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Background and Purpose: Abnormalities in endogenous fibrinolysis are associated with an increased risk for stroke in men and older adults. We tested the hypothesis that elevated plasma tissue plasminogen activator (tPA) antigen, a marker for impaired endogenous fibrinolysis, is an independent risk factor for stroke in young women., Methods: Subjects were 59 nondiabetic females ages 15 to 44 years with cerebral infarction from the Baltimore-Washington area and 97 control subjects frequency-matched for age who were recruited by random-digit dialing from the same geographic area. A history of cerebrovascular disease risk factors was obtained by face-to-face interview. Plasma tPA antigen was measured by enzyme-linked immunosorbent assay., Results: Mean plasma tPA antigen levels were significantly higher in stroke patients than control subjects (4. 80+/-4.18 versus 3.23+/-3.67 ng/mL; P=0.015). After adjustment for age, hypertension, cigarette smoking, body mass index, and ischemic heart disease, there was a dose-response association between tPA antigen and stroke with a 3.9-fold odds ratio of stroke (95% CI, 1.2 to 12.4; P=0.03) for the upper quartile (>4.9 ng/mL) of tPA antigen compared with the lowest quartile. The dose-response relationship between tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly attenuated this association., Conclusions: This population-based case-control study shows that elevated plasma tPA antigen level is independently associated with an increased risk for ischemic stroke in nondiabetic females 15 to 44 years of age. These findings support the hypothesis that impaired endogenous fibrinolysis is an important risk factor for stroke in young women.

To examine the independent association of depression following acute stroke with impairment in activities of daily living (ADL), the authors conducted a cross-sectional analysis of stroke patients enrolled in the Stroke Data Bank (U.S.A.) who had completed the Center for Epidemiological Studies Depression Scale (CES-D). Scores on the Barthel Index, a measure of ADL, were compared between depressed (CES-D > or = 16) and nondepressed patients (CES-D < or = 15) at 7-10 days after stroke. Of the 626 who completed CES-D, 160 were depressed. Depressed stroke patients evidenced greater impairment in ADL than nondepressed patients, independently of all other factors that influenced poststroke physical disabilities. CES-D scores were negatively correlated with Barthel scores in the entire stroke population. Neurological factors, greater age, poor prestroke physical activity, and prestroke disturbances in sexual functioning were also independently associated with limitations in functional status of stroke patients.

Purpose: To investigate the association between incident (first) stroke and the echogenicity of internal carotid arterial plaque at ultrasonography (US)., Materials and Methods: A cohort of 4, 886 individuals who, at baseline, were 65 years of age or older and without symptoms of cerebrovascular disease was followed up for an average of 3.3 years. Baseline clinical findings were from color Doppler and duplex US studies of the carotid arteries and a record of traditional risk factors: age, sex, presence of diabetes mellitus, pack-years of cigarette smoking, presence of hypertension, elevated systolic and diastolic blood pressure, elevated low-density lipoprotein cholesterol level., Results: Incident strokes, excluding hemorrhagic strokes and strokes of cardiac origin, were seen in 104 individuals (2.1%) at risk. Age- and sex-adjusted odds ratios for incident stroke were significant for hypoechoic plaque (odds ratio, 2.53; 95% CI, 1,42,4.53). After controlling for risk factors in a Cox proportional hazards model, the relative risk (RR) of incident stroke was 1.72 (p = .015) for hypoechoic plaque and 2.32 (P = .004) for internal carotid arterial narrowing of at least 50%. In addition, hypoechoic plaque (RR, 2.78; CI, 1.36,5.69) and 50%-100% stenosis (RR, 3.08; CI, 1.28, 7.41) were associated with ipsilateral, nonfatal stroke., Conclusion: In asymptomatic adults aged 65 years or older, that risk of incident stroke was associated with two US features: hypoechoic internal carotid arterial plaque and an estimated internal carotid arterial stenosis of 50%-100%.

Background and Purpose: We sought to determine risk factors for stroke and stroke type in persons with isolated systolic hypertension (ISH)., Methods: We performed proportional hazards analyses of data from the Systolic Hypertension in the Elderly Program, a double-blind, randomized, placebo-controlled trial of 4736 persons aged > or =60 years with ISH (systolic blood pressure, 160 to 219 mm Hg; diastolic blood pressure, <90 mm Hg). One treatment group received chlorthalidone (12.5 to 25 mg/d) with step-up to atenolol (25.0 to 50.0 mg/d) or reserpine (0.05 to 0.10 mg/d), if needed. The other treatment group received matching placebo. The main outcome measures were stroke, stroke or transient ischemic attack [TIA], and stroke types: ischemic (including lacunar, atherosclerotic, and embolic) and hemorrhagic., Results: During an average follow-up of 4.5 years, 384 strokes or TIAs and 262 strokes (including 217 ischemic, 66 lacunar, 26 atherosclerotic, and 25 embolic strokes) were documented. In multivariate analyses, placebo treatment, older age, smoking, history of diabetes, higher systolic blood pressure, lower HDL cholesterol, and ECG abnormality were significantly associated (P<0.05) with increased incidence of stroke or TIA, stroke, or ischemic stroke. Greater lacunar stroke risk was significantly related to placebo treatment, older age, history of diabetes (relative risk [RR] = 3.03; 95% confidence interval [CI], 1.70 to 5.40), and smoking (RR = 3.04; 95% CI, 1.73 to 5.37). Greater atherosclerotic and embolic stroke risk were significantly related to presence of carotid bruit (RR = 5.75; 95% CI, 2.50 to 13.24) and older age (RR = 1.65 per 5 years; 95% CI, 1.25 to 2.18), respectively., Conclusions: In older persons with ISH, history of diabetes and smoking are important risk factors for lacunar stroke, whereas carotid bruit and age are important risk factors for atherosclerotic and embolic stroke, respectively.

