HeadachePub Date : 2024-12-20DOI: 10.1111/head.14889
Ida Stisen Fogh-Andersen, Anja Sofie Petersen, Rigmor Højland Jensen, Jens Christian Hedemann Sørensen, Kaare Meier
{"title":"Transcutaneous electrical nerve stimulation of the occipital nerves as treatment for chronic cluster headache.","authors":"Ida Stisen Fogh-Andersen, Anja Sofie Petersen, Rigmor Højland Jensen, Jens Christian Hedemann Sørensen, Kaare Meier","doi":"10.1111/head.14889","DOIUrl":"https://doi.org/10.1111/head.14889","url":null,"abstract":"<p><strong>Background: </strong>Chronic cluster headache (CCH) is an excruciatingly painful condition that can be difficult to treat sufficiently with the available medical treatment options. The greater occipital nerves (GON) are of major interest in treating CCH, and various invasive treatment modalities, such as stimulating or blocking the nerves, have been applied. Because the terminal segment of the GON has a superficial course, the nerve is also accessible for non-invasive transcutaneous stimulation. Transcutaneous electrical nerve stimulation (TENS) has been suggested as a treatment for different chronic headaches, but evidence of the efficacy in patients with CCH is scarce. Additionally, no consensus exists on the optimal placement of the transcutaneous stimulation electrodes or the treatment usage pattern.</p><p><strong>Methods: </strong>In this explorative open-label clinical study, 36 patients with CCH were treated with TENS of the GON for 8-12 consecutive weeks between August 2021 and October 2023 as a separate part of the study protocol for a trial on stimulation of the GON (Clinicaltrials.gov identifier: NCT05023460). After a baseline period, TENS was used primarily as a preventive treatment, stimulating for 30 min twice daily at a minimum. The primary outcome was a change in attack frequency and safety with TENS treatment. Secondary outcomes were change in attack duration and pain intensity on the numeric rating scale, abortive treatments, and the Patient Global Impression of Change (PGIC) with TENS treatment. The change in attack frequency, duration, pain intensity, and use of abortive treatment was analyzed by comparing the baseline data with 4-weekly data from TENS treatment. The study aimed to systematically investigate the effect of TENS of the GON as a preventive treatment for CCH.</p><p><strong>Results: </strong>Weekly attack frequency decreased from a median of 15.7 (95% confidence interval [CI] 11.2-22.1) at baseline to 11.0 (95% CI 7.4-16.4) with TENS. In all, 13 of the 36 (36%) patients had a minimum 30% reduction in attack frequency. In the group of 30% responders, the number of weekly attacks decreased from 15.8 (95% CI 9.8-24.5) at baseline to 5.8 (95% CI 3.3-10.5) attacks with TENS. Five patients became entirely or nearly attack-free. For the entire cohort, attack duration and pain intensity were also significantly reduced with TENS. The use of oxygen was reduced by 42%, and triptan injections decreased by 55%. Overall, 15 (42%) patients reported a clinically important improvement with TENS treatment, rated on the PGIC scale. The 100 Hz stimulation programs were preferred over 10 Hz. No serious adverse events were registered.</p><p><strong>Conclusion: </strong>Transcutaneous electrical nerve stimulation of the GON significantly reduced the frequency, intensity, and duration of weekly headache attacks in patients with severe CCH. Not all patients benefitted from TENS, but the treatment responders had a substantial imp","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-12-11DOI: 10.1111/head.14885
Tzu-Hsuan Su, Jou-Kou Wang, Ping-Hung Kuo, Shu-Hui Chang, Lih-Chu Chiou, Wang-Tso Lee, Pi-Chuan Fan
{"title":"The pathogenic role of calcitonin gene-related peptide and predictors of new-onset migraine and long-term outcomes after transcatheter atrial septal defect closure.","authors":"Tzu-Hsuan Su, Jou-Kou Wang, Ping-Hung Kuo, Shu-Hui Chang, Lih-Chu Chiou, Wang-Tso Lee, Pi-Chuan Fan","doi":"10.1111/head.14885","DOIUrl":"https://doi.org/10.1111/head.14885","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate factors associated with new-onset migraine (NOM) after transcatheter atrial septal defect (ASD) closure and predictors of unremitting NOM. The pathogenic role of migraine biomarkers such as calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were also assessed.