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.

A sensitive and specific triage of patients with primary or secondary headache is a major concern in evaluating pediatric headache patients. History and physical examination are the major tools for differentiating primary headache disorders from symptomatic headaches caused by defined pathologies. If the criteria of the International Headache Society for a primary headache disorder are met, no further investigations are necessary. However, physicians should be familiar with subtle signs in history and physical examination that raise suspicion of intracranial pathology. These features, also named “red flags” and “relatively red flags,” are outlined in detail in this review. Any red flag should prompt neuroimaging. In case of relatively red flags, a more restrained approach can be appropriate depending on the individual setting. Excessive concerns of patients and parents regarding an underlying pathology can constitute an indication for neuroimaging. Offering neuroimaging implicates the important issues of incidental findings and of “false reassurance.” These risks should be discussed with patients and parents before the investigation. In any pediatric headache patient, regular clinical reevaluations should be warranted, even if neuroimaging is normal. The value of clinical follow-up examinations for a reasonable and reliable assessment of the patients cannot be overestimated. ^* Timo Roser and Michaela Bonfert share the first authorship.

Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Primary headache disorders are frequently encountered in the pediatric population. The therapeutic approach consists of a multimodal program, including lifestyle modification, psychotherapeutic intervention, pharmacotherapy, and complementary measures. This systematic review focuses on the pharmacotherapy of pediatric migraine and tension-type headache (TTH). In addition to the general treatment principles, the results of 33 clinical reports published on the topic since 2008 are outlined in detail. Furthermore, a tabular summary of previously investigated agents not studied since 2008 is given, as is an overview of promising pharmacologic approaches so far only evaluated in adults. A variety of pharmacologic options is available, but high-quality evidence is limited to single agents. At this time, approval is restricted to four triptans and flupirtine for the symptomatic treatment of pediatric acute migraine and TTH, respectively. No agent has been approved for the prevention of pediatric primary headaches. This review does not grade the drugs hierarchically because the complex profiles of many agents differ only slightly or even overlap. However, a detailed expert opinion is provided. On the basis of the outlined facts, the team of physician, patient, and parents has to decide on the most appropriate regimen for the individual situation in the sense of personalized medicine.

Complementary and alternative medicine (CAM) is widely used by both physicians and patients with primary headache syndromes. Despite a considerable number of articles addressing CAM in primary headache syndromes, the overall evidence for CAM is still poor. The aim of this review was to give an overview of the current evidence of the main alternative therapies used in the treatment of primary headache syndromes of childhood. MEDLINE and Cochrane Library were systematically searched for articles dealing with complementary and alternative treatment or prophylaxis of headache and migraine published within the past 20 years.