Four Decades of Occipital Nerve Stimulation for Headache Disorders: A Systematic Review.

PURPOSE OF REVIEW: Chronic headaches are a significant source of disability worldwide. Despite the development of conventional strategies, a subset of patients remain refractory and/or experience side effects following these treatments. Hence, occipital nerve stimulation (ONS) should be considered as an alternative strategy for intractable chronic headaches. This review aims to provide a comprehensive overview of the effectiveness, safety, mechanisms and practical application of ONS for the treatment of headache disorders. RECENT FINDINGS: Overall response rate of ONS is 35.7-100%, 17-100%, and 63-100% in patients with cluster headache, chronic migraine and occipital neuralgia respectively. Regarding the long-term effectivity in all groups, 41.6-88.0% of patients remain responders after ≥ 18.3 months. The most frequently reported adverse events include lead migration/fracture (13%) and local pain (7.3%). Based on our results, ONS can be considered a safe and effective treatment for chronic intractable headache disorders. To support more widespread application of ONS, additional research with larger sample sizes should be conducted.

Artificial Intelligence and Virtual Reality in Headache Disorder Diagnosis, Classification, and Management.

PURPOSE OF REVIEW: This review provides an overview of the current and future role of artificial intelligence (AI) and virtual reality (VR) in addressing the complexities inherent to the diagnosis, classification, and management of headache disorders. RECENT FINDINGS: Through machine learning and natural language processing approaches, AI offers unprecedented opportunities to identify patterns within complex and voluminous datasets, including brain imaging data. This technology has demonstrated promise in optimizing diagnostic approaches to headache disorders and automating their classification, an attribute particularly beneficial for non-specialist providers. Furthermore, AI can enhance headache disorder management by enabling the forecasting of acute events of interest, such as migraine headaches or medication overuse, and by guiding treatment selection based on insights from predictive modeling. Additionally, AI may facilitate the streamlining of treatment efficacy monitoring and enable the automation of real-time treatment parameter adjustments. VR technology, on the other hand, offers controllable and immersive experiences, thus providing a unique avenue for the investigation of the sensory-perceptual symptomatology associated with certain headache disorders. Moreover, recent studies suggest that VR, combined with biofeedback, may serve as a viable adjunct to conventional treatment. Addressing challenges to the widespread adoption of AI and VR in headache medicine, including reimbursement policies and data privacy concerns, mandates collaborative efforts from stakeholders to enable the equitable, safe, and effective utilization of these technologies in advancing headache disorder care. This review highlights the potential of AI and VR to support precise diagnostics, automate classification, and enhance management strategies for headache disorders.

Efficacy of Atogepant in Chronic Migraine With and Without Acute Medication Overuse in the Randomized, Double-Blind, Phase 3 PROGRESS Trial.

BACKGROUND AND OBJECTIVES: Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse. METHODS: This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures. RESULTS: Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse. DISCUSSION: Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.

Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.

Machine learning identifies factors most associated with seeking medical care for migraine: Results of the OVERCOME (US) study.

OBJECTIVE: Utilize machine learning models to identify factors associated with seeking medical care for migraine. BACKGROUND: Migraine is a leading cause of disability worldwide, yet many people with migraine do not seek medical care. METHODS: The web-based survey, ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (US), annually recruited demographically representative samples of the US adult population (2018-2020). Respondents with active migraine were identified via a validated diagnostic questionnaire and/or a self-reported medical diagnosis of migraine, and were then asked if they had consulted a healthcare professional for their headaches in the previous 12 months (i.e., "seeking care"). This included in-person/telephone/or e-visit at Primary Care, Specialty Care, or Emergency/Urgent Care locations. Supervised machine learning (Random Forest) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms identified 13/54 sociodemographic and clinical factors most associated with seeking medical care for migraine. Random Forest models complex relationships (including interactions) between predictor variables and a response. LASSO is also an efficient feature selection algorithm. Linear models were used to determine the multivariable association of those factors with seeking care. RESULTS: Among 61,826 persons with migraine, the mean age was 41.7 years (±14.8) and 31,529/61,826 (51.0%) sought medical care for migraine in the previous 12 months. Of those seeking care for migraine, 23,106/31,529 (73.3%) were female, 21,320/31,529 (67.6%) were White, and 28,030/31,529 (88.9%) had health insurance. Severe interictal burden (assessed via the Migraine Interictal Burden Scale-4, MIBS-4) occurred in 52.8% (16,657/31,529) of those seeking care and in 23.1% (6991/30,297) of those not seeking care; similar patterns were observed for severe migraine-related disability (assessed via the Migraine Disability Assessment Scale, MIDAS) (36.7% [11,561/31,529] vs. 14.6% [4434/30,297]) and severe ictal cutaneous allodynia (assessed via the Allodynia Symptom Checklist, ASC-12) (21.0% [6614/31,529] vs. 7.4% [2230/30,297]). Severe interictal burden (vs. none, OR 2.64, 95% CI [2.5, 2.8]); severe migraine-related disability (vs. little/none, OR 2.2, 95% CI [2.0, 2.3]); and severe ictal allodynia (vs. none, OR 1.7, 95% CI [1.6, 1.8]) were strongly associated with seeking care for migraine. CONCLUSIONS: Seeking medical care for migraine is associated with higher interictal burden, disability, and allodynia. These findings could support interventions to promote care-seeking among people with migraine, encourage assessment of these factors during consultation, and prioritize these domains in selecting treatments and measuring their benefits.

