New transient ischemic attack and stroke: outpatient management by primary care physicians.

BACKGROUND: Patients with transient ischemic attack (TIA) or stroke frequently first contact their primary care physician rather than seeking care at a hospital emergency department. The purpose of the present study was to identify a group of patients seen by primary care physicians in an office setting for a first-ever TIA or stroke and characterize their evaluation and management. METHODS: Practice audit based on retrospective, structured medical record abstraction from 27 primary care medical practices in 2 geographically separate communities in the eastern United States. RESULTS: Ninety-five patients with a first-ever TIA and 81 with stroke were identified. Seventy-nine percent of those with TIA vs 88% with stroke were evaluated on the day their symptoms occurred (P =.12). Only 6% were admitted to a hospital for evaluation and treatment on the day of the index visit (2% TIA; 10% stroke; P =.03); only an additional 3% were admitted during the subsequent 30 days. Specialists were consulted for 45% of patients. A brain imaging study (computed tomography or magnetic resonance imaging) was ordered on the day of the index visit in 30% (23% TIA, 37% stroke; P =.04), regardless of whether the patient was referred to a specialist. Carotid ultrasound studies were obtained in 28% (40% TIA, 14% stroke; P<.001), electrocardiograms in 19% (18% TIA, 21% stroke; P =.60), and echocardiograms in 16% (19% TIA, 14% stroke; P =.34). Fewer than half of patients with a prior history of atrial fibrillation (n = 24) underwent anticoagulation when evaluated at the index visit. Thirty-two percent of patients (31% TIA, 33% stroke; P =.70) were not hospitalized and had no evaluations performed during the first month after presenting to a primary care physician with a first TIA or stroke. Of these patients, 59% had a change in antiplatelet therapy on the day of the index visit. CONCLUSIONS: Further primary care physician education regarding the importance of promptly and fully evaluating patients with TIA or stroke may be warranted, and barriers to implementation of established secondary stroke prevention strategies need to be carefully explored. Arch Intern Med. 2000;160:2941-2946

Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities.

BACKGROUND: Most treatment of patients at risk for stroke is provided in the ambulatory setting. Although many studies have addressed the proportion of eligible patients with atrial fibrillation (AF) receiving warfarin sodium, few have addressed the quality of their anticoagulation management. OBJECTIVE: As a comprehensive assessment of quality, we analyzed the proportion of eligible patients receiving warfarin, the proportion of time their international normalized ratios (INRs) were within the target range, and, when an out-of-target range INR value occurred, the time until the next INR measurement was made. METHODS: Retrospective review of the medical records of 660 patients with AF managed by general internists and family practitioners in Rochester, NY, and the Research Triangle area of North Carolina. RESULTS: Only 34.7% of eligible patients with AF received warfarin. The INR values were out of the target range approximately half the time, and the response to these values was not always timely. For all the measures considered, both Rochester practices with access to an anticoagulation service had higher (albeit not ideal) quality of warfarin management than the remaining practices. CONCLUSIONS: We found significant deficiencies in the practice of warfarin management and suggestive evidence that anticoagulation services can partially ameliorate these deficiencies. More research is needed to describe the quality of anticoagulation management in typical practice and how this management can be improved.

Diagnosis of intracranial vasculitis: a multi-disciplinary approach.

Intracranial vasculitis, or primary angiitis of the central nervous system (PACNS), is an uncommon, often fatal disorder that frequently responds to aggressive immunosuppressive therapy. Magnetic resonance imaging (MRI), cerebral angiography, and brain biopsy are diagnostic modalities that vary in invasiveness and diagnostic accuracy. The purpose of this study was to determine whether certain clinical or radiologic features were predictive of a diagnostic biopsy. Thirty consecutive patients undergoing brain biopsy to "rule out vasculitis" were studied. Nine patients demonstrated granulomatous or lymphocytic vasculitis, 1 had lymphocytic vasculitis and encephalitis secondary to arbovirus infection, 5 had thickened vessels consistent with hypertensive changes, 5 had amyloid angiopathy and/or changes of Alzheimer disease, 5 demonstrated no pathologic abnormalities, and 1 each had acute infarct, vascular malformation, aneurysm, acellular fibrinoid necrosis, and demyelination. The spectrum of MRI and angiographic changes associated with PACNS were nonspecific, overlapping extensively with changes of chronic hypertension and amyloid deposition. The predictive values of brain biopsy (90-100%) were significantly higher than those of angiography (37-50%) or MRI (43-72%). In this study, morbidity associated with aggressive immunosuppression was significantly greater than that associated with cerebral angiography or brain biopsy. Thus, wedge biopsy of cortical and leptomeningeal tissues is central to the multi-disciplinary approach to a patient with clinical suspicion of PACNS.

