New daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients. This was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks. Fifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point’s reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively. rTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms. CTRI/2023/05/053247.
{"title":"Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study","authors":"M.M. Bharath, Vimal Kumar Paliwal, Swansu Batra, Prabhakar Mishra, Naina Mishra, Romil Saini","doi":"10.1186/s10194-024-01866-4","DOIUrl":"https://doi.org/10.1186/s10194-024-01866-4","url":null,"abstract":"New daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients. This was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks. Fifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point’s reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively. rTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms. CTRI/2023/05/053247.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1186/s10194-024-01854-8
Ana Matoso, Ana R. Fouto, Inês Esteves, Amparo Ruiz-Tagle, Gina Caetano, Nuno A. da Silva, Pedro Vilela, Raquel Gil-Gouveia, Rita G. Nunes, Patrícia Figueiredo
The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.
{"title":"Involvement of the cerebellum in structural connectivity enhancement in episodic migraine","authors":"Ana Matoso, Ana R. Fouto, Inês Esteves, Amparo Ruiz-Tagle, Gina Caetano, Nuno A. da Silva, Pedro Vilela, Raquel Gil-Gouveia, Rita G. Nunes, Patrícia Figueiredo","doi":"10.1186/s10194-024-01854-8","DOIUrl":"https://doi.org/10.1186/s10194-024-01854-8","url":null,"abstract":"The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1186/s10194-024-01855-7
Andrea M. Harriott, Melih Kaya, Cenk Ayata
Migraine is among the most prevalent and burdensome neurological disorders in the United States based on disability-adjusted life years. Cortical spreading depolarization (SD) is the most likely electrophysiological cause of migraine aura and may be linked to trigeminal nociception. We previously demonstrated, using a minimally invasive optogenetic approach of SD induction (opto-SD), that opto-SD triggers acute periorbital mechanical allodynia that is reversed by 5HT1B/1D receptor agonists, supporting SD-induced activation of migraine-relevant trigeminal pain pathways in mice. Recent data highlight hypothalamic neural circuits in migraine, and SD may activate hypothalamic neurons. Furthermore, neuroanatomical, electrophysiological, and behavioral data suggest a homeostatic analgesic function of hypothalamic neuropeptide hormone, oxytocin. We, therefore, examined the role of hypothalamic paraventricular nucleus (PVN) and oxytocinergic (OXT) signaling in opto-SD-induced trigeminal pain behavior. We induced a single opto-SD in adult male and female Thy1-ChR2-YFP transgenic mice and quantified fos immunolabeling in the PVN and supraoptic nucleus (SON) compared with sham controls. Oxytocin expression was also measured in fos-positive neurons in the PVN. Periorbital mechanical allodynia was tested after treatment with selective OXT receptor antagonist L-368,899 (5 to 25 mg/kg i.p.) or vehicle at 1, 2, and 4 h after opto-SD or sham stimulation using von Frey monofilaments. Opto-SD significantly increased the number of fos immunoreactive cells in the PVN and SON as compared to sham stimulation (p < 0.001, p = 0.018, respectively). A subpopulation of fos-positive neurons also stained positive for oxytocin. Opto-SD evoked periorbital mechanical allodynia 1 h after SD (p = 0.001 vs. sham), which recovered quickly within 2 h (p = 0.638). OXT receptor antagonist L-368,899 dose-dependently prolonged SD-induced periorbital allodynia (p < 0.001). L-368,899 did not affect mechanical thresholds in the absence of opto-SD. These data support an SD-induced activation of PVN neurons and a role for endogenous OXT in alleviating acute SD-induced trigeminal allodynia by shortening its duration.
