Biomarkers and functional outcomes from ischaemic cerebral events in women: a prospective cohort study.

BACKGROUND AND PURPOSE: Several biomarkers have been associated with an increased risk of ischaemic stroke. However, the association between these biomarkers and functional outcome from cerebral ischaemic events is unclear. We aimed to assess the patterns of association between cardiovascular disease biomarkers and functional outcomes after incident ischaemic cerebral events in women. METHODS: Prospective cohort study of 27,728 women enrolled in the Women's Health Study who provided information on blood samples and were free of stroke or transient ischaemic attack (TIA) at baseline. Multinomial logistic regression was used to determine the association between elevated biomarker levels and functional outcomes from ischaemic cerebral events. Possible functional outcomes included TIA and ischaemic stroke with modified Rankin Scale (mRS) score of 0-1, 2-3, or 4-6. RESULTS: After a mean follow-up of 15.1 years, 461 TIAs and 380 ischaemic strokes occurred. Elevated levels of total cholesterol were associated with the highest risk of poor functional outcome (mRS 4-6) after incident cerebral ischaemic events (relative risk = 2.02, 95% CI = 1.18-3.46). We observed significant associations between elevated levels of total cholesterol, Lp(a), C-reactive protein, and triglycerides, and mild or moderate functional outcomes after ischaemic cerebral events. Elevations in all other biomarkers were not significantly associated with functional outcomes. CONCLUSIONS: Whilst total cholesterol level was associated with highest risks of poor functional outcome after stroke, we overall observed an inconsistent pattern of association between biomarkers linked with an increased risk of vascular events and more impaired functional outcomes from stroke.

Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study.

BACKGROUND: Stroke risk predictions are traditionally based on current blood pressure (BP). The potential impact of a subject's past BP experience (antecedent BP) is unknown. We assessed the incremental impact of antecedent BP on the risk of ischemic stroke. METHODS: A total of 5197 stroke-free subjects (2330 men) in the community-based Framingham Study cohort were enrolled from September 29, 1948, to April 25, 1953, and followed up to December 31, 1998. We determined the 10-year risk of completed initial ischemic stroke for 60-, 70-, and 80-year-old subjects as a function of their current BP (at baseline), recent antecedent BP (average of readings at biennial examinations 1-9 years before baseline), and remote antecedent BP (average at biennial examinations 10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models incorporating antecedent BP were also adjusted for baseline BP. The effect of each BP component (systolic BP, diastolic BP, and pulse pressure) was assessed separately. RESULTS: Four hundred ninety-one ischemic strokes (209 in men) were observed in eligible subjects. The antecedent BP influenced the 10-year stroke risk at the age of 60 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92 [95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This effect was evident for recent and remote antecedent BP, consistent in hypertensive and nonhypertensive subjects, and demonstrable for all BP components. CONCLUSIONS: Antecedent BP contributes to the future risk of ischemic stroke. Optimal prevention of late-life stroke will likely require control of midlife BP.

Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

BACKGROUND: The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. METHODS: There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. RESULTS: During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). CONCLUSIONS: Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.

Sensorimotor stroke due to thalamocapsular ischemia.

A 61-year-old hypertensive diabetic man awoke with a numb, heavy right arm and leg; symptoms progressed within 30 hours to a dense right hemisensory syndrome involving head, face, trunk, arm, and leg, accompanied by a right hemiparesis, involving tongue, face, arm, and leg with extensor plantar response, leaving him barely able to move the arm and leg against gravity. No impairment in alertness, memory, language, praxic, or visual functions was evident at any time. Improvement in motor function began in 24 hours and progressed to walking status by discharge on day 23. Eight days passed before the sensory deficit showed improvement, and it was still prominent at discharge. Autopsy three months later showed a 4 X 2 X 4-mm lacune in the ventral posterior nucleus of the left thalamus, with a zone of pallor on stained microscopic sections extending into the immediately adjacent posterior limb of the internal capsule. This case appears to be unique in that a sensorimotor stroke has been produced by a confirmed thalamocapsular infarct.

Caudate infarcts.

Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

Interobserver reliability in the interpretation of computed tomographic scans of 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.

Interobserver agreement in the diagnosis of stroke type.

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.

Interobserver variability in the assessment of neurologic history and examination in the Stroke Data Bank.