Background/purpose: The Baltimore-Washington Cooperative Young Stroke Study is the largest biracial urban-suburban population-based study to examine the etiology of strokes in children., Methods: We identified all children aged 1 to 14 years discharged from all 46 hospitals in central Maryland and Washington, DC with a diagnosis of ischemic stroke and intracerebral hemorrhage in the years 1988 and 1991. Each medical record was reviewed by two neurologists for appropriateness of the diagnosis of stroke and for information on the patient's history, clinical presentation, pertinent investigations, hospital stay, and outcome at time of discharge., Results: Eighteen children with ischemic infarction and 17 with intracerebral hemorrhage were identified. The most common cause of ischemic stroke was sickle-cell disease (39%), followed by vasculopathic (33%) and indeterminate (28%) causes. Causes of intracerebral hemorrhages were arteriovenous malformation (29%), hematologic (23%), vasculopathy (18%), surgical complication (12%), coagulopathy (6%), and indeterminate (12%). The overall incidence for childhood stroke was 1.29 per 100,000 per year, with ischemic stroke occurring at a rate of 0.58 per 100,000 and intracerebral hemorrhage occurring at a rate of 0.71 per 100,000. The incidence of stroke among children with sickle-cell disease was estimated to be 0.28% or 285 per 100,000 per year., Conclusion: Sickle-cell disease plays a disproportionately high role in childhood stroke when a biracial population is surveyed.

Background: Limited information exists on the frequency, trends in occurrence, risk factors, mechanisms, and outcome of ischemic stroke associated with illicit drug use among young adults in a geographically defined population., Methods: We reviewed ischemic stroke in young adults (aged 15 to 44 years) in 46 regional hospitals for 1988 and 1991. We examined stroke mechanisms and outcome in patients with recent drug use., Results: Recent illicit drug use was noted in 51/422 (12.1%) stroke patients. Patients with drug use were more likely than other stroke patients to be black (p=0.01), aged 25 to 39 years (p=0.004), and smokers (p=0.006), and were less likely to have hypertension (p=0.004) or diabetes mellitus (p=0.004). Drug use was the probable cause of stroke in 20 (4.7%) patients. Among 31 (7.3%) patients with drug use as a possible stroke mechanism, more likely diagnoses included cardioembolic stroke in 18, hematologic/collagen vascular in 6, nonatherosclerotic vasculopathy in 5, and atherosclerosis in 3. There was no difference in outcome between drug-associated and non-drug associated stroke., Conclusions: Recent illicit drug use occurs in 12.1% of young adult stroke patients. Drug-associated young adult stroke seems to relate to vascular mechanisms other than those related to hypertension or diabetes. Case-control studies are needed.

Background and Purpose: Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease., Methods: Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study., Results: During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft. frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (P < .001). Aspirin users had a 52% higher risk of stroke (relative risk, 1.52; 95% confidence interval, 1.1 to 2.0; P < .007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84% higher risk (relative risk, 1.84; 95% confidence interval, 1.2 to 2.8)., Conclusions: Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent.

Atherosclerotic plaque ulcers > or = 2 mm in depth and width in the thoracic aorta have been implicated by autopsy study as a cause of unexplained or cryptogenic ischemic strokes. Transesophageal echocardiography (TEE) allows visualization of complex atherosclerotic lesions of the thoracic aorta. We compared the prevalence of thoracic aorta ulcerated plaques (ulcers > or = 2 mm in both depth and width) in three age-matched groups undergoing multiplane TEE: group 1, 23 patients with cryptogenic ischemic stroke; group 2, 26 patients with known-cause strokes; and group 3, 57 control patients without strokes. TEEs were interpreted in a blinded fashion. Ulcerated plaques were found in 9 (39%) group 1 patients but in only 2 (8%) group 2 patients and in only 4 (7%) group 3 patients (p < 0.001). There was an association between advancing age and the presence of ulcerated plaques (p < 0.02). We conclude that ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic ischemic stroke and should be considered a potential source of cerebral emboli.

