Pediatric migraine: Neurodevelopmental mechanisms, clinical phenotypes, and modern therapeutics

Abstract

Migraine is among the most prevalent neurological disorders in children and adolescents and is a leading cause of functional disability, school absenteeism, and impaired quality of life. Pediatric migraine is not merely a younger manifestation of the adult disease; rather, it exhibits distinct clinical phenotypes, developmental neurobiology, triggers, and treatment responses. The growing recognition of its long-term burden underscores the need for updated, pediatric-focused, evidence-based guidance. This narrative review synthesizes contemporary evidence on pediatric migraine across the lifespan, integrating epidemiology, genetic susceptibility, and age-dependent neurobiological mechanisms. Key clinical features, including migraine equivalents and episodic syndromes associated with migraine, are discussed alongside diagnostic considerations using the International Classification of Headache Disorders, third edition, and validated pediatric disability assessment tools. Acute and preventive management strategies are reviewed in detail, encompassing optimized use of non-steroidal anti-inflammatory drugs and triptans, antiemetics, nerve blocks, neuromodulation devices, and emerging targeted therapies such as calcitonin gene-related peptide monoclonal antibodies and gepants. Evidence-based non-pharmacological interventions, including lifestyle optimization, sleep hygiene, cognitive-behavioral therapy, and comorbidity management, are also integral components of care. Pediatric migraine should be recognized as a chronic, neurodevelopmentally modulated neurological disorder that warrants early diagnosis and a multimodal, individualized treatment approach. Advances in mechanistic understanding, neurostimulation technologies, and targeted biologic therapies are reshaping the therapeutic landscape and hold promise for more precise and effective migraine management in children and adolescents.

Keywords: Pediatric migraine; Episodic syndromes; Migraine equivalents; Diagnosis; Neuromodulation devices; Calcitonin gene-related peptide monoclonal antibodies; Gepants

Core Tip: Pediatric migraine is a common yet underrecognized neurodevelopmental disorder with age-specific clinical phenotypes, mechanisms, and treatment responses. Children are not “small adults”; migraine expression evolves with brain maturation, hormonal changes, and sensory processing, necessitating pediatric-specific diagnostic and therapeutic strategies. Early recognition of migraine equivalents, timely access to acute treatment, and avoidance of medication overuse are essential to prevent chronification. While traditional preventives offer limited efficacy, emerging mechanism-based therapies and neuromodulation devices are reshaping care. A multimodal, individualized approach integrating pharmacologic, behavioral, and educational interventions is critical to improving long-term outcomes.