Tooth Loss and Chronic Pain: A Population-based Analysis of the National Health and Nutrition Examination Survey.

Poor oral health conditions in adults are associated with chronic pain. A nationwide cross-sectional study was conducted to investigate the link between tooth loss and chronic pain. The study involved 8,662 participants from the National Health and Nutrition Examination Survey. Tooth count was categorized into 4 groups, and chronic pain was defined as persistent pain lasting over 3 months despite treatment. Location of the chronic pain, demographics, comorbidities, lifestyle determinants, and dietary intake were retrieved. Univariate and multivariate logistic regression were used to explore cross-sectional associations between tooth count and chronic pain. Compared to participants with more than 20 teeth, those with severe tooth loss presented greater odds of chronic pain (adjusted odds ratio [aOR] = 2.111, 95% confidence intervals (CI) = 1.213-3.676 for patients with 1-8 teeth). Edentulous participants presented with significantly higher odds of chronic pain in the lower extremities (78.4%) and buttocks (49.5%). In the multivariate model, apart from rheumatic arthritis (aOR = 4.004, 95% CI = 2.766-5.798), variables of higher chronic pain included smoking (aOR = 1.518, 95% CI = 1.228-1.878), and hypertension (aOR = 1.463, 95% CI = 1.013-2.112). On the contrary, being Mexican American (aOR = .603, 95% CI = .414-.880) was associated with lower odds of chronic pain. The findings suggested a significant link between chronic pain and tooth loss, independent of ethnicity, lifestyle determinants, and immune-mediated inflammatory diseases including rheumatoid arthritis. PERSPECTIVE: A U.S. nationwide study examined tooth loss and chronic pain. Those with severe tooth loss had increased odds of chronic pain. Edentulous individuals presented higher odds of pain in lower extremities and buttocks. This study highlighted the link between tooth loss and chronic pain, independent of comorbidities and lifestyle factors.

Virtual Reality in Acute and Chronic Pain Medicine: An Updated Review.

PURPOSE OF REVIEW: This review critically analyzes the recent literature on virtual reality's (VR) use in acute and chronic pain management, offering insights into its efficacy, applications, and limitations. RECENT FINDINGS: Recent studies, including meta-analyses and randomized controlled trials, have demonstrated VR's effectiveness in reducing pain intensity in various acute pain scenarios, such as procedural/acute pain and in chronic pain conditions. The role of factors such as immersion and presence in enhancing VR's efficacy has been emphasized. Further benefits have been identified in the use of VR for assessment as well as symptom gathering through conversational avatars. However, studies are limited, and strong conclusions will require further investigation. VR is emerging as a promising non-pharmacological intervention in pain management for acute and chronic pain. However, its long-term efficacy, particularly in chronic pain management, remains an area requiring further research. Key findings highlight that VR programs vary in efficacy depending on the specificity of the origin of pain.

Readability analysis and concept mapping of PROMs used for headache disorders.

