I got zero takeaways from this that could help stroke recovery. So useless.
Sex differences in the symptom presentation of stroke: A systematic review and meta-analysis
Sultana Shajahanhttps://orcid.org/0000-0002-7705-74491, Lingli Sun2, Katie Harris1, Xia Wanghttps://orcid.org/0000-0002-1684-70761, Else Charlotte Sandsethttps://orcid.org/0000-0003-4312-47783,4, Amy YX Yuhttps://orcid.org/0000-0002-7276-95515, Mark Woodward1,6, Sanne AE Peters1,6,7, and Cheryl Carcelhttps://orcid.org/0000-0001-8942-953X1,8
Background: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.
Aims:
Background: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.
Aims:
To quantify sex differences in the symptom presentation of stroke and assess whether these differences are associated with a delayed or missed diagnosis.
Methods:
Methods:
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.
Results: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.
Conclusion:
Results: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.
Conclusion:
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.
Keywords
Stroke, sex difference(s), symptom(s), presentation, gender, review, meta-analysis
1The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
2The George Institute for Global Health, Beijing, China
3Department of Neurology, Oslo University Hospital, Oslo, Norway
4Department of Research and Development, The Norwegian Air Ambulance Foundation, Oslo, Norway
5Department of Medicine (Neurology), University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
6The George Institute for Global Health, School of Public Health, Imperial College London, London, UK
7Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
8Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
Corresponding author(s):
Sultana Shajahan, The George Institute for Global Health, University of New South Wales, Sydney, NSW 2042, Australia. Email: SShajahan@georgeinstitute.org.au
Introduction
Women experience worse poststroke disability and are 3.5 times more likely to be institutionalized after stroke compared to men.1 There is also evidence to suggest that women with stroke are more likely than men to receive a delayed diagnosis,2,3 which can lead to missed opportunities for managing stroke early, resulting in worse outcomes for women.3 One of the possible reasons for a delay in diagnosis of stroke in women can be sex differences in the symptoms at presentation.4,5 In addition to focal neurological symptoms, women may be more likely than men to present with diffuse nonfocal symptoms, such as generalized weakness, fatigue, and mental status change.6 However, the selection of symptoms is not consistent among the limited number of studies which have analyzed sex differences in symptom presentation, where sex-stratified symptom data from different studies would be required. In addition, quality assessment of the evidence regarding sex differences in stroke symptoms is necessary to prepare appropriate sex-specific stroke diagnostic guidelines and to estimate the magnitude of the risk of delayed or missed diagnosis in women compared to men.
The purpose of this study was to systematically review the literature on the presence and extent of sex differences in the symptom presentation of stroke (ischemic stroke, hemorrhagic stroke, and transient ischemic attack (TIA)) and to determine whether sex differences in symptoms were associated with delayed diagnosis of stroke in women. Throughout this review, “sex” was referred to as the biological differences between men and women. “Gender” or the social and cultural differences between men and women were not included.
Methods
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.7 The protocol for this review was registered on PROSPERO; registration no.: CRD42020213153.
Eligibility criteria
We included all studies which reported on presenting symptoms in both women and men aged >18 years diagnosed with stroke (ischemic or hemorrhagic) or TIA, with results published in English. Studies were excluded if they had participants aged <18 years, had other neurological conditions (e.g. brain tumors or traumatic intracerebral hemorrhage), or recruited participants based on a particular symptom. Studies were also excluded if full texts were unavailable or if they were not original research, such as commentaries, reviews, or meta-analyses.
Search strategy
PubMed, EMBASE, and the Cochrane Library were searched up to January 2021 with no limit on the earliest date for eligible studies. Details of the search strategies are provided in Supplementary Data S1–S3. A combination of MeSH terms and keywords for symptom, presentation, sex, gender, diagnosis and epidemiology of stroke (ischemic or hemorrhagic), transient ischemic attack, and relevant synonyms of these terms were used.
Study selection, data extraction, and risk of bias assessment
All titles and abstracts retrieved by searching data sources were de-duplicated using reference management software EndNote V.X9 and screened independently against the eligibility criteria by SS and LS. The screened studies were then assessed further through full-text screening to find eligible studies for inclusion and all conflicts were resolved through discussion. Sex-stratified symptom data were extracted, as well as any available data linking symptom presentation to delayed or missed diagnosis of stroke for women and men. Details on data extraction and risk of bias assessment are provided in Supplementary Data S4 and S5.
Statistical analysis
The overall mean of study-specific percentages of each symptom with 95% CI was calculated for women and men. In addition, study-specific crude relative risks (RRs) with 95% CI of presenting a symptom were calculated for women relative to men, and pooled using a random-effects model with inverse variance weighting. Since multiple-adjusted RRs were not reported in all of the included studies, as a sensitivity analysis, adjusted odds ratios (ORs) with 95% CI were extracted when available and compared with the calculated crude ORs of the corresponding symptoms, to investigate the potential bias in unadjusted results. The I2 statistic was used to estimate the percentage of variability across studies due to between-study heterogeneity. Furthermore, random-effects meta-regression was conducted for age and study location, which is detailed in Supplementary Data S6. We only identified one study that reported sex differences in missed diagnosis; thus, no pooled OR could be reported. A p value of <0.05 was considered statistically significant. All statistical analyses were performed using Stata 16 and RStudio version 1.4.1106.
