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Ali M, van der Weerd N, van Os HJA, Wilms AE, Holswilder G, Linstra KM, van Harten TW, Cannegieter SC, Siegerink B, van Vlijmen BJM, Ruhaak LR, Kruyt ND, Kruit MC, Brink AMVD, Terwindt GM, Wermer MJH. Coagulation Factors and White Matter Hyperintensities in Middle-Aged Women With and Without Migraine and Ischemic Stroke. Eur J Neurol 2025; 32:e70063. [PMID: 40022462 PMCID: PMC11871085 DOI: 10.1111/ene.70063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 01/09/2025] [Accepted: 01/22/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND Migraine increases the risk of ischemic stroke and white matter hyperintensities (WMH), especially in women. Underlying shared mechanisms may include endothelial activation and hypercoagulability. We assessed these markers in middle-aged women with and without migraine and ischemic stroke to explore their role in WMH development. METHODS We cross-sectionally measured fibrinogen and von Willebrand factor antigen (VWF:Ag) levels as markers of endothelial activation, and factor (F)IX and FXI activity (FXI:C) as markers of hypercoagulability in four groups of women aged 40-60 years with (1)ischemic stroke, (2)migraine, (3)both ischemic stroke and migraine, and (4)no stroke or migraine. Multivariable linear regression estimated mean differences in coagulation factor levels between groups 1 and 3, with group 4 as the reference. RESULTS Among 166 women (mean age:51 years), (1) 45 had ischemic stroke, (2) 38 had migraine, (3) 48 had both, and (4) 35 had no stroke or migraine. Mean fibrinogen, FIX, and FXI:C levels were similar in all groups compared with group 4. VWF:Ag levels were higher in the ischemic stroke with migraine group (170 [57]%; adjusted β = 31%; 95% CI = 6%-56%) compared with group 4, but not in the other groups. There was no association between coagulation factors and WMH volume in any group. CONCLUSIONS In women with both stroke and migraine, VWF:Ag levels were increased, while fibrinogen, FIX, and FXI:C were not. This suggests that endothelial activation might be more relevant than a procoagulant state alone in the pathophysiology of ischemic stroke in women with migraine. Coagulation factors did not seem to be related to WMH volume, suggesting other mechanisms may be involved in their development.
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Affiliation(s)
- Mariam Ali
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
| | - Nelleke van der Weerd
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
- Human Genetics, LUMCLeidenthe Netherlands
| | - Hendrikus J. A. van Os
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
- Public Health & Primary Care, LUMCLeidenthe Netherlands
| | - Annelise E. Wilms
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
| | | | - Katie M. Linstra
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
| | - Thijs W. van Harten
- Radiology, LUMCLeidenthe Netherlands
- Neurology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
| | | | | | | | - L. Renee Ruhaak
- Clinical Chemistry & Laboratory Medicine, LUMCLeidenthe Netherlands
| | - Nyika D. Kruyt
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
| | | | | | | | - Marieke J. H. Wermer
- Neurology, Leiden University Medical Centre (LUMC)Leidenthe Netherlands
- Neurology, University Medical Centre GroningenGroningenthe Netherlands
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Borończyk M, Zduńska A, Węgrzynek-Gallina J, Grodzka O, Lasek-Bal A, Domitrz I. Migraine and stroke: correlation, coexistence, dependence - a modern perspective. J Headache Pain 2025; 26:39. [PMID: 39979846 PMCID: PMC11844069 DOI: 10.1186/s10194-025-01973-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/04/2025] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Migraine is a chronic neurological condition that has a well-documented, yet not fully understood connection to stroke, particularly in patients who experience migraine with aura (MA). Although migraine can rarely be directly related to stroke, in the form of migrainous infarction, it serves as an independent risk factor, particularly when combined with other factors such as smoking or hypertension. This study will thoroughly review and summarize the existing literature regarding the relationship between migraine and stroke. MAIN TEXT Several key processes are common to both stroke and migraine. These include cortical spreading depression, particularly in MA, endothelial dysfunction, which activates local inflammatory responses, and vasculopathy, which often appears as white matter hyperintensities on neuroimaging. Furthermore, microRNAs also play a significant role in the pathogenesis of both migraine and stroke by targeting genes such as CALCA, which regulates calcitonin gene-related peptide, a factor involved in the pathophysiology of both conditions. There are also several genetic links between migraine and stroke, including both monogenic diseases and common risk loci. Moreover, various conditions are linked to both migraine and stroke, including patent foramen ovale (PFO), atrial fibrillation, carotid artery dissection, platelet dysfunction, dyslipidemia, obesity, hyperhomocysteinemia, and elevated estrogen levels, such as in combined hormonal contraceptives. Notably, PFO is often found in patients who have experienced a cryptogenic stroke, as well as in those with MA. While microemboli associated with PFO may provoke ischemic events and migraine attacks, the effectiveness of PFO closure in alleviating migraine symptoms has produced varying results. Migraine is linked to worse outcomes after ischemic stroke, including larger stroke volumes and poorer functional outcomes, while the connection between migraines and hemorrhagic stroke is less understood. Furthermore, migraine may serve as a stroke mimic (condition presenting with symptoms similar to ischemic stroke) or a stroke chameleon (unrecognized stroke misdiagnosed as migraine), leading to significant diagnostic and treatment errors. CONCLUSIONS The interplay between migraine and stroke is complex, involving shared pathophysiology and overlapping risk factors. While migraine can serve as both a cause and a risk factor for stroke, the precise mechanisms remain unclear, warranting further research to clarify their connection and enhance clinical management.
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Affiliation(s)
- Michał Borończyk
- Department of Neurology, Faculty of Health Sciences in Katowice, Medical University of Silesia in Katowice, Ziołowa 45/47, Katowice, 40-635, Poland.
- Department of Neurology, Upper-Silesian Medical Centre in Katowice, Ziołowa 45/47, Katowice, 40-635, Poland.
| | - Anna Zduńska
- Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Bielanski Hospital, Cegłowska 80, Warsaw, 01-809, Poland
| | - Julia Węgrzynek-Gallina
- Department of Neurology, Faculty of Medical Sciences, University Clinical Centre of Medical University of Silesia, Medyków 14, Katowice, 40-752, Poland
| | - Olga Grodzka
- Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Bielanski Hospital, Cegłowska 80, Warsaw, 01-809, Poland
- Doctoral School, Medical University of Warsaw, Żwirki i Wigury 61, Warsaw, 02-091, Poland
| | - Anetta Lasek-Bal
- Department of Neurology, Faculty of Health Sciences in Katowice, Medical University of Silesia in Katowice, Ziołowa 45/47, Katowice, 40-635, Poland
- Department of Neurology, Upper-Silesian Medical Centre in Katowice, Ziołowa 45/47, Katowice, 40-635, Poland
| | - Izabela Domitrz
- Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Bielanski Hospital, Cegłowska 80, Warsaw, 01-809, Poland
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Reddy M, Vazquez S, Nolan B, Clare K, Feldstein E, Medicherla C, Kaur G, Rostanski SK, Czap AL, Li J, Gandhi CD, Al-Mufti F. Migraine and its Association with Stroke in Pregnancy: A National Examination. J Womens Health (Larchmt) 2024; 33:1476-1481. [PMID: 39435508 DOI: 10.1089/jwh.2023.1136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2024] Open
Abstract
Background: Migraine prevalence has been estimated to be as high as 25% during reproductive years. Despite this, and the known significantly lower odds of acute stroke being correctly diagnosed among women versus men, little is known about the migraine-stroke connection in this vulnerable population. Our study seeks to provide a consolidated examination of cerebrovascular and obstetric complications of migraines in pregnant women and to evaluate the role of concurrent comorbidities. Methods: We utilized the 2016-2020 Healthcare Cost and Utilization Project's National Inpatient Sample with the International Classification of Diseases, 10th Revision diagnostic codes to compare pregnant patients with migraines with those without migraines. Multivariable logistic regression was used to examine the incidence of subtypes of stroke while controlling for confounding variables. Results: Overall, 19,825,525 pregnant patients were evaluated; 219,175 (1.1%) had a concomitant diagnosis of migraine. Pregnant patients with migraines were more likely to suffer ischemic (0.1% versus 0.0%) or hemorrhagic stroke (0.3% versus 0.1%). On multivariate analysis, acute ischemic stroke was most strongly associated with migraine with aura (odds ratio [OR], 23.26; 95% confidence interval [CI], 18.46-29.31), followed by migraine without aura (OR, 8.15; 95% CI, 4.79-13.88). Conclusions: Pregnant women with migraine are at a significantly increased risk for both ischemic and hemorrhagic stroke. Pregnant women with migraines should be cautioned that they may be at an increased risk of stroke, particularly if they are experiencing an aura, and encouraged to contact their medical providers to rule out neurological complications.
