Edward Feldmann

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association

Intracerebral hemorrhage (ICH) is more than twice as common as subarachnoid hemorrhage (SAH) and is much more likely to result in death or major disability than cerebral infarction or SAH.1 Although >315 randomized clinical therapeutic trials for acute ischemic stroke and 78 trials for SAH were complete or ongoing (oral communication, Cochrane Collaboration, May 16, 1995) as of 1995, only the results of 4 small randomized surgical trials (353 total patients)2 3 4 5 and 4 small medical trials (513 total patients)6 7 8 9 of ICH had been published. In these small randomized studies, neither surgical nor medical treatment has been shown conclusively to benefit patients with ICH. Advancing age and hypertension are the most important risk factors for ICH.10 11 12 13 14 15 ICH occurs slightly more frequently among men than women and is significantly more common among young and middle-aged blacks than whites of similar ages.10 16 Reported incidence rates of ICH among Asian populations are also higher than those reported for whites in the United States and Europe. Pathophysiological change in small arteries and arterioles due to sustained hypertension is generally regarded as the most important cause of ICH.11 12 14 17 18 Cerebral amyloid angiopathy is increasingly recognized as a cause of lobar ICH in the elderly.19 20 21 22 23 Other causes of ICH include vascular malformations, ruptured aneurysms, coagulation disorders, use of anticoagulants and thrombolytic agents, hemorrhage into a cerebral infarct, bleeding into brain tumors, and drug abuse.10 Of the estimated 37 000 Americans who experienced an ICH in 1997, 35% to 52% were dead at 1 month; half of the deaths occurred within the first 2 days.1 17 24 Only 10% of patients were living independently at 1 month; 20% were independent …

Delayed hippocampal damage in humans following cardiorespiratory arrest.

Transient ischemia in animals produces delayed cell death in vulnerable hippocampal neurons. To see if this occurs in humans, we reexamined brain slides from all patients with anoxic-ischemic encephalopathy and a well-documented cardiorespiratory arrest. Eight patients dying 18 hours or less after cardiac arrest had minimal damage in hippocampus and moderate damage in cerebral cortex and putamen. Six patients living 24 hours or more had severe damage in all four regions. The increase in damage with time postarrest was significant only in the hippocampus. Delayed hippocampal injury now documented in humans provides a target for possible therapy that can be initiated after cardiopulmonary resuscitation.

Phenylpropanolamine and the Risk of Hemorrhagic Stroke

BACKGROUND Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study. METHODS Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient. RESULTS There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants. CONCLUSIONS The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.Objective:To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods:The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results:TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Chinese‐white differences in the distribution of occlusive cerebrovascular disease

The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (≥50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic temtories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterol-emia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.

The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trial

Background: Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography. Study Design: SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography. Results: SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained. Conclusions: Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.

Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia

We reviewed the clinical and laboratory data of 128 patients with cerebrovascular disease and antiphospholipid antibodies. Cases were evenly divided between men and women, and the mean age of the study group was 46 years. Cerebral infarction occurred in 97 patients, and transient hemispheric ischemic attacks without stroke were recorded in 19; 12 suffered ocular ischemia. Systemic lupus erythematosus was diagnosed in 16% of all cases. Histories of systemic thromboembolic events and recurrent miscarriages were noted in 14% of the patients and in 19% of the women, respectively. Evidence of cerebral infarction preceding the index event was present in 30% of cases. During a mean follow-up of 16 months, nine of 96 (9%) patients sustained new cerebral infarctions. Of 72 echocardiographic studies, 16 (22%) showed valvular abnormalities. Cerebral angiography detected intracranial lesions in 24 of 49 patients (49%). These data indicate that antiphospholipid antibodies can be identified in stroke patients without known autoimmune disorders. They also suggest that antiphospholipid antibody-associated cerebrovascular ischemia may be recurrent and often occurs in patients with systemic thromboembolic events. Our findings should help design a prospective clinical trial that will assess the risk of recurrent thromboembolism in this population, identify stroke risk factors, and address therapy.

