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Objective: Given the findings of central effects of erenumab in the literature, we aimed to conduct a rigorous placebo-controlled, double-blind, randomized study to elucidate whether the observed changes are directly attributable to the drug., Methods: We recruited 44 patients with migraine, randomly assigning them to either the erenumab 70 mg or the placebo group. 40 patients underwent fMRI scanning using a trigeminal nociceptive paradigm both, pre- and four weeks post-treatment. Participants kept a headache diary throughout the whole study period of two months in total. A clinical response was defined as a ≥30% reduction in headache frequency at follow-up. Details of this study have been preregistered in the open science framework: https://osf.io/ygf3t ., Results: Seven participants of the verum group (n=33.33%) and 4 of the placebo group (21.05%) experienced improvements in migraine activity, characterized by a minimum of 30% reduction in monthly headache frequency compared to baseline. The imaging data show an interaction between the verum medication and the response. Whilst numbers were too small for individual analyses (Verum vs. Placebo and Responder vs. Non-Responder), the variance-weighted analysis (Verum vs Placebo, scan before vs after weighted for response) revealed specific decrease in thalamic, opercular and putamen activity., Interpretation: The central effects of erenumab could be reproduced in a placebo randomized design, further confirming its central role in migraine modulation. The mechanism, whether direct or secondary to peripheral mode of action, needs further exploration. It is important to note that the response rate to erenumab 70mg in this study was not as substantial as anticipated in 2019, when this study was planned. This resulted in a too small sample size for a subgroup analysis based on the responder status was associated with both the verum drug and the relative reduction in headache days., (© 2024. The Author(s).)

Objective: We hypothesized that the response of trigeminal dermal blood flow (DBF) in the trigeminal system and consecutive expansion of flare response to capsaicin would differ from the somatosensory system (arm). We also investigated whether there are differences between patients with migraine and healthy controls (HC)., Background: Functional differences between the trigeminal and extracephalic somatosensory systems may partly explain the susceptibility for headaches in patients with migraine. Capsaicin-induced activation of nociceptive C-fibers in the skin is mainly mediated by calcitonin gene-related peptide (CGRP) and induces cutaneous vessel dilatation and flare response., Methods: Female patients with migraine (n = 38) and age-matched HC (n = 35) underwent DBF measurement at baseline and after topical capsaicin administration using laser speckle imaging. DBF before and after capsaicin stimulation was analyzed over ophthalmic nerve/maxillary nerve/mandibular nerve (V1/V2/V3) dermatomes and the forearm as an extracephalic control., Results: Capsaicin-induced DBF increased more in the trigeminal dermatomes than on the forearm. The V1 dermatome showed a smaller increase of DBF in patients with migraine compared to HC., Conclusion: Our results suggest that the trigeminovascular system reacts differently from extracephalic areas, which may explain the trigeminal susceptibility to CGRP-mediated pain attacks. By demonstrating a different reactivity of the V1 dermatome in patients with migraine, our finding suggests that the first trigeminal branch is functionally different from the second and third branches; however, only in patients with migraine., (© 2023 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Migraine is characterized by a well-defined premonitory phase occurring hours or even days before the headache. Also, many migraineurs report typical triggers for their headaches. Triggers, however, are not consistent in their ability to precipitate migraine headaches. When looking at the clinical characteristics of both premonitory symptoms and triggers, a shared pathophysiological basis seems evident. Both seem to have their origin in basic homeostatic networks such as the feeding/fasting, the sleeping/waking, and the stress response network, all of which strongly rely on the hypothalamus as a hub of integration and are densely interconnected. They also influence the trigeminal pain processing system. Additionally, thalamic and hormonal mechanisms are involved. Activity within all those networks is influenced by various endogenous and external factors and might even cyclically change dependent on physiological internal rhythms. This might affect the threshold for the generation of migraine headaches. Premonitory symptoms thus appear as the result of an already ongoing alteration within those networks, whereas triggers might in this special situation only be able to further stress the system over the threshold for attack generation as catalysts of a process already in motion., (Copyright © 2023 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Cluster headache and migraine are regarded as distinct primary headaches. While cluster headache and migraine differ in multiple aspects such as gender-related and headache specific features (e.g., attack duration and frequency), both show clinical similarities in trigger factors (e.g., alcohol) and treatment response (e.g., triptans). Here, we review the similarities and differences in anatomy and pathophysiology that underlie cluster headache and migraine, discuss whether cluster headache and migraine should indeed be considered as two distinct primary headaches, and propose recommendations for future studies. Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at https://www.youtube.com/watch?v=uUimmnDVTTE ., (© 2022. The Author(s).)