OBJECTIVE: To assess the readability and the comprehensiveness of patient-reported outcome measures (PROMs) utilized in primary headache disorders literature. BACKGROUND: As the health-care landscape has evolved toward a patient-centric model, numerous PROMs have been developed to capture treatment outcomes in patients with headache disorders. For these PROMs to advance our understanding of headache disorders and their treatment impact, they must be easy to understand (i.e., reading grade level 6 or less) and comprehensively capture what matters to patients with headache. The aim of this study was to (a) assess the readability of PROMs utilized in headache disorders literature, and (b) assess the comprehensiveness of PROMs by mapping their content to a health-related quality of life framework. METHODS: In this scoping review, recently published systematic reviews were used to identify PROMs used in primary headache disorders literature. Readability analysis was performed at the level of individual items and full PROM using established readability metrics. The content of the PROMs was mapped against a health-related quality-of-life framework by two independent reviewers. RESULTS: In total, 22 PROMs (15 headache disorders related, 7 generic) were included. The median reading grade level varied between 7.1 (interquartile range [IQR] 6.3-7.8) and 12.7 (IQR 11.8-13.2). None of the PROMs were below the recommended reading grade level for patient-facing material (grade 6). Three PROMs, the Migraine-Treatment Assessment Questionnaire, the Eurolight, and the European Quality of Life 5 Dimensions 3 Level Version, were between reading grade levels 7 and 8; the remaining 19 PROMs were above reading grade level 8. In total, the PROMs included 425 items. Most items (n = 134, 32%) assessed physical function (e.g., work, activities of daily living). The remaining items assessed physical symptoms (n = 127, 30%; e.g., pain, nausea), treatment effects on symptoms (n = 65, 15%; e.g., accompanying symptoms relief, headache relief), treatment impact (n = 56, 13%; e.g., function, side effects), psychological well-being (n = 41, 10%; e.g., anger, frustration), social well-being (n = 29, 7%; e.g., missing out on social activities, relationships), psychological impact (n = 14, 3%; e.g., feeling [not] in control, feeling like a burden), and sexual well-being (n = 3, 1%; e.g., sexual activity, sexual interest). Some of the items pertained to treatment (n = 27, 6%), of which most were about treatment type and use (n = 12, 3%; e.g., medication, botulinum toxin), treatment access (n = 10, 2%; e.g., health-care utilization, cost of medication), and treatment experience (n = 9, 2%; e.g., treatment satisfaction, confidence in treatment). CONCLUSION: The PROMs used in studies of headache disorders may be challenging for some patients to understand, leading to inaccurate or missing data. Furthermore, no available PROM comprehensively measures the health-related quality-of-life impact of headache disorders or their treatment, resulting in a limited understanding of patient-reported outcomes. The development of an easy-to-understand, comprehensive, and validated headache disorders-specific PROM is warranted.

Pericranial Muscle Stiffness, Pain Thresholds, and Tenderness during a Treatment Cycle of OnabotulinumtoxinA for Chronic Migraine Prevention.

BACKGROUND: Treatment with OnabotulinumtoxinA (BoNT-A) is effective as a preventive treatment for chronic migraine (CM). Preclinical studies suggest that the mechanism of action of BoNT-A in migraine is based on blocking unmyelinated C fibers. We aimed to investigate whether the muscle-relaxing effect of BoNT-A is associated with the preventive mechanism in patients with chronic migraine by measuring the stiffness, pain thresholds, and tenderness of the BoNT-A-applied muscles. METHODS: A total of 22 patients with CM who were already in BoNT-A treatment participated in this longitudinal prospective study. Pericranial muscle stiffness was measured using ultrasound shear wave elastography, which measures the speed of shear waves propagating through the muscle. Pressure pain thresholds (PPT) were obtained via algometry, and muscle tenderness was measured via manual palpation. Measurements were made before BoNT-A injections and six weeks after the treatment. The measurements were performed while the muscles were maximally relaxed. The patients also completed daily diaries on headache and neck pain. RESULTS: No change was observed in muscle stiffness (p = 0.737) or pericranial muscle tenderness (p = 0.400). The PPT over the trapezius muscles increased from 250 kPa before treatment to 304 kPa six weeks after treatment (p = 0.027). No change was observed on the temporalis muscles (p = 0.200) nor the non-dominant index finger (p = 0.067). BoNT-A decreased neck pain (p = 0.008) and headache (p = 0.007). CONCLUSIONS: The findings suggest that BoNT-A leads to the desensitization of cutaneous and muscle nociceptors in the head and neck regions, whereas muscle relaxation might not be an important part of the anti-migraine effect.

