Sex differences in the symptom presentation of stroke: A systematic review and meta-analysis

Early diagnosis through symptom recognition is vital in the management of acute stroke. However, women who experience stroke are more likely than men to be initially given a nonstroke diagnosis and it is unclear if potential sex differences in presenting symptoms increase the risk of delayed or missed stroke diagnosis.

To quantify sex differences in the symptom presentation of stroke and assess whether these differences are associated with a delayed or missed diagnosis.

PubMed, EMBASE, and the Cochrane Library were systematically searched up to January 2021. Studies were included if they reported presenting symptoms of adult women and men with diagnosed stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) and were published in English. Mean percentages with 95% confidence intervals (CIs) of each symptom were calculated for women and men. The crude relative risks (RRs) with 95% CI of symptoms being present in women, relative to men, were also calculated and pooled. Any data on the delayed or missed diagnosis of stroke for women compared to men based on symptom presentation were also extracted.

Pooled results from 21 eligible articles showed that women and men presented with a similar mean percentage of motor deficit (56% in women vs 56% in men) and speech deficit (41% in women vs 40% in men). Despite this, women more commonly presented with nonfocal symptoms than men: generalized nonspecific weakness (49% vs 36%), mental status change (31% vs 21%), and confusion (37% vs 28%), whereas men more commonly presented with ataxia (44% vs 30%) and dysarthria (32% vs 27%). Women also had a higher risk of presenting with some nonfocal symptoms: generalized weakness (RR 1.49, 95% CI 1.09-2.03), mental status change (RR 1.44, 95% CI 1.22-1.71), fatigue (RR 1.42, 95% CI 1.05-1.92), and loss of consciousness (RR 1.30, 95% CI 1.12-1.51). In contrast, women had a lower risk of presenting with dysarthria (RR 0.89, 95% CI 0.82-0.95), dizziness (RR 0.87, 95% CI 0.80-0.95), gait disturbance (RR 0.79, 95% CI 0.65-0.97), and imbalance (RR 0.68, 95% CI 0.57-0.81). Only one study linking symptoms to definite stroke/TIA diagnosis found that pain and unilateral sensory loss are associated with lower odds of a definite diagnosis in women compared to men.

Although women showed a higher prevalence of some nonfocal symptoms, the prevalence of focal neurological symptoms, such as motor weakness and speech deficit, was similar for both sexes. Awareness of sex differences in symptoms in acute stroke evaluation, careful consideration of the full constellation of presenting symptoms, and further studies linking symptoms to diagnostic outcomes can be helpful in improving early diagnosis and management in both sexes.