Richard Kay

Low-Molecular-Weight Heparin for the Treatment of Acute Ischemic Stroke

Background Despite doubts about their efficacy and concern about their safety, antithrombotic agents are often used to treat acute ischemic stroke. Recent experience in patients with other thromboembolic disorders suggests that low-molecular-weight heparin, which requires only subcutaneous administration once or twice daily, may be more effective and safer than standard (unfractionated) heparin. Methods We conducted a randomized, double-blind, placebo-controlled trial comparing two dosages of low-molecular-weight heparin with placebo in the treatment of ischemic stroke. Patients were randomly assigned within 48 hours of the onset of symptoms to receive high-dose nadroparin (4100 anti–factor Xa IU twice daily), low-dose nadroparin (4100 IU once daily), or placebo subcutaneously for 10 days. The primary measure of outcome was death or dependency regarding activities of daily living six months after randomization. Secondary outcomes were death, hemorrhagic transformation of the infarction, and other complica...

Use of Transcranial Doppler Ultrasound to Predict Outcome in Patients With Intracranial Large-Artery Occlusive Disease

Background and Purpose Intracranial large-artery occlusive disease is the predominant vascular lesion found in stroke patients of Asian, African, and Hispanic ancestry, making it numerically perhaps the most common vascular cause of stroke in the world. Relatively little is known about the clinical significance of finding such lesions. We investigate whether the presence and the extent of these vascular lesions help predict outcome after stroke. Methods On the basis of transcranial Doppler of the intracranial arteries with supplementary duplex ultrasound of the carotid arteries, we determined the number of occlusive arteries in the craniocervical circulation of consecutive patients who were hospitalized for acute cerebral ischemia. Patients were followed for 6 months for further vascular events (including transient ischemic attack, stroke, and acute coronary syndrome) or death. Results Among 705 consecutive Chinese patients studied, occlusive arteries were found in 345 patients (49%): 258 patients (37%) had intracranial lesions only, 71 (10%) had both extracranial and intracranial lesions, and 16 (2.3%) had extracranial lesions only. Sixty-three (18%) of the 345 patients with occlusive arteries and 35 (9.7%) of the 360 patients without occlusive arteries had further vascular event or death within 6 months. The risk of vascular events or death increased rapidly with rising numbers of occlusive arteries, after adjustment for vascular risk factors and stroke severity (adjusted odds ratio [OR] 1.25 per occlusive artery, 95% CI 1.12 to 1.39). Other independent risk factors included age (OR 1.03 per year of age, 95% CI 1.01 to 1.05) and atrial fibrillation (OR 3.00, 95% CI 1.40 to 6.69). Conclusions In patients with predominantly intracranial large-artery occlusive disease, the presence and the total number of occlusive arteries in the craniocervical circulation predict further vascular events or death within 6 months after stroke. Transcranial Doppler ultrasound is an important investigation for the evaluation of patients with stroke in populations at risk of intracranial atherosclerotic disease.

Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study.

Although most therapeutic efforts and experimental stroke models focus on the concept of complete occlusion of the middle cerebral artery as a result of embolism from the carotid artery or cardiac chamber, relatively little is known about the stroke mechanism of intrinsic middle cerebral artery stenosis. Differences in stroke pathophysiology may require different strategies for prevention and treatment. We prospectively studied 30 consecutive acute ischemic stroke patients with middle cerebral artery stenosis detected by transcranial Doppler and magnetic resonance angiography. Patients underwent microembolic signal monitoring by transcranial Doppler and diffusion‐weighted magnetic resonance imaging. Characteristics of acute infarct on diffusion‐weighted magnetic resonance imaging were categorized according to the number (single or multiple infarcts) and the pattern of cerebral infarcts (cortical, border zone, or perforating artery territory infarcts). The data of microembolic signals and diffusion‐weighted magnetic resonance imaging were assessed blindly and independently by separate observers. Diffusion‐weighted magnetic resonance imaging showed that 15 patients (50%) had single acute cerebral infarcts and 15 patients had multiple acute cerebral infarcts. Among patients with multiple acute infarcts, unilateral, deep, chainlike border zone infarcts were the most common pattern (11 patients, 73%), and for single infarcts, penetrating artery infarcts were the most common (10 patients, 67%). Microembolic signals were detected in 10 patients (33%). The median number of microembolic signals per 30 minutes was 15 (range, 3–102). Microembolic signals were found in 9 patients with multiple infarcts and in 1 patient with a single infarct (p = 0.002, χ2). The number of microembolic signals predicted the number of acute infarcts on diffusion‐weighted magnetic resonance imaging (linear regression, adjusted R2 =0.475, p < 0.001). Common stroke mechanisms in patients with middle cerebral artery stenosis are the occlusion of a single penetrating artery to produce a small subcortical lacuna‐like infarct and an artery‐to‐artery embolism with impaired clearance of emboli that produces multiple small cerebral infarcts, especially along the border zone region.

Vascular lesions in Chinese patients with transient ischemic attacks

Article abstract-We studied 96 Chinese patients with TIAs using transcranial Doppler and duplex ultrasonography. We found intracranial stenosis or occlusion in 51% of cases and extracranial disease in 19% of cases. The most common intracranial lesion was stenosis of the terminal internal carotid artery or proximal middle cerebral artery, whereas the most common extracranial lesion was stenosis of the carotid bifurcation. NEUROLOGY 1997;48: 524-525

Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese.