{"title":"Oxytocin shortens spreading depolarization-induced periorbital allodynia","authors":"Andrea M. Harriott, Melih Kaya, Cenk Ayata","doi":"10.1186/s10194-024-01855-7","DOIUrl":"https://doi.org/10.1186/s10194-024-01855-7","url":null,"abstract":"Migraine is among the most prevalent and burdensome neurological disorders in the United States based on disability-adjusted life years. Cortical spreading depolarization (SD) is the most likely electrophysiological cause of migraine aura and may be linked to trigeminal nociception. We previously demonstrated, using a minimally invasive optogenetic approach of SD induction (opto-SD), that opto-SD triggers acute periorbital mechanical allodynia that is reversed by 5HT1B/1D receptor agonists, supporting SD-induced activation of migraine-relevant trigeminal pain pathways in mice. Recent data highlight hypothalamic neural circuits in migraine, and SD may activate hypothalamic neurons. Furthermore, neuroanatomical, electrophysiological, and behavioral data suggest a homeostatic analgesic function of hypothalamic neuropeptide hormone, oxytocin. We, therefore, examined the role of hypothalamic paraventricular nucleus (PVN) and oxytocinergic (OXT) signaling in opto-SD-induced trigeminal pain behavior. We induced a single opto-SD in adult male and female Thy1-ChR2-YFP transgenic mice and quantified fos immunolabeling in the PVN and supraoptic nucleus (SON) compared with sham controls. Oxytocin expression was also measured in fos-positive neurons in the PVN. Periorbital mechanical allodynia was tested after treatment with selective OXT receptor antagonist L-368,899 (5 to 25 mg/kg i.p.) or vehicle at 1, 2, and 4 h after opto-SD or sham stimulation using von Frey monofilaments. Opto-SD significantly increased the number of fos immunoreactive cells in the PVN and SON as compared to sham stimulation (p < 0.001, p = 0.018, respectively). A subpopulation of fos-positive neurons also stained positive for oxytocin. Opto-SD evoked periorbital mechanical allodynia 1 h after SD (p = 0.001 vs. sham), which recovered quickly within 2 h (p = 0.638). OXT receptor antagonist L-368,899 dose-dependently prolonged SD-induced periorbital allodynia (p < 0.001). L-368,899 did not affect mechanical thresholds in the absence of opto-SD. These data support an SD-induced activation of PVN neurons and a role for endogenous OXT in alleviating acute SD-induced trigeminal allodynia by shortening its duration.\u0000","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1186/s10194-024-01865-5
Federico Cagnazzo, Max Villain, Liesjet EH van Dokkum, Răzvan Alexandru Radu, Riccardo Morganti, Gregory Gascou, Cyril Dargazanli, Pierre-Henri Lefevre, Emmanuelle Le Bars, Gaetano Risi, Nicola Marchi, Anne Ducros, Vincent Costalat
Idiopathic intracranial hypertension (IIH) is a cause of chronic headaches that are probably driven by raised intracranial pressure (ICP). Cerebral venous sinus pressure is thought to play a role in the underlying pathology, but its relation with intracranial pressure requires further investigation. We aimed to evaluate the concordance between lumbar puncture opening pressure (LPOP) as indicator of the ICP and cerebral venous sinus pressure in patients investigated for IIH. In this case-series replication study, all patients with IIH suspicion and who underwent cerebral venous sinus pressure measurement followed immediately by LP opening pressure (LPOP) measurement were retrospectively included. Pearson’s correlation and measurement agreement (Bland-Altman plots) between venous pressure and LPOP were analyzed. 52 consecutive patients (46 women; median age, 31 years [IQR = 25–42]) were included. The mean pressure in the superior sagittal sinus (SSS) and in the torcular were 20.9mmHg (SD ± 7.3) and 20.8 mmHg (SD ± 6.8), respectively. The mean LPOP was 22mmHg (SD ± 6.4). Pressure measured in the transverse venous sinus, the torcular, and the SSS correlated with LPOP (p < 0.001). Bland-Altman plots showed that torcular pressure strongly agreed with LPOP (mean difference of 1.7mmHg). The limit of agreement (LOA) (mean difference ± 1.96SD) contained 98.1% of the differences between the two methods, confirming the concordance between the two measures. Torcular pressure and LPOP were consistent in patients with a trans-stenotic pressure gradient ≥ or < to 8 mmHg (mean difference: 1mmHg and 2.4mmHg, respectively), and for those with a LP OP ≥ or < to 18mmHg (mean difference: 1.8mmHg and 1.95mmHg, respectively). In patients investigated for IIH, the ICP measured at the LP is correlated and concordant with the torcular pressure. These results confirm previous findings and further corroborate the hypothesis that cerebral venous system plays a major role in CSF dynamics and ICP.
