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Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI)-based technique using labeled blood-water of the brain-feeding arteries as an endogenous tracer to derive information about brain perfusion. It enables the assessment of cerebral blood flow (CBF)., Method: This review aims to provide a methodological and technical overview of ASL techniques, and to give examples of clinical use cases for various diseases affecting the central nervous system (CNS). There is a special focus on recent developments including super-selective ASL (ssASL) and time-resolved ASL-based magnetic resonance angiography (MRA) and on diseases commonly not leading to characteristic alterations on conventional structural MRI (e. g., concussion or migraine)., Results: ASL-derived CBF may represent a clinically relevant parameter in various pathologies such as cerebrovascular diseases, neoplasms, or neurodegenerative diseases. Furthermore, ASL has also been used to investigate CBF in mild traumatic brain injury or migraine, potentially leading to the establishment of imaging-based biomarkers. Recent advances made possible the acquisition of ssASL by selective labeling of single brain-feeding arteries, enabling spatial perfusion territory mapping dependent on blood flow of a specific preselected artery. Furthermore, ASL-based MRA has been introduced, providing time-resolved delineation of single intracranial vessels., Conclusion: Perfusion imaging by ASL has shown promise in various diseases of the CNS. Given that ASL does not require intravenous administration of a gadolinium-based contrast agent, it may be of particular interest for investigations in pediatric cohorts, patients with impaired kidney function, patients with relevant allergies, or patients that undergo serial MRI for clinical indications such as disease monitoring., Key Points: · ASL is an MRI technique that uses labeled blood-water as an endogenous tracer for brain perfusion imaging.. · It allows the assessment of CBF without the need for administration of a gadolinium-based contrast agent.. · CBF quantification by ASL has been used in several pathologies including brain tumors or neurodegenerative diseases.. · Vessel-selective ASL methods can provide brain perfusion territory mapping in cerebrovascular diseases.. · ASL may be of particular interest in patient cohorts with caveats concerning gadolinium administration.., Competing Interests: Stephan Kaczmarz is an employee of Philips GmbH, Hamburg, Germany. All other authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin have been reported to play a modulating role in migraine and contribute to its sex-dependent differences. The current narrative review explores the relationship between these two hormones and the pathophysiology of migraine. We describe the physiological role of prolactin and oxytocin, its relationship to migraine and pain, and potential therapies targeting these hormones or their receptors.In summary, oxytocin and prolactin are involved in nociception in opposite ways. Both operate at peripheral and central levels, however, prolactin has a pronociceptive effect, while oxytocin appears to have an antinociceptive effect. Therefore, migraine treatment targeting prolactin should aim to block its effects using prolactin receptor antagonists or monoclonal antibodies specifically acting at migraine-pain related structures. This action should be local in order to avoid a decrease in prolactin levels throughout the body and associated adverse effects. In contrast, treatment targeting oxytocin should enhance its signalling and antinociceptive effects, for example using intranasal administration of oxytocin, or possibly other oxytocin receptor agonists. Interestingly, the prolactin receptor and oxytocin receptor are co-localized with estrogen receptors as well as calcitonin gene-related peptide and its receptor, providing a positive perspective on the possibilities for an adequate pharmacological treatment of these nociceptive pathways. Nevertheless, many questions remain to be answered. More particularly, there is insufficient data on the role of sex hormones in men and the correct dosing according to sex differences, hormonal changes and comorbidities. The above remains a major challenge for future development., (© 2023. The Author(s).)

Background: Migraine is a highly prevalent primary headache disorder. Despite a high burden of disease, key disease mechanisms are not entirely understood. Functional magnetic resonance imaging is an imaging method using the blood-oxygen-level-dependent signal, which has been increasingly used in migraine research over recent years. This systematic review summarizes recent findings employing functional magnetic resonance imaging for the investigation of migraine., Methods: We conducted a systematic search and selection of functional magnetic resonance imaging applications in migraine from April 2014 to December 2021 (PubMed and references of identified articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). Methodological details and main findings were extracted and synthesized., Results: Out of 224 articles identified, 114 were included after selection. Repeatedly emerging structures of interest included the insula, brainstem, limbic system, hypothalamus, thalamus, and functional networks. Assessment of functional brain changes in response to treatment is emerging, and machine learning has been used to investigate potential functional magnetic resonance imaging-based markers of migraine., Conclusions: A wide variety of functional magnetic resonance imaging-based metrics were found altered across the brain for heterogeneous migraine cohorts, partially correlating with clinical parameters and supporting the concept to conceive migraine as a brain state. However, a majority of findings from previous studies have not been replicated, and studies varied considerably regarding image acquisition and analyses techniques. Thus, while functional magnetic resonance imaging appears to have the potential to advance our understanding of migraine pathophysiology, replication of findings in large representative datasets and precise, standardized reporting of clinical data would likely benefit the field and further increase the value of observations.

