Robert J. Wityk

PREGNANCY AND THE RISK OF STROKE

BACKGROUND It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk. METHODS We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the womens medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child. RESULTS Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, adjusted age and race, was 0.7 (95 percent confidence interval, 0.3 to 1.6), but it increased to 8.7 for the postpartum period (after a live birth or stillbirth) (95 percent confidence interval, 4.6 to 16.7). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy (95 percent confidence interval, 1.0 to 6.4) but 28.3 for the postpartum period (95 percent confidence interval, 13.0 to 61.4). Overall, for either type of stroke during or within six weeks after pregnancy, the adjusted relative risk was 2.4 (95 percent confidence interval, 1.6 to 3.6), and the attributable, or excess, risk was 8.1 strokes per 100,000 pregnancies (95 percent confidence interval, 6.4 to 9.7). CONCLUSIONS The risks of both cerebral infarction and intracerebral hemorrhage are increased in the six weeks after delivery but not during pregnancy itself.

Race and Sex Differences in the Distribution of Cerebral Atherosclerosis

BACKGROUND AND PURPOSE The purpose of this study was to assess the influence of race, sex, and other risk factors on the location of atherosclerotic occlusive lesions in cerebral vessels. Previous angiographic studies of patients with stroke or transient ischemic attack (TIA) suggest that extracranial atherosclerosis is more common in whites and intracranial disease is more common in blacks. Noninvasive techniques such as duplex ultrasound, transcranial Doppler (TCD), and magnetic resonance angiography (MRA) allow vascular assessment of a more representative proportion of patients than does conventional angiography alone. METHODS Consecutive patients evaluated at a community hospital for stroke or TIA over a 2-year period were reviewed. Lesions were defined as a 50% or greater atherosclerotic stenosis by angiography, duplex ultrasound, or TCD, or a moderate stenosis by MRA. RESULTS Whites were more likely than blacks to have extracranial carotid artery lesions (33% versus 15%, P = .001), but the proportion of patients with intracranial lesions was similar (24% versus 22%). Men were more likely to have intracranial lesions than women (29% versus 14%, P = .03). When multivariate logistic regression analysis was used, white race was the only predictor for extracranial carotid artery lesions, and male sex was the only predictor for intracranial lesions. The cause of stroke/TIA was extracranial carotid artery disease in 8% and intracranial disease in 8% of all patients in the study. CONCLUSIONS The distribution of cerebral atherosclerosis is influenced by race and sex but not by other vascular risk factors. In our patient population, intracranial disease is as common a cause of cerebral ischemia as extracranial carotid disease.

New England medical center posterior circulation registry

Among 407 New England Medical Center Posterior Circulation registry patients, 59% had strokes without transient ischemic attacks (TIAs), 24% had TIAs then strokes, and 16% had only TIAs. Embolism was the commonest stroke mechanism (40% of patients including 24% cardiac origin, 14% intraarterial, 2% cardiac and arterial sources). In 32% large artery occlusive lesions caused hemodynamic brain ischemia. Infarcts most often included the distal posterior circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes); the proximal (medulla and posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Severe occlusive lesions (>50% stenosis) involved more than one large artery in 148 patients; 134 had one artery site involved unilaterally or bilaterally. The commonest occlusive sites were: extracranial vertebral artery (52 patients, 15 bilateral) intracranial vertebral artery (40 patients, 12 bilateral), basilar artery (46 patients). Intraarterial embolism was the commonest mechanism of brain infarction in patients with vertebral artery occlusive disease. Thirty‐day mortality was 3.6%. Embolic mechanism, distal territory location, and basilar artery occlusive disease carried the poorest prognosis. The best outcome was in patients who had multiple arterial occlusive sites; they had position‐sensitive TIAs during months to years. Ann Neurol 2004;56:389–398

Serial assessment of acute stroke using the NIH Stroke Scale.

Background and Purpose The National Institutes of Health (NIH) Stroke Scale has been used in clinical trials to assess neurological outcome after investigational therapy for acute stroke. We used the NIH Stroke Scale to study the degree and time course of recovery in patients with acute stroke who were treated with conventional therapy. Methods We serially assessed 50 patients with ischemic stroke who presented within 24 hours of onset of symptoms. Patients were grouped by stroke subtype. Major neurological improvement was defined as a decrease in the stroke score by 4 points or more. Results The mean NIH stroke score for all patients improved significantly by 7 to 10 days and at last follow-up (average, 44 days). Major neurological improvement was seen in 5 of 41 patients (12%; 95% confidence interval [CI], 2% to 22%) by 24 hours, 11 of 40 patients (28%; 95% CI, 14% to 41%) by 48 hours, and 19 of 37 patients (51%; 95% CI, 35% to 67%) by follow-up. The subgroup of patients with middle cerebral artery territory embolism showed a similar pattern of improvement; in contrast, patients with lacunar infarcts did not show significant change in scores during the study period. The score on admission did not correlate with the degree of subsequent improvement or deterioration. Conclusions A significant percentage of patients with acute ischemic stroke treated with conventional therapy show early improvement as assessed by the NIH Stroke Scale. The degree and time course of recovery may be influenced by stroke type. (Stroke. 1994;25:362-365.)

