The role of prodromal symptoms in predicting headache onset: A longitudinal electronic momentary assessment study

This longitudinal observational study investigated the role of prodromal symptoms in predicting headache onset, using electronic headache diaries to assess symptom occurrence and predictive utility in individuals with migraine.

Prodromal symptoms are early indicators of migraine that occur 2-48 h before the headache phase. Whereas commonly reported symptoms include fatigue, stiff neck, and sensitivity to light and sound, few studies have assessed their predictive abilities for headache onset. Understanding the relationship and reliability of these symptoms is important for early migraine intervention strategies.

This is a secondary analysis of a longitudinal observational headache diary study. Participants with episodic migraine (N = 43) were recruited from Einstein College of Medicine between 2017 and 2021 and completed a mobile headache diary three times daily over 3 months. They reported the presence of 11 prodromal symptoms and headache anticipation during headache-free intervals. Associations between prodromal symptoms, anticipation, and subsequent headache onset were examined across multiple time lags. Headache anticipation was evaluated as a moderator of these relationships.

Across 7061 headache-free observations, prodromal symptoms were reported in 52.7% of cases (n = 3721). Phonophobia doubled the odds of head pain onset 6 h before head pain. Nausea, photophobia, and difficulty thinking/concentrating were associated with higher odds of head pain within 24 h of symptom reporting. Blurred vision was associated with higher odds of future head pain at all time points evaluated. Thirst and dizziness were associated with higher odds of head pain 18-36 h before head pain onset. All prodromal symptoms were associated with increased odds of headache anticipation. Headache anticipation itself was associated with higher odds of headache onset within the ~6, 12, and 36 h prior to headache onset (~6 h odds ratio [OR] = 3.35, 95% confidence interval [CI] [2.57, 4.36]). Anticipation weakened the predictive value of several symptoms on headache occurrence, including feeling tired/weary (OR = 0.50, 95% CI [0.37, 0.68]); difficulty thinking/concentrating (0.37, 95% CI [0.24, 0.58]); thirst (OR = 0.42, 95% CI [0.31, 0.58]); blurred vision (OR = 0.63, 95% CI [0.42, 0.93]); photophobia (OR = 0.15, 95% CI [0.07, 0.33]); phonophobia (OR = 0.19, 95% CI [0.12, 0.28]); nausea (OR = 0.33, 95% CI [0.17, 0.65]); and dizziness (OR = 0.17, 95% CI [0.08, 0.35]).

Cardinal (phonophobia, photophobia, and nausea) symptoms of migraine were all associated with higher odds of future head pain 24 h before head pain onset. Other neurologic and homeostatic symptoms also emerged as predictors for head pain. However, predictive performance was modest; therefore, these symptoms should not be considered stand-alone migraine predictors. Headache prediction was weaker when individuals anticipated a headache, suggesting that anticipation may influence symptom interpretation.