Abstract: Galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, is an emerging migraine preventative. We hypothesized that the preventive effects are conveyed via the modulation of somatosensory processing and that certain sensory profiles may hence be associated with different clinical responses. We recruited migraine patients (n = 26), who underwent quantitative sensory tests over the right V1 dermatome and forearm at baseline (T0), 2 to 3 weeks (T1) and 1 year (T12) after monthly galcanezumab treatment. The clinical response was defined as a reduction of ≥30% in headache frequency based on the headache diary. Predictors for clinical response were calculated using binary logistical regression models. After galcanezumab (T1 vs T0), the heat pain threshold (°C, 44.9 ± 3.4 vs 43.0 ± 3.3, P = 0.013) and mechanical pain threshold (log mN, 1.60 ± 0.31 vs 1.45 ± 0.26, P = 0.042) were increased exclusively in the V1 dermatome but not the forearm. These changes were immediate, did not differ between responders and nonresponders, and did not last in 1 year of follow-up (T12 vs T0). However, baseline heat pain threshold (OR: 2.13, 95% CI: 1.08-4.19, P = 0.029) on the forearm was a robust predictor for a clinical response 3 months later. In summary, our data demonstrated that galcanezumab modulates pain thresholds specifically in the V1 dermatome, but this modulation is short-lasting and irrelevant to clinical response. Instead, the clinical response may be determined by individual sensibility even before the administration of medication., (Copyright © 2022 International Association for the Study of Pain.)

Background: The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain., Methods: Forty healthy participants were enrolled in this double-blinded, randomized, placebo-controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin-induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing., Results: After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome., Conclusions: Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin-induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain., Significance: Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome-specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Background: The vasodilatory calcitonin-gene related peptide (CGRP) is understood as pivotal mediator in migraine pathophysiology. Blocking CGRP with small molecules or monoclonal antibodies (CGRP-mAb) reduces migraine frequency. However, prescription of CGRP-mAbs is still regulated and possible predictive measures of therapeutic success would be useful., Methods: Using standardized capsaicin-induced dermal blood flow model, 29 migraine patients underwent a laser speckle imaging measurement before and after administration of galcanezumab. At both sessions dermal blood flow before and after capsaicin stimulation as well as flare size were analyzed over all three trigeminal branches and the volar forearm for extracranial control. Long-term measures were repeated in 14 patients after continuous treatment ranging from 6 to 12 months., Results: Resting dermal blood flow remained unchanged after administration of galcanezumab. Capsaicin-induced dermal blood flow decreased significantly after CGRP-mAb in all tested areas compared to baseline and this was consistent even after 12 months of treatment. However, following galcanezumab administration, the flare size decreased only in the three trigeminal dermatomes, not the arm and was therefore specific for the trigemino-vascular system. None of these two markers distinguished between responders and non-responders., Conclusion: CGRP-mAb changed blood flow response to capsaicin stimulation profoundly and this effect did not change over a 12-month application. Neither capsaicin-induced flare nor dermal blood flow can be used as a predictor for treatment efficacy. These data suggest that the mechanism of headache development in migraine is not entirely CGRP-mediated.