One hundred twenty-seven patients undergoing coronary artery bypass graft surgery were monitored by transcranial Doppler ultrasonography. Five patients had more than 50% increases in middle cerebral artery mean flow velocity during the initial phase (10-120 sec) of cardiopulmonary bypass. Four of these 5 developed neurological complications including stroke and encephalopathy. These results indicate that overperfusion of the basal cerebral arteries during cardiopulmonary bypass procedures may contribute to neurological dysfunction after the surgery.

The objective of this article is to describe the methods of assessing cardiovascular conditions among older adults recruited to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke. Medicare eligibility lists from four US communities were used to obtain a representative sample of 5201 community-dwelling elderly, who answered standardized questionnaires and underwent an extensive clinic examination at baseline. For each cardiovascular condition, self-reports were confirmed by components of the baseline examination or, if necessary, by a validation protocol that included either the review of medical records or surveys of treating physicians. Potential underreporting of a condition was detected either by the review of medical records at baseline for other self-reported conditions or, during prospective follow-up, by the investigation of potential incident events. For myocardial infarction, 75.5% of the self-reports in men and 60.6% in women were confirmed. Self-reported congestive heart failure was confirmed in 73.3% of men and 76.6% of women; stroke, in 59.6% of men and 53.8% of women; and transient ischemic attack, in 41.5% of men and 37.0% of women. Underreporting was also common. During prospective follow-up of an average of about 3 years per person, approximately 50% of men and 38% of women were hospitalized or investigated for at least one potential incident event; for each cardiovascular condition, about 1 to 4% of those investigated during prospective follow-up were found to have had the cardiovascular condition prior to entry into the cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral dysfunction after coronary artery bypass operations represents some of the most serious and costly complications of cardiac surgery. We used transcranial Doppler ultrasonography to detect and quantify the number of microemboli in the right middle cerebral artery of patients undergoing elective first coronary bypass operations (n = 117) and second coronary bypass operations (n = 10). We hypothesized that total microemboli were related to clinical outcome. A 2 MHz transducer was positioned in front of the ear above the zygomatic arch and depth gated to 50 mm. Microemboli were recorded as perturbations of the blood flow velocity in the middle cerebral artery and aurally monitored. Each episode of microembolism was specified both by clock time and as a perfusion or surgical event. Forty-one patients (32%) completed neuropsychologic evaluation with a battery of tests for cognitive function. Anxiety states and traits were also assessed. The distribution of microembolism showed that there were three groups of patients: < 30 microemboli (n = 83); 30 to 59 (n = 24); and > 60 (n = 20). Seven of 10 patients with cerebral complications (stroke, coma, delirium, aberrant behavior) were in the > 60 microemboli group. Those with cerebral complications had 20.7 +/- 4.5 microemboli from perfusion and 57.4 +/- 15.6 from surgical events. The 13 patients in the > 60 microemboli group without central nervous system symptoms had 95.5 +/- 19.5 microemboli from perfusion and 36.0 +/- 6.9 from surgical events. Neuropsychologic scores were most often depressed for memory (73%), comprehension (49%), attention (46%), and constructional ability (44%). The greatest change was in total score in the > 60 microemboli group (-3.3 +/- 0.6) compared with -1.1 +/- 0.2 and -1.9 +/- 0.2 for the 30 to 59 and < 30 groups, respectively. The incidences of cardiac and pulmonary complications and mortality were different between those patients with < 60 microemboli versus those with > 60 microemboli. Cardiac and pulmonary complications and mortality percentages were 4.7%, 3.7%, and 0.9%, respectively, for the < 60 microemboli group and 20%, 20%, and 15%, respectively, for the > 60 microemboli group. We concluded that transcranial Doppler ultrasonography is a useful technique to quantify and detect the source of microemboli during coronary artery bypass operations and may be useful in assessing new operative strategies, the quality of the perfusion, and potentially as an indicator for pharmacologic therapy in the operating room in patients with high microemboli counts.

Aphasia was present in 19.4% of the men and 22.5% of the women in the Stroke Data Bank. There were no gender differences in aphasia incidence among the intracerebral hemorrhages. Aphasia was more frequent among women with infarcts (37.0%) than men (28.3%). When stroke mechanism was controlled for, there was an excess of aphasia among the women with stroke due to cardiac embolism. When stroke site was controlled for, there were no gender differences in aphasia frequency. Wernicke's, global, and anomic aphasias were more common in women than men; Broca's aphasia was somewhat more common in men. Although there were no gender differences in infarct size overall, men with aphasia had larger infarcts than women with aphasia. Although gender differences were small, the infarct lesions producing aphasia in men were more posteriorly placed and the infarct lesions in women were more anteriorly placed, suggesting possible gender differences in the positioning of the language zone in the brain.