Cerebral infarction in young adults The Baltimore-Washington Cooperative Young Stroke Study

Background: Few reports on stroke in young adults have included cases from all community and referral hospitals in a defined geographic region. Methods: At 46 hospitals in Baltimore City, 5 central Maryland counties, and Washington, DC, the chart of every patient 15 to 44 years of age with a primary or secondary diagnosis of possible cerebral arterial infarction during 1988 and 1991 was abstracted. Probable and possible etiologies were assigned following written guidelines. Results: Of 428 first strokes, 212 (49.5%) were assigned at least one probable cause, 80 (18.7%) had no probable cause but at least one possible cause, and 136 (31.8%) had no identified probable or possible cause. Of the 212 with at least one probable cause, the distribution of etiologies was cardiac embolism(31.1%), hematologic and other (19.8%), small vessel (lacunar) disease(19.8%), nonatherosclerotic vasculopathy (11.3%), illicit drug use (9.4%), oral contraceptive use (5.2%), large artery atherosclerotic disease (3.8%), and migraine (1.4%). There were an additional 69 recurrent stroke patients. Conclusions: In this hospital-based registry within a region characterized by racial/ethnic diversity, cardiac embolism, hematologic and other causes, and lacunar stroke were the most common etiologies of cerebral infarction in young adults. Nearly a third of both first and recurrent strokes had no identified cause.

Nonconvulsive Status Epilepticus in the Critically Ill Elderly

Summary: Purpose: To describe the electrographic and clinical features of nonconvulsive status epilepticus (NCSE) in the critically ill elderly and to identify potential predictors of outcome.

Infarct Volume as a Surrogate or Auxiliary Outcome Measure in Ischemic Stroke Clinical Trials

BACKGROUND AND PURPOSE Reduction in infarct volume is the standard measure of therapeutic success in animal stroke models. Reduction in infarct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit, disability, and global clinical scales. However, few studies have investigated correlations between infarct volume and clinical end points in acute ischemic stroke patients. METHODS CT scans at days 6 to 11 were acquired prospectively in 191 fully eligible patients enrolled in the Randomized Trial of Tirilazad Mesylate in Patients With Acute Stroke (RANTTAS). Patients were enrolled within 6 hours of onset of stroke in any vessel distribution. Infarct volume was measured by operator-assisted computerized planimetry. RESULTS One hundred thirty-two patients had visible new supratentorial infarcts, with median infarct volume of 28.0 cm3 (interquartile range, 9.0 to 93.0 cm3). Fifty-nine patients had no visible new infarct. Correlations with standard 3-month outcome scales and mortality were as follows: Barthel Index, r=0.43; Glasgow Outcome Scale, r=0.53; National Institutes of Health Stroke Scale, r=0.54; mortality, r=0.31. For visible infarcts alone, correlations were as follows: BI, r=0.46; GOS, r=0.59; NIHSS, r=0.56; mortality, r=0.32. CONCLUSIONS Subacute CT infarct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales. The modesty of this linkage constrains the use of infarct volume as a surrogate end point in ischemic stroke clinical trials.

Stroke in children and sickle-cell disease Baltimore-Washington Cooperative Young Stroke Study

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 patients 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.

A Pilot Randomized Trial of Induced Blood Pressure Elevation: Effects on Function and Focal Perfusion in Acute and Subacute Stroke

Background: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. Methods: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation (‘treated’ patients, n = 9) or conventional management (‘untreated’ patients, n = 6). Results: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6–8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. Conclusion: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

Stroke after cardiac surgery: short- and long-term outcomes

BACKGROUND Stroke remains a devastating complication of cardiac surgery, but stroke prevention remains elusive. Evaluation of early and long-term clinical outcomes and brain-imaging findings may provide insight into stroke prognosis, etiology, and prevention. METHODS Five thousand nine hundred seventy-one cardiac surgery patients were prospectively studied for clinical evidence of stroke. Stroke and nonstroke patients were compared by early outcomes. Data collected for stroke patients included brain imaging results, long-term functional status, and survival. Outcome predictors were then determined. RESULTS Stroke was diagnosed in 214 (3.6%) patients. Brain imaging demonstrated acute infarction in 72%; embolic in 83%, and watershed in 24%. Survival for stroke patients was 67% at 1 year and 47% at 5 years. Independent predictors of survival were cerebral infarct type, creatinine elevation, cardiopulmonary bypass time, preoperative intensive care days, postoperative awakening time, and postoperative intensive care days. Long-term disability was moderate to severe in 69%. CONCLUSIONS Stroke after cardiac surgery has profound repercussions that are independently related to infarct type and clinical factors. These data are essential for clinical decision making and prognosis determination.