Migraine-Related Stigma and Its Relationship to Disability, Interictal Burden, and Quality of Life: Results of the OVERCOME (US) Study

BACKGROUND AND OBJECTIVES: This population-based analysis characterizes the relative frequency of migraine-related stigma and its cross-sectional relationship to migraine outcomes. We hypothesized that migraine-related stigma would be inversely associated with favorable migraine outcomes across headache day categories. METHODS: OVERCOME (US) is a web-based observational study that annually recruited a demographically representative US sample and then identified people with active migraine using a validated migraine diagnostic questionnaire. It also assessed how frequently respondents experienced migraine-related stigma using a novel 12-item questionnaire (Migraine-Related Stigma, MiRS) that contained 2 factors; feeling that others viewed migraine as being used for Secondary Gain (8 items, α = 0.92) and feeling that others were Minimizing disease Burden (4 items, α = 0.86). We defined 5 groups: (1) MiRS-Both (Secondary Gain and Minimizing Burden often/very often; (2) MiRS-SG (Secondary Gain often/very often); (3) MiRS-MB (Minimizing Burden often/very often); (4) MiRS-Rarely/Sometimes; (5) MiRS-Never. Using MiRS group as the independent variable, we modeled its cross-sectional relationship to disability (Migraine Disability Assessment, MIDAS), interictal burden (Migraine Interictal Burden Scale-4), and migraine-specific quality of life (Migraine Specific Quality of Life v2.1 Role Function-Restrictive) while controlling for sociodemographics, clinical features, and monthly headache day categories. RESULTS: Among this population-based sample with active migraine (n = 59,001), mean age was 41.3 years and respondents predominantly identified as female (74.9%) and as White (70.1%). Among respondents, 41.1% reported experiencing, on average, ≥4 monthly headache days and 31.7% experienced migraine-related stigma often/very often; the proportion experiencing migraine-related stigma often/very often increased from 25.5% among those with <4 monthly headache days to 47.5% among those with ≥15 monthly headache days. The risk for increased disability (MIDAS score) was significant for each MiRS group compared with the MiRS-Never group; the risk more than doubled for the MiRS-Both group (rate ratio 2.68, 95% CI 2.56-2.80). For disability, interictal burden, and migraine-specific quality of life, increased migraine-related stigma was associated with increased disease burden across all monthly headache day categories. DISCUSSION: OVERCOME (US) found that 31.7% of people with migraine experienced migraine-related stigma often/very often and was associated with more disability, greater interictal burden, and reduced quality of life.

Telehealth and Virtual Reality Technologies in Chronic Pain Management: A Narrative Review.

PURPOSE OF REVIEW: This review provides medical practitioners with an overview of the present and emergent roles of telehealth and associated virtual reality (VR) applications in chronic pain (CP) management, particularly in the post-COVID-19 healthcare landscape. RECENT FINDINGS: Accumulated evidence points to the efficacy of now well-established telehealth modalities, such as videoconferencing, short messaging service (SMS), and mobile health (mHealth) applications in complementing remote CP care. More recently, and although still in early phases of clinical implementation, a wide range of VR-based interventions have demonstrated potential for improving the asynchronous remote management of CP. Additionally, VR-associated technologies at the leading edge of science and engineering, such as VR-assisted biofeedback, haptic technology, high-definition three-dimensional (HD3D) conferencing, VR-enabled interactions in a Metaverse, and the use of wearable monitoring devices, herald a new era for remote, synchronous patient-physician interactions. These advancements hold the potential to facilitate remote physical examinations, personalized remote care, and innovative interventions such as ultra-realistic biofeedback. Despite the promise of VR-associated technologies, several limitations remain, including the paucity of robust long-term effectiveness data, heterogeneity of reported pain-related outcomes, challenges with scalability and insurance coverage, and demographic-specific barriers to patient acceptability. Future research efforts should be directed toward mitigating these limitations to facilitate the integration of telehealth-associated VR into the conventional management of CP. Despite ongoing barriers to widespread adoption, recent evidence suggests that VR-based interventions hold an increasing potential to complement and enhance the remote delivery of CP care.

Narrow band green light effects on headache, photophobia, sleep, and anxiety among migraine patients: an open-label study conducted online using daily headache diary.