We examined a series of 59 patients with acute stroke lesions for the presence of comprehension emotional aprosody. Based on a standardized assessment of comprehension of emotional intonation, 29 patients (49%) showed emotional aprosody (17% "mild" aprosody [n = 10] and 32% "severe" aprosody [n = 19]). Patients with comprehension emotional aprosody showed a higher frequency of extinction on double-simultaneous stimulation, anosognosia, and deficits in facial emotion comprehension. Patients with comprehension emotional aprosody also showed a higher frequency of right-hemisphere lesions involving the basal ganglia and the temporoparietal cortex and more severe frontal and diencephalic atrophy. Comprehension emotional aprosody was not necessarily associated with poststroke depression (PSD) since patients with and without PSD showed similar impairments in emotional prosody comprehension.

Stroke recurrence has been investigated primarily with respect to prognostic factors predictive of recurrence. Several parametric functions are considered in modeling the distribution of ischemic stroke recurrences recorded within the Stroke Data Bank. A linear hazard function is shown to be the best-fitting function among those considered. This method of parametric modeling may lead to a more informed approach to treatment of ischemic stroke and secondary prevention and may enhance future investigations of prognostic factors as well.

Background and Purpose: Little information is available regarding black-white differences in stroke incidence in young adults., Methods: Cerebral infarction and intracerebral hemorrhage rates among adults 15 to 44 years of age were studied in Baltimore City and Baltimore County for 1988. Diagnoses were based on neurologist review of data obtained from medical records at 41 hospitals by neurological nurses., Results: The cerebral infarction rates per 100,000 were 22.8 for black males, 10.3 for white males, 20.7 for black females, and 10.8 for white females. The intracerebral hemorrhage rates per 100,000 were 14.2 for black males, 4.6 for white males, 4.8 for black females, and 1.5 for white females., Conclusions: Blacks had significantly (P < .05) higher rates than whites for both cerebral infarction and intracerebral hemorrhage. Cerebral infarction rates are high in Baltimore compared with Florence, Italy, or Stockholm, Sweden.

The Cardiovascular Health Study (CHS) is a longitudinal population-based study of coronary heart disease and stroke in men and women 65 years and older. The initial CHS cohort consisted of 5201 men and women recruited from a random sample of the Health Care Financing Administration (HCFA) Medicare eligibility lists in four communities in the United States. Extensive historical, physical, and laboratory evaluations were performed at the baseline examination in 1989 to 1990 to identify risk factors and subclinical disease. Periodic contacts are carried out to ascertain and verify incident cardiac and stroke events and their sequelae. Since only a short time has passed since entry of all the patients into the study, data are not available on time trends in the mortality rate of stroke, but we expect to contribute in this area in the years ahead. This article then is a description of the CHS, of methods of assessing stroke in the CHS cohort, and of prevalence of stroke and transient ischemic attacks at the initial examination.

Doppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA.

The frequency and correlates of the catastrophic reaction (CR) were examined in 52 consecutive patients with an acute stroke lesion. A new scale proved reliable for measuring the severity of CR. The CR was significantly associated with depression, a personal and family history of psychiatric disorder, and subcortical lesions, which were mostly located in the basal ganglia. Patients with and without a CR, when matched for the presence and type of depression, differed only in that CR patients had significantly more anterior lesions and a significantly higher frequency of subcortical damage. Results demonstrate that the CR is significantly associated with poststroke depression and may be a specific manifestation of certain types of poststroke depression.

A series of 309 admissions to a stroke unit was examined for anxiety symptoms. Patients were diagnosed with DSM-III-R generalized anxiety disorder (GAD) symptom criteria. They were divided into groups of no anxiety (59.2%), worried but not fulfilling GAD criteria (13.9%), and GAD (26.9%). Patients were then divided into depressed and nondepressed groups based on the existence of DSM-III major or minor (dysthymic) depression. These groups were not significantly different in their background characteristics, family or personal psychiatric history, social support or the severity of physical impairment. Anxiety plus depression was associated with left cortical lesions, whereas anxiety alone was associated with right hemisphere lesions. Patients with worry had anterior and patients with GAD had posterior right hemisphere lesions. These findings suggest that anxiety disorder (independent of depression) is not related to background characteristics or to severity of impairment but is, in part, influenced by the brain structures that are injured.

Objective: This study was undertaken to test the reliability and validity of the Pathological Laughter and Crying Scale and the effectiveness of nortriptyline treatment for patients with emotional lability following stroke., Method: Eighty-two patients with ischemic brain injury-54 who had been hospitalized with acute stroke and 28 others who requested treatment for pathological laughing and crying--were given standardized psychiatric and neurological assessments and then administered the Pathological Laughter and Crying Scale. The 54 acute stroke patients were used to evaluate the Pathological Laughter and Crying Scale, and the 28 patients with pathological emotional display were randomly assigned to nortriptyline treatment or placebo in a 6-week double-blind trial to assess the efficacy of a tricyclic antidepressant in treatment of this disorder., Results: The interrater reliability on the Pathological Laughter and Crying Scale for a subgroup of 15 patients was 0.93, and the test-retest reliability of the scale was excellent. After 4 and 6 weeks of treatment, scores on the Pathological Laughter and Crying Scale showed significantly greater improvement in the 14 patients given nortriptyline than in the 14 given placebo. Although almost one-half of these patients also had major depression, the improvement in emotional lability was independent of depression status. In addition, response to treatment was not significantly affected by lesion location or time since stroke., Conclusions: The severity of symptoms in pathological emotional display can be reliably quantified with the Pathological Laughter and Crying Scale, and treatment with nortriptyline can effectively ameliorate this emotional disorder.