{"title":"Concordance between venous sinus pressure and intracranial pressure in patients investigated for idiopathic intracranial hypertension","authors":"Federico Cagnazzo, Max Villain, Liesjet EH van Dokkum, Răzvan Alexandru Radu, Riccardo Morganti, Gregory Gascou, Cyril Dargazanli, Pierre-Henri Lefevre, Emmanuelle Le Bars, Gaetano Risi, Nicola Marchi, Anne Ducros, Vincent Costalat","doi":"10.1186/s10194-024-01865-5","DOIUrl":"https://doi.org/10.1186/s10194-024-01865-5","url":null,"abstract":"Idiopathic intracranial hypertension (IIH) is a cause of chronic headaches that are probably driven by raised intracranial pressure (ICP). Cerebral venous sinus pressure is thought to play a role in the underlying pathology, but its relation with intracranial pressure requires further investigation. We aimed to evaluate the concordance between lumbar puncture opening pressure (LPOP) as indicator of the ICP and cerebral venous sinus pressure in patients investigated for IIH. In this case-series replication study, all patients with IIH suspicion and who underwent cerebral venous sinus pressure measurement followed immediately by LP opening pressure (LPOP) measurement were retrospectively included. Pearson’s correlation and measurement agreement (Bland-Altman plots) between venous pressure and LPOP were analyzed. 52 consecutive patients (46 women; median age, 31 years [IQR = 25–42]) were included. The mean pressure in the superior sagittal sinus (SSS) and in the torcular were 20.9mmHg (SD ± 7.3) and 20.8 mmHg (SD ± 6.8), respectively. The mean LPOP was 22mmHg (SD ± 6.4). Pressure measured in the transverse venous sinus, the torcular, and the SSS correlated with LPOP (p < 0.001). Bland-Altman plots showed that torcular pressure strongly agreed with LPOP (mean difference of 1.7mmHg). The limit of agreement (LOA) (mean difference ± 1.96SD) contained 98.1% of the differences between the two methods, confirming the concordance between the two measures. Torcular pressure and LPOP were consistent in patients with a trans-stenotic pressure gradient ≥ or < to 8 mmHg (mean difference: 1mmHg and 2.4mmHg, respectively), and for those with a LP OP ≥ or < to 18mmHg (mean difference: 1.8mmHg and 1.95mmHg, respectively). In patients investigated for IIH, the ICP measured at the LP is correlated and concordant with the torcular pressure. These results confirm previous findings and further corroborate the hypothesis that cerebral venous system plays a major role in CSF dynamics and ICP.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"188 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1186/s10194-024-01847-7
Igor Petrušić, Woo-Seok Ha, Alejandro Labastida-Ramirez, Roberta Messina, Dilara Onan, Claudio Tana, Wei Wang
Artificial intelligence (AI) is revolutionizing the field of biomedical research and treatment, leveraging machine learning (ML) and advanced algorithms to analyze extensive health and medical data more efficiently. In headache disorders, particularly migraine, AI has shown promising potential in various applications, such as understanding disease mechanisms and predicting patient responses to therapies. Implementing next-generation AI in headache research and treatment could transform the field by providing precision treatments and augmenting clinical practice, thereby improving patient and public health outcomes and reducing clinician workload. AI-powered tools, such as large language models, could facilitate automated clinical notes and faster identification of effective drug combinations in headache patients, reducing cognitive burdens and physician burnout. AI diagnostic models also could enhance diagnostic accuracy for non-headache specialists, making headache management more accessible in general medical practice. Furthermore, virtual health assistants, digital applications, and wearable devices are pivotal in migraine management, enabling symptom tracking, trigger identification, and preventive measures. AI tools also could offer stress management and pain relief solutions to headache patients through digital applications. However, considerations such as technology literacy, compatibility, privacy, and regulatory standards must be adequately addressed. Overall, AI-driven advancements in headache management hold significant potential for enhancing patient care, clinical practice and research, which should encourage the headache community to adopt AI innovations.