Background: Narrow band green light (NbGL) has been shown to relieve headache in small numbers of subjects but large-scale real-world assessments are lacking. The goal of this prospective, observational, open-label, real world study was to determine whether treatment with NbGL during the ictal phase of migraine, improves patients' perception of their headache, photophobia, anxiety and same-night sleep. Methods: The study was conducted in purchasers of the NbGL Lamp in two phases. In Phase I purchasers of the Lamp completed a survey and were asked to participate in a 6-week diary study. In Phase 2 participants completed daily diaries for 6 weeks. Specifically, they were asked to use their judgement/impression/perception when choosing between headache-improved or headache-unimproved after using the NbGL during acute attacks. Diary outcomes of interest included rates of attacks improve in responders (≥50%), non-responders (<50%), super-responders (≥75%), and super non-responders (<30%). Results: Of 3,875 purchasers of the Lamp for migraine, 698 (18%) agreed to participate, filled out a pre-study survey, and agreed to a 6-week daily headache diary. Complete data were provided by 181 (26%) participants. Using criteria above, 61, 39, 42, and 27% of participants were classified responder, non-responder, super-responder and super non-responder, respectively. Headache improved in 55% of all 3,232 attacks, in 82% of the 1,803 attacks treated by responders, and in 21% of the 1,429 attacks treated by non-responders. Photophobia improved in 53% of all attacks, 68% of the attacks in responders and in 35% of the attacks in non-responders. Anxiety improved in 34% of all attacks, 46% of the responders' attacks, and 18% of the non-responders' attacks. Sleep improved in 49% of all attacks, 59% of the responders' attacks, and 36% of the non-responders' attacks. Conclusion: This open-label real world study suggests that 2 h of treatment with the lamp during migraine attacks is associated with relief of pain and photophobia, reduction in anxiety, and improved sleep. The absence of rigorous diagnosis and a blinded contemporaneous control group limits the rigor of this interpretation. Improvement in photophobia, anxiety and sleep among the responders may be secondary to the improvement in the headache itself. Clinical trial registration: ClinicalTrial.gov (NCT04841083).

Peripherally acting anti-CGRP monoclonal antibodies alter cortical gray matter thickness in migraine patients: A prospective cohort study.

Migraine is underpinned by central nervous system neuroplastic alterations thought to be caused by the repetitive peripheral afferent barrage the brain receives during the headache phase (cortical hyperexcitability). Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) are highly effective migraine preventative treatments. Their ability to alter brain morphometry in treatment-responders vs. non-responders is not well understood. Our aim was to determine the effects of the anti-CGRP-mAb galcanezumab on cortical thickness after 3-month treatment of patients with high-frequency episodic or chronic migraine. High-resolution magnetic resonance imaging was performed pre- and post-treatment in 36 migraine patients. In this group, 19 patients were classified responders (≥50 % reduction in monthly migraine days) and 17 were considered non-responders (<50 % reduction in monthly migraine days). Following cross-sectional processing to analyze the baseline differences in cortical thickness, two-stage longitudinal processing and symmetrized percent change were conducted to investigate treatment-related brain changes. At baseline, no significant differences were found between the responders and non-responders. After 3-month treatment, decreased cortical thickness (compared to baseline) was observed in the responders in regions of the somatosensory cortex, anterior cingulate cortex, medial frontal cortex, superior frontal gyrus, and supramarginal gyrus. Non-responders demonstrated decreased cortical thickness in the left dorsomedial cortex and superior frontal gyrus. We interpret the cortical thinning seen in the responder group as suggesting that reduction in head pain could lead to changes in neural swelling and dendritic complexity and that such changes reflect the recovery process from maladaptive neural activity. This conclusion is further supported by our recent study showing that 3 months after treatment initiation, the incidence of premonitory symptoms and prodromes that are followed by headache decreases but not the incidence of the premonitory symptoms or prodromes themselves (that is, cortical thinning relates to reductions in the nociceptive signals in the responders). We speculate that a much longer recovery period is required to allow the brain to return to a more 'normal' functioning state whereby prodromes and premonitory symptoms no longer occur.

Migraine and subsequent head and neck cancer: A nationwide population-based cohort study.