</p><p><strong>Background: </strong>New-onset migraine has been observed after transcatheter ASD closure. Neuropeptides like CGRP and NPY stored both in the brain and heart are implicated in migraine pathophysiology. The potential role of those migraine biomarkers in NOM, as well as the risk factors and long-term outcomes of NOM, remain largely unknown.</p><p><strong>Methods: </strong>We enrolled patients without previous migraine who underwent successful transcatheter ASD closure between 2001 and 2013. The parameters of transthoracic echocardiography, and plasma CGRP and NPY levels measured by enzyme-linked immunosorbent assay, were collected prospectively before and after ASD closure, and compared between patients with NOM and those without. Predictors of NOM were assessed. Telephone interviews were performed in 2022 to assess migraine status. Clinical and procedural characteristics were compared between patients with unremitting migraine and those with transient migraine that remitted within 1 year.</p><p><strong>Results: </strong>Of the 212 patients (median age, 21 years; 75.9% female), 43 (20.3%) had NOM. Potential predictors of NOM included a young age (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.96-0.99; p = 0.040), large ASD size (aOR 1.07, 95% CI 1.01-1.14; p = 0.022), and transient residual shunting after closure (aOR 2.78, 95% CI 1.05-7.36; p = 0.039). Post-closure plasma CGRP levels, but not NPY levels, were significantly higher than pre-closure levels (47.9 vs. 38.0 pg/mL, p = 0.023) among patients with NOM. Of the 27 patients with migraine who reported their migraine status at a median 14-year follow-up, 13 (48.1%) had unremitting migraine. Patients with unremitting migraine were more likely to have a smaller device-to-ASD size ratio (1.21 vs. 1.33, p = 0.039) and a larger pulmonary flow-to-systemic flow ratio (2.9 vs. 2.3, p = 0.012) than those with transient migraine.</p><p><strong>Conclusions: </strong>Calcitonin gene-related peptide may play a pathogenic role in NOM after transcatheter ASD closure. A young age, large ASD size, and transient residual shunting potentially predict migraine occurrence after ASD closure. NOM not reaching remission for years may result from a significant shunt before closure.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-12-10DOI: 10.1111/head.14881
Ming-Gang Deng, Xiuxiu Zhou, Fang Liu, Kai Wang, Lingli Luo, Min-Jie Zhang, Qianqian Feng, Jiewei Liu
{"title":"Investigating the causal and genetic relationship between migraine and Parkinson's disease.","authors":"Ming-Gang Deng, Xiuxiu Zhou, Fang Liu, Kai Wang, Lingli Luo, Min-Jie Zhang, Qianqian Feng, Jiewei Liu","doi":"10.1111/head.14881","DOIUrl":"https://doi.org/10.1111/head.14881","url":null,"abstract":"<p><strong>Objective: </strong>The relationship between migraine and Parkinson's disease (PD) remains controversial. We aimed to investigate the causal and genetic associations between migraine and PD.</p><p><strong>Methods: </strong>Genetic data for migraine [any migraine (AM), migraine without aura (MO), and migraine with aura (MA)] and PD were sourced from the latest genome-wide meta-analyses conducted by the International Headache Genetics Consortium and the International Parkinson's Disease Genomics Consortium, respectively. Various analyses were performed to evaluate the potential causal associations and explore genetic correlations between these conditions.</p><p><strong>Results: </strong>The analyses indicated that AM (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.91-1.14; p = 0.785), MO (OR 0.94, 95% CI 0.84-1.07; p = 0.358), and MA (OR 1.01, 95% CI 0.95-1.06; p = 0.846) were not significantly associated with the risk of PD. Similarly, reverse analyses also demonstrated no significant causality between PD and the risks of migraine or its subtypes. After adjusting for coronary heart disease, AM (OR 0.99, 95% CI 0.90-1.10; p = 0.897), MO (OR 0.94, 95% CI 0.86-1.03; p = 0.207), and MA (OR 1.00, 95% CI 0.93-1.07; p = 0.902) remained unrelated to PD risk. Likewise, PD was found to be unassociated with AM (OR 0.96, 95% CI 0.92-1.02; p = 0.168), MO (OR 0.95, 95% CI 0.86-1.05; p = 0.287), and MA (OR 1.02, 95% CI 0.93-1.13; p = 0.669). These null findings persisted even when adjusting for hypertension. Apart from above causal inference results, no significant genetic correlation was found between AM (r<sub>g</sub> = -0.06, p = 0.127), MA (r<sub>g</sub> = -0.05, p = 0.516), or MO (r<sub>g</sub> = -0.06, p = 0.492) and PD, and no correlations were observed across specific genomic regions. Additionally, no shared heritability was observed between PD and migraine, or its subtypes, in tissue expression.</p><p><strong>Conclusion: </strong>Our study suggests that there is no significant causal association or genetic correlation between migraine and PD from a genetic perspective.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-12-10DOI: 10.1111/head.14880