Purpose of Review: Research on migraine usually focuses on the headache; however, accumulating evidence suggests that migraine not only changes the somatosensory system for nociception (pain), but also the other modalities of perception, such as visual, auditory or tactile sense. More importantly, the multisensory changes exist beyond the headache (ictal) phase of migraine and show cyclic changes, suggesting a central generator driving the multiple sensory changes across different migraine phases. This review summarizes the latest studies that explored the cyclic sensory changes of migraine., Recent Findings: Considerable evidence from recent neurophysiological and functional imaging studies suggests that alterations in brain activation start at least 48 h before the migraine headache and outlast the pain itself for 24 h. Several sensory modalities are involved with cyclic changes in sensitivity that peak during the ictal phase., Summary: In many ways, migraine represents more than just vascular-mediated headaches. Migraine alters the propagation of sensory information long before the headache attack starts., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Monoclonal antibodies (mAbs) against calcitonin gene-related peptides (CGRP) are novel treatments for migraine prevention. Based on a previous functional imaging study which investigated the CGRP receptor mAb (erenumab), we hypothesized that (i) the CGRP ligand mAb galcanezumab would alter central trigeminal pain processing; (ii) responders to galcanezumab treatment would show specific hypothalamic modulation in contrast to non-responders; and (iii) the ligand and the receptor antibody differ in brain responses., Methods: Using an established trigeminal nociceptive functional magnetic imaging paradigm, 26 migraine patients were subsequently scanned twice: before and 2-3 weeks after administration of galcanezumab., Results: We found that galcanezumab decreases hypothalamic activation in all patients and that the reduction was stronger in responders than in non-responders. Contrasting erenumab and galcanezumab showed that both antibodies activate a distinct network. We also found that pre-treatment activity of the spinal trigeminal nucleus (STN) and coupling between the STN and the hypothalamus covariates with the response to galcanezumab., Conclusions: These data suggest that despite relative impermeability of the blood-brain barrier for CGRP mAb, mAb treatment induces certain and highly specific brain effects which may be part of the mechanism of their efficacy in migraine treatment., Funding: This work was supported by the German Ministry of Education and Research (BMBF) of ERA-Net Neuron under the project code BIOMIGA (01EW2002 to AM) and by the German Research Foundation (SFB936-178316478-A5 to AM). The funding sources did not influence study conduction in any way., Clinical Trial Number: The basic science study was preregistered in the Open Science Framework (https://osf.io/m2rc6)., Competing Interests: HB HB received consulting fees from Novartis and Teva. The author has no other competing interests to declare, LS, JM, KP, MS, AM No competing interests declared, (© 2022, Basedau et al.)

Objective: The presence of aura is rare in cluster headache, and even rarer in other trigeminal autonomic cephalalgias. We hypothesized that the presence of aura in patients with trigeminal autonomic cephalalgias is frequently an epiphenomenon and mediated by comorbid migraine with aura., Methods: The study retrospectively reviewed 480 patients with trigeminal autonomic cephalalgia in a tertiary medical center for 10 years. Phenotypes and temporal correlation of aura with headache were analyzed. Trigeminal autonomic cephalalgia patients with aura were further followed up in a structured telephone interview., Results: Seventeen patients with aura (3.5%) were identified from 480 patients with trigeminal autonomic cephalalgia, including nine with cluster headache, one with paroxysmal hemicrania, three with hemicrania continua, and four with probable trigeminal autonomic cephalalgia. Compared to trigeminal autonomic cephalalgia patients without aura, trigeminal autonomic cephalalgia patients with aura were more likely to have a concomitant diagnosis of migraine with aura (odds ratio [OR] = 109.0, 95% CI 30.9-383.0, p  < 0.001); whereas the risk of migraine without aura remains similar between both groups (OR = 1.10, 95% CI = 0.14-8.59, p  = 0.931). Aura was more frequently accompanied with migraine-like attacks, but not trigeminal autonomic cephalalgia attacks., Interpretation: In most patients with trigeminal autonomic cephalalgia, the presence of aura is mediated by the comorbidity of migraine with aura. Aura directly related to trigeminal autonomic cephalalgia attack may exist but remains rare. Our results suggest that aura may not be involved in the pathophysiology of trigeminal autonomic cephalalgia.