Interobserver reliability in obtaining neurologic histories and examinations was investigated among neurologists collaborating in the Stroke Data Bank (SDB). Seventeen in-hospital stroke patients were examined by six neurologists experienced in stroke over the course of three days. Patients were examined twice a day for two successive days, with each patient seen by four different neurologists. Data were recorded on SDB forms, according to definitions and procedures established for the SDB. Percent agreement and kappa coefficients were calculated to assess the levels of agreement for each item. Important differences in levels of agreement were found among items on both neurologic history and examination. Agreement among neurologists was higher for neurologic examination than for history. Patterns of agreement for items with low prevalence or with numerous unknown ratings are discussed. Improvement in interobserver agreement due to data editing for intra-observer consistency was shown.

Partial pontine hematomas.

Two hypertensive men presented clinically with small, largely unilateral hematomas of the pons and midbrain demonstrated by computerized tomography. Clinical manifestations included "ocular bobbing," complex forms of ophthalmoplegia, Cheyne-Stokes respiration, and pyramidal tract signs. The "typical" sings of massive pontine hemorrhage--including coma, pinpoint pupils, and hyperthermia--were absent.

Hemichorea-hemiballism and lacunar infarction in the basal ganglia.

We present a case of acute hemichorea-hemiballism associated with lacunar infarct documented by computerized tomography scan in the contralateral putamen and caudate nuclei. The pathoanatomic data of similar cases in the literature are reviewed with reference to the location of the responsible lesions. Acute hemichorea-hemiballism is most frequently caused by lacunar infarcts in the basal ganglia contralateral to the dyskinesia.

Intracerebral hemorrhage and phenylpropanolamine use.

Two patients developed intracerebral hemorrhage within hours from first-time ingestion of phenylpropanolamine-containing medications. One patient had marked hypertension, presented with three intracerebral hematomas, and developed a fourth hemorrhage 10 days later. Angiogram in one patient revealed "beading" of intracranial arteries, an abnormality also detected in a third patient who developed severe headache, vomiting, and acute hypertension following a single dose of phenylpropanolamine. These cases and others reported in the literature strongly suggest an association between phenylpropanolamine ingestion and hemorrhagic stroke. Direct questioning of use of this medication in cases of unexplained intracranial hemorrhage in previously healthy young individuals may reveal an unsuspected high frequency of this association.

Lobar intracerebral hematomas: clinical and CT analysis of 22 cases.

Twenty-two cases of lobar hematomas occurred among 93 consecutive patients presenting with intracerebral hemorrhage. Arterial hypertension was the leading cause. Most hematomas were found in the parietotemporal region. Common physical findings were hemiparesis, hemisensory syndrome, and visual field defects. Seizures occurred in 23% of the patients, and coma was infrequent at onset. Mortality rate was 32%. Hematoma size on CT correlated with outcome: Patients with small hematomas did well on medical treatment, and those with medium size and large hematomas had mortalities of 14 and 60%, respectively. One-half of the survivors in the latter groups were treated surgically. It is proposed that large and medium size hematomas might benefit from surgical treatment, especially when the level of consciousness progressively deteriorates or CT scan shows prominent midline shift.

Shotgun pellet embolus to the middle cerebral artery.

A 24-year-old man had a massive right cerebral infarction after occlusion of the middle cerebral artery trunk by a shotgun pellet that embolized from the heart during external cardiac massage for cardiac arrest. The cerebral infarct was followed by massive edema, uncal herniation, and death.

Cerebellar infarction in the superior cerebellar artery distribution.

Three patients with CT and angiographic documentation of cerebellar infarction in the superior cerebellar artery distribution had ataxic gait with little or no vertigo. Limb ataxia occurred in two patients. Transient chorea and signs of pontine infarction were also noted. CT demonstrated infarcts on the upper surface of a cerebellar hemisphere and/or vermis. Angiograms disclosed occlusion of the top of the basilar artery in two cases and distal superior cerebellar artery (SCA) branches in one. One patient later died after distal basilar artery occlusion; the others recovered.

Infarcts of the inferior division of the right middle cerebral artery: mirror image of Wernicke's aphasia.