Gina M Dumkrieger, Chia-Chun Chiang, Pengfei Zhang, Mia T Minen, Fred Cohen, Jennifer A Hranilovich
{"title":"Artificial intelligence terminology, methodology, and critical appraisal: A primer for headache clinicians and researchers.","authors":"Gina M Dumkrieger, Chia-Chun Chiang, Pengfei Zhang, Mia T Minen, Fred Cohen, Jennifer A Hranilovich","doi":"10.1111/head.14880","DOIUrl":"https://doi.org/10.1111/head.14880","url":null,"abstract":"<p><strong>Objective: </strong>The goal is to provide an overview of artificial intelligence (AI) and machine learning (ML) methodology and appraisal tailored to clinicians and researchers in the headache field to facilitate interdisciplinary communications and research.</p><p><strong>Background: </strong>The application of AI to the study of headache and other healthcare challenges is growing rapidly. It is critical that these findings be accurately interpreted by headache specialists, but this can be difficult for non-AI specialists.</p><p><strong>Methods: </strong>This paper is a narrative review of the fundamentals required to understand ML/AI headache research. Using guidance from key leaders in the field of headache medicine and AI, important references were reviewed and cited to provide a comprehensive overview of the terminology, methodology, applications, pitfalls, and bias of AI.</p><p><strong>Results: </strong>We review how AI models are created, common model types, methods for evaluation, and examples of their application to headache medicine. We also highlight potential pitfalls relevant when consuming AI research, and discuss ethical issues of bias, privacy and abuse generated by AI. Additionally, we highlight recent related research from across headache-related applications.</p><p><strong>Conclusion: </strong>Many promising current and future applications of ML and AI exist in the field of headache medicine. Understanding the fundamentals of AI will allow readers to understand and critically appraise AI-related research findings in their proper context. This paper will increase the reader's comfort in consuming AI/ML-based research and will prepare them to think critically about related research developments.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-12-03DOI: 10.1111/head.14879
Antonio Sánchez-Soblechero, Elisa Luque-Buzo, Alberto Lozano-Ros, Amparo Guillem
{"title":"Secondary nummular headache: Are they more common than we thought?","authors":"Antonio Sánchez-Soblechero, Elisa Luque-Buzo, Alberto Lozano-Ros, Amparo Guillem","doi":"10.1111/head.14879","DOIUrl":"https://doi.org/10.1111/head.14879","url":null,"abstract":"<p><strong>Objective: </strong>To provide a detailed description of symptomatic nummular headache (NH) and to compare them with primary cases in a large series.</p><p><strong>Background: </strong>While most published cases of NH are primary headache, some 'secondary' cases have been reported since its initial description. It remains uncertain why identical clinical presentations can result from primary and 'secondary' etiologies. Thanks to the possibility of offering specific treatments for symptomatic NH, it is crucial to be able to distinguish between them effectively.</p><p><strong>Methods: </strong>This monocentric retrospective study included a cohort of patients diagnosed with NH according to the International Classification of Headache Disorders, Second (ICHD-2) and Third Editions (ICHD-3), and the Pareja et al. first description, over a 20-year period (2002 to 2022). Established ICHD-3 diagnoses were used for each symptomatic case. Causality was attributed if (i) headache had developed in close temporal relation to other symptoms and/or clinical signs, or had led to its diagnosis, and (ii) either the headache had significantly worsened in parallel with other symptoms or clinical or radiological signs of worsening of the underlying disease, or the headache had resolved after treatment of the presumed causative disorder. Symptomatic NH were divided into two groups: \"definite\" or \"probable.\" A comparison between the \"primary\" and \"secondary\" groups is presented.