Trigger factors for stroke in young adults: a case-crossover study

Ekker, M.S.; Verhoeven, J.I.; Rensink, K.M.L.; Schellekens, M.M.I.; Boot, E.M.; Alebeek, M.E. van; ... ; Leeuw, F.E. de (2023)

Article / Letter to editor

Background and Objectives
Causes of stroke in young adults differ from those in the elderly individuals, and in a larger percentage,
no cause can be determined. To gain more insight into the etiology of (cryptogenic) stroke in the
young population, we investigated whether trigger factors, such as short-lasting exposure to toxins or
infection, may play a role.
Methods
Patients aged 18–49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17
participating centers in the Netherlands completed a questionnaire about exposure to 9 potential
trigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used to
assess relative risks (RRs) with 95% confidence intervals (95% CIs) by the Mantel-Haenszel case-
crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologic
subgroups of ischemic stroke.
Results
One thousand one hundred forty-six patients completed the questionnaire (1,043 patients with
an ischemic stroke and 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke, an
increased risk emerged within 1 hour of cola consumption (RR 2.0, 95% CI 1.5–2.8) and vigorous
physical exercise (RR 2.6, 95% CI 2.2–3.0), within 2 hours after sexual activity (RR 2.4, 95% CI
1.6–3.5), within 4 hours after illicit drug use (RR 2.8, 95% CI 1.7–4.9), and within 24 hours after
fever or flu-like disease (RR 14.1, 95% CI 10.5–31.2; RR 13.9, 95% CI 8.9–21.9). Four trigger
factors increased the risk of other determined and cryptogenic ischemic stroke, 3 that of car-
dioembolic stroke, 2 that of large vessel atherosclerosis and likely atherothrombotic stroke
combined and stroke with multiple causes, and none that of stroke due to small vessel disease.
Discussion
We identified cola consumption, vigorous physical exercise, sexual activity, illicit drug use, fever, and
flu-like disease as potential trigger factors for stroke in the young population and found differences
in the type and number of trigger factors associated with different etiologic subgroups of ischemic
stroke. These findings might help in better understanding the pathophysiologic mechanisms of
(cryptogenic) stroke in the young population.

• All authors: Ekker, M.S.; Verhoeven, J.I.; Rensink, K.M.L.; Schellekens, M.M.I.; Boot, E.M.; Alebeek, M.E. van; Brouwers, P.J.A.M.; Arntz, R.M.; Dijk, G.W. van; Gons, R.A.R.; Uden, I.W.M. van; Heijer, T. den; Kort, P.L.M. de; Laat, K.F. de; Norden, A.G.W. van; Vermeer, S.E.; Zagten, M. van; Oostenbrugge, R.J. van; Wermer, M.J.H.; Nederkoorn, P.J.; Kerkhoff, H.; Rooyer, F.; Rooij, F.G. van; Wijngaard, I.R. van den; Klijn, C.J.M.; Tuladhar, A.M.; Leeuw, F.E. de
• Date: 2023-01-03
• Journal: Neurology
• Volume: 100
• Issue: 1
• Pages: e49 - e61
• DOI: doi:10.1212/WNL.0000000000201341
• Link: https://www.neurology.org/doi/pdf/10.1212/WNL.0000000000201341