Migraine-like headaches: a systematic review of secondary etiologies, clinical features and therapeutic patterns...

Secondary headaches presenting similar clinical findings to migraine are known as migraine-like headaches. Currently, there is no broad consensus regarding their prevalence, characteristics, or underlying causes. Existing evidence is based primarily on descriptive studies and a single systematic review, with vascular, traumatic, and epileptic seizures as the most frequent causes. The aim of this systematic review was to describe and analyze secondary etiologies behind migraine-like headaches, including their epidemiological, clinical, and therapeutic characteristics.

A database search of studies between 1977 and 2024 was conducted in February 2025 on EBSCO, SCOPUS, PubMed, and Web of Science using the terms "migraine-like" or "migraine mimic". Included articles were human observational studies and case reports that documented a migraine-like headache with a diagnosed underlying cause. Articles lacking explicit causality, as well as review and experimental studies were excluded. Data on demographics, clinical features, etiology, imaging, and treatment were extracted and analyzed. Etiologies were categorized into vascular, neoplastic, traumatic, epileptic, autoimmune, infectious and others. Sensitivity analysis (SA) was performed using low-bias concern studies.

Of 745 studies retrieved, 220 met inclusion criteria, totaling 4,422 patients (mean age 33.7 years, 63.4% female). Most presented severe (68.8%), unilateral (66.9%), gradual onset (56.6%) headaches with aura (52.5% and 47.8% in SA), primarily localized to frontal (29.3%) and temporal (22.8%) regions. Stroke (6.4% and 7.8% in SA), epilepsy (7.3%), and traumatic brain injury (5%) were the most frequent causes, while NSAIDs and triptans were the most common treatments (30.5 and 18.2%). After SA the associations between younger age and parietal pain (p = 0.023) and between imaging modality and etiology (p < 0.001) remained significant, where magnetic resonance imaging was predominantly used for autoimmune diseases and post-traumatic headaches frequently lacked imaging. Sudden onset and post-traumatic headaches were identified as frequent red flags.

The present study findings underscore the importance of recognizing red flags in migraine-like headaches and early identification of underlying causes. Severe, sudden onset headaches alongside systemic symptoms or trauma history should prompt thorough evaluation. Future research should aim to refine the definition of migraine-like headache and to improve diagnostic precision and treatment timing in these patients.