</p><p><strong>Results: </strong>A total of 131 patients (88, 67.2% females) were included in the study. The median (interquartile range) age at onset of symptoms was 52 (36-63.2) years. In all, 34 patients (25.9%) were diagnosed as symptomatic NH (nine post-traumatic, seven attributed to a disorder of the cranial bones, six due to intracranial neoplasia, five attributed to arachnoid cysts, three attributed to vascular malformations, two due to cutaneous disturbances, and two attributed to hypertension). Eight patients were classified as \"definite symptomatic NH\" and 26 as \"probable symptomatic NH.\" Neuroimaging was performed in all cases. Any previous headache (52.9% vs. 29.9%; p = 0.016), a remote head trauma (26.5% vs. 9.3%; p = 0.015), and a longer disease duration (18 vs. 12 months; p = 0.036) were more likely in patients with symptomatic NH. Preventive treatment was more effective (achieved >50% reduction in monthly headache days) in patients with symptomatic NH (72.2% vs. 30.3%; p = 0.002) due to a cause-specific treatment.</p><p><strong>Conclusion: </strong>Symptomatic NH are frequent. The presence of any previous headache or remote head trauma may suggest a diagnosis of symptomatic NH; however, as certain NH might be an early symptom of intracranial mass lesions, neuroimaging is necessary. Finding the cause of NH is essential to offer the most effective targeted treatment.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-12-03DOI: 10.1111/head.14873
Kiersten I Mangold, Tapasya Katta, Vu Do, R Davis Moore, Chen Lin, X Michelle Androulakis
{"title":"White matter hyperintensities and headache in United States military veterans with mild traumatic brain injury.","authors":"Kiersten I Mangold, Tapasya Katta, Vu Do, R Davis Moore, Chen Lin, X Michelle Androulakis","doi":"10.1111/head.14873","DOIUrl":"https://doi.org/10.1111/head.14873","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to examine the association between white matter hyperintensities and migraine-like headache in United States military veterans with a history of mild traumatic brain injury.</p><p><strong>Background: </strong>White matter hyperintensities on magnetic resonance imaging (MRI) may be associated with migraine; however, little is currently known about the relationship between white matter hyperintensities and headache following mild traumatic brain injury in military veterans.</p><p><strong>Methods: </strong>This cross-sectional study consisted of a retrospective chart review of veterans from a Southeastern Department of Veterans Affairs polytrauma clinic who had a verified history of mild traumatic brain injury. Participants were included if they had undergone an MRI of the brain. Images were reviewed for the presence and severity of periventricular and deep white matter hyperintensities. Headache and migraine-like headache were defined based on responses from the Neurobehavioral Symptom Inventory.</p><p><strong>Results: </strong>This cohort included 83 veterans, mostly consisting of males (78/83 [94%]) with a median (interquartile range [IQR]) age of 36 (13) years, who were a median (IQR) of 9 (8) years since their most recent mild traumatic brain injury. Most of the veterans reported experiencing migraine-like headache (67/83 [81%]). Periventricular white matter hyperintensities were identified on MRI among 35% (29/83) of the cohort, and deep white matter hyperintensities were identified on MRI of 25% (21/83) of the cohort. There was no association between the odds of displaying white matter hyperintensities and the presence of migraine-like headache (periventricular: unadjusted odds ratio [OR] 2.75, 95% confidence interval [CI] 0.71-10.6; deep white matter: OR 0.69, 95% CI 0.208-2.29; all p > 0.05), nor headache severity (periventricular: moderate headache OR 2.92, 95% CI 0.67-12.8; severe headache OR 3.11, 95% CI 0.77-12.6; deep white matter: moderate headache OR 1.44, 95% CI 0.358-5.8; severe headache OR 0.94, 95% CI 0.246-3.62; all p > 0.05).</p><p><strong>Conclusions: </strong>Our findings suggest that neither migraine-like headache nor severity of headache is associated with increased prevalence of white matter hyperintensities in veterans with a history of mild traumatic brain injury.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-11-27DOI: 10.1111/head.14860
Gregory A Panza, Michael A L Johnson, Deena E Kuruvilla
