Migraine is a common disabling conditions which, globally, affects 15.2% of the population. It is the second cause of health loss in terms of years lived with disability, the first among women. Despite being so common, it is poorly recognised and too often undertreated. Specialty centres and neurologists with specific expertise on headache disorders have the knowledge to provide specific care: however, those who do not regularly treat patients with migraine will benefit from a synopsis on the most relevant and updated information about this condition. This paper presents a comprehensive view on the hallmarks of migraine, from genetics and diagnostic markers, up to treatments and societal impact, and reports the elements that identify migraine specific features. 

Hallmarks of primary headache: part 1 – migraine

Abstract Background The premonitory phase, or prodrome, of migraine, provides valuable opportunities to study attack initiation and for treating the attack before headache starts. Much that has been learned about this phase in recent times has come from the outcomes of functional imaging studies. This review will summarise these studies to date and use their results to provide some feasible insights into migraine neurobiology. Main body The ability to scan repeatedly a patient without radiation and with non-invasive imaging modalities, as well as the recognition that human experimental migraine provocation compounds, such as nitroglycerin (NTG) and pituitary adenylate cyclase activating polypeptide (PACAP), can trigger typical premonitory symptoms (PS) and migraine-like headache in patients with migraine, have allowed feasible and reproducible imaging of the premonitory phase using NTG. Some studies have used serial scanning of patients with migraine to image the migraine cycle, including the ‘pre-ictal’ phase, defined by timing to headache onset rather than symptom phenotype. Direct observation and functional neuroimaging of triggered PS have also revealed compatible neural substrates for PS in the absence of headache. Various imaging methods including resting state functional MRI (rsfMRI), arterial spin labelling (ASL), positron emission tomography (PET) and diffusion tensor imaging (DTI) have been used. The results of imaging the spontaneous and triggered premonitory phase have been largely consistent and support a theory of central migraine attack initiation involving brain areas such as the hypothalamus, midbrain and limbic system. Early dysfunctional pain, sensory, limbic and homeostatic processing via monoaminergic and peptidergic neurotransmission likely manifests in the heterogeneous PS phenotype. Conclusion Advances in human migraine research, including the use of functional imaging techniques lacking radiation or radio-isotope exposure, have led to an exciting opportunity to study the premonitory phase using repeated measures imaging designs. These studies have provided novel insights into attack initiation, migraine neurochemistry and therapeutic targets. Emerging migraine-specific therapies, such as those targeting calcitonin gene-related peptide (CGRP), are showing promise acutely when taken during premonitory phase to reduce symptoms and prevent subsequent headache. Therapeutic research in this area using PS for headache onset prediction and early treatment is likely to grow in the future. 

Neuroimaging in the pre-ictal or premonitory phase of migraine: a narrative review

Intelligent digital twins closely resemble their real-life counterparts. In health and medical care, they enable the real-time monitoring of patients, whereby large amounts of data can be collected to produce actionable information. These powerful tools are constructed with the aid of artificial intelligence, machine learning, and deep learning; the Internet of Things; and cloud computing to collect a diverse range of digital data (e.g., from digital patient journals, wearable sensors, and digitized monitoring equipment or processes), which can provide information on the health conditions and therapeutic responses of their physical twins. Intelligent digital twins can enable data-driven clinical decision making and advance the realization of personalized care. Migraines are a highly prevalent and complex neurological disorder affecting people of all ages, genders, and geographical locations. It is ranked among the top disabling diseases, with substantial negative personal and societal impacts, but the current treatment strategies are suboptimal. Personalized care for migraines has been suggested to optimize their treatment. The implementation of intelligent digital twins for migraine care can theoretically be beneficial in supporting patient-centric care management. It is also expected that the implementation of intelligent digital twins will reduce costs in the long run and enhance treatment effectiveness. This study briefly reviews the concept of digital twins and the available literature on digital twins for health disorders such as neurological diseases. Based on these, the potential construction and utility of digital twins for migraines will then be presented. The potential and challenges when implementing intelligent digital twins for the future management of migraines are also discussed.

