Methods for CaMEO-I have previously been described [15]. CaMEO-I was a cross-sectional, observational, web-based survey conducted in 2021–2022 in North America (Canada, United States), Europe (France, Germany, United Kingdom), and Asia (Japan). Respondents who met modified ICHD-3 (mICHD-3) migraine symptom criteria were offered the opportunity to participate. Pre- and post-headache symptoms were assessed by evaluating specific items selected from a standardized questionnaire designed by migraine experts. The conduct of the study was governed by the Declaration of Helsinki and its amendments, and any applicable national guidelines. All study participants were required to provide informed consent prior to enrollment in the study.

Respondents answered the questions “Over the past 12 months, how often have you had any premonitory or prodromal symptoms (such as neck pain or stiffness, difficulty thinking, feeling tired, irritable, lightheaded, yawning, vision problems, etc) within a day or two before the start of your migraine or severe headache pain?” and “After the headache pain ends, how often in the past 12 months did you experience a post-headache phase with “post-dromal” symptoms such as fatigue, mental slowness, body aches, and continued sensitivity to light or sound, etc?” using a 5-point scale: 0–never, 1–rarely, 2–less than half the time, 3–half the time or more (but not every time), and 4–with all or almost every headache. Respondents who reported symptoms with a rating of 2 or higher were classified as pre- or post-headache symptom cases for the analysis.

Monthly headache days (MHDs), migraine-associated disability (using the Migraine Disability Assessment [MIDAS]), clinically significant depression and anxiety symptoms (using the Patient Health Questionnaire-4 [PHQ-4]), the presence of cutaneous allodynia with headache (using the Allodynia Symptom Checklist [ASC-12]), and activity limitations due to migraine were assessed. MHDs were determined by responses to the question: “How many days did you have a headache in the past 30 days?” MIDAS is a 5-item questionnaire that evaluates days of missed activity or substantially reduced activity due to headache, including productivity at work or school, household work, and family, social, or leisure activities [16]. Based on the sum score of responses to the items, migraine-related disability was categorized as little or no disability (Grade I), mild disability (Grade II), moderate disability (Grade III), or severe disability (Grade IV). The PHQ-4 is a validated 4-item questionnaire that assesses how often respondents experienced clinically significant levels of depression symptoms (i.e., little interest or pleasure in doing things and feeling down, depressed or hopeless) and/or anxiety symptoms (i.e., feeling nervous, anxious, or on edge and not being able to stop or control worrying) over the previous 2 weeks [17]. PHQ-4 total scores ranged from 0 to 12. A score of ≥ 3 for depression or anxiety symptoms suggest the presence of depression or anxiety, respectively. The ASC-12 is a validated 12-item assessment that evaluates how often respondents experience increased pain or an unpleasant sensation on their skin during their migraine or severe headaches when they engage in various activities of daily living (e.g., combing hair, shaving face, wearing eyeglasses, taking a shower, being exposed to heat or cold) [18]. Based on response options of never, rarely, less than half the time, and half the time or more, total score ranges from 0 to 24. Respondents with an ASC-12 score of ≥ 3 were classified as having allodynia. To assess functional disability due to pre-headache, headache, and post-headache symptoms (assessed separately), respondents were asked to rate their performance of daily activities when they had these symptoms with the following response options: no disability, able to function normally; mildly impaired, can still do everything but with difficulty; moderately impaired, unable to do some things; and severely impaired, cannot do all or most things, bed rest may be necessary.

Among respondents who reported using acute medication for Migraine, acute treatment optimization was assessed using the Migraine Treatment Optimization Questionnaire (mTOQ). The mTOQ-6 is a 6-item questionnaire that evaluates the respondent’s perception of their acute treatment regimen by assessing efficacy at 2 and 24 h, tolerability, ability to plan daily activities, feeling of being in control, and ability to return to normal activities based on response options of never, rarely, less than half the time, and half the time or more [19]. A 4-item subset of the mTOQ-6 was used, referred to herein as the mTOQ-4. The sum of the items was used to categorize treatment optimization as very poor, poor, moderate, or maximal.

Respondents were grouped into the following categories based on their response patterns: with pre-headache symptoms only, with post-headache symptoms only, with both pre- and post-headache symptoms, and without pre- and post-headache symptoms.

Descriptive statistics were used in this observational study. Means and standard deviations were generated for age and body mass index. Counts and percentages were used to describe all other variables.

Regression modeling was used to highlight the unique and combined effects of having pre-headache, post-headache, or both types of symptoms on a series of outcomes. Model type reflected the type and distribution of the outcome. MHD categories were modeled with ordinal logistic regression reported with ordered cumulative odds ratios (ORs) and 95% confidence intervals (95% CIs); MIDAS was modeled with a negative binomial regression and reported using rate ratios (RRs) and 95% CIs; the anxiety and depression subscales of the PHQ-4 were modeled with binary logistic regression and reported with ORs and 95% CIs. Very poor to poor vs. moderate to maximum treatment optimization, evaluated via the mTOQ-4, was modeled with binary logistic regression and reported with ORs and 95% CIs. For each outcome (dependent variables), 3 sets of regression models were run: pre-headache only vs. neither, post-headache only vs. neither, and both pre- and post-headache vs. neither as independent variables. Covariates (MHDs, age, gender, country) were added after initial models including only dependent variables and independent variables were run.

Missing data were rare (less than 1% of cases for any variable), and no imputation measures were employed. All analyses were conducted with SPSS Statistics, version 29.0 (IBM, Armonk, NY, USA).