{"title":"Influence of next-generation artificial intelligence on headache research, diagnosis and treatment: the junior editorial board members’ vision – part 1","authors":"Igor Petrušić, Woo-Seok Ha, Alejandro Labastida-Ramirez, Roberta Messina, Dilara Onan, Claudio Tana, Wei Wang","doi":"10.1186/s10194-024-01847-7","DOIUrl":"https://doi.org/10.1186/s10194-024-01847-7","url":null,"abstract":"Artificial intelligence (AI) is revolutionizing the field of biomedical research and treatment, leveraging machine learning (ML) and advanced algorithms to analyze extensive health and medical data more efficiently. In headache disorders, particularly migraine, AI has shown promising potential in various applications, such as understanding disease mechanisms and predicting patient responses to therapies. Implementing next-generation AI in headache research and treatment could transform the field by providing precision treatments and augmenting clinical practice, thereby improving patient and public health outcomes and reducing clinician workload. AI-powered tools, such as large language models, could facilitate automated clinical notes and faster identification of effective drug combinations in headache patients, reducing cognitive burdens and physician burnout. AI diagnostic models also could enhance diagnostic accuracy for non-headache specialists, making headache management more accessible in general medical practice. Furthermore, virtual health assistants, digital applications, and wearable devices are pivotal in migraine management, enabling symptom tracking, trigger identification, and preventive measures. AI tools also could offer stress management and pain relief solutions to headache patients through digital applications. However, considerations such as technology literacy, compatibility, privacy, and regulatory standards must be adequately addressed. Overall, AI-driven advancements in headache management hold significant potential for enhancing patient care, clinical practice and research, which should encourage the headache community to adopt AI innovations. ","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Most real-world data on CGRP mAbs have been published from high-income countries such as the USA, Western countries, Japan, Korea, and Singapore. However, data from low- and middle-income countries in Southeast Asia is lacking. This is the first real-world study from Thailand to describe the efficacy of CGRP mAbs therapy in migraine patients and to analyze the response trends between episodic migraine and chronic migraine. We conducted a single-center, real-world retrospective chart review study with an observation period of 6 months after CGRP mAbs initiation. We aim to compare treatment responses to CGRP mAbs between EM and CM patients. A total of 47 Thai patients were enrolled (median [IQR] age 37.2 [28.6–50.4] years; 85.1%F, 44.7% EM; 70.2% galcanezumab). There was no difference in baseline characteristics and migraine disability assessment (MIDAS) between EM and CM. The overall ≥ 30%, ≥ 50%, and ≥ 70% monthly migraine day reduction rates at 6 months were 89.0%, 71.6%, and 58.5% with higher responders in EM. There was a significant decrease in monthly headache days (MHDs) over time (adjusted β = -0.42, p < 0.001) and a significant decrease in MIDAS score over time after the initiation of CGRP mAbs (adjusted β = -1.12, p = 0.003). However, there were no differences between the two diagnoses. There was no significant decrease in the number of abortive medication pills used over time after the initiation of CGRP mAbs. CM had a significantly steeper trend compared to those with EM. The first real-world study in Thailand demonstrated that CGRP mAbs therapy had efficacy for migraine treatment, as evidenced by a reduction in MHDs, decreased disability, and reduced use of abortive medications. Additionally, the response pattern to CGRP mAbs therapy was similar between EM and CM in terms of MHDs reduction and MIDAS score improvement.