Results
The systematic search of the literature yielded 6702 records. After deduplication, the titles and abstracts of 4649 records were screened against the eligibility criteria, leaving 112 articles eligible for full-text screening. After full-text screening, 21 articles were finally included in the systematic review. The study selection process with reasons for exclusion at each stage is shown in Figure 1.
Figure 1. Flow chart showing study selection with reasons for exclusion.
Keywords
Stroke, sex difference(s), symptom(s), presentation, gender, review, meta-analysis
1The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
2The George Institute for Global Health, Beijing, China
3Department of Neurology, Oslo University Hospital, Oslo, Norway
4Department of Research and Development, The Norwegian Air Ambulance Foundation, Oslo, Norway
5Department of Medicine (Neurology), University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
6The George Institute for Global Health, School of Public Health, Imperial College London, London, UK
7Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
8Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
Corresponding author(s):
Sultana Shajahan, The George Institute for Global Health, University of New South Wales, Sydney, NSW 2042, Australia. Email: SShajahan@georgeinstitute.org.au
Introduction
Women experience worse poststroke disability and are 3.5 times more likely to be institutionalized after stroke compared to men.1 There is also evidence to suggest that women with stroke are more likely than men to receive a delayed diagnosis,2,3 which can lead to missed opportunities for managing stroke early, resulting in worse outcomes for women.3 One of the possible reasons for a delay in diagnosis of stroke in women can be sex differences in the symptoms at presentation.4,5 In addition to focal neurological symptoms, women may be more likely than men to present with diffuse nonfocal symptoms, such as generalized weakness, fatigue, and mental status change.6 However, the selection of symptoms is not consistent among the limited number of studies which have analyzed sex differences in symptom presentation, where sex-stratified symptom data from different studies would be required. In addition, quality assessment of the evidence regarding sex differences in stroke symptoms is necessary to prepare appropriate sex-specific stroke diagnostic guidelines and to estimate the magnitude of the risk of delayed or missed diagnosis in women compared to men.
The purpose of this study was to systematically review the literature on the presence and extent of sex differences in the symptom presentation of stroke (ischemic stroke, hemorrhagic stroke, and transient ischemic attack (TIA)) and to determine whether sex differences in symptoms were associated with delayed diagnosis of stroke in women. Throughout this review, “sex” was referred to as the biological differences between men and women. “Gender” or the social and cultural differences between men and women were not included.
Methods
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.7 The protocol for this review was registered on PROSPERO; registration no.: CRD42020213153.
Eligibility criteria
We included all studies which reported on presenting symptoms in both women and men aged >18 years diagnosed with stroke (ischemic or hemorrhagic) or TIA, with results published in English. Studies were excluded if they had participants aged <18 years, had other neurological conditions (e.g. brain tumors or traumatic intracerebral hemorrhage), or recruited participants based on a particular symptom. Studies were also excluded if full texts were unavailable or if they were not original research, such as commentaries, reviews, or meta-analyses.
Search strategy
PubMed, EMBASE, and the Cochrane Library were searched up to January 2021 with no limit on the earliest date for eligible studies. Details of the search strategies are provided in Supplementary Data S1–S3. A combination of MeSH terms and keywords for symptom, presentation, sex, gender, diagnosis and epidemiology of stroke (ischemic or hemorrhagic), transient ischemic attack, and relevant synonyms of these terms were used.
Study selection, data extraction, and risk of bias assessment
All titles and abstracts retrieved by searching data sources were de-duplicated using reference management software EndNote V.X9 and screened independently against the eligibility criteria by SS and LS. The screened studies were then assessed further through full-text screening to find eligible studies for inclusion and all conflicts were resolved through discussion. Sex-stratified symptom data were extracted, as well as any available data linking symptom presentation to delayed or missed diagnosis of stroke for women and men. Details on data extraction and risk of bias assessment are provided in Supplementary Data S4 and S5.
Statistical analysis
The overall mean of study-specific percentages of each symptom with 95% CI was calculated for women and men. In addition, study-specific crude relative risks (RRs) with 95% CI of presenting a symptom were calculated for women relative to men, and pooled using a random-effects model with inverse variance weighting. Since multiple-adjusted RRs were not reported in all of the included studies, as a sensitivity analysis, adjusted odds ratios (ORs) with 95% CI were extracted when available and compared with the calculated crude ORs of the corresponding symptoms, to investigate the potential bias in unadjusted results. The I2 statistic was used to estimate the percentage of variability across studies due to between-study heterogeneity. Furthermore, random-effects meta-regression was conducted for age and study location, which is detailed in Supplementary Data S6. We only identified one study that reported sex differences in missed diagnosis; thus, no pooled OR could be reported. A p value of <0.05 was considered statistically significant. All statistical analyses were performed using Stata 16 and RStudio version 1.4.1106.
Results
The systematic search of the literature yielded 6702 records. After deduplication, the titles and abstracts of 4649 records were screened against the eligibility criteria, leaving 112 articles eligible for full-text screening. After full-text screening, 21 articles were finally included in the systematic review. The study selection process with reasons for exclusion at each stage is shown in Figure 1.
Figure 1. Flow chart showing study selection with reasons for exclusion.
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