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Affiliation(s)
- Medha Reddy
- School of Medicine, New York Medical College, Valhalla, New York, USA
| | - Sima Vazquez
- School of Medicine, New York Medical College, Valhalla, New York, USA
| | - Bridget Nolan
- School of Medicine, New York Medical College, Valhalla, New York, USA
- Department of Neurosurgery, Westchester Medical Center, Valhalla, New York, USA
| | - Kevin Clare
- School of Medicine, New York Medical College, Valhalla, New York, USA
- Department of Neurosurgery, Westchester Medical Center, Valhalla, New York, USA
| | - Eric Feldstein
- Department of Neurosurgery, Westchester Medical Center, Valhalla, New York, USA
| | | | - Gurmeen Kaur
- School of Medicine, New York Medical College, Valhalla, New York, USA
- Department of Neurosurgery, Westchester Medical Center, Valhalla, New York, USA
- Department of Neurology, Westchester Medical Center, Valhalla, New York, USA
| | - Sara K Rostanski
- Department of Neurology, NYU Grossman School of Medicine, New York, New York, USA
| | - Alexandra L Czap
- Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Jin Li
- School of Medicine, New York Medical College, Valhalla, New York, USA
- Department of Neurology, Westchester Medical Center, Valhalla, New York, USA
| | - Chirag D Gandhi
- School of Medicine, New York Medical College, Valhalla, New York, USA
- Department of Neurosurgery, Westchester Medical Center, Valhalla, New York, USA
| | - Fawaz Al-Mufti
- School of Medicine, New York Medical College, Valhalla, New York, USA
- Department of Neurosurgery, Westchester Medical Center, Valhalla, New York, USA
- Department of Neurology, Westchester Medical Center, Valhalla, New York, USA
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Nie Q, Qian H, Chen S, Xiang W, Shen Y. White Matter Lesions, Risk Factors, and Etiological Classification in Young versus Old Cerebral Infarction Patients: A Retrospective Study. Clin Interv Aging 2024; 19:1723-1730. [PMID: 39464418 PMCID: PMC11505487 DOI: 10.2147/cia.s485511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 10/18/2024] [Indexed: 10/29/2024] Open
Abstract
Objective To compare the differences in risk factors and etiological classification between cerebral infarction in young patients and elderly patients, and explore the correlation between cerebral infarction in young patients and white matter lesions (WMLs). Methods Sixty young patients with cerebral infarction and 142 elderly patients with cerebral infarction were included. The distributions of risk factors such as hypertension, diabetes, heart disease, smoking status, alcohol consumption status, migraine status, and WMLs in the two groups were carefully investigated and statistically analyzed. Results According to the univariate analysis, the proportions of males, obese patients, patients with migraine, and patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) in the young group were significantly greater than those in the elderly group. Hypertension, heart disease, and hyperhomocysteinemia were significantly more common in the elderly group than in the young group. According to the TOAST classification, the incidence of stroke of undetermined etiology in the young group was greater than that in the elderly group, whereas the incidence of large-artery atherosclerosis (LAA) in the elderly group was greater than that in the young group. Binary logistic regression analysis revealed that male sex, migraine status, and obstructive sleep apnea-hypopnea syndrome were independently associated with cerebral infarction in young adults, whereas hypertension, heart disease, and hyperhomocysteinemia were independently related to cerebral infarction in elderly individuals. In addition, the incidence of WMLs in the migraine group of young cerebral infarction patients was significantly greater than that in the nonmigraine group. Conclusion Compared with those in elderly patients with cerebral infarction, the risk factors for cerebral infarction in young patients are relatively controllable. Furthermore, more methods are needed to determine the etiology of unexplained cerebral infarction in young patients. WMLs are thought to have a relatively high incidence in young patients with cerebral infarction and are significantly associated with migraine.
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Affiliation(s)
- Quirui Nie
- Department of Gerontology, Nanchang First Hospital, Nanchang, People’s Republic of China
| | - Hui Qian
- Department of Neurology, Fengxin County People’s Hospital, Fengxin, People’s Republic of China
- Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China
| | - Shenjian Chen
- Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China
| | - Wenwen Xiang
- Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China
| | - Yu Shen
- Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China
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Varga E, Ghanem AS, Faludi E, Nguyen CM, Kovács N, Nagy AC. Medical comorbidities and other factors associated with migraine among individuals with diabetes mellitus in Hungary: a cross-sectional study using European Health Interview Surveys 2009-2019. Front Endocrinol (Lausanne) 2024; 15:1379127. [PMID: 39247924 PMCID: PMC11377266 DOI: 10.3389/fendo.2024.1379127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/07/2024] [Indexed: 09/10/2024] Open
Abstract
Introduction Migraine, a debilitating neurological disorder characterized by recurrent headaches, affects over 1.1 billion individuals globally. Diabetes mellitus (DM), a chronic metabolic condition marked by high blood sugar levels, affects 463 million individuals according to the International Diabetes Federation. Our study aimed to evaluate the association between migraine and DM and to identify several demographic, socioeconomic, and lifestyle factors, as well as medical and psychiatric comorbidities, associated with migraine among individuals with DM. Methods This cross-sectional study is based on data from the European Health Interview Surveys conducted in 2009, 2014, and 2019 in Hungary. Pearson's chi-squared tests and multiple logistic regression models were used to assess associations. Statistical significance was set at p<0.05. Results In multiple regression analyses, we found no significant association between DM and migraine after adjusting for socioeconomic status, various health conditions, and lifestyle factors (OR=0.84, 95% CI: 0.66-1.06). However, adults with DM who had comorbid conditions including stroke (OR=2.08, 95% CI: 1.06-4.08), low back pain (OR=3.52, 95% CI: 2.13-5.84), and depression (OR=4.91, 95% CI: 2.84-8.47) were significantly more likely to suffer from migraine. Discussion Our study found no significant difference in the prevalence of migraine among adults with and without diabetes mellitus. However, several comorbidities were found to be significantly associated with migraine occurrence in those with DM. Thus, the study's results highlight the need for proper management of diabetes, especially in terms of comorbidities, to mitigate migraine risk factors and improve patient outcomes.
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Affiliation(s)
- Eszter Varga
- Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Amr Sayed Ghanem
- Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary
| | - Eszter Faludi
- Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary
| | - Chau Minh Nguyen
- Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary
| | - Nóra Kovács
- Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Attila Csaba Nagy
- Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary
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Nanah A, Daw H, Abdelghaffar B. Venous Thromboembolic Disease Provoked by Hormone-Eluting Vaginal Rings. Am J Ther 2024; 31:e426-e430. [PMID: 37052675 DOI: 10.1097/mjt.0000000000001626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Affiliation(s)
| | - Hamed Daw
- Department of Hematology and Oncology, Cleveland Clinic Fairview Hospital, Cleveland, OH
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van der Weerd N, Pelzer N, Egberts E, Mertens M, Bakker W, Linstra KM, van den Maagdenberg AMJM, van Zwet EW, MaassenVanDenBrink A, Terwindt GM, Wermer MJH. Changes in Migraine Symptoms after Ischemic Stroke: A Cohort Study. Cerebrovasc Dis 2024:1-6. [PMID: 38781942 DOI: 10.1159/000539421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 05/13/2024] [Indexed: 05/25/2024] Open
Abstract
INTRODUCTION Migraine symptoms are postulated to improve post-stroke. We aimed to determine post-stroke changes in patients with active migraine pre-stroke and explored the relation with stroke location and stroke-preventive medication use. METHODS Patients with active migraine who had an ischemic stroke were retrieved from three research-cohorts between 2014 and 2021. By an interview, we retrospectively investigated first-year post-stroke changes for those ischemic stroke patients that suffered from migraine pre-stroke. Associations between change in migraine frequency/intensity/aura (decrease, no change, increase), stroke location (posterior location vs. other), and use of secondary stroke preventive medication were assessed by ordinal regression with adjustment for confounders. RESULTS We included 78 patients (mean age 48 years, 86% women, 47% with aura). Change in migraine symptomatology was reported by 63 (81%) patients; 51 (81%) noticed a decrease in attack frequency (27 no attacks) and 12 (19%) an increase. Pain intensity change was reported by 18 (35%) patients (50% increase, 50% decrease). Aura symptomatology improved in 4 (11%). Reduced attack frequency was not related to posterior stroke (OR = 1.5, 95% CI: 0.6-3.9), or preventive medication (antiplatelets OR = 1.0, 95% CI: 0.2-3.7; coumarin OR = 2.7, 95% CI: 0.4-20.6). CONCLUSIONS Most patients with active pre-stroke migraine experience improvement of their symptoms in the first year after ischemic stroke. This change does not seem to be related to secondary stroke preventive medication or posterior stroke location.
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Affiliation(s)
- Nelleke van der Weerd
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Nadine Pelzer
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Emma Egberts
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Marit Mertens
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Willemijn Bakker
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Katie M Linstra
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
| | | | - Erik W van Zwet
- Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands
| | | | - Gisela M Terwindt
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Marieke J H Wermer
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Neurology, Groningen University Medical Centre, Groningen, The Netherlands
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Wang TS, Jing LJ. Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction. World J Psychiatry 2024; 14:644-652. [PMID: 38808092 PMCID: PMC11129145 DOI: 10.5498/wjp.v14.i5.644] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/26/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Cerebral infarction (CI) is characterized by a high prevalence, disability, and mortality. Timely or improper treatment greatly affects patient prognosis. AIM To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life (QOL), anxiety and depression in CI patients. METHODS We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group (OG) (combination therapy of aspirin and edaravone, 65 patients) or a control group (CG) (aspirin monotherapy, 59 patients). The therapeutic effects, pre- and posttreatment National Institutes of Health Stroke Scale (NIHSS) scores, activities of daily living, degree of cognitive impairment, protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and S-100B, occurrence of adverse reactions, and serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated, detected and compared between the two groups. Finally, posttreatment QOL, anxiety, and depression were assessed by the Medical Outcomes Study 36- Item Short Form Health Survey Scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), respectively. RESULTS Compared with the CG, the OG had markedly better therapeutic effects, greater improvements in activities of daily living, and better alleviation in cognitive dysfunction after treatment, as well as lower posttreatment NIHSS scores and serum NSE, GFAP, S-100B, hs-CRP, IL-6, and TNF-α levels; the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL; and the OG also had lower SDS and SAS scores than the CG after treatment. CONCLUSION Aspirin plus edaravone had a good curative effect on CI. It can reverse cranial nerve damage in patients, improve neurological function and prognosis, and alleviate inflammation, anxiety, and depression; thus, it is considered safe and worthy of clinical application.
