Sex differences in human behavior have led to the hypothesis that sex differences in brain anatomy and physiology contribute to these behavioral differences. Furthermore, sex differences have an influence on the prevalence of certain neurological and psychiatric diseases. Some genetic diseases are different in women than in men. In many of these disorders, affected females show severe involvement of the nervous system with mental retardation. Sex-linked disorders include oral-facial-digital dysplasia type I, polycystic kidney-berry aneurysm disease, CHILD syndrome(congenital hemidysplasia with ichthyosiform erythroderma and limb defects), X-linked chondrodysplasia puncata 2, Aicardi syndrome, Rett syndrome, X-linked Kennedy spinobulbar atrophy, Lesch-Hyhan syndrome and certain metabolic encephalopathies.
Headaches, overall, are more frequently present in women. The prevalence of migraine is 12-18% in women and 3-6% in men; in early childhoodprevalence of migraine is equal among sexes, however in puberty the prevalence increases in females. On the contrary, cluster headache is 4 times more likely to occur in men over all ages. Studies have shown that there is a correlation between headaches, namely migraine with aura, and stroke which is of great importance if we take into consideration the fact that the prevalence of migraine is far greater in women than in men. One population based study examined the correlation between chronic unspecified headache and stroke and found that the risk of stroke in men who have had headaches during the past year is 4 times higher than in those without headaches, whereas that risk was only 2 times higher in men with headaches during the past 5 years. Among women, there was also a direct but statistically nonsignificant association between headache and the risk of stroke, thus the authors have concluded that chronic headache is an independent predictor of stroke among men and that it may be a marker of the underlying disease process leading to acute stroke seeing how the connection was strongest during a 1-year follow-up.
In a study including 3610 women with active migraine, 39.7% had migraine with aura; compared with women with no migraine history, these women had increased hazard ratios for stroke: 1.91 for ischemic stroke, 2.08 for myocardial infarction, 1.74 for coronary revascularization, 1.71 for angina, and 2.33 for death due to ischemic cardiovascular disease (68).
A similar study failed to find a correlation between migraine without aura or ordinary headache and ischemic or hemorrhagic stroke, but found a connection between migraine with aura and stroke; these women had a 1.71 times increased risk of ischemic stroke, even in women 55 years of age and younger. However, this is an increase in relative risk; in terms of absolute risk this means only 3.8 additional cases per year per 10 000 women (69).
Women aged 15-49 years with probable migraine with aura have a 1.5 increased risk for stroke, and women who use oral contraceptives or smoke have even a seven-fold increased risk for stroke compared with women with probable migraine with aura who are non-smokers or do not use oral contraceptives. Sub-analysis from the Women's Health Study revealed that women who have active migraine without aura do not have an increased risk for any cerebrovascular events, but women with active migraine with aura have a 2 fold increased risk for major cardiovascular disease and stroke compared with women with no migraine. Since migraine has a complex pathophysiology, especially migraine with aura, which include vascular mechanisms, connection between migraine and stroke may have similar background.
The incidence and prevalence rates for epilepsy are higher in men (3.4%) than in women (2.8%). Women with epilepsy have a greater risk for syndromes associated with infertility, such as hypotha-lamic-pituitary disruption, polycystic ovary-like syndrome and anovulatory cycles. Catamenial seizures are influenced by cyclical hormonal changes na doccur in one third to one-half of women with epilepsy.
Multiple sclerosis is the leading cause of neurologic disability in young adults. Multiple sclerosis is more common in women than in men, by a ratio of at least 2:1. Possible hormonal factors, maternal factors and X-linked gene factors are thought to be responsible for this sex preference. The majority of patients present with a relapsing-remitting disease, while a minority presents with a primary or secondary progressive disease.
Several peripheral diseases are more common in women. Idiopathic facial nerve palsy has a slightly higher incidence in women particularly of childbearing age, so do mononeuropathies in pregnancy (median, ulnar nerve). Pregnancy also appears to worsen episodes of weakness in patients with multifocal motor neuropathy. Acute neuropathies of the lower ectremity may develop during labor from injury at the spinal root, lumbosacral plexus or peripheral nerve.
