Gender and stroke symptoms: a review of the current literature.
Ischemic stroke accounts for 87% of the 780,000 strokes occurring annually in the United States and is a leading cause of death and functional limitations worldwide. The prompt recognition of stroke symptoms and timely arrival at the emergency room are important to stroke outcomes. Recent literature was suggestive that women may have different stroke symptoms compared with men. If women have nontraditional symptoms at stroke onset, this may contribute to delay in diagnosis and treatment. The purpose of this manuscript was to review the current literature regarding gender differences in stroke symptoms. Ten articles met the inclusion criteria for the review. Overall, the extant research was not indicative of robust gender differences in the classic symptoms of stroke or a greater frequency of nontraditional symptoms in women. One study found that women were significantly more likely than men to report nonspecific "somatic" symptoms, and in another study women were significantly more likely to have a change in mental status compared with men. Implications for nursing practice and suggestions for future research are discussed.
Stroke is a leading cause of death and functional limitations worldwide for both sexes, but there is evidence that the burden of stroke falls disproportionately on women. In comparison with men after stroke, women had greater limitations in activities of daily living (Di Carlo et al., 2003) and poorer quality of life in the areas of mental health and physical functioning (Gray et al., 2007). In addition, women had 30% lower odds of receiving tissue plasminogen activator (tPA) than men (Reeves, Bhatt, Jajou, Brown, & Lisabeth, 2009). These disparities are of concern because tPA is the only approved therapy to reduce the functional limitations caused by ischemic stroke, and there is evidence that women derive greater benefit from tPA than men (Kent, Price, Ringleb, Hill, & Selker, 2005).
The reasons for lower tPA rates in women are not yet fully understood. Delayed patient arrival at the hospital is considered the main reason for low tPA use (Deng et al., 2006), and some researchers found that women took longer to reach the hospital than men (Barr, McKinley, O'Brien, & Herkes, 2006; Mandelzweig, Goldbourt, Boyko, & Tanne, 2006). Delay seeking medical assistance for stroke is an important barrier to optimum stroke care because tPA should be administered within 4.5 hours after symptom onset (del Zoppo, Saver, Jauch, & Adams, 2009). There also was evidence in the literature that women were more likely to have "nontraditional" stroke symptoms than men (Labiche, Chan, Saldin, & Morgenstem, 2002). If women have a unique pattern of symptoms at stroke onset, this may contribute to their delay seeking medical assistance.
Although gender differences in the symptoms of myocardial infarction are well documented (Chen, Woods, Wilkie, & Puntillo, 2005; Lovlien, Schei, & Gjengedal, 2006), less is known about possible gender differences in stroke symptoms. The purpose of this article is to review the current literature regarding gender differences in stroke symptoms.
Ischemic stroke is emphasized in this article because it accounts for the 87% of the 780,000 strokes occurring annually in the United States (Rosamond et al., 2008).
Ischemic Stroke Etiology and Risk Factors
The World Health Organization defines stroke as "a focal (or at times global) neurological impairment of sudden onset, and lasting more than 24 hours (or leading to death), and of presumed vascular origin" (World Health Organization, 2006). There are two main types of stroke: hemorrhagic and ischemic. Hemorrhagic stroke occurs when there is bleeding from a vessel in the brain (intracerebral hemorrhage) or bleeding into the space between the inner and the outer layers of the tissue covering the brain (subarachnoid hemorrhage). Ischemic stroke is due to the occlusion of an artery in the cerebral circulation by atherosclerotic plaque, thrombus or embolus.
Well-documented risk factors for ischemic stroke include hypertension, diabetes, cigarette smoking, physical inactivity, obesity, cardiovascular disease, high levels of total cholesterol, and atrial fibrillation (Goldstein et al., 2006). Risk factors unique to women include pregnancy and puerperium (James, Bushnell, Jamison, & Myers, 2005) and combination (estrogen plus progesterone) postmenopausal hormone therapy (Wasserthiel-Smoller et al., 2003). Migraine headaches may increase ischemic stroke risk in younger women (Goldstein et al., 2006).
Certain groups have a higher incidence of stroke. African Americans are almost twice as likely as Caucasians to have a first-time stroke (Rosamond et al., 2008). In most age groups, men have a higher incidence of stroke than women. However, in the 34 and younger and the 75 and older age groups, the incidence of stroke is higher for women (Reeves et al., 2008). Because of their greater longevity, the female population in the United States has an excess of 60,000 strokes each year (Rosamond et al., 2008).
