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

Table 9 Comparison of key pediatric neuromodulation devices used for migraine management

Device/modality	Target/mechanism	Pediatric age approval	Acute use	Preventive use	Evidence and notes
Remote electrical neuromodulation (Nerivio®)	Upper-arm electrical stimulation enhancing conditioned pain modulation. This descending analgesic mechanism reduces pain in distant body regions (the head). It stimulates C and Aδ nerve fibers	FDA-cleared ≥ 12 years; expanding to 8 years in some jurisdictions	Yes	Yes	Open-label and real-world data show pain relief and functional improvement in adolescents; minimal AEs and high acceptability
External trigeminal nerve stimulation (Cefaly®)	Supraorbital trigeminal nerve stimulation. The device stimulates the supraorbital trigeminal nerve, the primary pathway for migraine pain, helping to modulate and desensitize it	Used off-label in pediatrics; FDA cleared for adults	Yes	Yes	Adult data supports efficacy/safety; device modulates trigeminal afferents with minimal side effects, and pediatric tolerability appears acceptable
Single-pulse transcranial magnetic stimulation (eNeura/SAVI Dual™)	Magnetic pulses modulating cortical excitability by creating a small electrical current in the cortex to “reset” overactive brain nerves associated with migraines, without causing pain	FDA-cleared ≥ 12 years (adolescents)	Yes	Yes	Open-label adolescent studies show feasibility and tolerability; larger RCTs needed for efficacy confirmation
Non-invasive vagus nerve stimulation (gammaCore®)	Cervical vagal nerve stimulation influencing brainstem pain pathways	FDA-cleared ≥ 12 years	Yes	Yes	Small pediatric studies suggest relief in adolescents; generally, well tolerated with mild neck discomfort
External combined occipital and trigeminal neurostimulation (Relivion®)	Dual occipital + trigeminal stimulation	Adult cleared; pediatric off label	Yes	Potential	Adult data supports acute migraine use, pediatric evidence currently limited

AEs: Adverse events; FDA: Food and Drug Administration; RCTs: Randomized controlled trials.