Migraine beyond attacks: Insights on the interictal phase
Marta Waliszewska-Prosół, Samiye Ulutas, Teresa Mateu, Sheharyar Ahmad, Prisca-Rolande Bassolé, Merve Ceren Akgor, Kinga Gecse, Marie Therese Kleinsorge, Nijanth Manohararaj, Selam Kifelew Melkamu, Ignacio del Pino de Laguno, Sena Uzun, Edoardo Caronna, Patricia Pozo-RosichBackground
Traditionally, migraine has been characterized by its paroxysmal attacks, with the interictal phase considered to be a symptom-free interval. However, emerging evidence suggests that the “migraine brain” remains in a state of altered neuro-excitability and impaired habituation between attacks, manifesting as debilitating interictal symptoms. This narrative review aims to describe the spectrum of interictal symptoms, their underlying mechanisms, and their impact on the cumulative disease burden, at the same time as exploring the implications for clinical management.
Methods
An extensive literature search of the PubMed database was performed using terms related to the migraine cycle, interictal phase, and disease burden. Original articles published within the last 10 years were prioritized, focusing on clinical trials, real-world evidence, and neurophysiological studies.
Results
Interictal symptoms, including sensory hypersensitivity (photophobia, phonophobia, osmophobia, allodynia), cognitive dysfunction (“brain fog”), vestibular symptoms, and affective dysregulation, affect between 26% and 76% of patients. These symptoms significantly contribute to the socioeconomic burden of migraine, leading to substantial productivity losses (absenteeism and presenteeism) and reduced quality of life. While non-specific preventives often fail to alleviate interictal symptoms, calcitonin gene-related peptide-pathway targeted therapies and onabotulinumtoxinA have demonstrated promising results in reducing the interictal burden, as measured by standardized tools such as the Migraine Interictal Burden Scale (MIBS-4).
Conclusions
Migraine management requires a paradigm shift from focusing solely on attack frequency to a more holistic approach that includes the interictal period. Standardizing interictal symptoms definitions and implementing specific outcome measures in clinical practice are essential to restore full functional capacity and provide comprehensive care for patients.