patients with headache disorders, and to help treat and reduce headache-associated disability.

    • Nathaniel M. Schuster
    •  & Alan M. Rapoport

  • News & Views |

    Recently published American Headache Society evidence-based guidelines for cluster headache management provide updated guidance on which therapies are superior to placebo in randomized controlled trials. These valuable recommendations do not always translate to real-world settings, however, and other criteria should be taken into account when attempting to treat cluster headache.

    • Paolo Martelletti
    •  & Martina Curto

  • News & Views |

    In a powerful display of international collaboration, a new genome-wide association study has mapped susceptibility loci for migraine on the basis of genetic data from 375,000 individuals. The study implicates several new loci in migraine — many of them suggestive of vascular pathophysiology — but the functional relevance of many now-detected risk alleles remains elusive.

    • Cenk Ayata

  • News & Views |

    Classification of migraine into different endophenotypes could aid diagnosis and treatment, but requires detailed characterization of different phenotypes. A new study provides insight into the clinical features of migraine with unilateral cranial autonomic symptoms, but raises questions about the value of such classifications.

    • Jes Olesen

  • News & Views |

    In the past 10 years, the realization that migraine is a brain disorder rather than a vascular disorder has facilitated development of various treatments, ranging from innovative immunopharmaceuticals through to neurostimulation. Many clinical trials have been successful, and such considerable progress holds promise for the coming decade of migraine treatment.

    • Peter J. Goadsby

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