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Affiliation(s)
- Tian-Shu Wang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Li-Jun Jing
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
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Golubnitschaja O, Polivka J, Potuznik P, Pesta M, Stetkarova I, Mazurakova A, Lackova L, Kubatka P, Kropp M, Thumann G, Erb C, Fröhlich H, Wang W, Baban B, Kapalla M, Shapira N, Richter K, Karabatsiakis A, Smokovski I, Schmeel LC, Gkika E, Paul F, Parini P, Polivka J. The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation. EPMA J 2024; 15:1-23. [PMID: 38463624 PMCID: PMC10923756 DOI: 10.1007/s13167-024-00356-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 02/08/2024] [Indexed: 03/12/2024]
Abstract
Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.
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Affiliation(s)
- Olga Golubnitschaja
- Predictive, Preventive and Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
| | - Jiri Polivka
- Department of Histology and Embryology, Faculty of Medicine in Plzen, Charles University, Prague, Czech Republic
- Biomedical Centre, Faculty of Medicine in Plzen, Charles University, Prague, Czech Republic
| | - Pavel Potuznik
- Department of Neurology, University Hospital Plzen and Faculty of Medicine in Plzen, Charles University, Prague, Czech Republic
| | - Martin Pesta
- Department of Biology, Faculty of Medicine in Plzen, Charles University, Prague, Czech Republic
| | - Ivana Stetkarova
- Department of Neurology, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Alena Mazurakova
- Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Lenka Lackova
- Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Peter Kubatka
- Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Martina Kropp
- Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland
- Ophthalmology Department, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Gabriele Thumann
- Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland
- Ophthalmology Department, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Carl Erb
- Private Institute of Applied Ophthalmology, Berlin, Germany
| | - Holger Fröhlich
- Artificial Intelligence & Data Science Group, Fraunhofer SCAI, Sankt Augustin, Germany
- Bonn-Aachen International Center for IT (B-It), University of Bonn, 53115 Bonn, Germany
| | - Wei Wang
- Edith Cowan University, Perth, Australia
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Babak Baban
- The Dental College of Georgia, Departments of Neurology and Surgery, The Medical College of Georgia, Augusta University, Augusta, USA
| | - Marko Kapalla
- Negentropic Systems, Ružomberok, Slovakia
- PPPM Centre, s.r.o., Ruzomberok, Slovakia
| | - Niva Shapira
- Department of Nutrition, School of Health Sciences, Ashkelon Academic College, Ashkelon, Israel
| | - Kneginja Richter
- CuraMed Tagesklinik Nürnberg GmbH, Nuremberg, Germany
- Technische Hochschule Nürnberg GSO, Nuremberg, Germany
- University Clinic for Psychiatry and Psychotherapy, Paracelsus Medical University, Nuremberg, Germany
| | - Alexander Karabatsiakis
- Department of Psychology, Clinical Psychology II, University of Innsbruck, Innsbruck, Austria
| | - Ivica Smokovski
- University Clinic of Endocrinology, Diabetes and Metabolic Disorders Skopje, University Goce Delcev, Faculty of Medical Sciences, Stip, North Macedonia
| | - Leonard Christopher Schmeel
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
| | - Eleni Gkika
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
| | | | - Paolo Parini
- Cardio Metabolic Unit, Department of Medicine Huddinge, and Department of Laboratory Medicine, Karolinska Institutet, and Medicine Unit of Endocrinology, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden
| | - Jiri Polivka
- Department of Neurology, University Hospital Plzen and Faculty of Medicine in Plzen, Charles University, Prague, Czech Republic
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10
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Zhang L, Zhang H, Zhou X, Zhao J, Wang X. Bibliometric Analysis of Research on Migraine-Stroke Association from 2013 to 2023. J Pain Res 2023; 16:4089-4112. [PMID: 38058980 PMCID: PMC10697147 DOI: 10.2147/jpr.s438745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 11/22/2023] [Indexed: 12/08/2023] Open
Abstract
Background Both migraine and stroke heavily burden individuals, health systems, and society. The migraine-stroke association is of concern and has been studied widely. Our objective is to explore and overview the current research status and emerging trends. Materials and Methods Studies on migraine-stroke association from January 2013 to May 2023 were retrieved and screened from the Web of Science Core Collection (WOSCC) database. Records fulfilling the selection criteria were downloaded and imported into CiteSpace for data mining and visualization. Results A total of 862 papers on migraine-stroke association were included. Annual publications grew slowly. The United States and European countries dominated research in this area. Harvard University published the largest number of articles, while the University of London was most active with other institutions. Ayata Cenk contributed the most articles, while KURTH T and NEUROLOGY were co-cited most. Research hotspots included migraine with aura, ischemic stroke, patent foramen ovale, cortical spreading depolarization, meta-analysis, cross-sectional study, and risk factors. Pathophysiology and small vessel disease represented research frontiers and emerging trends. Conclusion Our study scientifically outlines the migraine-stroke association over the past decade, presenting useful information.
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Affiliation(s)
- Long Zhang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
- Department of Traditional Chinese Medicine, Zibo TCM-Integrated Hospital, Zibo, Shandong, People’s Republic of China
| | - Hongyan Zhang
- Department of Traditional Chinese Medicine, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China
- Shaanxi Key Laboratory of Research on TCM Physical Constitution and Diseases Prevention and Treatment, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China
| | - Xue Zhou
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Jing Zhao
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Xingchen Wang
- Division of Neurology, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
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11
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Cortel-LeBlanc MA, Orr SL, Dunn M, James D, Cortel-LeBlanc A. Managing and Preventing Migraine in the Emergency Department: A Review. Ann Emerg Med 2023; 82:732-751. [PMID: 37436346 DOI: 10.1016/j.annemergmed.2023.05.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/24/2023] [Accepted: 05/25/2023] [Indexed: 07/13/2023]
Abstract
Migraine is a leading cause of disability worldwide, and acute migraine attacks are a common reason for patients to seek care in the emergency department (ED). There have been recent advancements in the care of patients with migraine, specifically emerging evidence for nerve blocks and new pharmacological classes of medications like gepants and ditans. This article serves as a comprehensive review of migraine in the ED, including diagnosis and management of acute complications of migraine (eg, status migrainosus, migrainous infarct, persistent aura without infarction, and aura-triggered seizure) and use of evidence-based migraine-specific treatments in the ED. It highlights the role of migraine preventive medications and provides a framework for emergency physicians to prescribe them to eligible patients. Finally, it evaluates the evidence for nerve blocks in the treatment of migraine and introduces the possible role of gepants and ditans in the care of patients with migraine in the ED.
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Affiliation(s)
- Miguel A Cortel-LeBlanc
- Department of Emergency Medicine, Queensway Carleton Hospital, Ottawa, ON, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Institut du Savoir Montfort, Ottawa, ON, Canada; 360 Concussion Care, Ottawa, ON, Canada.
| | - Serena L Orr
- Departments of Pediatrics, Community Health Sciences, and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada
| | - Maeghan Dunn
- Department of Emergency Medicine, Queensway Carleton Hospital, Ottawa, ON, Canada
| | - Daniel James
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Emergency Medicine, The Ottawa Hospital, Ottawa, ON, Canada; Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, ON, Canada
| | - Achelle Cortel-LeBlanc
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Institut du Savoir Montfort, Ottawa, ON, Canada; 360 Concussion Care, Ottawa, ON, Canada; Division of Neurology, Department of Medicine, Queensway Carleton Hospital, Ottawa, ON, Canada
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12
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González Mingot C, Santos Lasaosa S, Colàs Campàs L, Chilangua Canaval L, Gil Sánchez A, Brieva Ruiz L, Marzo Alonso MC, Peralta Moncusi S, Valls Marsal J, Cambray Carner S, Purroy García F. Prophylactic treatment can modify vascular risk biomarkers in high-frequency episodic and chronic migraine patients: a pilot study. Sci Rep 2023; 13:19416. [PMID: 37940678 PMCID: PMC10632400 DOI: 10.1038/s41598-023-44522-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 10/09/2023] [Indexed: 11/10/2023] Open
Abstract
To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months' treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM; p = 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL; p = 0.049, vWF antigen (133% vs. 110%; p = 0.020, vWF activity (111% vs. 90%; p = 0.010) and isoprostane levels (181 vs. 238 µM; p = 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm; p = 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2-13.8 µM; p = 0.022) and nitrites (10.4-3.43 µM; p = 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (p < 0.05), vWF activity levels decreased from 124 to 103 IU/dL (p = 0.003) and prothrombin activity decreased from 1.01 to 0.93 (p = 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (p = 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.
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Affiliation(s)
- Cristina González Mingot
- Neuroimmunology Group, Department of Medicine, University of Lleida (UdL)-IRBLleida, Alcalde Rovira Roure 80, 25198, Lleida, Spain.
