Skip to main content
Top
Published in: The Journal of Headache and Pain 1/2022

Open Access 01-12-2022 | Migraine | Research

Gradually shifting clinical phenomics in migraine spectrum: a cross-sectional, multicenter study of 5438 patients

Authors: Ye Ran, Ziming Yin, Yajun Lian, Yanmei Xu, Yajie Li, Jiale Liu, Qun Gu, Fanhong Yan, Zhaoli Ge, Yu Lian, Dongmei Hu, Sufen Chen, Yangyang Wang, Xiaolin Wang, Rongfei Wang, Xiaoyan Chen, Jing Liu, Mingjie Zhang, Xun Han, Wei Xie, Zhe Yu, Ya Cao, Yingji Li, Ke Li, Zhao Dong, Shengyuan Yu

Published in: The Journal of Headache and Pain | Issue 1/2022

Login to get access

Abstract

Background

The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum.

Methods

In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis.

Results

Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree’s accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM.

Conclusions

The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different “predominant regions” that generate attacks.
Appendix
Available only for authorised users
Literature
1.
go back to reference Steiner TJ, Stovner LJ, Vos T et al (2018) Migraine Is First Cause of Disability in under 50s: Will Health Politicians Now Take Notice? J Headache Pain. 19(1):17PubMedPubMedCentralCrossRef Steiner TJ, Stovner LJ, Vos T et al (2018) Migraine Is First Cause of Disability in under 50s: Will Health Politicians Now Take Notice? J Headache Pain. 19(1):17PubMedPubMedCentralCrossRef
2.
go back to reference IHS H. C. C. o. t. I. H. S (2018) The International Classification of Headache Disorders, 3rd Edition. Cephalalgia: an international journal of headache. 38(1):1–211CrossRef IHS H. C. C. o. t. I. H. S (2018) The International Classification of Headache Disorders, 3rd Edition. Cephalalgia: an international journal of headache. 38(1):1–211CrossRef
3.
go back to reference Ranson R, Igarashi H, MacGregor EA et al (1991) The Similarities and Differences of Migraine with Aura and Migraine without Aura: A Preliminary Study. Cephalalgia: an international journal of headache. 11(4):189–192CrossRef Ranson R, Igarashi H, MacGregor EA et al (1991) The Similarities and Differences of Migraine with Aura and Migraine without Aura: A Preliminary Study. Cephalalgia: an international journal of headache. 11(4):189–192CrossRef
4.
go back to reference R MB, R BK, F K et al (1996) Migraine without aura and migraine with aura are distinct clinical entities: a study of four hundred and eighty-four male and female migraineurs from the general population. Cephalalgia: an international journal of headache 16(4):239–45CrossRef R MB, R BK, F K et al (1996) Migraine without aura and migraine with aura are distinct clinical entities: a study of four hundred and eighty-four male and female migraineurs from the general population. Cephalalgia: an international journal of headache 16(4):239–45CrossRef
5.
go back to reference Manzoni GC, Torelli P (2008) Migraine with and without aura: a single entity? Neurological sciences: official journal of the Italian neurological society and of the Italian. Society Clin Neurophysiol 29(Suppl 1):S40–S43 Manzoni GC, Torelli P (2008) Migraine with and without aura: a single entity? Neurological sciences: official journal of the Italian neurological society and of the Italian. Society Clin Neurophysiol 29(Suppl 1):S40–S43
7.