Objective: Depression has been linked to higher than expected mortality from natural causes, particularly among elderly patients with physical illness. The authors examined the effect of depression on mortality among a group of stroke patients followed up for 10 years., Method: A consecutive series of 103 patients was assessed for major or dysthymic (minor) depression approximately 2 weeks after stroke with the use of a structured mental status examination and DSM-III diagnostic criteria. Vital status was determined for 91 of these patients 10 years later., Results: Forty-eight (53%) of the 91 patients had died. Patients with diagnoses of either major or minor depression were 3.4 times more likely to have died during the follow-up period than were nondepressed patients, and this relationship was independent of other measured risk factors such as age, sex, social class, type of stroke, lesion location, and level of social functioning. The mortality rate among depressed patients with few social contacts was especially high: over 90% had died., Conclusions: These results indicate that depressed mood following stroke is associated with an increased risk of subsequent mortality. Patients who are depressed and socially isolated seem to be particularly vulnerable.

Ischemic and hemorrhagic stroke frequently occur in temporal association with use or abuse of illicit and over-the-counter (OTC) sympathomimetic drugs. However, little information is available on the proportion of strokes associated with use/abuse of drugs in specific hospital populations. Between September 1, 1988, and August 1, 1989, 167 of 178 stroke patients entered into the Maryland Stroke Data Bank were asked for a history of drug use or abuse. Information was incomplete in 51 of 167 (31%) patients due to neurologic deficit or lack of inquiry. Eleven of the remaining 116 cases (9.5%) were historically associated with drug use. Age range was 25 to 56 years (mean, 41 years). Stroke associated with drug use occurred in four of 62 (6%) cerebral infarcts, two of 28 (7%) intracerebral hemorrhages, and five of 26 (19%) subarachnoid hemorrhages (p = ns). Drugs included cocaine in five (45%), OTC sympathomimetics in three (27%), phencyclidine in two (18%), and heroin in one (9%).

Objective: Some investigators have suggested that major depression might be overdiagnosed in stroke patients because of changes in appetite, sleep, or sexual interest caused by their medical illness; others have suggested that depression may be underdiagnosed in stroke patients who deny symptoms of depression because of anosognosia, neglect, or aprosody. The authors' goal was to determine how frequently depressive symptoms occur in acute stroke patients with and without depressed mood to estimate how often diagnostic errors of inclusion or exclusion may be made., Method: They examined the rate of autonomic and psychological symptoms of depression in 205 patients who were consecutively hospitalized for acute stroke. Eighty-five (41%) of these patients had depressed mood, and 120 (59%) had no mood disturbance. Forty-six (54%) of the 85 patients with depressed mood (22% of all patients) were assigned the DSM-III diagnosis of major depression., Results: The 120 patients without mood disturbance had a mean of one autonomic symptom, but the 85 patients with depressed mood had a mean of almost four. Tightening the diagnostic criteria to account for one more nonspecific autonomic symptom decreased the number of patients with major depression by only three; adding two more criteria decreased the number by only five. Thus, the rate of DSM-III major depression was 1% higher than the rate with one extra nonspecific autonomic symptom and 2% higher than the rate with two extra criteria. Conversely, loosening diagnostic criteria to account for denial of depressive illness increased the rate of major depression by only 5%., Conclusions: Both autonomic and psychological depressive symptoms are strongly associated with depressed mood in acute stroke patients.

Evaluation of the young stroke patient often requires an interdisciplinary approach because of the complexity of the problems encountered. We discuss some of the less common causes of stroke and present an approach to the patient.

We have discussed some of the more common etiologic categories found in young patients with stroke. Though many of the causes are rare, in the aggregate they account for many of the conditions leading to stroke. In Part II of this series (July 1991), we will explore some of the less common causes of stroke in the young and outline an approach to the patient.

The pattern of brain asymmetries was visualized on computed tomography (CT) scan in patients with a single acute cerebrovascular lesion. Patients were divided into those with typical or reversed frontal and/or occipital asymmetries. Among patients with a typical occipital asymmetry, those with left frontal or left basal ganglia lesions showed a significantly higher frequency of major depression and significantly higher depression scores than patients with similar lesion location but with reversed occipital asymmetry or those with a typical asymmetry and lesions in other (left or right) brain areas. Among patients with a reversed occipital asymmetry, there was no significant association between left frontal or left basal ganglia lesions and depression. This study demonstrates that the previously reported significant association between post-stroke major depression and lesion location is restricted to patients with a typical occipital asymmetry and is not present in patients with a reversed occipital asymmetry.