When an artery in the brain is occluded by atherosclerotic plaque, thrombus or embolus, ischemia may result. Ischemia is defined as a reduction in cerebral blood flow sufficient to cause an alteration of cerebral function (Smith, 2004). Ischemia triggers a complex series of cellular metabolic processes during which glucose and oxygen deprivation cause acidosis, depolarization of the cell membrane, and disturbances in intracellular calcium and sodium (Siejo, 1992). Cell death from ischemia occurs through two mechanisms: In apoptosis, the cell nucleus degrades and initiates a self-destruct sequence, and in necrosis there is a breakdown of cellular architecture (Smith, 2004). It is estimated that 2 million brain cells die every minute after ischemic stroke onset (Saver, 2006).
An area of tissue on the periphery of the main site of infarction undergoes a lesser degree of ischemia because of collateral circulation (Smith, 2004). The cells in this area, which is called the ischemic penumbra, remain viable for several hours after the onset of ischemia and may be salvaged if blood flow is restored through spontaneous recanalization or therapy with tPA. The tPA restores blood flow by cleaving the enzyme precursor plasminogen into plasmin, which dissolves the insoluble protein component of the blood clot blocking the artery (Ouriel, 2004).
It is customary to describe the symptoms of ischemic stroke with reference to the artery in which the occlusion occurs and the region of the brain supplied by that artery, which is called an arterial territory (de Freitas & Bogousslavsky, 2004). This practice is followed because stroke symptoms generally correspond to the brain functions of an arterial territory. Table 1 presents the main arteries in the cerebral circulation, arterial territories, and stroke symptoms.
The American Stroke Association (ASA) lists five main categories of stroke symptoms: (a) numbness or weakness of the face, arm, or leg, especially on one side of the body; (b) confusion or trouble speaking or understanding; (c) trouble seeing in one or both eyes; (d) trouble walking, dizziness, or loss of balance or coordination; and (e) severe headache with no known cause (www.strokeassociation.org). Of these symptoms, the most frequent at the onset of ischemic stroke were motor weakness (70%), speech disturbances (46%), and gait disturbances (37%) (Kimura, Kazui, Minematsu, & Yamaguchi, 2004). Dizziness or vertigo without other symptoms usually is not indicative of a stroke (Kerber, Brown, Lisabeth, Smith, & Morgenstern, 2006). Subarachnoid hemorrhage often is associated with the sudden onset of a severe headache (Naguma et al., 2008).
Although stroke usually is characterized by the sudden onset of neurological symptoms, prodromal symptoms may occur before the day of hospital admission (Stuart-Shor, Wellenius, DelloIacono, & Mittleman, 2009). After symptom onset, new symptoms may develop or existing symptoms may worsen over the course of several days. Stroke symptoms may appear at any time of the day or night, but there is a circadian pattern with a peak incidence between 6 a.m. and noon and the lowest incidence between midnight and 6 a.m. (Turin et al., 2009). Multiple factors likely contribute to the timing of stroke onset including circadian fluctuations in vascular tone, blood pressure, and coagulation factors (Manfredini et al.,
The PubMed database was searched for English-language journal articles published in the years 1994-2009 using the keywords stroke, ischemic, symptoms, clinical presentation, women, and gender. To be included in the review, the aim of the study must have been to compare stroke symptoms between women and men or this comparison must have been part of a larger study. The reference lists from the articles generated by the database search were examined to identify additional articles of relevance.
Ten publications were found on the basis of the search criteria. The articles included six prospective studies and four retrospective studies. Two of the prospective studies obtained data about stroke symptoms through interviews with the patient or a proxy. In two studies, stroke symptoms were classified as "traditional" or "nontraditional," and in one study researchers assessed "somatic" symptoms. One study included data about prodromal symptoms. Regarding the types of stroke represented in the studies' samples, three studies consisted of ischemic stroke only, two studies included both ischemic stroke and transient ischemic attack (TIA), four studies included both ischemic and hemorrhagic stroke, and one study included ischemic stroke, TIA, and hemorrhagic stroke.
The results of the review are structured according to the ASA symptom categories, and an additional section describes studies that included nontraditional, somatic, and prodromal symptoms. Not every study presented data on all stroke symptoms, and the terms used to delineate stroke symptoms sometimes varied between studies. Of the five studies with both hemorrhagic and ischemic stroke, only one study conducted a symptom by gender by stroke type analysis.
Details of the sample, design, and methods for the studies in this review are presented in Table 2.