{"title":"Filling the data gap on CGRP mAb therapy in low- to middle-income countries in Southeast Asia: insights from a real-world study in Thailand","authors":"Prakit Anukoolwittaya, Akarin Hiransuthikul, Thanakit Pongpitakmetha, Sekh Thanprasertsuk, Wanakorn Rattanawong","doi":"10.1186/s10194-024-01859-3","DOIUrl":"https://doi.org/10.1186/s10194-024-01859-3","url":null,"abstract":"Most real-world data on CGRP mAbs have been published from high-income countries such as the USA, Western countries, Japan, Korea, and Singapore. However, data from low- and middle-income countries in Southeast Asia is lacking. This is the first real-world study from Thailand to describe the efficacy of CGRP mAbs therapy in migraine patients and to analyze the response trends between episodic migraine and chronic migraine. We conducted a single-center, real-world retrospective chart review study with an observation period of 6 months after CGRP mAbs initiation. We aim to compare treatment responses to CGRP mAbs between EM and CM patients. A total of 47 Thai patients were enrolled (median [IQR] age 37.2 [28.6–50.4] years; 85.1%F, 44.7% EM; 70.2% galcanezumab). There was no difference in baseline characteristics and migraine disability assessment (MIDAS) between EM and CM. The overall ≥ 30%, ≥ 50%, and ≥ 70% monthly migraine day reduction rates at 6 months were 89.0%, 71.6%, and 58.5% with higher responders in EM. There was a significant decrease in monthly headache days (MHDs) over time (adjusted β = -0.42, p < 0.001) and a significant decrease in MIDAS score over time after the initiation of CGRP mAbs (adjusted β = -1.12, p = 0.003). However, there were no differences between the two diagnoses. There was no significant decrease in the number of abortive medication pills used over time after the initiation of CGRP mAbs. CM had a significantly steeper trend compared to those with EM. The first real-world study in Thailand demonstrated that CGRP mAbs therapy had efficacy for migraine treatment, as evidenced by a reduction in MHDs, decreased disability, and reduced use of abortive medications. Additionally, the response pattern to CGRP mAbs therapy was similar between EM and CM in terms of MHDs reduction and MIDAS score improvement.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s10194-024-01850-y
Yu-Chin An, Kuo-Sheng Hung, Chih-Sung Liang, Chia-Kuang Tsai, Chia-Lin Tsai, Sy-Jou Chen, Yu-Kai Lin, Guan-Yu Lin, Po-Kuan Yeh, Fu-Chi Yang
Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine. We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database. Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure. The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology. Not applicable.
{"title":"Genetic variants associated with response to anti-CGRP monoclonal antibody therapy in a chronic migraine Han Chinese population","authors":"Yu-Chin An, Kuo-Sheng Hung, Chih-Sung Liang, Chia-Kuang Tsai, Chia-Lin Tsai, Sy-Jou Chen, Yu-Kai Lin, Guan-Yu Lin, Po-Kuan Yeh, Fu-Chi Yang","doi":"10.1186/s10194-024-01850-y","DOIUrl":"https://doi.org/10.1186/s10194-024-01850-y","url":null,"abstract":"Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine. We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database. Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure. The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology. Not applicable.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1186/s10194-024-01857-5
Paul Theo Zebhauser, Henrik Heitmann, Elisabeth S. May, Markus Ploner
Magnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3–8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches.
{"title":"Resting-state electroencephalography and magnetoencephalography in migraine–a systematic review and meta-analysis","authors":"Paul Theo Zebhauser, Henrik Heitmann, Elisabeth S. May, Markus Ploner","doi":"10.1186/s10194-024-01857-5","DOIUrl":"https://doi.org/10.1186/s10194-024-01857-5","url":null,"abstract":"Magnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3–8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1186/s10194-024-01853-9
Zhonghua Xiong, Lei Zhao, Yanliang Mei, Dong Qiu, Xiaoshuang Li, Peng Zhang, Mantian Zhang, Jin Cao, Yonggang Wang
Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10–6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets—FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3—that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.