- Neurology Service of Hospital Arnau de Vilanova of Lleida, Lleida, Spain.
| | | | | | | | - Anna Gil Sánchez
- Neuroimmunology Group, Department of Medicine, University of Lleida (UdL)-IRBLleida, Alcalde Rovira Roure 80, 25198, Lleida, Spain
| | - Luis Brieva Ruiz
- Neuroimmunology Group, Department of Medicine, University of Lleida (UdL)-IRBLleida, Alcalde Rovira Roure 80, 25198, Lleida, Spain
- Neurology Service of Hospital Arnau de Vilanova of Lleida, Lleida, Spain
| | | | - Silvia Peralta Moncusi
- Neuroimmunology Group, Department of Medicine, University of Lleida (UdL)-IRBLleida, Alcalde Rovira Roure 80, 25198, Lleida, Spain
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13
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Sadamoto Y. A Case of Reversible Posterior Leukoencephalopathy Syndrome (PRES) With a History of Migraine and Onset With Initial Visual Aura and Migraine-Like Headache, With a Significant Response to Lasmiditan: A Case Report. Cureus 2023; 15:e49311. [PMID: 38024055 PMCID: PMC10667572 DOI: 10.7759/cureus.49311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2023] [Indexed: 12/01/2023] Open
Abstract
Posterior reversible encephalopathy syndrome (PRES) is a neurological disease that presents with various neurological symptoms and is often accompanied by elevated blood pressure at onset. Neuroimaging, especially magnetic resonance imaging (MRI), often shows a characteristic parieto-occipital pattern with a symmetrical distribution of changes, reflecting vasogenic edema. Hypertension and endothelial cell damage are the most common causes of PRES. An association between migraine and endothelial cell damage has been suggested, but the relationship between migraine and PRES is unknown. Reports on PRES triggered by migraines are scarce. We report a case of PRES in a 59-year-old woman with migraine without aura. At the onset, the patient experienced a first-ever visual aura and a migraine-like headache. In this case, it was also difficult to distinguish between PRES headache and headache caused by a pre-existing migraine; however, lasmiditan, an acute migraine treatment without vasoconstrictive properties, was remarkably effective for headaches.
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14
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Tietjen GE. Virtual issue: Recent advances in the headache-cerebrovascular disease relationship. Headache 2023; 63:1201-1202. [PMID: 37655525 DOI: 10.1111/head.14620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 08/03/2023] [Indexed: 09/02/2023]
Affiliation(s)
- Gretchen E Tietjen
- University of Toledo College of Medicine & Life Sciences, Toledo, Ohio, USA
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15
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Martami F, Holton KF. Targeting Glutamate Neurotoxicity through Dietary Manipulation: Potential Treatment for Migraine. Nutrients 2023; 15:3952. [PMID: 37764736 PMCID: PMC10537717 DOI: 10.3390/nu15183952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 09/08/2023] [Accepted: 09/09/2023] [Indexed: 09/29/2023] Open
Abstract
Glutamate, the main excitatory neurotransmitter in the central nervous system, is implicated in both the initiation of migraine as well as central sensitization, which increases the frequency of migraine attacks. Excessive levels of glutamate can lead to excitotoxicity in the nervous system which can disrupt normal neurotransmission and contribute to neuronal injury or death. Glutamate-mediated excitotoxicity also leads to neuroinflammation, oxidative stress, blood-brain barrier permeability, and cerebral vasodilation, all of which are associated with migraine pathophysiology. Experimental evidence has shown the protective effects of several nutrients against excitotoxicity. The current review focuses on the mechanisms behind glutamate's involvement in migraines as well as a discussion on how specific nutrients are able to work towards restoring glutamate homeostasis. Understanding glutamate's role in migraine is of vital importance for understanding why migraine is commonly comorbid with widespread pain conditions and for informing future research directions.
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Affiliation(s)
- Fahimeh Martami
- Department of Health Studies, American University, Washington, DC 20016, USA;
| | - Kathleen F. Holton
- Department of Health Studies, American University, Washington, DC 20016, USA;
- Department of Neuroscience, American University, Washington, DC 20016, USA
- Center for Neuroscience and Behavior, American University, Washington, DC 20016, USA
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16
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Osteraas ND, Dafer RM. Advances in Management of the Stroke Etiology One-Percenters. Curr Neurol Neurosci Rep 2023; 23:301-325. [PMID: 37247169 PMCID: PMC10225785 DOI: 10.1007/s11910-023-01269-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2023] [Indexed: 05/30/2023]
Abstract
PURPOSE OF REVIEW Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from "standard" care. RECENT FINDINGS Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in "high-risk" patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of L-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance. Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.
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Affiliation(s)
| | - Rima M Dafer
- Rush University Medical Center, Chicago, IL, USA.
- Department of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison St., Suite 1118, Chicago, IL, 60612, USA.
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17
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Qiu T, Zhou Y, Hu L, Shan Z, Zhang Y, Fang Y, Huang W, Zhang L, Fan S, Xiao Z. 2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine. Front Neurol 2023; 14:1115318. [PMID: 37090989 PMCID: PMC10117646 DOI: 10.3389/fneur.2023.1115318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 03/14/2023] [Indexed: 04/08/2023] Open
Abstract
BackgroundTargeting metabolic pathways has emerged as a new migraine treatment strategy as researchers realize the critical role metabolism plays in migraine. Activated inflammatory cells undergo metabolic reprogramming and rely on glycolysis to function. The objective of this study was to investigate the glycolysis changes in the experimental model of migraine and the effect of glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) in the pathophysiology of migraine.MethodsWe used a rat model of migraine that triggered migraine attacks by applying inflammatory soup (IS) to the dura and examined changes in glycolysis. 2-DG was used to inhibit glycolysis, and the effects of 2-DG on mechanical ectopic pain, microglial cell activation, calcitonin gene-related peptides (CGRP), c-Fos, and inflammatory factors induced by inflammatory soup were observed. LPS stimulated BV2 cells to establish a model in vitro to observe the effects of 2-DG on brain-derived neurotrophic factor (BDNF) after microglia activation.ResultsIn the experimental model of migraine, key enzymes involved in glycolysis such as phosphofructokinase platelet (PFKP), hexokinase (HK2), hypoxia inducible factor-1α (HIF-1α), lactate dehydrogenase (LDH) and pyruvate kinase (PKM2) were expressed in the medullary dorsal horn. While the expression of electronic respiratory transport chain complex IV (COXIV) decreased. There were no significant changes in glucose 6-phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway. The glycolysis inhibitor 2-DG alleviated migraine-like symptoms in an experimental model of migraine, reduced the release of proinflammatory cytokines caused by microglia activation, and decreased the expression of CGRP and c-Fos. Further experiments in vitro demonstrated that glycolysis inhibition can reduce the release of Iba-1/proBDNF/BDNF and inhibit the activation of microglia.ConclusionThe migraine rat model showed enhanced glycolysis. This study suggests that glycolytic inhibitor 2-DG is an effective strategy for alleviating migraine-like symptoms. Glycolysis inhibition may be a new target for migraine treatment.
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18
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Imai M, Shimoda M, Oda S, Hoshikawa K, Osada T, Aoki R, Sunaga A. Reversible Cerebral Vasoconstriction Syndrome Patients with a History of Migraine: A Retrospective Case-control Study. Intern Med 2023; 62:355-364. [PMID: 35831115 PMCID: PMC9970822 DOI: 10.2169/internalmedicine.9776-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Objective We investigated the clinical characteristics of patients with reversible cerebral vasoconstrictor syndrome who had a history of migraine before the onset and considered the relationship between these two pathologies. Methods We investigated 98 patients who underwent magnetic resonance angiography within 14 days of the onset of reversible cerebral vasoconstriction syndrome at our hospital. Of these, 11 cases involved recurrences, so data from 87 patients were analyzed. Materials All consecutive patients diagnosed with reversible cerebral vasoconstrictor syndrome at our institution between October 2010 and July 2021. Results Fifty of the 87 patients (57%) had a history of migraine. A multivariate analysis revealed that the following clinical factors were significantly more frequent in patients with a history of migraine than in those without such a history: female sex; emotional situations as a trigger of the onset; presence of deep and subcortical white matter hyperintensity, absence of vasoconstriction in the M1 portion of the middle cerebral artery, and absence of other cerebral lesions on initial magnetic resonance imaging; absence of vasoconstriction of the basilar artery on follow-up magnetic resonance imaging; and progression of deep and subcortical white matter hyperintensity in the chronic stage. Conclusion Reversible cerebral vasoconstrictor syndrome patients with a history of migraine showed clinical features of migraine, including one aspect of cerebral small-vessel disease due to endothelial dysfunction, as a common causative condition.
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Affiliation(s)
- Masaaki Imai
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
| | - Masami Shimoda
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
| | - Shinri Oda
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
| | - Kaori Hoshikawa
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
| | - Takahiro Osada
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
| | - Rie Aoki
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
| | - Azusa Sunaga
- Department of Neurosurgery, Tokai University Hachioji Hospital, Japan
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19
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Kang EJ, Prager O, Lublinsky S, Oliveira-Ferreira AI, Reiffurth C, Major S, Müller DN, Friedman A, Dreier JP. Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD. J Cereb Blood Flow Metab 2023; 43:210-230. [PMID: 36329390 PMCID: PMC9903222 DOI: 10.1177/0271678x221135085] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na+ homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α2-isoform of Na+/K+-ATPase (α2NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α2NaKA. Thus, α2NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α2NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α2NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke.
