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AimThe TACHIS study (from the ancient Greek adjective "tachýs" meaning rapid) aimed to evaluate eptinezumab effectiveness and tolerability in routine clinical practice, integrating patient-reported outcomes and use of International Headache Society (IHS)-endorsed categories of migraine control by treatment.BackgroundEptinezumab is the only intravenous anti-calcitonin gene related peptide (CGRP) monoclonal antibody (mAb) approved for migraine prevention. While its efficacy has been demonstrated in RCTs, real-world evidence in patients with prior preventive treatment failures is still limited.MethodsTACHIS is a prospective, multicenter, observational study conducted in Italy. Adults with episodic or chronic migraine initiating eptinezumab were followed for 24 weeks. Primary outcomes included change from baseline in monthly migraine days (MMDs) and ≥50% responder rate. Secondary outcomes included changes from baseline in acute medication use, Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) and IHS-defined residual burden categories. Logistic regression identified factors of response status.ResultsA total of 128 patients were included (82% female; 82% chronic migraine). MMDs decreased overall by 5.7 days (95% CI: -7.2 to -4.3) at week 12 and 6.9 (95% CI: -8.5 to -5.2) at week 24 (p < 0.001). A ≥ 50% response was achieved in 43.8% and 48.2% of patients at weeks 12 and 24, respectively. Over 40% of patients achieved optimal or modest migraine control. CGRP targeted therapy-naïve patients experienced significant greater benefit, though non-naïve patients also improved. Female sex and chronic migraine diagnosis were independently associated with response at 12 weeks. Adverse events were infrequent (4.7%) and mild, with no discontinuations due to safety concerns.ConclusionsEptinezumab demonstrated effectiveness and tolerability in a real-world population of patients with migraine and prior preventive treatment failures. The integration of migraine control metrics provides a comprehensive evaluation of therapeutic impact and supports eptinezumab use in routine care.Trial RegistrationThe TACHIS study was preregistered on clinicaltrial.gov, NCT06409845.

AimPost-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) frequently co-occurs with other physical, cognitive, and emotional symptoms. This study assessed associations between PTH improvement and these symptoms in individuals with acute headaches (APTH) and compared symptoms between those who had recently developed persistent PTH (PPTH) to those who had long-standing PPTH.MethodsThis study included 105 individuals with APTH (mean age = 43.4, SD = 15.8; 70 females, 35 males) and 46 individuals with PPTH (mean age = 38.2, SD = 10.9; 16 females, 30 males) with an average duration of 11.3 years from two prospective longitudinal studies. For those who had APTH, PTH improvement was assessed at three months post-enrollment using an electronic headache diary. Participants completed questionnaires evaluating physical (including headache symptoms, photosensitivity, hyperacusis, insomnia, autonomic symptoms, and disability), emotional (including depression, anxiety, pain catastrophizing, and post-traumatic stress disorder screening), and cognitive symptoms (including memory and attention). The APTH cohort completed questionnaires at baseline, follow-up #1 (three to four months from baseline), and follow-up #2 (six to seven months from baseline). Mixed Effects Models were used to analyze the temporal trend of symptoms among the APTH improved and non-improved groups.ResultsAmong the 105 individuals with APTH, 60 experienced PTH improvement and 45 did not. At baseline, compared to those who had PTH improvement, those who did not have PTH improvement had higher SCAT total scores and physical subscores, greater levels of hyperacusis, pain catastrophizing, anxiety and depression. At follow-up #1 (three to four months), these individuals continued to show more pronounced physical and emotional symptoms and worse cognitive function and insomnia. Most of these group differences persisted at follow-up #2 (six to seven months). Most symptoms showed progressive improvement over three months for individuals who had PTH improvement but not for those without PTH improvement. Furthermore, individuals with long-standing PPTH showed more severe insomnia, pain catastrophizing, and PTSD compared to those who had recently developed PPTH.ConclusionIndividuals with APTH who did not experience PTH improvement at three months had more severe physical, cognitive, and emotional symptoms at baseline compared to those who had PTH improvement. While most symptoms normalized in individuals with PTH improvement, symptoms overall persisted at three and at six months for those with PTH persistence. Individuals who had long-standing PPTH had more severe insomnia and more negative cognitive/emotional responses to pain compared to those who had recently developed PPTH.

BackgroundThe diagnosis of migraine currently relies on clinical criteria based on expert consensus. Despite advances in neuroimaging, a sensitive and reliable morphological biomarker for episodic migraine (EM) remains elusive. Fractal dimension (FD), a novel morphometric metric, offers promise for detecting minor cortical alterations and may offer more precise quantification of cerebral folding than conventional cortical thickness (CT) analysis.MethodsThis study compared 50 EM patients and 50 matched healthy controls (HC) using both FD and CT analyses of magnetic resonance imaging (MRI) across hemispheres, cerebral lobes and 68 cortical regions. After evaluating data normality, group differences were assessed using false discovery rate-corrected t-tests and validated through permutation testing. Unsupervised k-means clustering was applied to evaluate classification performance.ResultsFD showed lower variance and narrower data distribution, revealing more significant cortical alterations than CT, especially in the temporal lobe. Notably, FD uniquely identified structural changes in the insula, a region implicated in high-frequency migraine attacks, where CT showed no differences. The FD-based classifier achieved 81.62% accuracy in distinguishing EM from HC, significantly outperforming CT (54.03%).ConclusionsFD-based analysis of structural MRI shows greater sensitivity than conventional method in detecting migraine-related cortical changes, effectively distinguishing EM from HC, even in low-frequency cases with minor alterations previously undetectable by MRI. This approach may hold promise for supporting clinical diagnosis and enabling future automated screening.