Connective tissue diseases and autoimmune disorders are more prevalent in women such as Sjogren's syndrome (peripheral neuropathy), rheumatoid arthritis and systemiclupus erithematosus. Takayasu arteritis is a large-vessel vasculitis (aorta and major branches) which has a sex ratio women:men = 9:1 and is more commonly found in Asia. Giant cell arteritis is more common in women, affecting patients over 50 years of age. Typical presentations include headache, amaurosis fugax, muscle and joint aches and pains. Muscular dystrophy has several forms; Duchenne muscular dystrophy and Becker muscular dystrophy are allelic X-linked recessive disorders; boys become symptomatic for Duchenne dystrophy at approximately 5 years of age, become wheelchair bound at 10-12 years and die by the age of 20. In 5-10% a female carrier of an altered dystrophin gene will develop myopathic features similar to but milder than those that develop in boys.
Myasthenia gravis is an autoimmune disorder in which polyclonal antibodies are directed against the nicotinic acetylcholine receptor of skeletal muscles. . Female predominance is slight before puberty but becomes marked during and after puberty (female:male incidence = 14:1).
Polymyositis and dermatomyositis are inflammatory disorders that affect striated and cardiac muscles and are more prevalent in women. Dermatomyositis and to a lesser extent polymyositis carry an increased risk of cancer, which can occur before, at the time of, or years after the diagnosis is established.
It is a well known fact that genetic pre-disposition has great influence on risk for stroke and several genes for certain risks factors were identified. However lately a study has established that heritability of ischemic stroke is greater in women than in men: stroke in female family members was more frequent if other female family members previously suffered from it, while male family members were less likely to suffer from stroke. This difference was statistically significant even if traditional risk factors that could explain these gender differences were taken into consideration.
In some studies, women presented with a profile of higher baseline risk factors. A study evaluating the prevalence of risk factors in patients with myocardial infarction and their association with recurrent ischemic events (including myocardial infarction, stroke and coronary death) showed that women have more risk factors, and the risk of recurrent ischemic events in women increased with hypertension, diabetes and hypercholesterolemia, but for men, no increase in risk was detected with any risk factor.
Another study in patients undergoing coronary artery bypass graft surgery showed that risk factors significantly differ among sexes: women have more frequently hypertension and intracranial artery stenosis while men more frequently had hyperlipidemia, peripheral vascular disease, abdominal aortic aneurysm, severe carotid stenosis and severe aortic atherosclerosis. A study evaluating risk factors in middle aged (45-65 years) stroke patients showed that women significantly more often had diabetes, hypertension and hypercholesterolemia while men more often had a history of ischemic heart disease, smoking and alcohol consumption Reference Kurth, Kase, Berger, Gaziano, Cook and Buring(6)). Male stroke patients are more likely to have a history of ischemic heart disease, whereas female stroke patients are more likely to have hypertension and atrial fibrillation (AF); some studies found diabetes more commonly in women, others in men. Men are more likely to smoke cigarettes, or to have been smokers previously in their lives than women.
A study designed to identify risk factors for cryptogenic stroke revealed that low levels of high density lipoprotein (HDL) cholesterol and high factor VII activity were more frequently present in women while low level of plasma folate, hypertension and current smoking for the risk factors for stroke in men.
One study showed that women more often suffer from cardioem-bolic strokes and men from atherothrombotic and lacunar strokes.
A study from Spain showed that women more often suffered from aphasic disorders, visual field disturbances and dysphagia than men, and women who survived stroke were more disabled at discharge. Study from Israel showed no gender differences in clinical presentation or imaging studies, and the in-hospital mortality rate among women was higher.
Early arrival to an emergency facility is one of the major requirements for treatment with thrombolysis, yet a study from Germany found that women have a 10% lower chance of being admitted within the first 3 hours than men and this chance is further decreased in older women; however. In the time window between 0 and 3 hours, men compared to women had elevated mortality but were approximately three times as likely to have good functional outcomes. However, women were significantly more likely to benefit from rtPA compared with men in a therapy window between 0 and 6 hours. Similarly, the PROACT-2 study of intra-aerterial stroke thrombolysis with prourokinase has shown that women have 20% absolute benefit compared with men (10% absolute benefit) (34). In contrast to these studies, a study from Switzerland has shown no differences between sex and recanalization or outcome after 3 months in patients treated with intra-arterials thrombolysis. Observations from these studies need to be proved in future studies, sex may be an important factor for selection for thrombolysis especially in patients presenting at later time from symptom onset.