Purpose of Review: The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last few years., Recent Findings: Various new triggers and different NDPH mimics have been reported. The association with both cephalic and extracephalic pathologies suggests that NDPH is rather a syndrome with more than one disease mechanism. Recent clinical studies confirmed that migrainous headache remained the most prominent phenotype of NDPH, echoing the change of the diagnostic criteria in 2013. Diagnostic workup, including imaging studies, was unremarkable, except serving to exclude secondary etiologies. Studies on treatment options have yet shown promising targets, and randomized clinical trials are still lacking. Multiple mechanisms, both cranial and systemic, may be involved synergically in the generation of NDPH-like headaches. The search for effective treatment options should base on better understanding of disease mechanisms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Migraine is defined by attacks of headache with a specific length and associated symptoms such as photophobia, phonophobia and nausea. It is long recognized that migraine is more than just the attacks and that migraine should be understood as a cycling brain disorder with at least 4 phases: interictal, preictal, ictal and postictal. However, unlike the pain phase, the other phases are less well defined, which renders studies focusing on these phases susceptible to bias. We herewith review the available clinical, electrophysiological, and neuroimaging data and propose that the preictal phase should be defined as up to 48 hours before the headache attack and the postictal phase as up to 24 hours following the ictal phase. This would allow future studies to specifically investigate these migraine phases and to make study results more comparable.

Purpose: The current review provides a recapitulation of recent advances in pharmacological neuroimaging in headache, a promising tool to understanding of how a drug works in the brain and how it may lead to new insights of disease mechanisms of headache., Results: Pharmacological positron emission tomography with radioligand-labeled medication may provide evidence whether and where a medication binds in the brain but is still mostly restricted to animal work. Pharmacological functional MRI using task-specific approaches identified central modulation patterns as a consequence of attack and preventative headache medication, which may be distinct to a specific drug mechanism. Pharmacological neuroimaging and specifically in combination with functional imaging is a promising tool to better understand not only certain medications but also certain disease mechanisms., Summary: Pharmacological imaging techniques have advanced over the last few years and showed great potential of providing new insights into drug pharmacodynamics and disease mechanism. There are still limitations and challenges to be overcome., (© 2020 Elsevier B.V. All rights reserved.)

Background: Migraine is associated with syncope. We investigated risk factors for syncope and burden of syncope in migraine patients., Methods: Participants were recruited from a headache clinic. All participants provided information on lifestyle, co-morbidity, syncope, headache and suicide, and completed the MIDAS and HADS questionnaires. Genetic data were available for a subset of participants. Risk of syncope in relation to participant's characteristics and migraine susceptibility loci, and risks of psychological disorders associated with syncope, were calculated using logistic regression., Results: Underweight, regular tea intake, diabetes mellitus, and migraine with aura were associated with increased syncope risks, with adjusted ORs of 1.76 (95% CI 1.03-3.03), 1.84 (95% CI 1.22-2.79), 4.70 (95% CI 1.58-13.95), and 1.78 (95% CI 1.03-3.10), respectively. Preliminary results showed that rs11172113 in LRP1 was associated with syncope risks. Comorbid syncope in migraine patients was associated with increased risks of depression (OR 1.95, 95% CI 1.18-3.22) and suicide attempt (OR 2.85, 95% CI 1.48-5.48)., Conclusion: Our study showed the potential roles of vascular risk factors in the association between migraine and syncope. Modifiable risk factors for syncope in patients with migraine include body mass index and tea intake. The debilitating psychological impact of co-morbid syncope in migraine patients warrants clinical attention of treating physicians.