Numbness or Weakness in Face, Arm, and Leg
Weakness in an arm, a leg, or the face is a frequent symptom of ischemic stroke and was present in 70% of persons in a large sample (N = 15,831; Kimura et al., 2004). The results of this literature review were mixed regarding gender differences in weakness. Barrett et al. (2007) reported that weakness was significantly more frequent in women (69%) than in men (59%) (p = .03) on one of two scales used to assess neurological status at time of hospital admission. Di Carlo et al. (2003) found that weakness was more common in men (46% of men versus 43%, p = .05) but the reverse for paralysis (42% female versus 36% male, p < .001). Although Labiche et al. (2002) reported greater motor weakness in males (24% male versus 19% female; OR = 0.76, 95% CI = 0.57-1.02), when a more conservative confidence interval was applied, the statistical significance of this finding was diminished. In the other six studies reporting data about this symptom cluster, there were no gender differences.
Sensory symptoms such as numbness and tingling were less frequent at ischemic stroke onset than weakness and were reported by 15% of persons in the sample of Kimura et al. (2004). No gender differences in sensory symptoms were found in the studies in this review.
Confusion, Trouble Speaking, or Understanding
An analysis of data from the NINDS Stroke Data Bank was conducted to assess gender differences in aphasia because of previous reports of excess female aphasia with stroke (Hier, Yoon, Mohr, Price, & Wolf, 1994). The results of the analysis of Hier et al. (1994) were indicative that women with ischemic stroke (23%) were more likely to have aphasia compared with men (19%) (p = .09). Roquer, Campello, and Gomis (2003) also found greater aphasia in women (29%) than in men (22%) (p < .001, OR = 1.47, 95% CI = 1.17-1.85). Similarly, compared with men, women were more likely to have aphasia (30% male versus 34% female, p < .001) and dysarthria (36% versus 32%, p < .001) in an analysis by Di Carlo et al. (2003). Because Di Carlo et al. assessed clinical state at time of maximal impairment during the first 7 days after stroke, the gender differences in aphasia and dysarthria found in this study may not be reflective of symptoms at hospital admission. No gender differences in communication abilities were found in the remaining seven studies.
Trouble Seeing in One or Both Eyes
Visual disturbances are not a frequent symptom of ischemic stroke and were present in only 4% of patients (Kimura et al., 2004). Gender differences in visual symptoms were found in two studies in this review. Roquer et al. (2003) reported that women (17%) were more likely to report visual problems than men (14%) (p = .05, OR = 1.35, 95% CI = 1.02-1.78). Lisabeth, Brown, Hughes, Majersik, and Morgenstem (2009) found a female excess of double vision, but it was of marginal significance (p = .06). In the six other studies in the review containing data on visual disturbances, there were no gender differences.
Trouble Walking, Dizziness, or Loss of Balance or Coordination
The combination of gait disturbances and vertigo/dizziness accounted for 46% of the symptoms associated with ischemic stroke onset (Kimura et al., 2004). Gender differences for this cluster of symptoms were found in three of the studies in this review. Gargano, Wehner, and Reeves (2009) reported that 14% of men had trouble walking, dizziness, or loss of balance or coordination compared with 9% of women (p < .01). More men (14%) than women (6%) had gait disturbances in another analysis (Rathore, Hinn, Cooper, Tyroler, & Rosamond, 2002). Imbalance was more frequent in men (20% male versus 15% female; OR = 0.70, 95% CI = 0.51-0.97) in the Labiche et al. (2002) analysis, but after statistical adjustment, the significance of this finding was reduced. Four studies in the review did not report data on this cluster of symptoms, and in the remaining three that did so, there was no significant gender difference in trouble walking, dizziness, or loss of balance or coordination.
In the literature, the frequency with which persons with ischemic stroke reported headache varied between 3% (Kimura et al., 2004) and 23% (Tentschert, Wimmer, Greiseneggerm Lang, & Lalouscheck, 2005). In one study, headache was more common in women (31% women versus 22% men, p = .0001; Kapral et al., 2005). However, 19% of the Kapral et al. (2005) sample had hemorrhagic stroke with a female excess of SAH, which could have accounted for the excess of headache in women. The other four studies containing data about headache in this review did not reveal evidence of gender differences in headache.