Patients with major depression admitted to hospital with acute stroke (n = 44), acute myocardial infarction (n = 25), or acute spinal cord injury (n = 12) were examined for differences in their phenomenological presentation of major depression. Depressed stroke patients were found to have significantly higher scores on the syndrome clusters for generalized anxiety and ideas of reference than depressed cardiac or spinal cord injury patients. In addition, significantly more stroke patients met diagnostic criteria for generalized anxiety disorder compared with the other two groups. Although spinal cord injury patients were younger, more likely to be treated with benzodiazepines, and less likely to be treated with beta-blockers, none of these factors distinguished stroke patients with anxious depression from stroke patients with depression only. These findings are consistent with the hypothesis that the etiology of depression following stroke may be different from that associated with myocardial infarction or spinal cord injury.

Lacunar stroke was diagnosed in 337 (26%) of the 1,273 patients with cerebral infarction among the 1,805 total in the Stroke Data Bank. We analyzed the 316 patients with classic lacunar syndromes. Among these, 181 (57%) had pure motor hemiparesis, 63 (20%) sensorimotor syndrome, 33 (10%) ataxic hemiparesis, 21 (7%) pure sensory syndrome, and 18 (6%) dysarthria-clumsy hand syndrome. No striking differences were found among the risk factors for the lacunar subtypes, but differences were found between lacunar stroke as a group and other types of infarcts. Compared to 113 patients with large-vessel atherosclerotic infarction, those with lacunar stroke had fewer previous transient ischemic attacks and strokes. Compared to 246 with cardioembolic infarction, patients with lacunar stroke more frequently had hypertension and diabetes and less frequently had cardiac disease. We found a lesion in 35% of the lacunar stroke patients' computed tomograms, with most lesions located in the internal capsule and corona radiata. The mean infarct volume was greater in patients with pure motor hemiparesis or sensorimotor syndrome than in those with the other lacunar stroke subtypes. In patients with pure motor hemiparesis and infarcts in the posterior limb of the internal capsule, there was a correlation between lesion volume and hemiparesis severity except for the few whose infarct involved the lowest portion of the internal capsule; in these patients severe deficits occurred regardless of lesion volume. Taken together, the computed tomographic correlations with the syndromes of hemiparesis showed only slight support for the classical view of a homunculus in the internal capsule.

We prospectively studied stroke recurrence in 1,273 patients with ischemic stroke who were entered into the Stroke Data Bank. Median follow-up was 13 months. The 2-year cumulative recurrence rate among these patients was 14.1%. Age, sex, race, history of hypertension, atrial fibrillation, or transient ischemic attacks, and stroke location were not associated with a higher risk of stroke recurrence. Patients with an elevated blood pressure, an abnormal initial computed tomogram, or a history of diabetes mellitus were at a higher risk of stroke recurrence. In contrast, patients with an infarct of unknown cause were at a lower risk of stroke recurrence than patients with a defined stroke mechanism, such as lacune, embolism, or atherosclerosis. A multivariate model suggests that patients at the lowest risk for stroke recurrence have a low diastolic blood pressure, no history of stroke, no history of diabetes mellitus, and an infarct of unknown cause.

The frequency of stroke among patients in six recent placebo-controlled trials of thrombolytic therapy for acute myocardial infarction is reviewed. Three trials used streptokinase and three used tissue plasminogen activator as the thrombolytic agent. While thrombolytic therapy greatly reduces the morbidity and mortality of acute myocardial infarction, it increases the rate of intracerebral hemorrhage.

We report 2 patients who developed a neglect syndrome, anosognosia, and major depression immediately after a right hemisphere cerebrovascular lesion. These cases demonstrate that neglect, anosognosia, and major depression may coexist in the same patient, and that the presence of anosognosia does not preclude the patient's recognition of emotional impairment.

The impact of clinically diagnosed depression on recovery in activities of daily living over a 2-year follow-up was examined in a prospective study of 63 stroke patients. Although impairment in activities of daily living, neurologic diagnoses and findings, lesion location and volume as measured on computed tomographic scan, demographic variables, cognitive impairment, and social functioning were comparable between depressed (n = 25) and nondepressed (n = 38) patients during their acute hospitalization, the two groups had different patterns of recovery in activities of daily living. At 2 years after suffering a stroke, patients with an in-hospital diagnosis of depression (either major or minor depression) were significantly more impaired in both physical activities and language functioning than were non-depressed patients. Among patients with major depression, this disparity in the recovery profile was present even after the depression had remitted. This study emphasizes the need for early recognition and treatment of poststroke depression.