Migraine encompasses a broader spectrum of sensory symptoms than just headache. These "other" symptoms, eg, sensory phobias, cognitive and mood changes, allodynia, and many others indicate an altered sensitivity to sensory input which can be measured, in principle, by quantifying sensory threshold changes longitudinally over time. Photophobia, for example, can be quantified by investigating the discomfort thresholds towards the luminance of light. The aim of this review is to look into how thresholds change in patients with migraine. We performed a PubMed search up to June 2018 targeting all peer-reviewed articles evaluating the changes in threshold, sensory phobia, or sensitivity in patients with migraine. Migraineurs, in general, exhibit lower sensory thresholds compared with healthy controls. These threshold changes seem to follow the different phases during a migraine cycle. In general, thresholds reach a nadir when the headache starts (the ictal phase), rise after the headache ends, and then gradually descend towards the next attack. The sensory modality of measurement-mechanical, thermal, or nociceptive-and the location of measurement-trigeminal vs somatic dermatome-also influence the sensory threshold. Functional imaging studies provide evidence that the hypothalamo-thalamo-brainstem network may be the driving force behind the periodic threshold changes. In summary, there is evidence in the literature that migraine could be understood as a periodic sensory dysregulation originating from the brain. Nevertheless, the interstudy discrepancy is still high due to different study designs and a lack of focus on distinct migraine phases. Further well-designed and harmonized studies with an emphasis on the cyclic changes still need to be conducted.

Background The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. Method A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Results Both cohorts ( n = 119,017 each) were followed for a mean period of 3.6 ± 1.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. Compared to the comparison cohort, patients with migraine were at an increased risk of ischemic stroke (aHR: 1.24, 95% CI: 1.12-1.38, p < 0.001). Subgroup analysis by age and sex revealed the highest risk in women aged ≤ 45 years (aHR: 3.44, 95% CI: 2.20-5.39, p < 0.001), especially among those with migraine with aura (aHR: 4.58, 95% CI: 2.45 - 8.56, p < 0.001). A trend for increased stroke risk was observed in men aged ≤ 45 years (aHR: 1.54, 95% CI: 0.96-2.48, p = 0.075). Conclusion Migraine is associated with an increased risk of ischemic stroke, especially in younger (age ≤ 45 years) women with migraine with aura. The trend toward ischemic stroke in younger men merits further exploration.

Objective: Whether migraine is associated with urinary calculi is an unresolved issue, although topiramate, a migraine-preventive agent, is known to contribute to this complication. This study investigates the association between migraine and the risk of urinary calculi., Methods: We identified a total of 147,399 patients aged ≥18 years with migraine diagnoses recorded in the Taiwan National Health Insurance Research Database between 2005 and 2009. Each patient was randomly matched with one individual without headache using propensity scores. All participants were followed from the date of enrollment until urinary calculi development, death, or the end of 2010., Results: The risk of urinary calculi was greater in the migraine than the control cohort (adjusted hazard ratio (aHR), 1.58; 95% confidence interval (CI), 1.52-1.63; p < 0.001, irrespective of the influence of topiramate. The risk was higher in younger and female patients. The magnitude of the risk was proportional to the annual frequency of clinic visits for headache (≥6 vs. <3, aHR = 1.11; 95% CI, 1.04-1.17; p = 0.002), but did not differ between migraine patients with and without aura., Conclusions: Our study showed migraine was associated with an increased risk of urinary calculi, independent of topiramate use. A higher frequency of clinic visits was associated with a greater risk., (© International Headache Society 2014.)

Background: The International Burden of Migraine Study (IBMS) showed chronic migraine (CM) was associated with a higher disease burden than episodic migraine (EM). However, in this study Asians with CM were underrepresented. Objectives We investigated if CM and EM differed in headache-related disability, health-related quality of life (HRQoL) and health care resource utilization in Taiwan., Methods: This study recruited patients with EM and CM from two headache clinics in Taiwan. Diagnosis was made by physicians based on Silberstein-Lipton criteria. Participants completed a questionnaire including sociodemographics, Migraine Disability Assessment (MIDAS), EuroQol five-dimensions (EQ-5D), Migraine-Specific Quality of Life v2.1 (MSQ), Patient Health Questionnaire-4 (PHQ-4), productivity and health care resource utilization., Results: A total of 331 patients (EM, n = 164 (49.5%); CM, n = 167 (50.5%)) completed the study. CM patients reported a significantly higher MIDAS score, lower generic (EQ-5D visual analogue scale score and EQ-5D index score) and migraine-specific (all three domains of MSQ) HRQoL, higher levels of anxiety and depression (PHQ-4 ≥ 6) and greater health care resource utilization and productivity loss than those with EM. Positive correlations were found between these instruments and levels of anxiety and depression., Conclusion: Compared to EM, CM was significantly associated with higher disability, lower HRQoL and greater health care resource utilization and productivity loss.