go back to reference Szabó N, Faragó P, Király A et al (2018) Evidence for Plastic Processes in Migraine with Aura: A Diffusion Weighted Mri Study. Front Neuroanat. 11:138–138PubMedPubMedCentralCrossRef Szabó N, Faragó P, Király A et al (2018) Evidence for Plastic Processes in Migraine with Aura: A Diffusion Weighted Mri Study. Front Neuroanat. 11:138–138PubMedPubMedCentralCrossRef
8.
go back to reference Frid A, Shor M, Shifrin A et al (2020) A Biomarker for Discriminating between Migraine with and without Aura: Machine Learning on Functional Connectivity on Resting-State Eegs. Annals of Biomedical Engineering. 48(1):403–412PubMedCrossRef Frid A, Shor M, Shifrin A et al (2020) A Biomarker for Discriminating between Migraine with and without Aura: Machine Learning on Functional Connectivity on Resting-State Eegs. Annals of Biomedical Engineering. 48(1):403–412PubMedCrossRef
9.
go back to reference Hansen JM, Goadsby PJ, Charles A (2015) Reduced Efficacy of Sumatriptan in Migraine with Aura Vs without Aura. Neurology 84(18):1880–5PubMedCrossRef Hansen JM, Goadsby PJ, Charles A (2015) Reduced Efficacy of Sumatriptan in Migraine with Aura Vs without Aura. Neurology 84(18):1880–5PubMedCrossRef
10.
go back to reference Magon S, May A, Stankewitz A et al (2019) Cortical Abnormalities in Episodic Migraine: A Multi-Center 3t Mri Study. Cephalalgia: an international journal of headache. 39(5):665–673PubMedCrossRef Magon S, May A, Stankewitz A et al (2019) Cortical Abnormalities in Episodic Migraine: A Multi-Center 3t Mri Study. Cephalalgia: an international journal of headache. 39(5):665–673PubMedCrossRef
11.
go back to reference Oedegaard KJ, Neckelmann D, Mykletun A et al (2006) Migraine with and without Aura: Association with Depression and Anxiety Disorder in a Population-Based Study. The Hunt Study. Cephalalgia: an international journal of headache 26(1):1–6PubMedCrossRef Oedegaard KJ, Neckelmann D, Mykletun A et al (2006) Migraine with and without Aura: Association with Depression and Anxiety Disorder in a Population-Based Study. The Hunt Study. Cephalalgia: an international journal of headache 26(1):1–6PubMedCrossRef
12.
go back to reference Marmura MJ, Silberstein SD, Schwedt TJ (2015) The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache 55(1):3–20. Marmura MJ, Silberstein SD, Schwedt TJ (2015) The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache 55(1):3–20.
13.
go back to reference Lampl C, Katsarava Z, Diener HC et al (2005) Lamotrigine Reduces Migraine Aura and Migraine Attacks in Patients with Migraine with Aura. Journal of neurology, neurosurgery, and psychiatry. 76(12):1730–1732PubMedPubMedCentralCrossRef Lampl C, Katsarava Z, Diener HC et al (2005) Lamotrigine Reduces Migraine Aura and Migraine Attacks in Patients with Migraine with Aura. Journal of neurology, neurosurgery, and psychiatry. 76(12):1730–1732PubMedPubMedCentralCrossRef
14.
go back to reference Mahmoud AN, Mentias A, Elgendy AY et al (2018) Migraine and the Risk of Cardiovascular and Cerebrovascular Events: A Meta-Analysis of 16 Cohort Studies Including 1 152 407 Subjects. BMJ Open. 8(3):e020498PubMedPubMedCentralCrossRef Mahmoud AN, Mentias A, Elgendy AY et al (2018) Migraine and the Risk of Cardiovascular and Cerebrovascular Events: A Meta-Analysis of 16 Cohort Studies Including 1 152 407 Subjects. BMJ Open. 8(3):e020498PubMedPubMedCentralCrossRef
15.
go back to reference IHS (2013) The International Classification of Headache Disorders, 3rd Edition (Beta Version). Cephalalgia: an international journal of headache. 33(9):629–808CrossRef IHS (2013) The International Classification of Headache Disorders, 3rd Edition (Beta Version). Cephalalgia: an international journal of headache. 33(9):629–808CrossRef