The interaction between anxiety disorder and major depressive disorder in patients with cerebrovascular lesions was examined in a controlled, 2 x 2 study design. A consecutive series of 24 patients who met criteria for major depression only were compared with 6 patients who met criteria for both major depression and generalized anxiety disorder, and 45 patients who did not meet criteria for either major depression of generalized anxiety. Among patients with positive computed tomographic scans, the anxious-depressed group (n = 19) showed a significantly higher frequency of cortical lesions, while patients with major depression only (n = 15) had a significantly higher frequency of subcortical (basal ganglia) strokes. No significant between-group differences were found in other variables, such as demographic variables, familial and personal history of psychiatric disorders, and neurologic deficits. These findings suggest that, in this mostly black, low-socioeconomic-status population, cortical vs subcortical lesion location may play an important role in determining whether severe anxiety occurs in patients with post-stroke major depression.

Patients with computed tomographic scan-verified unilateral lesions in the basal ganglia or thalamus were examined for the presence of poststroke mood disorders. Patients with left-sided basal ganglia lesions (mainly in the head of the caudate nucleus) showed a significantly higher frequency and severity of depression, as compared with patients with right-sided basal ganglia or thalamic (left- or right-sided) lesions. Results suggest that damage to biogenic amine pathways and/or frontocaudate projections may play an important role in the modulation of mood.

A consecutive series of 103 stroke patients capable of undergoing a psychiatric interview were evaluated for mood disorders. Nearly 50% of patients studied in the acute stroke period had clinically significant depressions and one fourth had symptom clusters found in major depressive disorders. We confirmed our previous findings that lesion location is most important in determining frequency and severity of depression. In addition, we have identified other variables including functional physical impairment, intellectual impairment, quality of social support, and age which contribute to or modify depression. Post-stroke depressive disorders are multifactorial in their determination and expression and include both neurophysiological-neurochemical mechanisms and psychological factors in their etiology.

Patients with right-hemisphere strokes (N = 9) more than 1 year after injury had greater cortical binding of (3-N-[11C]methyl)spiperone than a similar group of patients with left-hemisphere strokes (N = 8) or normal control subjects (N = 17). The higher S2 serotonin receptor binding occurred in uninjured regions of the right parietal and temporal cortex. The ratio of binding in the ipsilateral to contralateral cortex showed a significant negative correlation with severity of depression scores in the left temporal cortex. These findings suggest that the biochemical response of the brain may be different depending on which hemisphere is injured and that some depressions may be a consequence of the failure to upregulate serotonin receptors after stroke.

The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients.

Interobserver reliability in interpretation of computed tomographic images was studied by six senior neurologists who independently evaluated on a standardized Stroke Data Bank form the brain lesions of 17 patients. The results analyzed with kappa statistics yielded moderate to substantial agreement on most items of interest including the stroke pathology and anatomy. In general, the levels of agreement were as high as previously reported for the diagnosis of the mechanism of the stroke, and much higher than on many stroke history items and items of neurologic examination. Excellent agreement was obtained for the detection of infarcts and intracerebral hemorrhage, and substantial agreement was obtained on whether the computed tomographic images were normal or indicative of small deep infarcts, superficial and deep infarcts, and aneurysms. The level of agreement on anatomy of the lesions was best for the frontal, parietal, and temporal lobes, putamen, cerebellum, and subarachnoid space. Implications for clinical research and diagnosis are discussed.

Previous brain infarctions seen on CT are common in the absence of history of stroke. Eleven percent of patients (135/1,203) without stroke history had ischemic lesions on their first CT, unrelated to the presenting stroke. Stroke Data Bank files were reviewed to determine whether the occurrence, location, and CT characteristics of those lesions are associated with their undetected status. Two distinct patterns were seen: (1) Small lesions of 1 cm or less were left hemisphere predominant and involved the deep structures of the brain; the majority of these were clinically silent. (2) Lesions greater than 1 cm occurred more frequently in the right hemisphere and were mostly superficial; these infarcts produced signs unrecognized by the patient or family. Risk factors for silent stroke were similar to those for stroke in general. Frequencies of in-hospital complications and 30-day fatality rates from the presenting stroke were not influenced by the existence of a prior silent stroke.

We are prospectively studying a group of 103 stroke patients over the first 2 years after infarction to determine the variables which are associated with the development of depression. At both 3 and 6 months post-stroke, patients with left hemisphere infarcts showed a strong relationship between severity of depression and distance of the lesion on CT scan from the frontal pole. The strength of this association was unchanged from the immediate post-infarction period. In contrast, the correlation between degree of functional physical impairment and severity of depression steadily increased over the 6 month follow-up. The correlation between severity of depression and Mini-Mental score or between depression and social functioning score dropped between in-hospital and 3 months but then increased significantly between 3 and 6 months post-stroke. Age did not correlate with depression beyond the acute post-stroke period. Whether the increasing strength of the relationships between impairment and depression over the first 6 months post-stroke indicates that continued depression led to delayed recovery or whether continued severe impairments led to depression is not known, however, this issue will be addressed in further data evaluation from this prospective study.