Nontraditional, Somatic, and Prodromal Symptoms
Labiche et al. (2002) classified stroke symptoms into 14 categories and then grouped the categories into traditional symptoms (sensory, gait, imbalance, motor, dysarthria, aphasia, facial droop, visual abnormalities, and vertigo/dizziness) and nontraditional symptoms (pain, change in level of consciousness/disorientation, and unclassifiable neurological and nonspecific symptoms). Twenty-eight percent of women compared with 19% of men reported a nontraditional stroke symptom (OR = 1.62, 95% CI = 1.2-2.2). More women (12%) than men (8%) had pain. The type/location of pain was not specified. Change in level of consciousness/disorientation was more common in women (17% female versus 12% male). The magnitude of these differences was diminished after statistical adjustment. The excess of hemorrhagic stroke in women (12% female versus 6% male) in this sample may have contributed to the greater female frequency in change in level of consciousness/disorientation. Efstathious et al. (2002) found that decreased level of consciousness predicated intracranial hemorrhage but not ischemic stroke.
Lisabeth et al. (2009) defined nontraditional stroke symptoms as face or body pain, mental status change (disorientation, confusion, or loss of consciousness), lightheadedness, headache, general neurological symptoms (nausea, hiccups, and nonfocal weakness), and nonneurological symptoms (chest pain, palpitations, or shortness of breath). Compared with men, women were significantly more likely to a have a change in mental status (p = .03). Gargano et al. (2009) found a trend that did not reach statistical significance for the nontraditional symptom of "pain other than headache" for women with ischemic stroke and TIA.
Stuart-Shor et al. (2009) created a "somatic" cluster of symptoms by grouping together headache, change in behavior, difficulty understanding, nausea, and change in vision, feels "funny," fatigue, malaise, or "other" symptoms. Because this study included only persons with ischemic stroke, the authors considered headache a somatic rather than classic stroke symptom. Compared with men, women with ischemic stroke were more likely to report that they had at least one "somatic" symptom within 24 hours of hospital admission (p = .008). However, there were no significant gender differences in specific somatic symptoms. There also were no gender differences in the classic symptoms of stroke (weakness, numbness, difficulty speaking or understanding, trouble walking, vision change, headache, and clumsiness) between women and men within 24 hours of hospital admission.
The preceding study was the only study found in the database search in which gender differences in prodromal symptoms of stroke were examined. Stuart-Shor et al. (2009) defined prodromal symptoms as either classic or somatic symptoms occurring before 24 hours of hospital admission. When somatic symptoms were grouped into one variable, women were more likely than men to report any somatic prodromal symptom (p = .03). With regard to specific symptoms in the prodromal period, men were more likely than women to report weakness or clumsiness (50% men versus 37% women, p = .008).
Implications for Nursing
Reaching a definitive conclusion from this review of gender differences in stroke symptoms was hampered by the relatively small body of literature on this topic and methodological differences among the studies. In particular, the inclusion of both hemorrhagic and ischemic stroke in several of the studies in this review may have obscured potential gender differences in symptoms for each type of stroke.
On the whole, the results of this review were not indicative of robust gender differences in the classic symptoms of stroke or a greater frequency of nontraditional or unique symptoms in women. One study found that women were significantly more likely than men to report nonspecific "somatic" symptoms (Stuart-Shor et al., 2009), and in another study women were significantly more likely to have a change in mental status compared with men (Lisabeth et al., 2009). Importantly, neither of these two studies included persons with hemorrhagic stroke, thus avoiding confounding of the results due to differences in symptom patterns between the two main types of stroke. Therefore, nurses who perform triage in the emergency room or practice in a primary care setting and neuroscience nurses who may witness a first or recurrent stroke should be aware that a change in mental status or somatic symptoms may be indicative of stroke in women.
On the basis of the lack of consistent gender differences in stroke symptoms in the present literature, it seems advisable that in their patient education efforts, nurses should continue to emphasize the classic symptoms of stroke provided by the ASA. In the analysis by Stuart-Shor et al. (2009), 97% of both women and men reported at least one of the ASA symptoms in the 24 hours before hospital admission. Nurses also should discuss with clients the importance of seeking prompt medical assistance once these symptoms are noticed. An analysis by the Centers for Disease Control and Prevention found that fewer than half (42%) of 7,901 stroke patients arrived at the emergency department within 2 hours of symptom onset (Centers for Disease Control and Prevention, 2007).
A recent public education campaign stressed the importance of calling 911 for suspected stroke symptoms (www.strokealert.org). Persons with stroke who are transported to the hospital by ambulance arrived significantly earlier than people who used other means of transportation, and these individuals were seven times more likely to receive tPA than persons who arrived at the hospital by other means (Deng et al., 2006). Thus, nurses should encourage the use of emergency medical services for suspected stroke symptoms.
