Classifying migraine subtypes and their characteristics by latent class analysis using data of a nation-wide population-based study

DOI: https://doi.org/10.1038/s41598- 021- 01107- 7

Abstract-Summary Migraine neither presents with a definitive single symptom nor has a distinct bio- marker; thus, its diagnosis is based on combinations of typical symptoms.

We aimed to identify natural subgroups of migraine based on symptoms listed in the diagnostic criteria of the third edition of the International Classification of Headache Disorders.

We selected a three-class model based on Akaike and Bayesian information cri- teria and characterized the three identified classes as “mild and low frequency,” “photophobia and phonophobia,” and “severe and high frequency.”

52.0% (65/125) of the participants were classified as “mild and low frequency,” showing the highest frequency of mild headache intensity but the lowest overall headache frequency.

“severe and high frequency” included 14.4% (18/125) of the participants, and they presented the highest frequency of severe headache intensity and highest head- ache frequency.

Introduction Individuals with migraine have varying symptom combinations.

Previous studies on subtyping of migraine symptoms were mostly performed during genetic analyses among individuals with headache, mostly using data of twins and their relatives [66–71].

Although these subtyped migraine symptoms, involved individuals included

both non-migraine headache and those with migraine.

Further, although two studies have subtyped clinical symptoms exclusively in individuals with migraine, these studies used cohort data of health professionals [72, 73].

The Korean Sleep-Headache Survey (KSHS) was a nationwide population-based cross-sectional survey about headaches and sleep that provides an opportunity to evaluate and to subtype clinical symptoms of individuals with migraine in a general population.

This study aimed to identify the subtypes of migraine symptoms in individuals

with migraine through LCA using the data of KSHS.

Results There were significant differences in the distribution of headache intensity, unilat- eral pain, aggravation by routine physical activity, nausea, vomiting, photophobia and phonophobia among the three classes but not in pulsating quality.

Unilateral pain and mild headache intensity were the most frequent symptoms, and aggravation by routine physical activity was the least frequent in Class 1, while photophobia and phonophobia were the most frequent in Class 2.

3.1 Classification

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Class 3 showed the highest frequency of nausea, aggravation of routine physical

activity and severe headache intensity.

The multiple comparisons revealed that the frequency of unilateral pain, aggra- vation by routine physical activity, nausea, photophobia and phonophobia was sig- nificantly different between Class 1 and Class 2.

The frequency of unilateral pain, aggravation by routine physical activity and

vomiting differed significantly between Class 1 and Class 3.

Headache intensity, photophobia and phonophobia were significantly different

between Class 2 and Class 3.

Discussion These studies found subtypes of high, intermediate, low and minimal frequency of migraine symptoms [66, 67, 69, 70, 74].

Our study found several noteworthy findings on the subtypes and symptoms of

migraine.

Class 2 (photophobia and phonophobia) showed the highest rate of osmophobia (i.e., intolerance of or hypersensitivity to smells), which is a common symptom of migraine and has high specificity for migraine diagnosis [75, 76].

Our findings support that there is a migraine subtype that presents with a high

frequency of sensory hypersensitivity symptoms.

Considering that the intensity and frequency of headache are key parameters for determining migraine severity [77], we found that each symptom is closely related to severity.

The three symptom subtypes of migraine identified in our study based on LCA may provide clues in understanding the pathophysiologic and genetic mechanisms of migraine.

LCA identified three classes of migraine that showed distinct characteristics.

Methods The presence of a visual aura was assessed using the self-administered VARS, for which the Korean version has been validated, with a score of ≥ 3 defined as having a visual aura [78, 79].

Participants who fulfilled the ICHD-3 diagnostic criteria of migraine without aura but reported visual aura were diagnosed with migraine with aura (code 1.2) [16].

All participants with migraine satisfied criteria A (total attack number), B (typi- cal duration) and E (exclusion of other diagnosis), we used items in criteria C and D of migraine without aura (code 1.1) [16] as variables for LCA.

The headache frequency per month was categorized into a four-class variable (<

2, ≥ 2 but < 8, ≥ 8 but < 15 and ≥ 15).

There was no missing data except for monthly headache frequency in one partici-

pant with migraine which was adjusted as mean value.

Acknowledgement A machine generated summary based on the work of Lee, Wonwoo; Min, In Kyung; Yang, Kwang Ik; Kim, Daeyoung; Yun, Chang-Ho; Chu, Min Kyung. 2021  in Scientific Reports.

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3 Diagnosis

Need of guidance in disabling and chronic migraine identification in the primary care setting, results from the european MyLife anamnesis survey