{"title":"A post hoc analysis of migraine-associated symptoms from the phase 3 randomized, double-blind, sham-controlled Trial of External trigeminal nerve stimulation for the Acute treatment of Migraine (TEAM) study.","authors":"Gregory A Panza, Michael A L Johnson, Deena E Kuruvilla","doi":"10.1111/head.14860","DOIUrl":"https://doi.org/10.1111/head.14860","url":null,"abstract":"<p><strong>Background: </strong>The Trial of External trigeminal nerve stimulation (eTNS) for the Acute treatment of Migraine (TEAM) study demonstrated that eTNS use during active migraine resulted in significantly higher rates of resolution of migraine-associated most bothersome symptom (MBS) compared to sham. However, no previous studies have examined the association between pretreatment MBS subtype and efficacy of eTNS treatment for active migraine.</p><p><strong>Objective: </strong>We conducted a post hoc analysis examining efficacy of eTNS for different pretreatment MBS subtypes using TEAM study data.</p><p><strong>Methods: </strong>Pretreatment MBS subtypes included photophobia (n = 345), nausea (n = 109), phonophobia (n = 73), and vomiting (n = 11). We examined MBS sub-group × treatment group (verum n = 259; sham n = 279) interaction for each post-treatment outcome to explore differential effects conditional on the total sample. We further explored direct, between treatment group comparisons for each MBS subtype, as well as compared treatment outcomes among all MBS subtypes within the sham, verum, and total sample. Finally, clinical heterogeneity of treatment effect (HTE) was assessed using a 1% absolute treatment effect difference as the clinically important threshold.</p><p><strong>Results: </strong>Significant sub-group × treatment interactions were found for resolution of MBS at 2 h (p = 0.008), pain relief at 2 h (p = 0.001), rescue medication between 2 and 24 h (p = 0.012), sustained pain freedom at 24 h (p = 0.033), and sustained pain relief at 24 h (p = 0.003). Significant sub-group × treatment interactions were not found for pain freedom at 2 h (p = 0.054) or absence of all symptoms at 2 h (p = 0.265). Between treatment group comparisons indicated that pain freedom after 2 h of eTNS was not significantly different between the verum and sham groups for any pretreatment MBS. The verum group had a significantly greater proportion of participants who had resolution of nausea MBS after 2 h of treatment compared to sham (37/55 [67.3%] vs. 25/54 [46.3%], respectively; p = 0.028) and resolution of photophobia MBS compared to sham (85/162 [52.5] vs. 71/183 [38.8%], respectively; p = 0.011). There were no significant differences between treatment groups for phonophobia or vomiting. Pain freedom after 2 h of eTNS was not significantly different among pretreatment MBS groups. Within the sham group and total sample, a greater proportion of participants who had vomiting MBS had resolution of their MBS compared to any other pretreatment MBS (p < 0.05 after Bonferroni adjustment). A greater proportion of participants with nausea MBS used rescue medications between 2 and 24 h after eTNS compared to participants with photophobia or phonophobia MBS within the verum and total sample (p < 0.05 after Bonferroni adjustment). No statistical differences were found among MBS groups for any other treatment outcomes. Clinically important HTE was present in v","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-11-27DOI: 10.1111/head.14877
Richard B Lipton, John A Kollins, Detlef Albrecht
{"title":"Relationship of dihydroergotamine pharmacokinetics, clinical efficacy, and nausea-A narrative review.","authors":"Richard B Lipton, John A Kollins, Detlef Albrecht","doi":"10.1111/head.14877","DOIUrl":"https://doi.org/10.1111/head.14877","url":null,"abstract":"<p><strong>Objective: </strong>To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.</p><p><strong>Background: </strong>Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.</p><p><strong>Methods: </strong>A literature search identified RCTs evaluating the efficacy (2-h pain relief [2hPR]) of different DHE dosage forms. The PK profiles for these DHE dosage forms were determined from published literature. Univariate regression analyses were performed to determine the PK parameters that best predicted 2hPR across DHE dosage forms. The relationship between maximum plasma concentration (C<sub>max</sub>) and nausea incidence for various dosage forms was determined from published Phase 1 trials.