On the basis of the results of this review, several directions for further research are suggested. First, more studies are needed in which data about stroke symptoms are obtained through interviews. This method of data collection may enable researchers to identify atypical and/or nonspecific symptoms in addition to those identified by Stuart-Shor et al. (2009). If such symptoms are found, studies can be designed and conducted to look for gender differences in these symptoms. Second, studies in which data are analyzed according to stroke type will reduce any effect that the inclusion of all types of stroke may have on study outcomes. Third, replication of the Lisabeth et al. (2009) study will provide further evidence of gender differences in change in mental status as a presenting symptom of ischemic stroke.
Another area of future research concerns the presence of prodromal symptoms. Although public education materials emphasize the sudden onset of stroke symptoms, Stuart-Shor et al. (2009) found that 35% of persons in their ischemic stroke sample reported prodromal symptoms, with a greater frequency in women. The fact that women tended to report a prodromal symptom more often than men is intriguing in light of research suggestive of greater delay in women's help seeking for stroke symptoms. Although it cannot be definitively known if these prodromal symptoms were related to stroke, a better understanding of the type and time frame of these symptoms may eventually have implications for earlier diagnosis and treatment of stroke in women.
A coming epidemic of stroke in women is anticipated because of the combination of an aging population, the women's greater longevity, and the increase of stoke incidence with age (Reeves et al., 2008). Because of these trends, nurses increasingly will provide care to women who have had a stroke or may be at risk for stroke. Nurses should be aware that the symptoms of stroke as provided by the ASA are the usual presenting symptoms of stroke in both women and men and that women may be more likely to experience nonspecific somatic symptoms and a change in mental status associated with stroke onset.
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Questions or comments about this article may be directed to Claudia C Beal, MN RN, at email@example.com. She is a doctoral candidate at The University of Texas at Austin, Austin, TX.
TABLE 1. Arterial Territories and Stroke Symptoms Artery Arterial Territory Symptoms Internal Ipsilateral blindness; carotid contralateral hemiparesis; sensory loss; aphasia Middle Lateral cerebral Hemiparesis; sensory loss; cerebral hemisphere; internal homonymous hemianopia capsule; basal ganglia (blindness in one half of the visual field of both eyes); contralateral gaze paresis; aphasia; sensory loss Anterior Frontal lobe Hemiparesis; motor neglect; cerebral (medial aspect) speech disturbance; sensory loss in contralateral leg Posterior Occipital lobe; medial Homonymous hemianopia; color cerebral aspect of temporal lobe blindness; oculomotor palsy; memory disturbance; sensory loss; amnesia Basilar Thalamus; cerebellum; Contralateral hemiparesis; artery medulla; pons ipsilateral facial weakness; branches eye movement disturbance; dysarthria Note. Adapted from "Cerebral Infarction," by J. C. Brust in Merritt's Neurology (pp. 295-303), edited by L. Rowland, 2005, Philadelphia: Lippincott Williams & Wilkins. TABLE 2. Details of Studies in Literature Review Sample n (% Female), Author/Country Stroke Type (%) Design Barrett et al. (2007)/ 505 (45) Prospective United States I (100) Multicenter DiCado et al. (2003)/ 4,499 (50) Prospective Europe I (61) Multicenter H (12) Gargano et al. (2009)/ 1922 (54) Prospective United States I (67) Multicenter TIA (23) H (10) Hier et al. (1994)/ 805 (53) Retrospective United States I (70) H (27) Kapral et al. (2005)/ 3323 (46) Prospective, Canada I (78) stroke registry H (19) Labiche et al. (2002)/ 1124 (58) Prospective United States I (65) Multicenter TIA (22) H (8.7) Lisabeth et al. (2009)/ 461 (49) Prospective United States I/TIA (100) Rathore et al. (2002)/ 474 (47) Retrospective United States I (85) H (15) Roquer et al. (2003)/ 1581 (48) Prospective Spain I (100) Stuart-Shore et al. (2009)/ 1107 (55) Retrospective United States I (100) Author/Country Variables to Assess Stroke Symptoms Barrett et al. (2007)/ Two stroke scales that assess United States neurological status DiCado et al. (2003)/ Clinical status at time of maximal Europe impairment Gargano et al. (2009)/ Symptom report at admission United States Hier et al. (1994)/ Data bank records United States Kapral et al. (2005)/ Data on symptoms abstracted from Canada medical records Labiche et al. (2002)/ Symptoms assessed by interview United States Lisabeth et al. (2009)/ Symptoms assessed by interview United States Rathore et al. (2002)/ Medical record review United States Roquer et al. (2003)/ Clinical state at admission Spain Stuart-Shore et al. (2009)/ Medical record review United States Note. I = ischemic stroke; TIA = transient ischemic attack; H = hemorrhagic stroke.