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Affiliation(s)
- Eun-Jeung Kang
- Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Ofer Prager
- Department of Physiology & Cell Biology, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,Department of Cognitive & Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Svetlana Lublinsky
- Department of Cognitive & Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ana I Oliveira-Ferreira
- Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Clemens Reiffurth
- Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Sebastian Major
- Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Dominik N Müller
- Experimental and Clinical Research Center (ECRC), a Joint Cooperation between the Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.,Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Alon Friedman
- Department of Physiology & Cell Biology, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,Department of Cognitive & Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,Department of Medical Neuroscience and Brain Repair Center, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Jens P Dreier
- Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany.,Einstein Center for Neurosciences Berlin, Berlin, Germany
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20
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Liao CC, Chien CH, Shih YH, Tsai FJ, Li JM. Acupuncture Is Effective at Reducing the Risk of Stroke in Patients with Migraines: A Real-World, Large-Scale Cohort Study with 19-Years of Follow-Up. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1690. [PMID: 36767053 PMCID: PMC9914783 DOI: 10.3390/ijerph20031690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/09/2023] [Accepted: 01/15/2023] [Indexed: 06/18/2023]
Abstract
Migraines are common headache disorders and risk factors for subsequent strokes. Acupuncture has been widely used in the treatment of migraines; however, few studies have examined whether its use reduces the risk of strokes in migraineurs. This study explored the long-term effects of acupuncture treatment on stroke risk in migraineurs using national real-world data. We collected new migraine patients from the Taiwan National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2017. Using 1:1 propensity-score matching, we assigned patients to either an acupuncture or non-acupuncture cohort and followed up until the end of 2018. The incidence of stroke in the two cohorts was compared using the Cox proportional hazards regression analysis. Each cohort was composed of 1354 newly diagnosed migraineurs with similar baseline characteristics. Compared with the non-acupuncture cohort, the acupuncture cohort had a significantly reduced risk of stroke (adjusted hazard ratio, 0.4; 95% confidence interval, 0.35-0.46). The Kaplan-Meier model showed a significantly lower cumulative incidence of stroke in migraine patients who received acupuncture during the 19-year follow-up (log-rank test, p < 0.001). Acupuncture confers protective benefits on migraineurs by reducing the risk of stroke. Our results provide new insights for clinicians and public health experts.
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Affiliation(s)
- Chung-Chih Liao
- Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung 41354, Taiwan
| | - Chi-Hsien Chien
- Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung 41354, Taiwan
| | - Ying-Hsiu Shih
- Management Office for Health Data, China Medical University Hospital, Taichung 40201, Taiwan
- College of Medicine, China Medical University, Taichung 40402, Taiwan
| | - Fuu-Jen Tsai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
- Division of Medical Genetics, China Medical University Children’s Hospital, Taichung 40447, Taiwan
- Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan
| | - Jung-Miao Li
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
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Altamura C, Viticchi G, Rizzo AC, Maggio P, Brunelli N, Marcosano M, Lazzaro VD, Fiacco F, Agostoni EC, Silvestrini M, Vernieri F. Stroke territory and atherosclerosis in ischemic stroke patients with a history of migraine with aura. Front Neurol 2023; 14:1142424. [PMID: 36923493 PMCID: PMC10008946 DOI: 10.3389/fneur.2023.1142424] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 02/02/2023] [Indexed: 03/01/2023] Open
Abstract
Introduction The mechanisms subtending the increased stroke risk in migraine with aura (MA) are not fully understood. Our study aims to evaluate if the clinical profile in stroke patients with MA differentiates from those without MA. Methods We retrieved the prospective registered electronic clinical dossiers of adult patients younger than 60 years with acute ischemic stroke admitted in four hospitals between January 2016 and June 2022. Patients were classified by the history of MA (MA+ and MA-). Results We identified 851 stroke patients (59 MA+, 6.9%). Compared to MA-, MA+ patients were characterized by younger age (44.0 ± 10.6 vs 50.1 ± 8.2 years), female sex (59.3% vs 29.0%), and affected by cryptogenic (OR 2.594 95% CI 1.483-4.537), and cerebellar stroke (OR 3.218 95% CI 1.657-6.250; p ≤ 0.001 for all comparisons). After adjusting for age and sex, MA+ patients presented less frequently hypertension (OR 0.349 95% CI 0.167-0.470; p=0.005) and dyslipidemia (OR 0.523 95% CI 0.280-0.974; p = 0.041). After adjusting also for risk factors, the MA+ group had less frequently symptomatic large vessel stenosis (OR 0.126 95% CI 0.017-0,924; p = 0.042) and clinical atherosclerosis (OR 0.103 95% CI 0.014-0.761; p = 0.026), while intima-media thickness did not differ (p = 0.395). Discussion Cryptogenic and cerebellar stroke and fewer vascular risk factors and clinical atherosclerosis seem to characterize stroke patients with MA.
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Affiliation(s)
- Claudia Altamura
- Department of Medicine and Surgery, Unit of Headache and Neurosonology, Università Campus Bio-Medico di Roma, Roma, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
- *Correspondence: Claudia Altamura ✉
| | | | - Angelo Cascio Rizzo
- Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Paola Maggio
- Neurology Unit, ASST Bergamo Est, Seriate, Italy
| | - Nicoletta Brunelli
- Department of Medicine and Surgery, Unit of Headache and Neurosonology, Università Campus Bio-Medico di Roma, Roma, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Marilena Marcosano
- Department of Medicine and Surgery, Unit of Headache and Neurosonology, Università Campus Bio-Medico di Roma, Roma, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Vincenzo Di Lazzaro
- Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
- Department of Medicine and Surgery, Unit of Neurology, Neurophysiology, Neurobiology, and Psychiatry, Università Campus Bio-Medico di Roma, Roma, Italy
| | | | | | | | - Fabrizio Vernieri
- Department of Medicine and Surgery, Unit of Headache and Neurosonology, Università Campus Bio-Medico di Roma, Roma, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
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22
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Robertson CE, Benarroch EE. The anatomy of head pain. HANDBOOK OF CLINICAL NEUROLOGY 2023; 198:41-60. [PMID: 38043970 DOI: 10.1016/b978-0-12-823356-6.00001-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Pain-sensitive structures in the head and neck, including the scalp, periosteum, meninges, and blood vessels, are innervated predominantly by the trigeminal and upper cervical nerves. The trigeminal nerve supplies most of the sensation to the head and face, with the ophthalmic division (V1) providing innervation to much of the supratentorial dura mater and vessels. This creates referral patterns for pain that may be misleading to clinicians and patients, as described by studies involving awake craniotomies and stimulation with electrical and mechanical stimuli. Most brain parenchyma and supratentorial vessels refer pain to the ipsilateral V1 territory, and less commonly the V2 or V3 region. The upper cervical nerves provide innervation to the posterior scalp, while the periauricular region and posterior fossa are territories with shared innervation. Afferent fibers that innervate the head and neck send nociceptive input to the trigeminocervical complex, which then projects to additional pain processing areas in the brainstem, thalamus, hypothalamus, and cortex. This chapter discusses the pain-sensitive structures in the head and neck, including pain referral patterns for many of these structures. It also provides an overview of peripheral and central nervous system structures responsible for transmitting and interpreting these nociceptive signals.
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Affiliation(s)
- Carrie E Robertson
- Department of Neurology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.
| | - Eduardo E Benarroch
- Department of Neurology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
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Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach. EPMA J 2022; 13:535-545. [PMID: 36415625 PMCID: PMC9670046 DOI: 10.1007/s13167-022-00307-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 11/04/2022] [Indexed: 11/18/2022]
Abstract
Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 — 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15–49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the “tip of the iceberg”: it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:
Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarction Application of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transition Application of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patterns Application of innovative screening programmes which adequately consider the needs of young populations Stroke is a severe brain disease which has reached an epidemic scale worldwide: in 2019, the global stroke prevalence was 101.5 million people. The World Stroke Organisation predicted that globally, 1 in 4 adults over the age of 25 will get a stroke in their lifetime. Not only old people but also teenagers and young adults are affected. Current global costs of stroke are estimated at 721 billion US dollars. Due to undiagnosed so-called “silent” brain infarction, the number of affected individuals is about 14 times greater in the population than clinically recorded. If it remains untreated, silent brain infarction may cause many severe and fatal disorders such as dementia, depression and even suicide. In this position paper, the consortium describes how the rudimental approach to treating severely diseased people could be replaced by an innovative predictive and preventive one to protect people against the health-to-disease transition.
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24
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Adnyana IMO, Widyadharma IPE, Tedyanto EH, Wijayanti IAS, Mahadewi NPAP. Migraine as a risk factor for ischemic stroke: a systematic review and meta-analysis of cohort studies. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2022. [DOI: 10.1186/s41983-022-00562-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Abstract
Background
Migraine and stroke are neurovascular diseases that have become a public health problem and a relatively high economic burden. The relationship between migraine and stroke has been described in the literature for a long time. Several studies reveal that migraine can be a risk factor for stroke.
Methods
We systematically searched PubMed using the PRISMA method and keywords according to MeSH terms to prepare this systematic review. We included published articles discussing migraine as a risk factor for ischemic stroke with a cohort study design and English article and listed the statistical value of the study.
Results
In our meta-analysis, we found that migraine significantly increases the incidence of ischemic stroke. There were 12 studies included in this systematic review, and a meta-analysis was performed. The results showed a significant association between migraine and ischemic stroke (HR 1.205, 95% CI 1.151–1.262 p = 0.000), migraine with aura and ischemic stroke (HR 1.442, 95% CI 1.241–1.675 p = 0.000), and migraine without aura and ischemic stroke (HR 1.126, 95% CI 1.048–1.211 p = 0.001). The exact mechanism of stroke caused by migraine is still unclear, although, in some theories, several mechanisms have been described that are thought to be the cause of stroke. Several important points of the cause of stroke in migraine are hemodynamic changes, endothelial dysfunction, cervical artery dissection, vascular reactivity, hypercoagulability, and abortive migraine drugs.
