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Papers of the Week

Papers: 25 Apr 2020 - 1 May 2020

Human Studies


2020 Apr 22


Premonitory symptoms in glyceryl trinitrate triggered migraine attacks: a case-control study.


Onderwater GLJ, Dool J, Ferrari MD, Terwindt GM
Pain. 2020 Apr 22.
PMID: 32332251.


Spontaneous and pharmacologically-provoked migraine attacks are frequently preceded by nonheadache symptoms called premonitory symptoms. Here, we systematically evaluated premonitory symptoms in migraine patients and healthy controls following glyceryl trinitrate (GTN) infusion. In women with migraine without aura (n=34) and age-matched female controls (n=24) we conducted systematically a semi-structured interview assessing 21 possible premonitory symptoms every 15 minutes in the 5 hours following GTN infusion (0.5 µg/kg/min over 20 min). Migraine-like headaches occurred in 28/34 (82.4%) migraineurs (GTN responders). After GTN, 26/28 (92.9%) responders, 6/6 (100%) non-responders, and 13/24 (54.2%) controls reported at least one possible premonitory symptom. Concentration difficulties (p=0.011), yawning (p=0.009), nausea (p=0.028), and photophobia (p=0.001) were more frequently reported by those migraineurs who developed a migraine-like attack versus healthy controls. Importantly, concentration difficulties were exclusively reported by those who developed a migraine-like attack. Thus, our findings support the view that GTN is able to provoke the naturally occurring premonitory symptoms, and show that yawning, nausea, photophobia, and concentration difficulties are most specific for an impending GTN-induced migraine-like headache. We suggest that these symptoms may also be helpful as early warning signals in clinical practice with concentration difficulties exclusively reported by those who develop a migraine-like attack.