OBJECTIVES: The association of migraine with the risk of certain cancer has been reported. The aim of this pilot study was to examine the associations between migraine and the onset of head and neck cancers (HNC). MATERIALS AND METHODS: A total of 1755 individuals were identified through a nationwide population-based cohort registry in Taiwan between 2000 and 2013. The primary end point variable was new-onset head and neck cancers in patients with migraine versus non-migraine controls. Cox proportional hazard regression was used to derive the risk of HNC. Subgroup analyses were performed to determine subpopulations at risk of migraine-associated HNC. Sub-outcome analyses were carried out to provide the subtypes of migraine-associated HNC. Propensity score matching was utilized to validate the findings. RESULTS: A total of four patients out of 351 patients with migraine and seven out of 1404 non-migraine controls developed HNC. The incidence of HNC was higher in patients with migraine than that in non-migraine controls (108.93 vs. 48.77 per 100,000 person-years) (adjusted hazard ratio, aHR = 2.908, 95% CI = 0.808-10.469; p = 0.102). The risk of HNC in patients with migraine with aura (aHR = 5.454, 95% CI = 0.948-26.875; p = 0.264) and without aura (aHR = 2.777, 95% CI = 0.755-8.473; p = 0.118) was revealed. The incidence of non-nasopharyngeal HNC secondary to migraine (112.79 per 100,000 person-years) was higher than that of nasopharyngeal cancer secondary to migraine (105.33 per 100,000 person-years). CONCLUSION: A higher incidence of HNC was observed in a small sample of patients with migraine, especially in those with migraine with aura. Migraine-associated HNC included non-nasopharyngeal HNC. Studies with a larger sample are needed to confirm the finding of the high risk of HNC in people with migraine.

Debate: differences and similarities between tension-type headache and migraine.

Tension-type headache (TTH) and migraine are two common primary headaches distinguished by clinical characteristics according to the 3rd edition of the International Classification of Headache Disorders. Migraine is identified by specific features such as being more prevalent in females, being aggravated by physical activity, certain genetic factors, having photophobia, phonophobia, nausea, vomiting, or aura, and responding to specific drugs. Nonetheless, TTH and migraine share some common characteristics, such as onset occurring in the 20 s, and being triggered by psychological factors like stress, moderate pain severity, and mild nausea in chronic TTH. Both conditions involve the trigeminovascular system in their pathophysiology. However, distinguishing between TTH and migraine in clinical practice, research, and epidemiological studies can be challenging, as there is a lack of specific diagnostic tests and biomarkers. Moreover, both conditions may coexist, further complicating the diagnostic process. This review aims to explore the similarities and differences in the pathophysiology, epidemiology, burden and disability, comorbidities, and responses to pharmacological and non-pharmacological treatments of TTH and migraine. The review also discusses future research directions to address the diagnostic challenges and improve the understanding and management of these conditions.

Neck pain and headache: Pathophysiology, treatments and future directions.

INTRODUCTION: Neck pain is a prevalent neurologic and musculoskeletal complaint in the general population and is often associated with primary headache disorders such as migraine and tension-type headache (TTH). A considerable proportion, ranging from 73% to 90%, of people with migraine or TTH also experience neck pain, and there is a positive correlation between headache frequency and neck pain. Furthermore, neck pain has been identified as a risk factor for migraine and TTH. Although the exact underlying mechanisms linking neck pain to migraine and TTH remain uncertain, pain sensitivity appears to play an important role. People with migraine or TTH exhibit lower pressure pain thresholds and higher total tenderness scores compared with healthy controls. PURPOSE: This position paper aims to provide an overview of the current evidence on the relationship between neck pain and comorbid migraine or TTH. It will encompass the clinical presentation, epidemiology, pathophysiology, and management of neck pain in the context of migraine and TTH. IMPLICATIONS: The relationship between neck pain and comorbid migraine or TTH is incompletely understood. In the absence of robust evidence, the management of neck pain in people with migraine or TTH relies mostly on expert opinion. A multidisciplinary approach is usually preferred, involving pharmacologic and non-pharmacologic strategies. Further research is necessary to fully dissect the linkage between neck pain and comorbid migraine or TTH. This includes the development of validated assessment tools, evaluation of treatment effectiveness, and exploration of genetic, imaging, and biochemical markers that might aid in diagnosis and treatment.

Galcanezumab effects on incidence of headache after occurrence of triggers, premonitory symptoms, and aura in responders, non-responders, super-responders, and super non-responders.