Conclusions
Both migraine with aura and without aura are risk factors for ischemic stroke. Several mechanisms that may cause ischemic stroke in migraine have been described, of which CSD-induced endothelial dysfunction is the primary pathophysiology of ischemic stroke in migraine.
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Chiang C, Schwedt TJ, Dodick DW. Exploring the association between migraine and atrial fibrillation utilizing a novel artificial intelligence‐ECG algorithm. Headache 2022; 62:933-934. [DOI: 10.1111/head.14366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 06/23/2022] [Indexed: 11/30/2022]
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Chiang C, Chhabra N, Chao C, Wang H, Zhang N, Lim E, Baez‐Suarez A, Attia ZI, Schwedt TJ, Dodick DW, Cutrer FM, Friedman PA, Noseworthy PA. Migraine with aura associates with a higher artificial intelligence:
ECG
atrial fibrillation prediction model output compared to migraine without aura in both women and men. Headache 2022; 62:939-951. [DOI: 10.1111/head.14339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 05/17/2022] [Accepted: 05/18/2022] [Indexed: 11/29/2022]
Affiliation(s)
| | - Nikita Chhabra
- Department of Neurology Mayo Clinic Scottsdale Arizona USA
| | - Chieh‐Ju Chao
- Department of Cardiovascular Diseases Mayo Clinic Rochester Minnesota USA
| | - Han Wang
- Department of Neurology Mayo Clinic Mankato Minnesota USA
| | - Nan Zhang
- Department of Quantitative Health Research Mayo Clinic Scottsdale Arizona USA
| | - Elisabeth Lim
- Department of Quantitative Health Research Mayo Clinic Scottsdale Arizona USA
| | | | - Zachi I. Attia
- Department of Cardiovascular Diseases Mayo Clinic Rochester Minnesota USA
| | | | | | - Fred M. Cutrer
- Department of Neurology Mayo Clinic Rochester Minnesota USA
| | - Paul A. Friedman
- Department of Cardiovascular Diseases Mayo Clinic Rochester Minnesota USA
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Borogovac A, Tarasco E, Kremer Hovinga JA, Friedman KD, Asch AS, Vesely SK, Prodan CI, Terrell DR, George JN. Prevalence of neuropsychiatric symptoms and stroke in patients with hereditary thrombotic thrombocytopenic purpura. Blood 2022; 140:785-789. [PMID: 35584244 PMCID: PMC9389633 DOI: 10.1182/blood.2022016044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/03/2022] [Indexed: 11/20/2022] Open
Abstract
In this article, Borogovac et al emphasized the burden of stroke and neuropsychiatric symptoms in patients with hereditary thrombotic thrombocytopenic purpura (hTTP) based on an analysis of the International hTTP Registry. Given the rarity of hTTP, patient numbers were small; nevertheless, the prevalence of stroke reached 100% in patients over the age of 50. Nearly all patients also had evidence of neuropsychiatric symptoms. These data confirm the need to diagnose hTTP as early as possible and support the use of prophylaxis to prevent future events.
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Affiliation(s)
- Azra Borogovac
- Hematology-Oncology Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Erika Tarasco
- Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Johanna A Kremer Hovinga
- Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Kenneth D Friedman
- Hematology-Oncology Section, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
| | - Adam S Asch
- Hematology-Oncology Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Sara K Vesely
- Department of Biostatistics and Epidemiology, Hudson College of Public Health, Oklahoma City, OK; and
| | - Calin I Prodan
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Deirdra R Terrell
- Department of Biostatistics and Epidemiology, Hudson College of Public Health, Oklahoma City, OK; and
| | - James N George
- Hematology-Oncology Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK
- Department of Biostatistics and Epidemiology, Hudson College of Public Health, Oklahoma City, OK; and
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Carcel C, Caso V, Aguiar de Sousa D, Sandset EC. Sex differences in neurovascular disorders. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 164:69-99. [PMID: 36038210 DOI: 10.1016/bs.irn.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Neurovascular disorders is a heterogenous group of diseases, including one of the most time critical disorders in emergency medicine; stroke. Sex differences are extensively described in neurovascular disorders, ranging from differences in symptom presentation, risk factors, treatment and outcomes. For example, women with stroke, more often present with generalized weakness, reduced consciousness and headache than men. Furthermore, there are differences in risk factors, outcomes and in the effect of secondary prevention. Women have a higher risk of cerebral venous thrombosis and developing cerebral aneurysms. In general, women have been underrepresented in trials on neurovascular disorders. This chapter provides an extensive overview of sex differences in stroke in general and in the differences specially seen in ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage and in cerebral venous thrombosis.
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Affiliation(s)
- Cheryl Carcel
- The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Valeria Caso
- Stroke Unit, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Diana Aguiar de Sousa
- Stroke Center, Lisbon Central University Hospital, Lisbon, Portugal; CEEM and Institute of Anatomy, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
| | - Else Charlotte Sandset
- Department of Neurology, Oslo University Hospital, Oslo, Norway; The Norwegian Air Ambulance Foundation, Oslo, Norway.
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29
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Konstantinos F, Tsolaki V, Georgakopoulou VE, Aravantinou A, Fotakopoulos G. Value of Combination Therapy With Antiepileptic Drugs (AEDs) for Migraine to Prevent Ischemic Stroke in Young Women. Cureus 2022; 14:e26972. [PMID: 36000114 PMCID: PMC9389468 DOI: 10.7759/cureus.26972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2022] [Indexed: 11/28/2022] Open
Abstract
The aim of this study was to systematically assess the efficacy of a combination of levetiracetam and sumatriptan as a preventive treatment for migraine and stroke in young women. This was a retrospective study with 342 female patients, who experienced migraines. All patients were divided into three groups: Group A (124 patients (36.2%) with triptan (sumatriptan) monotherapy), Group B (111 patients (32.4%) with a combined triptan and antiepileptic drug (AED) therapy with levetiracetam (LEV)), and Group C (107 (31.2%) patients with placebo treatment), in a 1.4:1.1:1 ratio respectively. Significant differences were found in Group B when compared with Groups A and C with respect to the use of combination hormonal contraception, smoking, a family history of migraine, and seizures. The results of this study suggested that combination treatment with levetiracetam and sumatriptan was more effective in preventing migraines and reducing the risk of stroke in young women than sumatriptan monotherapy.
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30
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Lee SJ, Yoon S, Bae YJ, Bushnell CD, Kim HJ, Kang D. Increased Risk of Cardio-Cerebrovascular Diseases in Migraine Patients: A Nationwide Population-Based, Longitudinal Follow-Up Study in South Korea. J Clin Neurol 2022; 18:323-333. [PMID: 35589320 PMCID: PMC9163934 DOI: 10.3988/jcn.2022.18.3.323] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 11/01/2021] [Accepted: 11/02/2021] [Indexed: 11/17/2022] Open
Abstract
Background and Purpose Migraine is reportedly associated with several cardio-cerebrovascular diseases (CCDs), but some of these diseases have not received sufficient attention. We thus attempted to determine the associations of migraine with peripheral arterial disease (PAD), ischemic heart disease (IHD), atrial fibrillation/flutter (AF), ischemic stroke (IS), and hemorrhagic stroke (HS). Methods The study population was recruited by applying International Classification of Diseases, Tenth Revision (ICD-10) codes to the database of the Korean National Health Insurance Service from 2002 to 2018. Cumulative incidence curves were plotted to compare the incidence rates of CCDs between the migraine (ICD-10 code G43; n=130,050) and nonmigraine (n=130,050) groups determined using 1:1 propensity-score matching. Cox proportional-hazards regression models were used to obtain adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CCDs in patients with any migraine, migraine with aura (n=99,751), and migraine without aura (n=19,562) compared with nonmigraine controls. Results For all CCDs, the cumulative incidence rates were higher in the migraine group than the nonmigraine group (p<0.001 in log-rank test). Any migraine, irrespective of the presence of aura, was associated with PAD (aHR 2.29, 95% CI 2.06–2.53), IHD (aHR 2.17, 95% CI 2.12–2.23), AF (aHR 1.84, 95% CI 1.70–1.99), IS (aHR 2.91, 95% CI 2.67–3.16), and HS (aHR 2.46, 95% CI 2.23–2.71). aHR was higher in female than in male migraineurs for all of the CCDs. Conclusions Associations of migraine with CCDs have been demonstrated, which are stronger in females than in males.
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Affiliation(s)
- Seung-Jae Lee
- Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
| | - Seok Yoon
- Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Yoon-Jong Bae
- Department of Data Science, Hanmi Pharm. Co., Ltd., Seoul, Korea
| | - Cheryl D Bushnell
- Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Hyung Jun Kim
- Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Korea
| | - Dongwoo Kang
- Department of Data Science, Hanmi Pharm. Co., Ltd., Seoul, Korea
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Pavlović JM, Derby CA. Pain in midlife women: a growing problem in need of further research. Womens Midlife Health 2022; 8:4. [PMID: 35509086 PMCID: PMC9068256 DOI: 10.1186/s40695-022-00074-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 03/01/2022] [Indexed: 11/10/2022] Open
Abstract
More than 10% of American adults experience some level of daily pain, and nearly 40 million (17.6%) experience episodes of severe pain annually. Women are particularly impacted by both episodic and chronic pain with higher prevalence and a greater level of pain-related disability compared to men. Midlife is a critical period for women during which the frequency of pain complaints begins to increase. Although pain is known to be influenced and controlled by sex hormones, it has not been widely recognized as a symptom of the menopausal transition outside of the menopause research community. The recent thematic series in this journal has specifically highlighted pain related conditions including rheumatoid arthritis, migraine and abdominal pain for which the significance among midlife women is not typically recognized. The studies presented in this thematic series present a small fraction of relevant, understudied questions regarding pain and its impact on women in midlife. Addressing the gaps in knowledge will require longitudinal studies that consider the emergence of pain symptomatology in relation to midlife trajectories of other symptoms and health determinants, as well as further study of new and emerging therapies.