Out of patients with atrial fibrillation, women have higher annual rates of ischemic stroke than men (3.5% women, 1.8% men); however, there was no significant difference by sex in 30-day mortality or annual rates of hemorrhage (1% of both minor and major hemorrhage within one-years follow-up) (36). The authors of this study have concluded that the female sex is an independent risk factor for thromboembolism which goes in favour of introducing anticoagulant therapy in women with AF.
Another study has shown gender-related differences in patients with AF. Women were older, had a lower quality of life, more often had heart failure with preserved left ventricular systolic function, less frequently underwent electrical cardioversion and achieved rhythm control, and had a higher level of risk for stroke. However, prescription of oral anticoagulants was identical in both genders (65%) and so was the mortality. Yet another study, which examined gender-related differences in warfarin treatment of patients with AF, showed that women were older than men, had more risk factors, experienced more overall (major and minor) hemorrhages and had a higher rate of thromboembolism.
Epidemiological data have shown that the risk of death 1 year after stroke is somewhat lower in women than men, especially among elderly patients. Case fatality (deaths caused by cerebrovascular diseases among cases of acute stroke) for both ischemic stroke and all types of stroke combined was higher in men than in women, as was case mortality (deaths attributable to any cause among cases of acute stroke); however there was no difference in mortality caused by SAH. It has been observed that women are more prone for a hyperco-agulable state than men early after injury. Possibly underlying mechanisms such as coagulation status is an important factor in patients with stroke as well. Differences in coagulation parameters have been observed between men and women: women with diabetes mellitus have abnormalities in euglobulin clot lysis time and increased plasminogen activator inhibitor-1. Elevated levels of factor VIIa are associated with an increased risk of recurrent cardiac events in post infarction women but not in men while D-dimers are more predictive in men for cardiac events. These observations indicate possible gender-related differences in the pathophysiologic mechanisms of recurrent cardiac events.
The existing literature provides conflicting evidence concerning the risks of carotid endarterectomy (CEA) in women as compared with men. The initial NASCET and ECST studies have found that asymptomatic women benefit, in terms of postoperative results, from CEA less than asymptomatic men or symptomatic patients in general, however recent studies have shown that these differences are not clear enough to suggest that women shouldn't be surgically treated. A recent study on 3422 CEA patients has shown that women were at higher risk for a postoperative TIA or stroke and for postoperative stroke or mortality. This difference was visible only in asymptomatic women while there was no gender association for postoperative stroke or mortality for patients who were symptomatic. The authors of this study have concluded that although the combined TIA or stroke and stroke or mortality rates are higher in asymptomatic women as compared with men in the postoperative period, CEA is still appropriate in both women who are asymptomatic and women who are symptomatic but only if the postoperative TIA, stroke, and mortality rates are appreciably lower than in the natural history of medical management of these patients. Subgroup analysis in a study evaluating CEA in asymptomatic patients showed that women had a lower risk of ipsilateral ischemic stroke on medical treatment and a higher operative risk than did men, whereas CEA was beneficial in symptomatic severe carotid stenosis. Another study found no difference in 30-day surgical mortality after CEA.
A study done on a sample of 6038 CEA patients (out of which 35% were women), there was no significant difference in the perioperative risk of stroke or death, however, after a 2-year follow-up, women were more likely to have a stroke yet less likely to die. Another study, which evaluated the perioperative risks of over 1200 CEA patients (out of which 39% were women) during a 21-year period, found that survival rates at 1.5 and 8 years were higher for asymptomatic and symptomatic women compared with men, thus concluding that CEA does not carry a higher level of risk for women. Yet another study, examined the data collected over a period of 8 years, evaluating the outcome of 1298 CEA patients, and found that women were more likely to be asymptomatic than men but that there was no gender-difference in the frequency of postoperative cardiac (2.5% women, 1.5% men) or neurological events (1.6% women, 2.1% men); the postoperative stroke rate was 1.5% with no significant difference between men and women, and late recurrent stenosis developed in 1.5% of women and 0.8% of men, once again showing no significant gender-difference.