16.
go back to reference Dong Z, Yin Z, He M et al (2014) Validation of a Guideline-Based Decision Support System for the Diagnosis of Primary Headache Disorders Based on Ichd-3 Beta. The journal of headache and pain 15:40PubMedPubMedCentralCrossRef Dong Z, Yin Z, He M et al (2014) Validation of a Guideline-Based Decision Support System for the Diagnosis of Primary Headache Disorders Based on Ichd-3 Beta. The journal of headache and pain 15:40PubMedPubMedCentralCrossRef
17.
go back to reference Yin Z, Dong Z, Lu X et al (2015) A Clinical Decision Support System for the Diagnosis of Probable Migraine and Probable Tension-Type Headache Based on Case-Based Reasoning. The journal of headache and pain 16:29PubMedPubMedCentralCrossRef Yin Z, Dong Z, Lu X et al (2015) A Clinical Decision Support System for the Diagnosis of Probable Migraine and Probable Tension-Type Headache Based on Case-Based Reasoning. The journal of headache and pain 16:29PubMedPubMedCentralCrossRef
18.
go back to reference Wang X, Yin Z, Lian Y et al (2021) Premonitory Symptoms in Migraine from China: A Multi-Clinic Study of 4821 Patients. Cephalalgia: an international journal of headache. 41(9):991–1003PubMedCrossRef Wang X, Yin Z, Lian Y et al (2021) Premonitory Symptoms in Migraine from China: A Multi-Clinic Study of 4821 Patients. Cephalalgia: an international journal of headache. 41(9):991–1003PubMedCrossRef
19.
go back to reference Olesen J, Steiner TJ (2004) The International classification of headache disorders, 2nd edn (ICDH-II). J Neurology, Neurosurg Psychiatry 75(6):808–811 Olesen J, Steiner TJ (2004) The International classification of headache disorders, 2nd edn (ICDH-II). J Neurology, Neurosurg Psychiatry 75(6):808–811
21.
go back to reference Wang SJ, Fuh JL, Young YH et al (2000) Prevalence of Migraine in Taipei, Taiwan: A Population-Based Survey. Cephalalgia: an international journal of headache. 20(6):566–572CrossRef Wang SJ, Fuh JL, Young YH et al (2000) Prevalence of Migraine in Taipei, Taiwan: A Population-Based Survey. Cephalalgia: an international journal of headache. 20(6):566–572CrossRef
22.
go back to reference Takeshima T, Ishizaki K, Fukuhara Y et al (2004) Population-based door-to-door survey of migraine in Japan: the daisen study. Headache 44(1):8–19 Takeshima T, Ishizaki K, Fukuhara Y et al (2004) Population-based door-to-door survey of migraine in Japan: the daisen study. Headache 44(1):8–19
23.
go back to reference Mb R, Bk R, P T., et al (1995) Prevalence and sex-ratio of the subtypes of migraine. Int J Epidemiol 24(3):612–8CrossRef Mb R, Bk R, P T., et al (1995) Prevalence and sex-ratio of the subtypes of migraine. Int J Epidemiol 24(3):612–8CrossRef
24.
go back to reference Launer LJ, Terwindt GM, Ferrari MD (1999) The Prevalence and Characteristics of Migraine in a Population-Based Cohort: The Gem Study. Neurology. 53(3):537–42PubMedCrossRef Launer LJ, Terwindt GM, Ferrari MD (1999) The Prevalence and Characteristics of Migraine in a Population-Based Cohort: The Gem Study. Neurology. 53(3):537–42PubMedCrossRef
25.
go back to reference Bánk J, Márton S (2000) Hungarian Migraine Epidemiology. Headache. 40(2):164–169PubMed Bánk J, Márton S (2000) Hungarian Migraine Epidemiology. Headache. 40(2):164–169PubMed
26.
