Clinical Studies in the Premonitory Phase
Premonitory symptoms have been noted by clinicians and patients for a long time, for example, Gowers mentioned somnolence in the 19th century. There have been several attempts to study the prevalence of these symptoms in migraineurs. However, these studies have been retrospective and therefore subject to recall bias, reporting a prevalence of between 7–88%. Two studies have tried to investigate premonitory symptoms in a prospective way. Quintela et al studied 100 patients with migraine. Patients visited the research office 2–5 days after a migraine attack started and were asked to fill out a questionnaire regarding the occurrence of premonitory symptoms present 20 hours before the start of the headache. Thus, patient ascertainment was prospective, although data collection was not. Of these patients, 84% had one or more premonitory symptoms. The average number of premonitory symptoms was 7 for each patient. The most frequent symptoms were anxiety, phonophobia, irritability, unhappiness, yawning, photophobia, asthenia, and difficulties with concentration. About two thirds of symptoms were present in at least 2 out of 3 attacks, and more than half were present in 3 out of 3 attacks, indicating that these were highly consistent.
Giffin et al used electronic diaries to study premonitory symptoms in 120 selected patients who experienced these symptoms habitually during migraine. Patients were asked to make daily entries of their symptoms that could not be changed once entered, making this the only truly prospective study of premonitory symptoms. Migraine was correctly predicted to occur within 72 hours by 72% of entries. For 82% of selected patients, premonitory symptoms were followed by a migraine headache within 72 hours more than 50% of the time. The most common symptoms were tiredness, difficulty concentrating, and stiff neck. However, these were not the most predictive for a migraine attack as can be estimated by the lack of specificity and common occurrence of these symptoms in the population. The symptoms with the highest predictive value were yawning, difficulties in speech and reading, and emotional disturbance, correctly predicting a migraine headache in more than two thirds of patients. Yawning and increased energy and hunger/cravings were the only symptoms that became less common with the occurrence of headache. Other symptoms were common before, during, and after the headache. The study mentioned that mild pain was frequently mentioned by patients in the premonitory phase in the form of neck discomfort, dull pain behind the eyes, or pain around the ears.