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Affiliation(s)
- Jelena M Pavlović
- Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA. .,Montefiore Headache Center, Montefiore Medical Center, Bronx, NY, USA.
| | - Carol A Derby
- Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.,Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
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Merki-Feld GS, Sandor PS, Nappi RE, Pohl H, Schankin C. Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study. Acta Neurol Belg 2022; 122:401-409. [PMID: 33928470 PMCID: PMC8986701 DOI: 10.1007/s13760-021-01677-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 04/10/2021] [Indexed: 12/02/2022]
Abstract
Many studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.
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Chiang CC, Shahid AH, Harriott AM, Tietjen GE, Savastano LE, Klaas JP, Lanzino G. Evaluation and treatment of headache associated with moyamoya disease - a narrative review. Cephalalgia 2021; 42:542-552. [PMID: 34786968 DOI: 10.1177/03331024211056250] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic. METHODS We searched PubMed for keywords including moyamoya disease, moyamoya syndrome, headache in moyamoya, surgical revascularization, surgical bypass, migraine and moyamoya, and calcitonin gene-related peptide (CGRP). We summarized the literature and provide a comprehensive review of the headache presentation, possible mechanisms, the impact of various surgical revascularizations on headache in patients with moyamoya disease, and the medical management of headache incorporating novel migraine-specific treatments.Results and conclusion: The most common headache phenotype is migraine; tension-type headache, hemiplegic migraine, and cluster headache have also been reported. Most patients experience improvement of headache after surgical revascularization, though some patients report worsening, or new-onset headache after surgery. Given the complexity of moyamoya disease, careful consideration of different types of medical therapy for headache is necessary to improve the quality of life while not increasing the risk of adverse cerebrovascular events. More prospective studies are warranted to better understand and manage headache in patients with moyamoya disease.
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Affiliation(s)
- Chia-Chun Chiang
- Department of Neurology, 6915Mayo Clinic, Mayo Clinic, Rochester, MN
| | | | | | | | | | - James P Klaas
- Department of Neurology, 6915Mayo Clinic, Mayo Clinic, Rochester, MN
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Chiang MC, Dumitrascu OM, Chhabra N, Chiang CC. Migraine with Visual aura and the Risk of Stroke- a Narrative Review. J Stroke Cerebrovasc Dis 2021; 30:106067. [PMID: 34461446 DOI: 10.1016/j.jstrokecerebrovasdis.2021.106067] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 07/20/2021] [Accepted: 08/15/2021] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVES Patients with migraine with visual aura (MwvA) often present to eye care providers for evaluation. A thorough ophthalmological history and examination is needed to exclude ophthalmologic disorders. Additionally, it has been increasingly recognized that MwvA is associated with ischemic stroke (IS). The aim of this narrative review is to provide a comprehensive overview of the differential diagnosis of MwvA and its association with IS. MATERIALS AND METHODS We conducted a PubMed search using key words including "migraine aura", "visual aura without headache", "late onset migraine accompaniment", "migraine and stroke", "migraine and atrial fibrillation", and "migraine and patent foramen ovale (PFO)". We narratively summarized the main findings of the identified studies in sections including age of onset and frequency of migraine with aura, stroke subtypes, and the role of cardioembolism in the migraine-stroke association. RESULTS AND CONCLUSION For women younger than 50 years, MwvA is associated with an increased risk of IS, and the risk further increases in patients who also smoke and use oral contraceptives. Age of onset of MwvA 50 years or greater is associated with IS that occurs in late life. Studies reported that increased frequency of aura is associated with an increased risk of IS in women. MwvA is associated with an increased risk of cardioembolic stroke and a higher incidence of atrial fibrillation compared to migraine without aura. Most studies that assessed the migraine-stroke association were based on patients with MwvA. The risks of stroke associated with other types of migraine aura or aura without headache, as well as such association in men require further investigation. More data is needed to determine the absolute risk of stroke when evaluating MwvA in situations including smoking and low dose estrogen use, new or late onset (>50 years) MwvA, to facilitate the development of practice guidelines for stroke prevention in specific clinical scenarios.
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Affiliation(s)
- Meng-Chun Chiang
- Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan.
| | | | - Nikita Chhabra
- Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
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Lucas C. Migraine with aura. Rev Neurol (Paris) 2021; 177:779-784. [PMID: 34384631 DOI: 10.1016/j.neurol.2021.07.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 01/04/2023]
Abstract
Around 15% to one-third of migraineurs experience aura. Aura is a fully reversible focal neurological phenomenon involving visual, sensory, speech, and/or motor symptoms that develops gradually and usually precedes the headache phase. The pivotal role of cortical spreading depression (CSD) as a mechanism underlying aura has been widely supported by a large body of studies. The diagnosis is based on the International Headache Classification Disorders III edition criteria. Aura is characterized by gradual development, duration of each symptom no longer than one hour, a mix of positive and negative features, and complete reversibility. Visual aura is the most common type of aura, occurring in over 90% of patients. When aura symptoms are multiple, they usually follow one another in succession, beginning with visual, then sensory, then aphasic; but the reverse and other orders have been noted. The accepted duration for most aura symptoms is one hour, but motor symptoms, which are rare, are often longer lasting. When a patient experiences for the first time a possible aura phase it's sometimes difficult to know if there was gradual or brutal onset of the symptoms. If the patient has no visual aura symptoms or simultaneous neurological symptoms, or presents neurological symptoms corresponding to a cerebral vascular territory, emergency exploration of a possible transient ischemic attack is necessary. Long duration (greater than one hour) of what may or may not be an aura phase, late onset of aura, or a dramatic increase in aura attacks should also be explored. The relative risk of ischemic stroke is significantly increased in migraine with aura. Combined hormonal contraception with estrogens significantly increases the risk of stroke in women with migraine with aura. It is recommended to start non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin as soon as possible during the aura phase, not to treat the aura, but to avoid or to diminish the headache phase. In case of failure of NSAIDs or aspirin it is recommended to use a triptan when the headache begins. The prophylactic treatments for migraine with aura are those used in migraine without aura based on very few randomized clinical trials specifically dedicated to migraine with aura.
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Affiliation(s)
- C Lucas
- Centre d'evaluation et de traitement de la douleur, service de neurochirurgie, hôpital Salengro, CHU de Lille, 59037 Lille Cedex, France.
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Ducros A, de Gaalon S, Roos C, Donnet A, Giraud P, Guégan-Massardier E, Lantéri-Minet M, Lucas C, Mawet J, Moisset X, Valade D, Demarquay G. Revised guidelines of the French headache society for the diagnosis and management of migraine in adults. Part 2: Pharmacological treatment. Rev Neurol (Paris) 2021; 177:734-752. [PMID: 34340810 DOI: 10.1016/j.neurol.2021.07.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 07/09/2021] [Indexed: 12/21/2022]
Abstract
The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the second part of the guidelines, which is focused on the pharmacological treatment of migraine, including both the acute treatment of attacks and the prophylaxis of episodic migraine as well as chronic migraine with and without medication overuse. The specific situations that can be encountered in women with migraine are also discussed, including pregnancy, menstrual migraine, contraception and hormonal replacement therapy.
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Affiliation(s)
- A Ducros
- Department of neurology, Gui-de-Chauliac hospital, CHU Montpellier, university of Montpellier, 34000 Montpellier, France
| | - S de Gaalon
- Department of neurology, Laënnec hospital, CHU de Nantes, Nantes, France
| | - C Roos
- Emergency headache center (centre d'urgences céphalées), department of neurology, Lariboisière hospital, Assistance publique-Hôpitaux de Paris, Paris, France
| | - A Donnet
- Centre d'évaluation et de traitement de la douleur, FHU INOVPAIN, hôpital de La Timone, Marseille, France
| | - P Giraud
- Department of neurology, Annecy Genevois hospital, Annecy, France
| | | | - M Lantéri-Minet
- Pain department, FHU InovPain, CHU Nice Côte Azur université, Nice, France
| | - C Lucas
- Centre d'évaluation et de traitement de la douleur, service de neurochirurgie, hôpital Salengro, CHRU de Lille, Lille, France
| | - J Mawet
- Emergency headache center (centre d'urgences céphalées), department of neurology, Lariboisière hospital, Assistance publique-Hôpitaux de Paris, Paris, France
| | - X Moisset
- Neuro-Dol, université Clermont Auvergne, CHU de Clermont-Ferrand, INSERM, Clermont-Ferrand, France
| | - D Valade
- Department of neurosurgery, hôpital Pitié-Sapêtrière, Paris, France
| | - G Demarquay
- Neurological hospital, Lyon, neuroscience research center (CRNL), INSERM U1028, CNRS UMR5292, Lyon, France.