go back to reference Zivadinov R, Willheim K, Jurjevic A et al (2001) Prevalence of Migraine in Croatia: A Population-Based Survey. Headache. 41(8):805–812PubMedCrossRef Zivadinov R, Willheim K, Jurjevic A et al (2001) Prevalence of Migraine in Croatia: A Population-Based Survey. Headache. 41(8):805–812PubMedCrossRef
27.
go back to reference Wang Y, Zhou J, Fan X et al (2011) Classification and Clinical Features of Headache Patients: An Outpatient Clinic Study from China. The journal of headache and pain 12(5):561–7PubMedPubMedCentralCrossRef Wang Y, Zhou J, Fan X et al (2011) Classification and Clinical Features of Headache Patients: An Outpatient Clinic Study from China. The journal of headache and pain 12(5):561–7PubMedPubMedCentralCrossRef
28.
go back to reference Fukui PT, Gonçalves TRT, Strabelli CG et al (2008) Trigger Factors in Migraine Patients. Arq Neuropsiquiatr 66(3A):494–499PubMedCrossRef Fukui PT, Gonçalves TRT, Strabelli CG et al (2008) Trigger Factors in Migraine Patients. Arq Neuropsiquiatr 66(3A):494–499PubMedCrossRef
29.
go back to reference Granella F, Sances G, Pucci E et al (2000) Migraine with Aura and Reproductive Life Events: A Case Control Study. Cephalalgia: an international journal of headache. 20(8):701–707CrossRef Granella F, Sances G, Pucci E et al (2000) Migraine with Aura and Reproductive Life Events: A Case Control Study. Cephalalgia: an international journal of headache. 20(8):701–707CrossRef
30.
go back to reference Smith LJ, Henderson JA, Abell CW et al (2004) Effects of Ovarian Steroids and Raloxifene on Proteins That Synthesize, Transport, and Degrade Serotonin in the Raphe Region of Macaques. Neuropsychopharmacology. 29(11):2035–45PubMedCrossRef Smith LJ, Henderson JA, Abell CW et al (2004) Effects of Ovarian Steroids and Raloxifene on Proteins That Synthesize, Transport, and Degrade Serotonin in the Raphe Region of Macaques. Neuropsychopharmacology. 29(11):2035–45PubMedCrossRef
31.
go back to reference Wagner EJ, Ronnekleiv OK, Bosch MA et al (2001) Estrogen Biphasically Modifies Hypothalamic Gabaergic Function Concomitantly with Negative and Positive Control of Luteinizing Hormone Release. The Journal of neuroscience: the official journal of the Society for Neuroscience 21(6):2085–93CrossRef Wagner EJ, Ronnekleiv OK, Bosch MA et al (2001) Estrogen Biphasically Modifies Hypothalamic Gabaergic Function Concomitantly with Negative and Positive Control of Luteinizing Hormone Release. The Journal of neuroscience: the official journal of the Society for Neuroscience 21(6):2085–93CrossRef
32.
go back to reference Wang D, Zhao J, Wang J et al (2014) Deficiency of Female Sex Hormones Augments Pge2 and Cgrp Levels within Midbrain Periaqueductal Gray. Journal of the neurological sciences. 346(1–2):107–11PubMedCrossRef Wang D, Zhao J, Wang J et al (2014) Deficiency of Female Sex Hormones Augments Pge2 and Cgrp Levels within Midbrain Periaqueductal Gray. Journal of the neurological sciences. 346(1–2):107–11PubMedCrossRef
33.
go back to reference Facchinetti F, Martignoni E, Fioroni L et al (1990) Opioid Control of the Hypothalamus-Pituitary-Adrenal Axis Cyclically Fails in Menstrual Migraine. Cephalalgia: an international journal of headache 10(1):51–6CrossRef Facchinetti F, Martignoni E, Fioroni L et al (1990) Opioid Control of the Hypothalamus-Pituitary-Adrenal Axis Cyclically Fails in Menstrual Migraine. Cephalalgia: an international journal of headache 10(1):51–6CrossRef
34.
go back to reference Nag S, Mokha SS (2004) Estrogen Attenuates Antinociception Produced by Stimulation of Kölliker-Fuse Nucleus in the Rat. Eur J Neurosci 20(11):3203–7PubMedCrossRef Nag S, Mokha SS (2004) Estrogen Attenuates Antinociception Produced by Stimulation of Kölliker-Fuse Nucleus in the Rat. Eur J Neurosci 20(11):3203–7PubMedCrossRef