We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke.

Prevalence of migraine and other headaches in Hong Kong.

From July 1992 to March 1993, we conducted a community-based prevalence survey of migraine and other types of recurrent headache by a telephone interview of 2,240 households with 7,356 persons aged 15 and above. 311 patients with recurrent headache were successfully interviewed. Of these, 101 were clinically validated. The overall prevalence rates were 1% for migraine, 2% for tension-type headache and 1% for unclassified headache. Adjusted for misclassification and non-response, the estimated prevalence rates for the three categories were 1.5, 3 and 0.4%, respectively. Agreement between clinical method and questionnaire interview was good for migraine, fair for tension-type headache and poor for unclassified headache. For all three types of recurrent headache, there was a female preponderance with a peak in the 25-44 age group. The prevalence of migraine was much lower than in Western communities but higher than that found in mainland China [1-8]. Common predisposing and aggravating factors for all three types of headaches as reported by the patients were mental stress, physical exertion and menstruation among females. Despite the low prevalence, the overall socioeconomic impact to a populous community is considerable.

Outcomes of Elderly Stroke Patients Day Hospital Versus Conventional Medical Management

BACKGROUND AND PURPOSE Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients, and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals. We carried out a prospective, randomized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management. METHODS One hundred twenty elderly patients with acute stroke were randomized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team. Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential. Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital. Family or community support was arranged when necessary for both treatment groups. On recruitment, patient demographics, medical history, clinical features related to stroke, and functional ability as measured by the Barthel Index were noted. Subjects were reviewed at 3 and 6 months to assess functional level, hospital and outpatient services received, general well-being, mood, and level of satisfaction. Costs of treatment of the two groups were also compared. RESULTS Functional improvement (Barthel Index score) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months (P = .03). There were also fewer outpatient visits among the day hospital patients at 6 months (P = .03). No significant difference was found in costs between the two treatment groups. CONCLUSIONS Compared with conventional medical management, care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost.

Stroke subtypes among Chinese living in Hong Kong The Shatin Stroke Registry

The Shatin Stroke Registry is a prospective study of all patients admitted with acute stroke to a generd hospital in Hong Kong where thc population is predominantly Chinese. Each patient was examined by a neurologist and 95.5% of the patients had a brain CT. Of 777 patients included in the study, 44.0% had a cortical/subcortical infarct, 18.5% a supratentorial lacunar infarct, 24.2% a supratentorial intracerebral hemorrhage, 5.8% brainstem/cerebellar infarct, 2.9% a brainstem/cerebellar hemorrhage, and 4.5% an uncertain diagnosis. The overall 30-day case fatality rate was 25.4% Comparison with five stroke registries from the West suggests that intracerebral hemorrhage occurs between two and three times more frequently in the Chinese than in Westerners. Whether there is any difference in the relative frequencies for lacunar infarction remains unclear.

Apolipoprotein E genotype and Alzheimer's disease in Hong Kong elderly Chinese

Article abstract-We studied the apolipoprotein E (apoE) allele frequencies in 65 Chinese patients with late-onset Alzheimers disease (AD) and 82 age- and sex-matched controls. The apoE epsilon 4 allele frequency was significantly higher in the AD group than in the control group (0.169 versus 0.067, p < 0.01). There were five homozygotes for epsilon 4 in the AD group but none among the controls. The odds ratio for AD was 1.6 for epsilon 4 heterozygotes. The age at onset was lower with the presence of the epsilon 4 allele and higher with the epsilon 2 allele, although neither of these differences reached statistical significance. The association between apoE alleles and AD previously reported in Caucasian populations was also present in this first reported study in Chinese.However, the lower epsilon 4 frequency in the Chinese population is compatible with previous reports of lower prevalence of AD compared with the prevalence of multi-infarct dementia. NEUROLOGY 1996;46: 146-149

Acute and long-term changes in serum lipids after acute stroke.

We studied serum lipid profiles in 171 patients less than or equal to 48 hours after the onset of acute stroke and 3 months later. The 83 patients suffering cerebral infarction had significantly higher serum concentrations of total cholesterol, low density lipoprotein-cholesterol, and apolipoprotein B and significantly lower serum concentrations of triglycerides and lipoprotein (a) less than or equal to 48 hours after ictus than 3 months later. The lipid profiles of the 53 patients suffering lacunar infarction were similar on both occasions, the only significant differences being higher total cholesterol and low density lipoprotein-cholesterol concentrations less than or equal to 48 hours after ictus. No significant changes were observed among the 35 patients suffering cerebral hemorrhage apart from a significantly higher concentration of high density lipoprotein3-cholesterol less than or equal to 48 hours after ictus. Our study, with many patients classified according to stroke subtype, gives results different from those of previous studies with much fewer patients. We conclude that in studies of serum lipid and lipoprotein concentrations as risk factors for cerebral infarction, comparing values obtained less than or equal to 48 hours after admission with control values may incorrectly identify certain lipid fractions as risk factors.