Patients with ischaemic lesions of the left cerebral hemisphere were examined for depression and intellectual impairment: in non-depressed patients, the severity of impairment was related to both lesion volume and location, as assessed by CT scan analysis. Cognitive impairment in patients with major depression was greater than predicted by lesion volume alone, and when patients were matched for severity of impairment, depressed patients had smaller lesion volumes than the non-depressed. After six months, non-depressed patients had significantly less cognitive impairment than depressed patients who showed no improvement. Both depression and lesion volume were significantly and independently related to cognitive impairment. These findings suggest that post-stroke depression can produce a true dementia in its own right, and that treatment of post-stroke depression might benefit cognitive function.

Interobserver agreement is essential to the reliability of clinical data from cooperative studies and provides the foundation for applying research results to clinical practice. In the Stroke Data Bank, a large cooperative study of stroke, we sought to establish the reliability of a key aspect of stroke diagnosis: the mechanism of stroke. Seventeen patients were evaluated by six neurologists. Interobserver agreement was measured when diagnosis was based on patient history and neurologic examination only, as well as when it was based on results of a completed workup, including a computed tomographic scan. Initial clinical impressions, based solely on history and one neurologic examination, were fairly reliable in establishing the mechanism of stroke (ie, distinguishing among infarcts, subarachnoid hemorrhages, and parenchymatous hemorrhages). Classification into one of nine stroke subtypes was substantially reliable when diagnoses were based on a completed workup. Compared with previous findings for the same physicians and patients, the diagnosis of stroke type was generally more reliable than individual signs and symptoms. These results suggest that multicentered studies can rely on the independent diagnostic choices of several physicians when common definitions are employed and data from a completed workup are available. Furthermore, reliability may be less for individual measurements such as signs or symptoms than for more-complex judgments such as diagnoses.

In a prospective study of mood disorders in stroke patients, variables obtained during the acute hospitalization were examined for their relationship to outcome at either 3- or 6-month follow-up. Distance of the lesion on computerized axial tomography scan from the frontal pole in patients with left anterior infarcts was significantly associated with severity of depression at 3 and 6 months poststroke. In addition, intellectual and functional physical impairment in-hospital were significantly correlated with severity of depression and social functioning scores at 3 and 6 months poststroke. Thus, patients who develop depression during the first 6 months poststroke may be responding to the severity of their impairment whereas the patients who develop depressions during the acute poststroke period may have a neuroanatomical and neurophysiological basis for their depression. Although other explanations might be proposed, the dynamic nature of the relationship between depression and associated variables during the first 6 months poststroke indicates that etiology of poststroke depression may be different depending upon the time of onset of the depression after brain injury.

Patients who developed post-stroke depression 3 to 24 months after hospital discharge (N = 21) were compared with patients who developed depression during hospitalization (N = 26) and patients who never developed depression over 24 months of follow-up (N = 15). During the acute hospitalization and at follow-up, the three groups were not significantly different in their demographic characteristics, neurological impairment, intellectual impairment, or quality of social support. The acute depression group, however, showed an increased correlation between impairment and depression from hospitalization to follow-up. Findings suggest that impairment does not produce depression, but, once depression occurs, it may interact with impairment to influence post-stroke recovery.

One hundred three patients attending a stroke clinic were evaluated for post-stroke depressive disorders using repeated quantitative assessment of psychopathology during a 12 month period. Almost one-third of these patients were depressed at the time of the initial assessment and two-thirds of these depressed patients who were re-evaluated remained depressed for 7 to 8 months. The prevalence and severity of depressive disorders was significantly elevated in those patients who were between 6 months and 2 years post-stroke. Demographic variables however did not distinguish depressed and non-depressed patients, nor did type of neurological symptoms, degree of impairment in activities of daily living or global cognitive impairment. However, patients with left hemisphere brain injury were significantly more depressed than patients with right hemisphere or brain stem infarctions. Based on this work and previous studies, we have suggested a profile for patients who are at high risk for developing post stroke depressive disorders: patients with left hemisphere frontal lobe infarctions who are within 2 years of the stroke. In spite of the fact that these depressions were clinically significant, none of the patients were presently receiving treatment. Effective treatment methods for these patients need to be developed.

As part of a prospective study of 103 stroke patients, we have analyzed the relation between depression and associated variables at 3 months, 6 months, 1 year, and 2 years after stroke. At all intervals up to and including 1 year poststroke, patients with left hemisphere strokes showed a strong relation between severity of depression and distance of the lesion on computed tomography scan from the frontal pole. At 2 years poststroke, this relation was no longer significant. The correlation between depression and impairment in activities of daily living peaked at 6 months and thereafter fell but remained significant at 1 and 2 years poststroke. The correlation between depression and cognitive impairment and between depression and social functioning fluctuated--with most correlations at 1 and 2 years follow-up nonsignificant. Although the conclusions that can be drawn from this study are limited by the fact that less than half of the original patients were followed up at each time, these declining correlations between depression and associated variables at 1 and 2 years follow-up may reflect the natural course of major depression which spontaneously remits between 1 and 2 years after stroke. The persisting significant association of impairment in activities of daily living with depression may reflect the effect of severe depression in sustaining and possibly retarding recovery from physical impairment.