35.
go back to reference Kelman L (2007) The Triggers or Precipitants of the Acute Migraine Attack. Cephalalgia: an international journal of headache. 27(5):394–402CrossRef Kelman L (2007) The Triggers or Precipitants of the Acute Migraine Attack. Cephalalgia: an international journal of headache. 27(5):394–402CrossRef
36.
37.
go back to reference H AW, K M, O J (2010) Trigger factors in migraine with aura. Cephalalgia: an international journal of headache 30(3):346–53CrossRef H AW, K M, O J (2010) Trigger factors in migraine with aura. Cephalalgia: an international journal of headache 30(3):346–53CrossRef
38.
go back to reference Brown RE, Basheer R, McKenna JT et al (2012) Control of Sleep and Wakefulness. Physiological reviews. 92(3):1087–1187PubMedCrossRef Brown RE, Basheer R, McKenna JT et al (2012) Control of Sleep and Wakefulness. Physiological reviews. 92(3):1087–1187PubMedCrossRef
39.
go back to reference Bao A-M, Swaab DF (2019) The Human Hypothalamus in Mood Disorders: The Hpa Axis in the Center. IBRO Reports. 6:45–53PubMedCrossRef Bao A-M, Swaab DF (2019) The Human Hypothalamus in Mood Disorders: The Hpa Axis in the Center. IBRO Reports. 6:45–53PubMedCrossRef
40.
go back to reference Martin VT, Behbehani MM (2001) Toward a Rational Understanding of Migraine Trigger Factors. The Medical clinics of North America. 85(4):911–941PubMedCrossRef Martin VT, Behbehani MM (2001) Toward a Rational Understanding of Migraine Trigger Factors. The Medical clinics of North America. 85(4):911–941PubMedCrossRef
41.
go back to reference Stankewitz A, May A (2011) Increased Limbic and Brainstem Activity During Migraine Attacks Following Olfactory Stimulation. Neurology. 77(5):476–482PubMedCrossRef Stankewitz A, May A (2011) Increased Limbic and Brainstem Activity During Migraine Attacks Following Olfactory Stimulation. Neurology. 77(5):476–482PubMedCrossRef
42.
go back to reference Karsan N, Goadsby PJ (2018) Biological Insights from the Premonitory Symptoms of Migraine. Nature reviews. Neurology. 14(12):699–710PubMedCrossRef Karsan N, Goadsby PJ (2018) Biological Insights from the Premonitory Symptoms of Migraine. Nature reviews. Neurology. 14(12):699–710PubMedCrossRef
43.
go back to reference Knight YE, Bartsch T, Kaube H et al (2002) P/Q-Type Calcium-Channel Blockade in the Periaqueductal Gray Facilitates Trigeminal Nociception: A Functional Genetic Link for Migraine? The Journal of neuroscience: the official journal of the Society for Neuroscience. 22(5):RC213CrossRef Knight YE, Bartsch T, Kaube H et al (2002) P/Q-Type Calcium-Channel Blockade in the Periaqueductal Gray Facilitates Trigeminal Nociception: A Functional Genetic Link for Migraine? The Journal of neuroscience: the official journal of the Society for Neuroscience. 22(5):RC213CrossRef
44.
go back to reference Goadsby PJ, Lambert GA, Lance JW (1982) Differential Effects on the Internal and External Carotid Circulation of the Monkey Evoked by Locus Coeruleus Stimulation. Brain research. 249(2):247–254PubMedCrossRef Goadsby PJ, Lambert GA, Lance JW (1982) Differential Effects on the Internal and External Carotid Circulation of the Monkey Evoked by Locus Coeruleus Stimulation. Brain research. 249(2):247–254PubMedCrossRef
45.