</p><p><strong>Results: </strong>The literature search identified nine RCTs with DHE dosage forms that reported 2hPR: DHE liquid nasal spray (four studies), DHE administered subcutaneously (three), and DHE administered via oral pulmonary inhalation (two). The DHE PK parameters that best predicted 2hPR rates were C<sub>max</sub> and area under the curve from time zero to 0.5 h post-dose (AUC<sub>0-0.5h</sub>) (R<sup>2</sup> = 0.59 for each). Across Phase 1 trials, nausea incidence was minimal when C<sub>max</sub> was <2500 pg/mL but increased in a log-linear manner when C<sub>max</sub> exceeded ~2500 pg/mL.</p><p><strong>Conclusions: </strong>The maximum concentration and AUC over the first 30 min following DHE administration were associated with increasing rates of 2hPR and a C<sub>max</sub> below ~2500 pg/mL was associated with low incidences of nausea. We suggest that this may be an optimal profile for a DHE delivery form. Further research to test this hypothesis is warranted.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HeadachePub Date : 2024-11-27DOI: 10.1111/head.14875
Juan Ángel Aibar-Durán, Nerea González, Rosa M Mirapeix, Noemi Morollón Sánchez-Mateos, Clara Roig Arsequell, Maria Borrell Pichot, Robert Belvís Nieto, Gemma Piella Fenoy, Cristian de Quintana Schmidt, Fernando Muñoz Hernandez, Fernando Seijoo Fernández, Rodrigo Rodríguez Rodríguez
{"title":"Deep brain stimulation for chronic refractory cluster headache: A case series about long-term outcomes and connectivity analysis.","authors":"Juan Ángel Aibar-Durán, Nerea González, Rosa M Mirapeix, Noemi Morollón Sánchez-Mateos, Clara Roig Arsequell, Maria Borrell Pichot, Robert Belvís Nieto, Gemma Piella Fenoy, Cristian de Quintana Schmidt, Fernando Muñoz Hernandez, Fernando Seijoo Fernández, Rodrigo Rodríguez Rodríguez","doi":"10.1111/head.14875","DOIUrl":"https://doi.org/10.1111/head.14875","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to provide long-term clinical results-including \"sweet spot\" identification and connectomic imaging analysis-in a series of patients treated with deep brain stimulation for refractory chronic cluster headache.</p><p><strong>Background: </strong>Deep brain stimulation is a relatively recent indication for the treatment of refractory chronic cluster headache. This indication has generated substantial debate in recent years due to uncertainty surrounding the mechanism of action and the lack of long-term efficacy data.</p><p><strong>Methods: </strong>Case retrospective series of adult patients diagnosed with refractory chronic cluster headache and treated with deep brain stimulation. Demographic and clinical data were registered preoperatively and at 3, 6, 12, and 24 months. The primary endpoint was reduction in headache load, a composite score of frequency, severity, and duration of each attack. Imaging analyses (sweet spot and connectomic analyses) were performed to identify the brain regions most closely correlated with the reduction in headache load and to identify the structural networks involved. Treatment response was categorized according to the reduction in headache load, as follows: poor (<30% reduction), partial (30-50%), or high (>50%).</p><p><strong>Results: </strong>A total of 14 patients were included, with a mean (standard deviation [SD]) age of 42.4 (10.7) years and mean (SD) headache duration of 8.0 (5.8) years. Headache load scores decreased significantly from baseline to Month 24: mean (SD) 424.2 (325.9) versus 135.9 (155.7) (p = 0.001). In most patients (eight patients [58.0%]), headache load scores decreased by 50% after treatment. The other six patients showed either a partial (three [21.0%]) or poor (three [21.0%]) response. The optimized sweet spot was the lateral ventral tegmental area ((Montreal Neurological Institute) MNI coordinates of the center of mass: x = ± 9.0 mm, y = -10.6 mm, z = -3.5 mm). The connectomic analysis pointed to the probable implication of corticorubral tracts.</p><p><strong>Conclusion: </strong>These findings suggest that a substantial proportion of patients with refractory chronic cluster headache obtain significant long-term clinical benefits from deep brain stimulation. Good responders were characterized by a robust improvement in headache load within 3-6 months after surgery. The lateral ventral tegmental area was identified as the best target for this indication, with the likely participation of corticorubral tracts.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}