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Altamura C, Cascio Rizzo A, Viticchi G, Maggio P, Costa CM, Brunelli N, Giussani G, Paolucci M, Fiacco F, Di Lazzaro V, Agostoni EC, Silvestrini M, Vernieri F. Shorter visual aura characterizes young and middle-aged stroke patients with migraine with aura. J Neurol 2021; 269:897-906. [PMID: 34169343 DOI: 10.1007/s00415-021-10671-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 06/14/2021] [Accepted: 06/14/2021] [Indexed: 01/02/2023]
Abstract
OBJECTIVE To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA-) MwA and aura features in MwA patients with (S+MwA+) or without (S-MwA+) stroke. METHODS In this retrospective multicenter case-control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA- patients younger than 60 years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S-MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). RESULTS 539 stroke (7.7% S+MwA+) and 94 S-MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12-11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15-6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26-14.18)] than S+MwA- subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S-MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36-10.66)] and shorter-lasting (20.0 min IQr 13.1 vs 30.0 min IQr 25.0; p < 0.001) aura, and PFO [OR 1.26 (95% CI 1.03-1.54)]. Regression analysis evidenced that only shorter aura duration associated with stroke (p = 0.001). High-risk PFO was equally represented in S+MwA-, S+MwA+, S-MwA+ groups. CONCLUSIONS Shorter visual aura and CIS characterize MwA patients with stroke. Although more prevalent, PFO can not be considered the main responsible for the increased stroke risk in MwA patients but as a part of a complex multifactorial condition.
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Affiliation(s)
- Claudia Altamura
- Headache and Neurosonology Unit, Neurology, Università Campus Bio-Medico Di Roma, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128, Rome, Italy.
| | - Angelo Cascio Rizzo
- Neurologia E Stroke Unit ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | | | | | - Carmelina Maria Costa
- Headache and Neurosonology Unit, Neurology, Università Campus Bio-Medico Di Roma, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128, Rome, Italy
| | - Nicoletta Brunelli
- Headache and Neurosonology Unit, Neurology, Università Campus Bio-Medico Di Roma, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128, Rome, Italy
| | - Giuditta Giussani
- Neurologia E Stroke Unit ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Matteo Paolucci
- Headache and Neurosonology Unit, Neurology, Università Campus Bio-Medico Di Roma, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128, Rome, Italy
| | | | - Vincenzo Di Lazzaro
- Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy
| | | | | | - Fabrizio Vernieri
- Headache and Neurosonology Unit, Neurology, Università Campus Bio-Medico Di Roma, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128, Rome, Italy
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Abstract
PURPOSE OF REVIEW Women are greatly overrepresented among patients seeking treatment for symptoms of headache pain in general and migraine in particular. Understanding the presentation of headache in women in relation to hormonal changes both during the menstrual cycle and throughout the life span is essential for appropriate diagnosis and treatment. RECENT FINDINGS Although perimenstrual migraine attacks are generally without aura, the diagnosis of migraine with aura has been added to the headache classification for menstrual migraine to account for women with the diagnosis of migraine with aura who experience menstrual migraine attacks. Emerging knowledge regarding the differences between menstrual and nonmenstrual attacks, the variability of attack triggering within and between women, and the response of women with menstrually related migraine to new migraine drug classes is contributing to better understanding and more effective treatment of these particularly burdensome and refractory attacks. Given the burden of migraine, almost one-fourth of women with migraine avoid or delay pregnancy. Women who experience migraine during pregnancy are more likely to have a hypertensive disorder and stroke during pregnancy and/or delivery and the postpartum period. Treatment of headache in general and migraine in particular in pregnancy is challenging because of fetal and maternal risks; however, a 2021 systematic review suggests that triptans and low-dose aspirin may not be associated with fetal/child adverse effects and could be more strongly considered for headache treatment in pregnancy. SUMMARY Headache in general and migraine in particular are extraordinarily common in women of reproductive age and fluctuate with hormonal changes and phases of life. Improved knowledge of the epidemiology, pathophysiology, and response to treatment of perimenstrual attacks is essential for more effective response to this most burdensome headache type. Treatment of headache in pregnancy remains challenging.
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Zucker R, Reisman T, Safer JD. Minimizing Venous Thromboembolism in Feminizing Hormone Therapy: Applying Lessons From Cisgender Women and Previous Data. Endocr Pract 2021; 27:621-625. [PMID: 33819637 DOI: 10.1016/j.eprac.2021.03.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To review he impact of estrogen-containing feminizing hormone regimens on transgender individuals' risk for VTE. METHODS We evaluated VTE risk by screening 1170 relevant studies published from 1994 to 2020, focusing on meta-analysis data. RESULTS The type of oral estrogen, route of administration, patient demographics, and comorbidities may affect the risk of VTE. Venous thrombosis is the most common vascular complication associated with HT. CONCLUSION Conjugated equine estrogens and 17-β estradiol appear to be safer than oral ethinyl estradiol. Transdermal estrogen formulations appear to be the least thrombogenic estrogens. Estrogens used concomitantly with progestins increase the risk of VTE compared to estrogens alone. To date, there are no data to demonstrate the benefit of holding HT prior to vaginoplasty or other gender affirming surgeries. For most young, healthy transgender women, there is little risk of VTE with HT, while older patients with risk factors should be discussed case by case.
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Affiliation(s)
- Roy Zucker
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Tamar Reisman
- Icahn School of Medicine at Mount Sinai, New York, New York; Center for Transgender Medicine and Surgery, Mount Sinai Health System, New York, New York
| | - Joshua D Safer
- Icahn School of Medicine at Mount Sinai, New York, New York; Center for Transgender Medicine and Surgery, Mount Sinai Health System, New York, New York.
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Guo Y, Rist PM, Sabater-Lleal M, de Vries P, Smith N, Ridker PM, Kurth T, Chasman DI. Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis. Neurology 2021; 96:e2481-e2487. [PMID: 33795393 DOI: 10.1212/wnl.0000000000011931] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 02/24/2021] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis. METHODS Two-sample Mendelian randomization instrumental analyses leveraging available genome-wide association study (GWAS) summary statistics were applied to hemostatic measures as potentially causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of 8 hemostatic factors and 2 fibrinopeptides together with 2 hemostasis clinical tests. RESULTS There were significant instrumental effects between increased coagulation factor VIII activity (FVIII; odds ratio [95% confidence interval] 1.05 [1.03, 1.08]/SD, p = 6.08 × 10-05), von Willebrand factor level (vWF; 1.05 [1.03, 1.08]/SD, p = 2.25 × 10-06), and phosphorylated fibrinopeptide A level (1.13 [1.07, 1.19]/SD, p = 5.44 × 10-06) with migraine susceptibility. When extended to migraine subtypes, FVIII, vWF, and phosphorylated fibrinopeptide A showed slightly stronger effects with MA than overall migraine. Fibrinogen level was inversely linked with MA (0.76 [0.64, 0.91]/SD, p = 2.32 × 10-03) but not overall migraine. None of the hemostatic factors was linked with MO. In sensitivity analysis, effects for fibrinogen and phosphorylated fibrinopeptide A were robust, whereas independent effects of FVIII and vWF could not be distinguished, and FVIII associations were potentially affected by pleiotropy at the ABO locus. Causal effects from migraine to the hemostatic measures were not supported in reverse Mendelian randomization. However, MA was not included due to lack of instruments. CONCLUSIONS The findings support potential causality of increased FVIII, vWF, and phosphorylated fibrinopeptide A and decreased fibrinogen in migraine susceptibility, especially for MA, potentially revealing etiologic relationships between hemostasis and migraine.
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Affiliation(s)
- Yanjun Guo
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Pamela M Rist
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Maria Sabater-Lleal
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Paul de Vries
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Nicholas Smith
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Paul M Ridker
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Tobias Kurth
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany
| | - Daniel I Chasman
- From the Division of Preventive Medicine (Y.G., P.M. Rist, P.M. Ridker, D.C.), Brigham and Women's Hospital; Harvard Medical School (Y.G., P.M. Rist, P.M. Ridker, D.I.C.); Department of Epidemiology (Y.G., P.M. Rist, P.M. Ridker, T.K., D.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Genomics of Complex Diseases (M.S.-L.), Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine (M.S.-L.), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences (P.d.V.), School of Public Health, The University of Texas Health Science Center at Houston; Department of Epidemiology (N.S.), University of Washington; Kaiser Permanente Washington Health Research Institute (N.S.), Seattle; Seattle Epidemiologic Research and Information Center (N.S.), Department of Veterans Affairs Office of Research and Development, WA; and Institute of Public Health (T.K.), Charité-Universitätsmedizin Berlin, Germany.
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Abstract
PURPOSE OF REVIEW Gender differences exist in headache disorders. A greater understanding of the role of hormones in headache can help the clinician better approach and manage common primary headache disorders. RECENT FINDINGS Recent studies highlight differences in how migraine and cluster headache present in women and men. Updates to the ongoing debate of how to manage the use of hormones in women with migraine, especially with aura, have been well reviewed in the last 18 months. A new meta-analysis evaluates gender differences in response to triptans. SUMMARY This review will focus on recent updates on the role of gender and hormones on migraine and cluster headache and how this may influence treatment.
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Menstrual and perimenopausal migraine: A narrative review. Maturitas 2020; 142:24-30. [DOI: 10.1016/j.maturitas.2020.07.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/01/2020] [Accepted: 07/08/2020] [Indexed: 12/12/2022]
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Tietjen GE. The American Headache Society and the New Women's Health Research Award. Headache 2020; 60:824-825. [PMID: 32337723 DOI: 10.1111/head.13819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 04/01/2020] [Indexed: 11/29/2022]
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Roberts J, Ward TN. This May 2020 Issue of Headache Contains Several Articles of Significance. Headache 2020; 60:819. [PMID: 32337721 DOI: 10.1111/head.13817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 11/26/2022]
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