Sex Differences in Presentation of Stroke

A Systematic Review and Meta-Analysis

Mariam Ali, BSc; Hendrikus J.A. van Os, MD; Nelleke van der Weerd, MSc; Jan W. Schoones, MA; Martijn W. Heymans, PhD; Nyika D. Kruyt, MD, PhD; Marieke C. Visser, MD, PhD; Marieke J.H. Wermer, MD, PhD

Disclosures

Stroke. 2022;53(2):345-354. 

In This Article

Abstract and Introduction

Abstract

Background and Purpose: Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack.

Methods: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were (1) cohort, cross-sectional, case-control, or randomized controlled trial design; (2) admission for (suspicion of) ischemic or hemorrhagic stroke or transient ischemic attack; and (3) comparisons possible between sexes in ≥1 nonfocal or focal acute stroke symptom(s). A random-effects model was used for our analyses. We performed sensitivity and subanalyses to help explain heterogeneity and used the Newcastle-Ottawa Scale to assess bias.

Results: We included 60 studies (n=582 844; 50% women). In women, headache (pooled odds ratio [OR], 1.24 [95% CI, 1.11–1.39]; I2=75.2%; 30 studies) occurred more frequently than in men with any type of stroke, as well as changes in consciousness/mental status (OR, 1.38 [95% CI, 1.19–1.61]; I2=95.0%; 17 studies) and coma/stupor (OR, 1.39 [95% CI, 1.25–1.55]; I2=27.0%; 13 studies). Aspecific or other neurological symptoms (nonrotatory dizziness and non-neurological symptoms) occurred less frequently in women (OR, 0.96 [95% CI, 0.94–0.97]; I2=0.1%; 5 studies). Overall, the presence of focal symptoms was not associated with sex (pooled OR, 1.03) although dysarthria (OR, 1.14 [95% CI, 1.04–1.24]; I2=48.6%; 11 studies) and vertigo (OR, 1.23 [95% CI, 1.13–1.34]; I2=44.0%; 8 studies) occurred more frequently, whereas symptoms of paresis/hemiparesis (OR, 0.73 [95% CI, 0.54–0.97]; I2=72.6%; 7 studies) and focal visual disturbances (OR, 0.83 [95% CI, 0.70–0.99]; I2=62.8%; 16 studies) occurred less frequently in women compared with men with any type of stroke. Most studies contained possible sources of bias.

Conclusions: There may be substantive differences in nonfocal and focal stroke symptoms between men and women presenting with acute stroke or transient ischemic attack, but sufficiently high-quality studies are lacking. More studies are needed to address this because sex differences in presentation may lead to misdiagnosis and undertreatment.

Introduction

Women with stroke have a higher mortality rate and a worse functional outcome compared with men.[1] It has been hypothesized that this is, at least in part, due to misdiagnosis with consequent delays to or even deferral of acute or secondary preventive treatment.[2,3]

The higher frequency of misdiagnosis in women may in turn be explained by a higher prevalence of nonfocal or atypical stroke symptoms compared with men.[4–7] These nonfocal symptoms include confusion, impaired consciousness, headache, generalized weakness, and non-neurological symptoms such as chest pain and palpitations. Nonfocal symptoms could mistakenly be interpreted as symptoms with another pathophysiology than stroke (a so-called stroke mimic) such as a conversion disorder or a migraine attack.[8] Interestingly, a previous cohort study indicated that women who presented with a transient ischemic attack (TIA) or minor stroke more frequently received a diagnosis of stroke mimic compared with men with similar symptomatology.[3] However, stroke recurrence rates within 90 days were similar for both sexes, raising the possibility of biases or sex-specific differences in TIA/stroke diagnosis.[9,10] Several pathophysiological mechanisms could explain sex differences in acute stroke symptoms, including differences in cause of stroke or stroke subtype, presence of comorbidities, or sex aspects resulting in different subjective experiences of symptoms.[11]

We systematically reviewed and meta-analyzed the literature on possible disparities between stroke symptoms in women and men to investigate whether there are sex differences in clinical acute stroke symptoms.

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