BackgroundHigh-quality research studies on therapeutic approaches for migraine management in pediatrics are scarce. Therefore, we conducted a systematic review of current clinical practice guidelines for the diagnosis and management of migraine in children and adolescents to identify areas of consensus and disagreement, as well as critical gaps, paving the way for future updates and improvements.MethodsWe searched PubMed, WOS, and SCOPUS for guidelines published in the English language in the last 10 years focused on the diagnosis and management of migraine in children and adolescents.ResultsFollowing a systematic search, eight eligible guidelines were identified. These guidelines were authored by the American Academy of Neurology (AAN), the European Headache Federation/European Academy of Neurology (EHF/EAN), the International Headache Society (IHS), National Institute for Health and Care Excellence (NICE), the Danish Headache Society, and the German Migraine and Headache Society and the German Society of Neurology. There was a broad consensus on considering the International Classification of Headache Disorders-3rd edition as the diagnostic reference. As regards management, paracetamol and ibuprofen were considered first line in the acute management of migraine, with sumatriptan and zolmitriptan nasal sprays rated as second line. Injectable medications for acute management were overlooked in most guidelines. On the other hand, targeted age groups, dosing, and preventive treatment choices showed areas of variability. Various non-pharmacological measures gained attention in all guidelines. Notably, CGRP antagonists and non-invasive neuromodulation techniques were identified as major gaps.ConclusionThe current systematic review highlights areas of agreement and disagreement between existing guidelines on the management of childhood and adolescent migraine and emphasizes the current gaps and opportunities, thus offering a solid foundation for future studies and guidelines.

ObjectiveTo evaluate the eligibility of migraine for classification as a Primary Care-Sensitive Condition (PCSC), and to discuss the public health, clinical, and economic implications of this designation in enhancing access to care across different healthcare systems.BackgroundPrimary Care-Sensitive Conditions are health issues for which timely and effective management in primary care can reduce the need for hospitalization and specialist care. Although migraine is a leading cause of disability worldwide and frequently results in emergency visits and productivity loss, it remains underrecognized in PCSC classifications. This narrative review explores whether migraine fulfills the criteria for PCSC designation and how such recognition may contribute to improved outcomes and system efficiency, particularly in low- and middle-income countries.MethodsWe conducted a narrative review based on the five criteria established by Solberg and Weissman for defining PCSCs: (1) existence of evidence supporting primary care management; (2) public health relevance; (3) diagnostic clarity at the primary care level; (4) potential to avoid hospitalizations through early intervention; and (5) the possibility of hospitalization in severe cases. Global data on migraine epidemiology, diagnosis, treatment, and health system impact were analyzed in this framework.ResultsMigraine fulfills all five criteria for classification as a PCSC. It is highly prevalent and disabling, with substantial economic and social impacts. Diagnosis can be reliably established in primary care using the International Classification of Headache Disorders (ICHD-3) and screening tools like ID-Migraine™, while management is feasible through patient education and preventive strategies. Despite this, underdiagnosis, lack of provider training, and limited access to effective therapies - especially in resource-constrained settings - continue to drive unnecessary hospitalizations. Integrating migraine care into primary care has shown promising outcomes in pilot initiatives globally. Structured interventions, such as professional training and non-pharmacological strategies, have demonstrated cost-effectiveness and improved patient outcomes. Classifying migraine as a PCSC could guide policy reforms, enhance early intervention, and reduce reliance on emergency services.ConclusionMigraine meets criteria for a PCSC and recognizing that offers an opportunity to reframe policy, guide resource allocation and reduce avoidable hospitalizations decreasing the global burden of the disease by promoting timely diagnosis and improving equitable access to care. Strengthening primary care systems and embedding migraine management into routine practice are critical for achieving better health outcomes and more sustainable healthcare delivery.

AimCorneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique for evaluating the corneal microstructure, particularly the subepithelial nerve plexus. This dense, dynamic plexus contains small nerve fibers from the ophthalmic branch of the trigeminal nerve. This study aimed to evaluate corneal nerve alterations in individuals with migraine, including its subtypes and visual hypersensitivity (measured with the Leiden visual sensitivity scale (L-VISS), a validated nine-item questionnaire).MethodsIn total, 55 migraine participants were included, including 26 with episodic migraine and 29 with chronic migraine, as well as 55 age- and sex-matched controls. All subjects underwent CCM, and automated corneal nerve fiber density (ACNFD), length (ACNFL) and branch density (ACNBD) were assessed using the Rostock Cornea Module (Heidelberg Retina Tomograph III). Data were compared with age- and sex-matched healthy volunteers.ResultsReduced ACNFD, ACNFL and ACNBD were found in migraine participants compared to controls (all p < 0.001). No difference was found between episodic migraine and chronic migraine, and regression analysis showed no significant effect for (inter)ictal visual hypersensitivity.ConclusionsThese findings support the utility of CCM as a sensitive tool for detecting nerve fiber pathology in migraine and highlight its potential in further understanding migraine pathophysiology. The observed nerve changes, present irrespective of migraine frequency status or visual hypersensitivity, suggest a broader role for peripheral nerve dysfunction in migraine beyond sensory hypersensitivity symptoms.