Major Risk Factors for Aneurysmal Subarachnoid Hemorrhage in the Young Are Modifiable

Background and Purpose— To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH. Methods— Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject. Results— Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to ∞; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable). Conclusions— Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.

Factors associated with early presentation of acute stroke.

Background and Purpose Patients with stroke symptoms commonly delay many hours before seeking medical attention. We sought to explore the factors associated with early presentation of stroke patients to physicians. Methods We prospectively studied 100 consecutive acute stroke patients presenting to three large, urban medical centers. Using a standardized, structured interview and chart review, we assessed patient education about stroke, risk factors, clinical features of the stroke, source of stroke recognition, and timing of presentation. We did not study the distance from the site of stroke onset to the site of physician contact. Results Stroke onset time was known in 96 of the patients. Mean patient age was 71.3 years, 79% had at least one stroke risk factor, 26% had prior transient ischemic attack, 19% had prior stroke, 74% had some high school education, and 86% had regular physicians. Only 8% had been previously educated about stroke symptoms. Eighty one percent of strokes were ischemic. The mean time to physician contact was 13.4 ± 2.3 hours (median, 4.0 hours) and to neurologist contact was 21.2 ± 2.9 hours. A skewed distribution of presentation times accounts for the mean-median differences. A small number of patients presenting very late could have an effect on the correlations between presentation time and the variables studied. Early presentation time was associated with increased age, the sudden onset of a stable deficit, and recognition that the symptoms signified stroke. Only the sudden onset of a stable deficit correlated independently with early presentation time (P=.0048). There was no correlation between presentation time and prior transient ischemic attack or stroke, headache, vomiting, loss of consciousness or seizures at onset, or stroke subtype, but a type II error could not be excluded. Conclusions Despite their education level, regular health care, and risk factors, especially prior stroke and transient ischemic attack, these patients were not knowledgeable about stroke and delayed many hours before contacting physicians. The course of symptoms and recognition that they signified stroke were associated with earlier presentation. Patient education focused on groups at risk may hasten the presentation and treatment of acute stroke.

Major Risk Factors for Intracerebral Hemorrhage in the Young Are Modifiable

Background and Purpose— To identify risk factors for intracerebral hemorrhage (ICH), we examined data from the Hemorrhagic Stroke Project (HSP), a case-control study of hemorrhagic stroke among men and women aged 18 to 49 years. Methods— Case subjects for the HSP were recruited from 44 hospitals in the United States. Eligibility criteria included an ICH within 30 days preceding enrollment, no history of stroke or known brain lesion. For this report, we focused on patients with primary ICH, defined as not associated with an aneurysm, arteriovenous malformation or other structural lesion. Two control subjects were sought for each case subject. A multivariate regression analysis was performed to determine risk factors for primary ICH. Results— A total of 1714 patients with hemorrhagic stroke were identified for participation in the HSP. Of these, 217 cases met the criteria for primary ICH. Cases with primary ICH were matched to 419 controls. Independent risk factors for ICH included hypertension (adjusted odds ratio [OR], 5.71; 95% CI, 3.61 to 9.05), diabetes (adjusted OR, 2.40; 95% CI, 1.15 to 5.01), menopause (adjusted OR, 2.50; 95% CI, 1.06 to 5.88), current cigarette smoking (adjusted OR, 1.58; 95% CI, 1.02 to 2.44), alcoholic drinks≥2/day (adjusted OR, 2.23; 95% CI, 1.16 to 4.32), caffeinated drinks≥5/day (adjusted OR, 1.73; 95% CI, 1.08 to 2.79), and caffeine in drugs (adjusted OR, 3.55; 95% CI, 1.24 to 10.20). Conclusions— Among young men and women, the major risk factors for primary ICH can be modified, suggesting that this type of stroke may be preventable. Our findings for caffeine and menopause warrant further study.