OC-01 | Evolution of nitroglycerin-triggered premonitory symptoms in participants with migraine

Gabriele Sebastianelli,^1,2 Catarina Fernandes,^1,3 Peter J. Goadsby^,1 Nazia Karsan¹ | ¹NIHR King’s Clinical Research Facility, SLaM Biomedical Research Centre and Wolfson SPaRC, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK; ²Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino ICOT, Sapienza University of Rome, Latina, Italy; ³Neurology Department, Local Health Unit of Coimbra, Portugal

Background: While the hypothalamus is reliably shown with functional neuroimaging to be active in the premonitory phase of migraine, other areas, including visual, brainstem, and limbic areas may also be seen. To understand how the premonitory phase evolves, the temporal chronology of premonitory symptoms (PS) triggered by nitroglycerin (NTG) was evaluated.

Methods: Fifty-three subjects with migraine and a history of spontaneous PS were exposed to NTG infusion (0.5 mcg/kg/min; first visit, V1). Participants who developed PS and migraine-like headache were invited to be re-exposed to NTG for a maximum of three triggered visits (V2, n = 29; V3, n = 11). The frequency and chronology of PS were collected for all the visits (n = 93). The median time of onset in minutes of each symptom was recorded for all subjects during V1 (n = 53).

Results: PS were triggered in 92 out of 93 (99%) of visits. The five most common PS were: photophobia (77%), fatigue (74%), neck stiffness (63%), difficulty concentrating (62%), and yawning (50%). The premonitory phase started with one PS in 40% (n = 37) of the cases, and more than one in the remainder. Neck stiffness (38%), photophobia (38%), and fatigue (33%) were the most common PS occurring as the first symptom across all 93 NTG infusions. In contrast, thirst (14%), food cravings (2%), and yawning (13%) occurred as the first PS in a minority of cases. The median time of onset [interquartile range] of the most common PS (frequency ≥35%) during V1 were: neck stiffness 10 minutes (6–16), photophobia 11 minutes (8–20), thirst 19 minutes (10–81), fatigue 20 minutes (10–46), difficulty concentrating 20 minutes (10–34), and yawning 40 minutes (16–69).

Conclusion: Neck stiffness and photophobia are the earliest PS to arise during NTG-triggered migraine attacks. Symptoms that are attributed to the hypothalamus typically begin after. These results may suggest an early dysmodulation of the thalamus, while the hypothalamus could be a later structure involved in the migraine attack, rather than be involved in attack initiation.