Phenotypic Classes of Headache Disorders: A Population-based Latent Class Analysis
Wonwoo Lee1, Seok-Jae Heo2, Jungyon Yum1, Min Kyung Chu3
1Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 2Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, 3Severance Hospital, Yonsei University College of Medicine
Objective:
To compare statistically derived headache classes with diagnoses by International Classification of Headache Disorders, 3rd edition (ICHD-3).
Background:

Despite well-established pathophysiological distinctions across ICHD-3 diagnostic categories, diagnoses are still based on combinations of clinical symptoms. In consequence, wide variability and diagnostic overlap (e.g., coexisting tension-type headache [TTH] and probable migraine [PM]) are common. We evaluated natural classes of headache disorders using a statistical approach and compared their characteristics with current diagnostic categories.

Design/Methods:

We analyzed data from a nationwide, population-based web survey on headache and sleep conducted in South Korea in October 2020 (N=3,030). Participants reporting headache within the previous year (n=1,938) were included. Latent class analysis (LCA) was performed on categorical indicators frequently used in ICHD-3 diagnostic algorithms (e.g., intensity, duration, laterality, pulsating quality, nausea/vomiting, photophobia, phonophobia). The optimal number of classes was selected by standard fit criteria and interpretability. We then examined the characteristics of each class and distribution of ICHD-3 diagnoses (migraine, PM, TTH, other headache disorders) within each class.

Results:

Nine classes featured unique characteristics, comprising 626,54,248,148,187,79,61, and 392 individuals respectively. Classes showed distinct phenotypes, including: (i) mild, short-duration bilateral headaches without nausea, (mild classic TTH); (ii) bilateral moderate headaches with nausea not meeting PM criteria (other headaches); (iii) mild headaches with nausea (other headaches); (iv) a typical migraine phenotype; (v–vi) two PM–dominant classes differing by sensory sensitivity and disability; (vii) mixed-type with photophobia; (viii) bilateral moderate headaches >4 hours without migraine features (severe TTH); and (ix) mild unilateral TTH.

Conclusions:

Latent class analysis identified 9 classes corresponding to TTH, PM, migraine, and other headache disorders that differed chiefly in central sensitization and severity. PM was clearly distinct from both TTH and migraine, supporting more specific diagnostic delineation than current criteria.

10.1212/WNL.0000000000214997
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