go back to reference Aurora SK (2009) Spectrum of Illness: Understanding Biological Patterns and Relationships in Chronic Migraine. Neurology. 72(5 Suppl):S8-13PubMed Aurora SK (2009) Spectrum of Illness: Understanding Biological Patterns and Relationships in Chronic Migraine. Neurology. 72(5 Suppl):S8-13PubMed
46.
go back to reference Aurora SK (2009) Is Chronic Migraine One End of a Spectrum of Migraine or a Separate Entity? Cephalalgia: an international journal of headache. 29(6):597–605CrossRef Aurora SK (2009) Is Chronic Migraine One End of a Spectrum of Migraine or a Separate Entity? Cephalalgia: an international journal of headache. 29(6):597–605CrossRef
47.
go back to reference Leao AAP (1944) Spreading Depression of Activity in the Cerebral Cortex. Journal of Neurophysiology. 7(6):359–390CrossRef Leao AAP (1944) Spreading Depression of Activity in the Cerebral Cortex. Journal of Neurophysiology. 7(6):359–390CrossRef
48.
go back to reference Vgontzas A, Burch R (2018) Episodic Migraine with and without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks. Current pain and headache reports. 22(12):78PubMedCrossRef Vgontzas A, Burch R (2018) Episodic Migraine with and without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks. Current pain and headache reports. 22(12):78PubMedCrossRef
49.
go back to reference Schulte LH, May A (2016) The Migraine Generator Revisited: Continuous Scanning of the Migraine Cycle over 30 Days and Three Spontaneous Attacks. Brain: a journal of neurology. 139(Pt 7):1987–1993CrossRef Schulte LH, May A (2016) The Migraine Generator Revisited: Continuous Scanning of the Migraine Cycle over 30 Days and Three Spontaneous Attacks. Brain: a journal of neurology. 139(Pt 7):1987–1993CrossRef
50.
go back to reference Schulte LH, Mehnert J, May A (2020) Longitudinal Neuroimaging over 30 Days: Temporal Characteristics of Migraine. Annals of neurology. 87(4):646–651PubMedCrossRef Schulte LH, Mehnert J, May A (2020) Longitudinal Neuroimaging over 30 Days: Temporal Characteristics of Migraine. Annals of neurology. 87(4):646–651PubMedCrossRef
51.
go back to reference Peng K-P, May A (2018) Quantitative Sensory Testing in Migraine Patients Must Be Phase-Specific. Pain. 159(11):2414–2416PubMedCrossRef Peng K-P, May A (2018) Quantitative Sensory Testing in Migraine Patients Must Be Phase-Specific. Pain. 159(11):2414–2416PubMedCrossRef
52.
go back to reference Peng K-P, May A (2019) Migraine Understood as a Sensory Threshold Disease. Pain. 160(7):1494–1501PubMedCrossRef Peng K-P, May A (2019) Migraine Understood as a Sensory Threshold Disease. Pain. 160(7):1494–1501PubMedCrossRef
53.
go back to reference Rasmussen BK (1995) Migraine with Aura and Migraine without Aura Are Two Different Entities. Cephalalgia: an international journal of headache 15(3):183–6CrossRef Rasmussen BK (1995) Migraine with Aura and Migraine without Aura Are Two Different Entities. Cephalalgia: an international journal of headache 15(3):183–6CrossRef
Metadata
Title
Gradually shifting clinical phenomics in migraine spectrum: a cross-sectional, multicenter study of 5438 patients
Authors
Ye Ran
Ziming Yin
Yajun Lian
Yanmei Xu
Yajie Li
Jiale Liu
Qun Gu
Fanhong Yan
Zhaoli Ge
Yu Lian
Dongmei Hu
Sufen Chen
Yangyang Wang
Xiaolin Wang
Rongfei Wang
Xiaoyan Chen
Jing Liu
Mingjie Zhang
Xun Han
Wei Xie
Zhe Yu
Ya Cao
Yingji Li
Ke Li
Zhao Dong
Shengyuan Yu
Publication date
01-12-2022
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2022
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-022-01461-5

Other articles of this Issue 1/2022

The Journal of Headache and Pain 1/2022 Go to the issue