BACKGROUND: The goal of this observational, open-label, cohort study was to determine whether prophylactic migraine treatment with galcanezumab, a peripherally acting drug, alters the incidence of premonitory symptoms, and/or occurrence of headache after exposure to triggers or aura episodes in treatment-responders (≥ 50% reduction in monthly migraine days [MMD]), super-responders (≥ 70%), non-responders (< 50%) and super non-responders (< 30%). METHODS: Participants were administered electronic daily headache diaries to document migraine days and associated symptoms one month before and during the three months of treatment. Questionnaires were used to identify conscious prodromal and trigger events that were followed by headache prior to vs. after 3 months of treatment. RESULTS: After 3 months of galcanezumab treatment, (a) the incidence of premonitory symptoms that were followed by headache decreased by 48% in the 27 responders vs. 28% in the 19 non-responders, and by 50% in the 11 super-responders vs. 12% in the 8 super non-responders; (b) the incidence of visual and sensory aura that were followed by headache was reduced in responders, non-responders, and super-responders, but not in super non-responders; (c) the number of triggers followed by headache decreased by 38% in responders vs. 13% in non-responders, and by 31% in super-responders vs. 4% in super non-responders; and (d) some premonitory symptoms (e.g., cognitive impairment, irritability, fatigue) and triggers (e.g., stress, sleeping too little, bright light, aura) were followed by headache only in super non-responders. CONCLUSIONS: Mechanistically, these findings suggest that even a mild decrease in migraine frequency is sufficient to partially reverse the excitability and responsivity of neurons involved in the generation of certain triggers and potentially premonitory symptoms of migraine. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04271202. Registration date: February 10, 2020.

Psychotherapy Treatment of Generalized Anxiety Disorder Improves When Conducted Under Narrow Band Green Light.

Background and Goals: Psychotherapy is one of the most highly recommended and practiced approaches for the treatment of Generalized anxiety disorder (GAD). Commonly defined as excessive worry that is uncontrollable, GAD is one of the most prevalent psychiatric disorders. Anxiety is also one of the most common associated symptoms of migraine. Exposing migraineurs to narrow band green light (nbGL) reduces their anxiety and anxiety-like physiological symptoms such as throat tightness, shortness of breath, and palpitations. Here, we sought to determine whether the reduced anxiety described by our patients was secondary to the reduced headache or independent of it. The goal of the current study was therefore to determine whether exposure to nbGL can reduce anxiety in GAD patients who are not migraineurs. Patients and Methods: Included in this open-label, proof-of-concept, prospective study were 13 patients diagnosed with moderate-to-severe GAD. We used the State-Trait Anxiety Inventory Questionnaire (Y-1) to compare anxiety level before and after each 45-minutes psychotherapy session conducted in white light (WL) (intensity = 100±5 candela/m2) vs nbGL (wavelength = 520±10nm (peak ± range), intensity = 10±5 candela/m2). Results: Here, we show that psychotherapy sessions conducted under nbGL increase positive and decrease negative feelings significantly more than psychotherapy sessions conducted under regular room light (χ2 = 0.0001). Conclusion: The findings provide initial evidence for the potential benefit of conducting psychotherapy sessions for patients suffering GAD under nbGL conditions. Given the absence of side effects or risks, we suggest that illuminating rooms used in psychotherapy with nbGL be considered an add-on to the treatment of GAD.

Medication overuse headache.

Medication overuse headache (MOH) is a secondary headache disorder attributed to overuse of acute headache medications by a person with an underlying headache disorder, usually migraine or tension-type headache. MOH is common among individuals with 15 or more headache days per month. Although MOH is associated with substantial disability and reductions in quality of life, this condition is often under-recognized. As MOH is both preventable and treatable, it warrants greater attention and awareness. The diagnosis of MOH is based on the history and an unremarkable neurological examination, and is made according to the diagnostic criteria of the International Classification of Headache Disorders third edition (ICHD-3). Pathophysiological mechanisms of MOH include altered descending pain modulation, central sensitization and biobehavioural factors. Treatment of MOH includes the use of headache preventive therapies, but essential to success is eliminating the cause, by reducing the frequency of use of acute headache medication, and perhaps withdrawing the overused medication altogether. Appropriate treatment is usually highly effective, leading to reduced headache burden and acute medication consumption.