Migraine is a common and disabling disorder with a 1-year prevalence of 4.5-6% in men and 14.5-18% in women. The diagnosis of migraine is usually made according to the second edition of the International Classification of Headache Disorders (ICHD-2) criteria; however, not all physicians are familiar with the diagnostic criteria. Underdiagnosis remains a major issue in general practice, resulting in inadequate treatment. Several instruments are designed to improve the diagnosis of migraine, to identify the comorbid psychological disturbances, to measure the burden and disability, and to access any reduction in quality of life (QoL) that occurs due to migraine attacks with good reliability and validity. Furthermore, the disability and QoL measured by certain instruments serve as surrogate targets when treating migraines. In this review, we examine the instruments that are in common use in daily practice and current research on migraines, focusing on the purpose of each instrument, clinical applications, pitfalls in interpretation, and, if any, minimally clinically important difference(s) (MCID). In general, a structured intake form and a headache diary are recommended in approaching patients with headache. In addition, ID-Migraine, a three-item screening test, has been validated in primary care settings as a way to improve the rapid diagnosis of migraine. The Visual Aura Rating Scale (VARS) is helpful for the diagnosis of migraine with aura. In addition, migraine is commonly associated with psychiatric comorbidities, which can be assessed by the Beck Depression Inventory (BDI), 9-item Patient Health Questionnaire (PHQ-9), and Hospital Anxiety and Depression Scale (HADS). To evaluate the impact of migraines, disability can be assessed using the Migraine Disability Assessment Questionnaire (MIDAS). Reduction in QoL can be evaluated using the Migraine-Specific Quality of Life Survey (MSQ 2.1), European Quality of Life-Five Dimensions (EQ-5D), or Short-Form 36 (SF-36). Despite all these instruments, proper selection and interpretation of each instrument remain crucial., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: International Classification of Headache Disorders (ICHD-2) criteria for new daily persistent headache (NDPH) require tension-type headache features. Many patients with 'new-onset persistent' headache fail to fulfil such criteria due to prominent migrainous features., Subjects and Methods: We reviewed all NDPH patients in our headache clinic, using the definition of persistent headache < 3 days after onset for > 3 months. The patients were dichotomised: patients meeting ICHD-2 criteria (NDPH-S) and patients failing to meet ICHD-2 criteria due to prominent migrainous features (NDPH-M). All patients had completed a structured intake form including demographics, headache profiles, Beck Depression Inventory (BDI), Short Form 36 (SF-36) Health Survey, and Migraine Disability Assessment (MIDAS). A telephone interview was conducted for follow-up., Results: A total of 92 NDPH patients were enrolled (59 (64.1%) NDPH-M, 33 (35.9%) NDPH-S). Between the two subgroups, the sociodemographics were indistinguishable, but the patients with NDPH-M had higher headache intensity, BDI scores, MIDAS scores, and lower scores of most SF-36 subscales. After an average of 2 years of follow-up, 57 (66%) had a good outcome (≥ 50% reduction in headache frequency). Cox proportional analysis showed that disease duration ≤ 6 months and NDPH-S diagnosis predicted good outcomes., Conclusion: Migrainous features were common in patients with NDPH. Unlike prior studies, our study showed NDPH-M represented a more severe subgroup with a poorer outcome compared with NDPH-S.