We searched the Stroke Data Bank and personal files to find patients with CT-documented infarcts in the territory of the inferior division of the right middle cerebral artery. The most common findings among the 10 patients were left hemianopia, left visual neglect, and constructional apraxia (4 of 5 tested). Five patients had an agitated confusional state that was characterized by hyperactivity, restlessness, and easy distractibility. Motor and sensory abnormalities were not severe or persistent. The most common cause was cardiogenic embolism.

Silent stroke in the NINCDS Stroke Data Bank.

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.

Molecular signatures of brain injury after intracerebral hemorrhage.

BACKGROUND: The mechanisms of cellular death in the tissue surrounding an intracerebral hemorrhage (ICH) are not defined. OBJECTIVE: To investigate the relationship of markers of excitotoxicity and inflammation to brain injury after ICH. METHODS: A total of 124 consecutive patients with spontaneous ICH admitted within 24 hours of stroke onset were prospectively investigated. The volumes of the initial ICH, peripheral edema on days 3 to 4, and the residual cavity at 3 months were measured on CT scan. Glutamate, cytokines, and adhesion molecules were measured in blood samples obtained on admission. Stroke severity and neurologic outcome were evaluated with the Canadian Stroke Scale. RESULTS: Poor neurologic outcome at 3 months (Canadian Stroke Scale < 7) was observed in 53 patients (43%). Stroke severity and glutamate concentrations (by each increment of 10 micromol/L, odds ratio 1.23; 95% CI 1.09 to 1.41), but not the initial volume of ICH, were independent predictors of poor outcome. In the multiple linear regression analyses, tumor necrosis factor-alpha concentration was correlated (r = 0.83, p < 0.0001) with the volume of perihematoma edema, and glutamate concentrations were correlated (r = 0.78, p < 0.0001) with the volume of the residual cavity. These same results were observed when lobar (n = 58) and deep (n = 66) ICH were analyzed separately. CONCLUSIONS: High plasma levels of proinflammatory molecules within 24 hours of intracerebral hemorrhage onset are correlated with the magnitude of the subsequent perihematoma brain edema, whereas poor neurologic outcome and the volume of the residual cavity are related to increased plasma glutamate concentrations.

Precursors of extracranial carotid atherosclerosis in the Framingham Study.

To investigate cardiovascular risk factors and carotid atherosclerosis, we related previously measured risk factors to carotid atherosclerosis as determined by duplex ultrasonography in the Framingham Study cohort. Risk factors measured prospectively on 1,116 cohort members, ages 66 to 93, were related to the severity of carotid atherosclerosis measured by carotid ultrasonography performed during biennial examination no. 20 (1988 to 1990). The degree of carotid atherosclerosis was expressed as a percent carotid stenosis and, for statistical analysis, subjects were divided into four groups according to percent carotid stenosis. The prevalence of significant carotid stenosis in the general population was low--7% in women and 9% in men. A multivariate logistic regression model showed that age, cigarette smoking, systolic blood pressure, and cholesterol were independently related to carotid atherosclerosis. Alcohol consumption was also significant in men, but not in women. In addition, our results indicate that both current and former smoking in both sexes was related to the degree of carotid atherosclerosis.

Caudate hemorrhage.

We studied 12 patients with intracerebral hemorrhage in the head of the caudate nucleus. These cases accounted for 7% of a consecutive series of intracerebral hemorrhage. The clinical findings differed from more common varieties of supratentorial hemorrhage. All patients had acute onset of vomiting, headache, stiff neck, decreased level of consciousness, and behavioral changes in a pattern that simulated subarachnoid hemorrhage. Seven patients had gaze paresis and hemiparesis, with or without sensory loss. Two of these seven patients had, in addition, elements of Horner's syndrome. The prognosis for recovery was good. No patient had recurrent hemorrhage or persistent hydrocephalus.

Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank: historical features.

To gain insight into the historical features relevant to the diagnosis of cardiac embolic strokes, we studied the 1,290 patients with cerebral infarcts in the NINCDS Stroke Data Bank. Based solely on the presence of cardiac sources of embolism, we divided the patients into groups of high (n = 250), medium (n = 166), and low (n = 874) risk of a cardiogenic mechanism for their stroke. There was a highly significant graded relationship between increasing risk of a cardiac source and a history, or presence of, systemic embolism, abrupt onset, and diminished level of consciousness at onset. These clinical features may be useful for assessing the likelihood of a cardiac embolic mechanism in patients with cerebral infarcts.