By Dara G. Jamieson, MD
Knowledge of the differentiation between the triggers for a potential migraine attack and the prodromal symptoms of an initiated migraine attack reveals strategies that decrease migraine disability. Recognition of migraine triggers allows for a modification of behavior to avoid precipitating an attack. Recognition of common migraine prodromal symptoms creates an early time window when rapid treatment enhances the therapeutic intervention’s efficacy.
Sebastianelli G, Atalar AC, Cetta I, et al. Insights from triggers and prodromal symptoms on how migraine attacks start: The threshold hypothesis. Cephalalgia. 2024;44(10):3331024241287224.
Schwedt TJ, Lipton RB, Goadsby PJ, et al. Characterizing prodrome (premonitory phase) in migraine: Results from the PRODROME trial screening period. Neurol Clin Pract. 2025;15(1):e200359.
Migraine prodromal (premonitory) symptoms, which include mood and cognitive changes, homeostatic and hormonal changes, and sensory sensitivities, may occur in the 24 to 48 hours prior to the onset of pain and the accompanying symptoms of a migraine attack. The prevalence of these early symptoms of a migraine attack is reported to be 30% to 80%. Some of the prodromal symptoms are correlated with activation of specific areas of the brain, including the hypothalamus (e.g., food craving), the trigemino-cervical complex (e.g., neck pain), and the visual cortex (e.g., light sensitivity). However, these prodromal symptoms may be confused with triggers for a migraine attack. Even people with a long history of migraines may perceive these early migraine symptoms as triggers for migraines, and the onset of these symptoms may not be identified as the initial stage of a migraine attack, occurring prior to the onset of the familiar head pain.
Two recently published papers, the results of a clinical trial by Schwedt et al and a systematic review of medical literature by Sebastianelli et al, examined prodromal symptoms and migraine triggers. Both publications concluded that the differentiation between these two sets of migraine-related experiences facilitates appropriate interventions to decrease migraine disability.
Schwedt et al reviewed the results of PRODROME, a multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults with two to eight migraine attacks per month with identifiable prodromal symptoms prior to head pain. An eDiary was used by 920 participants to report 4,802 qualifying prodrome symptoms, most commonly sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), difficulty either thinking or concentrating (30.0%), dizziness (27.8%), and irritability (26.4%).
Prodrome events were reliably followed by headaches of any intensity within one to six hours in most participants. Most prodromal symptoms were of mild intensity, but more than one-third of the heralding symptoms of migraine were of moderate to severe intensity. Neck pain and fatigue were the prodrome symptoms with the greatest intensity.
A subgroup of people with migraine in the PRODROME trial were consistently able to self-identify prodromal symptoms that were followed by migraine headache. The findings suggest the potential for initiating treatment during the prodrome to prevent the development of head pain. Treatment with the calcitonin gene-related peptide receptor antagonist ubrogepant 100 mg, administered during a qualifying prodrome event, significantly reduced the development of headache of any intensity and functional disability for 24 hours post-dose in the PRODROME trial as compared to placebo treatment. The ability to reliably predict the onset of a migraine attack from the prodromal symptoms opens an early treatment time window, resulting in a more successful prevention of disabling pain and accompanying symptoms.
Sebastianelli et al performed a comprehensive narrative review of the published literature on clinical, neurophysiological, and imaging evidence of migraine prodromal symptoms and triggers. The authors described migraine triggers as environmental events that can initiate a sequence of events that culminate in the migraine attack. They listed stress and stress relief, disrupted sleep, fatigue, bright lights, odors, menses, noise, skipping meals, weather changes, certain foods, and alcohol as among the most reported triggers in published clinical studies.
Avoidance of modifiable triggers is crucial in decreasing the disability of migraine. Prodromal symptoms most misinterpreted as migraine triggers include neck pain, food cravings, and sensitivity to light and sound. The authors determined that the recognition of migraine triggers and prodromal symptoms as distinct entities can shed light on migraine pathophysiology and improve migraine management.
Sebastianelli et al formulated a theory to unify migraine triggers and prodromal symptoms. Neuroimaging studies have identified activation and increased excitability of interconnected brain regions starting hours to days prior to the onset of head pain, indicating that a prodromal phase may occur even in the absence of identifiable symptoms.
The initial symptoms of a migraine attack are mediated by the hypothalamus as the central hub for integrating external and internal body signals. A hyperexcitatory state, which may be facilitated by hypothalamic-thalamic-brainstem connections, can influence cortical excitability and its threshold for the migraine attack. Trigeminovascular thalamic neurons receive direct projections from the hypothalamus and are continuously influenced by modulatory inputs, enabling the thalamus to dynamically regulate the transmission of sensory signals to the cortex, based on changing physiological, behavioral, and environmental events.
When the excitation level exceeds a thalamic sensory threshold, a widespread enhanced activation of different cortical and subcortical brain regions occurs with a transition from the prodromal to the ictal migraine phase. Then, activation of the trigeminovascular system facilitates pain processing, leading to the headache phase, along with the accompanying symptoms of brainstem and cortical activation.
Commentary
These two publications, which explain the separate yet overlapping events that are migraine triggers and prodromal symptoms, reveal strategies to recognize and avoid migraine triggers and to use the recognition of these preliminary symptoms to initiate early therapeutic intervention. Understanding these triggering and premonitory components of a migraine attack leads to behavioral and therapeutic strategies that decrease the initiation, severity, and duration of migraine headaches and reduce their associated disability.
Recognition of migraine triggers enables avoidance and decreased risk of a migraine attack. But even people with decades of migraine attacks have difficulty discerning their triggers. Some well-known presumed triggers of migraine actually are the initial symptoms of the ongoing migraine attack.
Interestingly, prodromal symptoms may lead to behaviors that mistakenly apply a trigger label. For example, chocolate is an alleged migraine trigger; however, a craving for chocolate appears to be a prodromal symptom of migraine that leads to chocolate consumption, an activity that should not be disparaged. Other food triggers, such as cheap red wine, appear to be actual headache triggers, best avoided by vulnerable people with migraine.
It is a truth universally acknowledged that earlier initiation of acute abortive migraine treatment improves its efficacy. Recognition of the onset of a migraine attack can be difficult, and people with migraine usually wait for increasingly severe head pain and accompanying gastrointestinal and sensitivity symptoms before taking an acute pain medication or initiating an acute treatment. This delay in a therapeutic intervention prolongs the time of debilitating symptomatology and decreases the efficacy of treatment. Recognition of the prodromal symptoms of migraine allows someone who experiences migraine to initiate treatment earlier with greater efficacy in decreasing the severity of the subsequent phases of the migraine attack.
Dara G. Jamieson, MD, is Clinical Associate Professor of Neurology, Weill Cornell Medical College.