Intelligent Digital Twins for Personalized Migraine Care

Chronic migraine is a highly debilitating condition that is often difficult to manage, particularly in the presence of medication overuse headache. Drugs targeting the calcitonin gene-related peptide (CGRP), or its receptor have shown promising results in treating this disorder.We searched Pubmed and Embase to identify randomized clinical trials and real-world studies reporting on the use of medication targeting the calcitonin gene-related peptide in patients with chronic migraine.A total of 270 records were identified. Nineteen studies qualified for the qualitative analysis. Most studies reported on monoclonal antibodies targeting CGRP (anti-CGRP mAbs), that overall prove to be effective in decreasing monthly migraine days by half in about 27.6-61.4% of the patients. Conversion from chronic to episodic migraine was seen in 40.88% of the cases, and 29-88% of the patients stopped medication overuse. Obesity seems to be the main negative predictor of response to anti-CGRP mAbs. There is no evidence to suggest the superiority of one anti-CGRP mAb. Despite the lack of strong evidence, the combination of anti-CGRP medication with onabotulinumtoxinA in chronic migraine is likely to bring benefits for resistant cases. Atogepant is the first gepant to demonstrate a significant decrease in monthly migraine days compared to placebo in a recent trial. Further, anti-CGRP mAb and gepants have a good safety profile.There is strong evidence from randomized trials and real-world data to suggest that drugs targeting CGRP are a safe and effective treatment for chronic migraine. 

CGRP-targeted medication in chronic migraine - systematic review

Oxidative Stress and Migraine.

Abstract Migraine is an extremely disabling, common neurological disorder characterized by a complex neurobiology, involving a series of central and peripheral nervous system areas and networks. A growing increase in the understanding of migraine pathophysiology in recent years has facilitated translation of that knowledge into novel treatments, which are currently becoming available to patients in many parts of the world and are substantially changing the clinical approach to the disease. In the first part of this review, we will provide an up to date overview of migraine pathophysiology by analyzing the anatomy and function of the main regions involved in the disease, focusing on how these give rise to the plethora of symptoms characterizing the attacks and overall disease. The second part of the paper will discuss the novel therapeutic agents that have emerged for the treatment of migraine, including molecules targeting calcitonin gene-related peptide (gepants and monoclonal antibodies), serotonin 5-HT 1F receptor agonists (ditans) and non-invasive neuromodulation, as well as providing a brief overview of new evidence for classic migraine treatments. 

/pdf/migraine-from-pathophysiology-to-treatment-1n5jetgv.pdf

Migraine: from pathophysiology to treatment

Visual snow syndrome is a neurological condition characterized by ongoing prominent phenomena described consistently as tiny dots moving across the entire visual field, often associated with complex visual symptoms. These can take the form of afterimages, entoptic phenomena, nyctalopia and light sensitivity. Although some of these symptoms can be benign, they can nonetheless become significantly impactful for many who experience them, particularly in cases that have a sudden and abrupt start. As visual snow syndrome becomes increasingly recognized in clinical practice we begin to learn about its typical presentation and underlying pathophysiology. Treatment of visual snow, however, still proves quite challenging, and efforts need to be focused on unravelling the biological mechanisms of the syndrome. This endeavour has characterized the most recent research on visual snow, mostly involving neuroimaging, neurophysiological and neurobehavioral studies aimed at understanding its underlying neural signature. Another important aspect of the syndrome, which will likely prove critical in deepening our understanding of visual snow, is represented by the intricate biological and historical connexion with migraine. This narrative review focused on visual snow syndrome will explore its clinical, pathophysiological and treatment aspects in detail.摘要: 视雪综合征是一种神经系统疾病, 特征为持续性的在整个视野中移动的小点, 通常与复杂的视觉症状有关。这些症状可能以视觉残像、内视现象、夜盲症和光敏感的形式表现。尽管部分症状可能是良性的, 但它们仍然可能会对经历过这些症状的人造成重大影响, 尤其是在突然发作的情况下。 随着视雪综合征在临床实践中越来越多被认识和鉴别, 我们开始了解其典型的表现和潜在的病理生理学。然而, 视雪综合征的治疗仍然具有相当大的挑战性, 需要聚焦于阐明该综合征的生物学机制。这也是目前视雪综合征研究的主要方向, 主要涉及神经影像学、神经生理学和神经行为学研究, 旨在了解其潜在的神经学特征。 该综合征的另一重要方面是其与偏头痛之间复杂的生物和历史联系, 这可能在加深我们对视雪综合征的理解上至关重要。 这篇关于视雪综合征的综述将详细探讨其临床、病理生理和治疗方面的问题。. 

