An update on the differential diagnosis of migraine in adults: when and how neuroimaging makes the difference

Introduction: Migraine is a highly prevalent and disabling neurological disorder whose diagnosis remains clinical. However, overlap with secondary headache disorders represents a major diagnostic challenge, particularly in patients with atypical features or changes in headache pattern, making neuroimaging crucial in selected cases. Areas covered: This review provides an updated overview of the differential diagnosis of migraine in adults, focusing on the role of clinical assessment, red flags, and neuroimaging in identifying secondary causes. A comprehensive, narrative review of the literature was conducted, integrating current guidelines and recent evidence on imaging indications and modalities. We discuss key conditions that may mimic migraine, including vascular, neoplastic, infectious, cerebrospinal fluid pressure–related, and cervicogenic disorders, highlighting their clinical and radiological features. Attention is given to the concept of pretest probability to guide imaging decisions and to the limitations of red flags in clinical practice. Expert opinion: Neuroimaging should not be routinely performed in patients with typical migraine and normal neurological examination but rather tailored to the individual clinical context. An integrated approach combining clinical judgment, awareness of red flags, and targeted imaging is essential to avoid both underdiagnosis of secondary headaches and overuse of unnecessary investigations.