Author: Nicolas Martinez-Majander, MD
Clinical Neurosciences, Department of Neurology, University of Helsinki and Department of Neurology, Helsinki University Hospital, Helsinki, Finland
Incidence of young-onset ischemic stroke is currently about 13/100 000 per year in high-income countries and has been increasing since 1980s. In young patients, stroke affects social life, family, and working ability for years after the event. In addition to well-known risk factors, such as diabetes mellitus, hypertension, and hypercholesterolemia, young patients also have unconventional, age-specific risk factors as pregnancy and puerperium, migraine, and cardiac abnormalities. However, there are still many unanswered questions in terms of risk factors for stroke in the young, and so far study results have been inconsistent.
There is a statistically stronger association between migraine and ischemic stroke in the young than with elderly. Especially migraine with aura should be considered a risk factor for young-onset ischemic stroke, while evidence regarding migraine without aura still remains inconsistent.
The pill, pregnancy, and the postpartum period are also known risk factors for ischemic stroke in the young women. In a recent Cochrane review, women using the pill had a 1.7-fold increased risk for ischemic stroke compared to non-users (Roach et al. 2015). The risk is highest for women using the pill with higher levels of estrogen, and the combination of obesity, smoking, migraine with aura and hypertension may increase the risk of stroke even more. Both pregnancy and puerperium are associated with an increased risk of all stroke subtypes. Kittner et al. showed that the relative risk of ischemic stroke was up to 8.7 (95% CI, 4.6-16.7) during puerperium. In a single-center Canadian study, most ischemic strokes occurred during the third trimester, around delivery, or during postnatal period with an incidence of 18 strokes per 100.000 deliveries (Jaigobin et al. 2000)
In young cryptogenic stroke patients the risk of having patent foramen ovale (PFO) was 4.7 (95% CI, 1.9-11.7) compared with those who had a known cause for stroke (Alsheikh-Ali AA et al. 2009). However, we must keep in mind that PFO can be merely an innocent bystander in many cases. Actually, to date, no association of PFO and ischemic stroke has been demonstrated in large population-based studies.
Other less documented risk factors in the young include alcohol – both as a chronic risk factor and a transient trigger – and other illicit drugs, such as opiates, cocaine, amphetamine and related substances. The causality of drug use and ischemic stroke is probably best shown for acute cocaine use, especially for crack cocaine (Cheng et al. 2016).
Furthermore, as many as 10% of the young ischemic stroke patients may have preceding acute infections such as upper respiratory tract infections, gastrointestinal infections, and skin or mucous membrane infections (Heikinheimo et al. 2013). Other documented chronic and acute infections include dental infections, chronic and active Chlamydia pneumoniae infection, HIV, and in endemic areas syphilis and tuberculosis, for example.
Conditions such as antiphospholipid syndrome (Urbanus et al. 2009) and genetic thrombophilias (e.g. factor V Leiden G1691A and prothrombin G20210A mutations) can increase the risk of young-onset ischemic as well, especially in combination with the pill or smoking.
In conclusion, stroke incidence is increasing in the younger population and a much wider spectrum of potential chronic and transient risk factors should be considered in these patients. An extensive and timely diagnostic work-up is mandatory in order to prevent any future events.
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