{"title":"Proteome-wide Mendelian randomization identified potential drug targets for migraine","authors":"Zhonghua Xiong, Lei Zhao, Yanliang Mei, Dong Qiu, Xiaoshuang Li, Peng Zhang, Mantian Zhang, Jin Cao, Yonggang Wang","doi":"10.1186/s10194-024-01853-9","DOIUrl":"https://doi.org/10.1186/s10194-024-01853-9","url":null,"abstract":"Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10–6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets—FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3—that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1186/s10194-024-01856-6
Otgonbayar Luvsannorov, Byambasuren Tsenddorj, Dorjkhand Baldorj, Selenge Enkhtuya, Delgermaa Purev, Andreas Husøy, Timothy J. Steiner
Having previously shown headache disorders to be prevalent in Mongolia, here we elaborate on headache as a public-health concern in this country, reporting symptom burden and headache-attributed impaired participation at individual and societal levels, and conducting a health-care needs assessment. The study followed the standardized methodology developed by the Global Campaign against Headache, generating a representative general-population sample through multi-level randomized cluster sampling. Participants aged 18–65 years were interviewed at unannounced household visits by interviewers administering the HARDSHIP questionnaire. Symptom burden was established through questions on frequency, duration and intensity of headache, with proportion of time in ictal state calculated from frequency and duration. Individual impaired participation was established through the HALT questionnaire, enquiring into lost time from paid and household work and from leisure activities. Symptom burden and impaired participation yesterday were also assessed in those reporting headache yesterday. Population-level estimates were derived by factoring in prevalence. The total sample included 2,043 participants. Those reporting any headache in the last year (n = 1,351) spent, on average, 9.7% of all their time with headache, losing 1.3 workdays and 2.4 household days/3 months. These losses were considerably higher among those with probable medication-overuse headache (37.5%, 3.5 workdays, 6.7 household days) or other headache on ≥ 15 days/month (H15+) (21.9%, 2.4 workdays, 5.1 household days). At population-level (including those with and without headache), 6.2–7.4% of all time was spent with headache, 3.1% with H15+; 0.8 workdays and 1.4 household days/person/3 months were lost to headache, 0.3 workdays and 0.6 household days to migraine (the biggest contributor of all headache types). Our needs assessment estimated that one third (33.2%) of the adult population of Mongolia have headache (mostly migraine or H15+) likely to benefit from health care. This first population-based study on headache burden in Mongolia shows high levels of individual and societal burden, with H15 + the cause of greater burden at population level than migraine and TTH combined. Migraine, however, has the biggest impact on the nation’s productivity. From a purely economic perspective, Mongolia, with limited health resources, would probably be best served by focusing on mitigating migraine-attributed burden.
{"title":"The burden of headache disorders in the adult population of Mongolia: estimates, and a health-care needs assessment, from a cross-sectional population-based study","authors":"Otgonbayar Luvsannorov, Byambasuren Tsenddorj, Dorjkhand Baldorj, Selenge Enkhtuya, Delgermaa Purev, Andreas Husøy, Timothy J. Steiner","doi":"10.1186/s10194-024-01856-6","DOIUrl":"https://doi.org/10.1186/s10194-024-01856-6","url":null,"abstract":"Having previously shown headache disorders to be prevalent in Mongolia, here we elaborate on headache as a public-health concern in this country, reporting symptom burden and headache-attributed impaired participation at individual and societal levels, and conducting a health-care needs assessment. The study followed the standardized methodology developed by the Global Campaign against Headache, generating a representative general-population sample through multi-level randomized cluster sampling. Participants aged 18–65 years were interviewed at unannounced household visits by interviewers administering the HARDSHIP questionnaire. Symptom burden was established through questions on frequency, duration and intensity of headache, with proportion of time in ictal state calculated from frequency and duration. Individual impaired participation was established through the HALT questionnaire, enquiring into lost time from paid and household work and from leisure activities. Symptom burden and impaired participation yesterday were also assessed in those reporting headache yesterday. Population-level estimates were derived by factoring in prevalence. The total sample included 2,043 participants. Those reporting any headache in the last year (n = 1,351) spent, on average, 9.7% of all their time with headache, losing 1.3 workdays and 2.4 household days/3 months. These losses were considerably higher among those with probable medication-overuse headache (37.5%, 3.5 workdays, 6.7 household days) or other headache on ≥ 15 days/month (H15+) (21.9%, 2.4 workdays, 5.1 household days). At population-level (including those with and without headache), 6.2–7.4% of all time was spent with headache, 3.1% with H15+; 0.8 workdays and 1.4 household days/person/3 months were lost to headache, 0.3 workdays and 0.6 household days to migraine (the biggest contributor of all headache types). Our needs assessment estimated that one third (33.2%) of the adult population of Mongolia have headache (mostly migraine or H15+) likely to benefit from health care. This first population-based study on headache burden in Mongolia shows high levels of individual and societal burden, with H15 + the cause of greater burden at population level than migraine and TTH combined. Migraine, however, has the biggest impact on the nation’s productivity. From a purely economic perspective, Mongolia, with limited health resources, would probably be best served by focusing on mitigating migraine-attributed burden.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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