/pdf/visual-snow-syndrome-and-migraine-a-review-3iy2c14s.pdf

Visual snow syndrome and migraine: a review

Objective To provide an up-to-date narrative literature review of imaging in migraine with typical aura, as a means to understand better migraine subtypes and aura biology. Background Characterizing subtypes of migraine with typical aura and appreciating possible biological differences between migraine with and without aura, are important to understanding the neurobiology of aura and trying to advance personalized therapeutics in this area through imaging biomarkers. One means of doing this over recent years has been the use of increasingly advanced neuroimaging techniques. Methods We conducted a literature review of neuroimaging studies in migraine with aura, using a PubMed search for terms ‘imaging migraine’, ‘aura imaging’, ‘migraine with aura imaging’, ‘migraine functional imaging’ and ‘migraine structural imaging’. We collated the findings of the main studies, excluding small case reports and series with n < 6, and have summarized these and their implications for better understanding of aura mechanisms. Results Aura is likely mediated by widespread brain dysfunction in areas involving, but not limited to, visual cortex, somatosensory and insular cortex, and thalamus. Higher brain excitability in response to sensory stimulation and altered resting-state functional connectivity in migraine sufferers with aura could have a genetic component. Pure visual aura compared to visual aura with other sensory or speech symptoms as well, may involve different functional reorganization of brain networks and additional mitochondrial dysfunction mediating more aura symptoms. Conclusion There is a suggestion of at least some distinct neurobiological differences between migraine with and without aura, despite the shared phenotypic similarity in headache and other migraine-associated symptoms. It is clear from the vast majority of aura phenotypes being visual that there is a particular predisposition of the occipital cortex to aura mechanisms. Why this is the case, along with the relationships between cortical spreading depression and headache, and the reasons why aura does not consistently present in affected individuals, are all important research questions for the future.

/pdf/evaluating-migraine-with-typical-aura-with-neuroimaging-11wmtgoe.pdf

Evaluating migraine with typical aura with neuroimaging

INTRODUCTION
The interaction of antiseizure medication with contraceptives, its potential teratogenicity and implications in pregnancy and breastfeeding are aspects to consider in the neurological care of women with epilepsy of childbearing age. To ensure the commitment in therapeutic decisions and the appropriate planning of maternity, it is essential that women are informed about the implications of their disease in these domains. The main aim of this study was to assess the knowledge of women of childbearing age with epilepsy concerning the impact of epilepsy in contraception, pregnancy and breastfeeding. As secondary aims we defined (1) the demographic, clinical and therapeutic characterization of this group of patients, (2) the identification of variables that correlated with the level of knowledge of women with epilepsy, and (3) the identification of preferential methods to acquire new knowledge about epilepsy.


MATERIAL AND METHODS
The study was observational, cross-sectional and multicentric, and was carried out in five hospitals of the Lisbon metropolitan area. After identifying all women of childbearing age with epilepsy followed in the epilepsy clinic of each center, we applied an electronic questionnaire based on a non-systematic review of the literature.


RESULTS
One hundred and fourteen participants were validated, with a median age of 33 years. Half of the participants were on monotherapy, and the majority had no seizures in the last six months. We identified important gaps in the participants' knowledge. Sections about complications and administration of antiseizure medication during pregnancy were the ones with the worst results. None of the clinical and demographic variables correlated with the final questionnaire score. Having had a previous pregnancy and the desire to breastfeed in a future pregnancy were positively correlated with the performance in breastfeeding section. Face-to-face discussion during medical outpatient visits was selected as the preferential method to learn about epilepsy, and the internet and social media were the least preferred ones.


CONCLUSION
The knowledge of women of childbearing age with epilepsy in the Lisbon metropolitan area concerning the impact of epilepsy in contraception, pregnancy and breastfeeding seems to have significant gaps. Medical teams should consider engaging in patient education particularly during outpatient clinics.

[Evaluation of the Knowledge of Women of Childbearing Age with Epilepsy about the Impact of Their Disease in Contraception, Pregnancy and Breastfeeding: A Multicenter Cross-Sectional Study].

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Migraine: from pathophysiology to treatment

Visual snow syndrome and migraine: a review

Evaluating migraine with typical aura with neuroimaging

[Evaluation of the Knowledge of Women of Childbearing Age with Epilepsy about the Impact of Their Disease in Contraception, Pregnancy and Breastfeeding: A Multicenter Cross-Sectional Study].