Introduction: Repetitive neuromuscular magnetic stimulation (rNMS) was previously applied in adult patients with episodic migraine, showing beneficial effects on headache characteristics, high safety, and convincing satisfaction. This study aims to assess rNMS as a personalized intervention in pediatric headache., Methods: Retrospective chart review including patients with migraine, TTH, mixed type headache, or PTH, who had received at least one test rNMS session targeting the upper trapezius muscles (UTM)., Results: 33 patients (13.9 ± 2.5 years; 61% females) were included in the primary analysis, resulting in a total of 182 rNMS sessions. 43 adverse events were documented for 40 of those sessions (22%). Most common side effects were tingling (32.6%), muscle sore (25.5%), shoulder (9.3%) and back pain (9.3%). Secondly, in patients (n = 20) undergoing the intervention, headache frequency (p = 0.017) and minimum and maximum intensities (p = 0.017; p = 0.023) significantly decreased from baseline to 3-month after intervention. 11 patients (44%) were classified as ≥25% responders, with 7 patients (28%) experiencing a ≥75% reduction of headache days. After 73% of interventions, patients reported rNMS helped very well or well. A majority of patients would repeat (88.5%) and recommend rNMS (96.2%) to other patients., Conclusion: rNMS seems to meet the criteria of safety, feasibility, and acceptance among children and adolescents with three age-typical headache disorders. A significant reduction in headache frequency and intensity during a 3 months follow-up was documented. Larger, prospective, randomized, sham-controlled studies are urgently needed to confirm if rNMS may become a new valuable non-invasive, non-pharmacological treatment option for pediatric headache disorders., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

The objective of this study was to assess the burden of disease and prevalence of lifestyle factors for adolescents and young adults with frequent episodic migraine. We conducted a secondary comparative analysis of data collected during two previous studies. Inclusion criteria for this analysis were age 15-35 years, 15 to 44 migraine episodes within 12 weeks, and completeness of Migraine Disability Assessment and lifestyle questionnaire data. Datasets of 37 adults (median age [interquartile range]: 25 [6]) and 27 adolescents (median age [interquartile range]: 15 [1]) were analyzed. 81% ( n = 30) of adults reported severe disability (16% [ n = 3] of adolescents; p < 0.001). Headache frequency (24 vs. 17 days; p = 0.005) and prevalence of regular analgesic use (60% [ n = 22] vs. 18% [ n = 5]; p = 0.002) were significantly higher in adults. In adults, sleep duration on weekdays was significantly lower (8.5 vs. 10 h; p < 0.001). Any consumption of caffeine tended to be higher in adolescents and alcohol consumption tended to be higher in adults ( p > 0.05). This study underlines the importance of educating adolescents and young adults with migraine about lifestyle habits that are likely to interfere with the condition.

Migraine is a common and invalidating disorder worldwide. Patients of all ages experience the disorder as very impairing regarding their personal and occupational lives. The current approach in migraine therapy is multimodal including lifestyle management, psychoeducation and, if available, psychotherapeutic interventions, and pharmacotherapy. The lack of non-pharmacological and non-invasive treatment options call for new and innovative therapeutic approaches. Peripheral neurostimulation is a relatively new method in migraine management offering a painless and non-pharmacological way of targeting specific mechanisms involved in migraine. This review summarizes 15 recent randomized clinical trials to provide an overview of non-invasive peripheral neurostimulation methods currently available for the treatment of migraine. Efficacy, tolerability, and safety of the different interventions and their feasibility in the pediatric setting are evaluated. Vagal nerve stimulation (VNS), remote electrical neuromodulation (REN) and supraorbital nerve stimulation (SNS) are considered effective in treating acute migraine attacks, the latter being more pronounced in migraine without aura. Regarding migraine prevention, occipital nerve stimulation (ONS) and supraorbital nerve stimulation (SNS) demonstrated efficacy, whereas repetitive neuromuscular magnetic stimulation (rNMS) may represent a further effective option in episodic migraine. REN and rNMS were found to be well-accepted with fewer patients discontinuing treatment than those receiving direct cranial nerve stimulation. In summary, peripheral neurostimulation represents a promising option to complement the multimodal therapy concept for pediatric migraine. In particular, rNMS opens a new field for research and treatment fitting the requirements of "non-invasiveness" for children. Given the reported efficacy, safety, and feasibility, the therapy decision should be made on an individual level., Competing Interests: Declaration of competing interest The Division of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, LMU Hospital, Munich Germany is provided by an emFieldPro magnetic stimulator by Zimmer MedizinSysteme GmbH (Neu-Ulm, Germany). N.S. and S.M.K. received honoraria from Nexstim Plc (Helsinki, Finland). S.M.K. received honoraria from Brainlab AG (Munich, Germany), Spineart (Frankfurt, Germany), Ulrich Medical (Ulm, Germany), Zeiss Meditec (Jena, Germany), and Medtronic (Dublin, Ireland). A.S. received honoraria from electroCore (New Yersey, US). M.N.L. received grants from DLR. M.N.L. and F.H. received a grant “Innovationsfonds” of the joint federal committee of health insurance companies (GBA) for a nation-wide study on an early multimodal intervention program for children with migraine. No further conflicts of interest are reported., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Although migraine is a relevant health issue in children and adolescents, clinical care and research are still underrepresented and underfunded in this field. Quality of life can be significantly reduced when living with frequent episodes of pain. Due to the high level of vulnerability of the developing brain during adolescence, the risk of chronification and persistence into adulthood is high. In this narrative review, we describe the corner stones of a patient-centered, multimodular treatment regimen. Further, an update on the pathophysiology of migraine is given considering the concept of a periodically oscillating functional state of the brain in migraine patients ("migraine is a brain state"). Besides central mechanisms, muscular structures with the symptoms of muscular pain, tenderness, or myofascial trigger points play an important role. Against this background, the currently available nonpharmacological and innovative neuromodulating approaches are presented focusing on the method of repetitive peripheral magnetic stimulation.