Diagnostic testing for coagulopathies in patients with ischemic stroke.

BACKGROUND: Hypercoagulable states are a recognized, albeit uncommon, etiology of ischemic stroke. It is unclear how often the results of specialized coagulation tests affect management. Using data compiled from a systematic review of available studies, we employed quantitative methodology to assess the diagnostic yield of coagulation tests for identification of coagulopathies in ischemic stroke patients. SUMMARY OF REVIEW: We performed a MEDLINE search to identify controlled studies published during 1966-1999 that reported the prevalence of deficiencies of protein C, protein S, antithrombin III, plasminogen, activated protein C resistance (APCR)/factor V Leiden mutation (FVL), anticardiolipin antibodies (ACL), or lupus anticoagulant (LA) in patients with ischemic stroke. The cumulative prevalence rates (pretest probabilities) and positive likelihood ratios for all studies and for those including only patients aged

Retrospective assessment of initial stroke severity: comparison of the NIH Stroke Scale and the Canadian Neurological Scale.

BACKGROUND AND PURPOSE: The NIH Stroke Scale (NIHSS) and the Canadian Neurological Scale (CNS) have been reported to be useful for the retrospective assessment of initial stroke severity. However, unlike the CNS, the NIHSS requires detailed neurological assessments that may not be reflected in all patient records, potentially limiting its applicability. We assessed the reliability of the retrospective algorithms and the proportions of missing items for the NIHSS and CNS in stroke patients admitted to an academic medical center (AMC) and 2 community hospitals. METHODS: Randomly selected records of patients with ischemic stroke admitted to an AMC (n=20) and community hospitals with (CH1, n=19) and without (CH2, n=20) acute neurological consultative services were reviewed. NIHSS and CNS scores were assigned independently by 2 neurologists using published algorithms. Interrater reliability of the scores was determined with the intraclass correlation coefficient, and the numbers of missing items were tabulated. RESULTS: The intraclass correlation coefficient for NIHSS and CNS, respectively, were 0.93 (95% CI, 0.82 to 1.00) and 0.97 (95% CI, 0.90 to 1.00) for the AMC, 0.89 (95% CI, 0.75 to 1.00) and 0.88 (95%, 0.73 to 1.00) for the CH1, and 0.48 (95% CI, 0.26 to 0.70) and 0.78 (95% CI, 0.60 to 0.96) for the CH2. More NIHSS items were missing at the CH2 (62%) versus the AMC (27%) and the CH1 (23%, P:=0.0001). In comparison, 33%, 0%, and 8% of CNS items were missing from records from CH2, AMC, and CH1, respectively (P:=0.0001). CONCLUSIONS: The levels of interrater agreement were almost perfect for retrospectively assigned NIHSS and CNS scores for patients initially evaluated by a neurologist at both an AMC and a CH. Levels of agreement for the CNS were substantial at a CH2, but interrater agreement for the NIHSS was only moderate in this setting. The proportions of missing items are higher for the NIHSS than the CNS in each setting, particularly limiting its application in the hospital without acute neurological consultative services.

Improving the reliability of stroke subgroup classification using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria.

BACKGROUND AND PURPOSE: We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for retrospective use in clinical, health services, and quality of care outcome studies. The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings. Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians. However, the investigators cautioned that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible. METHODS: In preparation for a study of outcomes and management practices for patients with ischemic stroke within Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first retrospectively classified a series of 14 randomly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement. A 2-phase process was then used to improve the reliability of subtype assignment. In the first phase, a computerized algorithm was developed to assign the TOAST diagnostic category. The reliability of the computerized algorithm was tested with a series of synthetic cases designed to provide data fitting each of the 11 definitions. In the second phase, critical disagreements in the data abstraction process were identified and remaining variability was reduced by the development of standardized procedures for retrieving relevant information from the medical record. RESULTS: The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of the 14 cases (29%) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings (kappa=0.42; 95% CI, 0.32 to 0.53). There was 100% agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases. The algorithm was then applied to the original 14 cases, and the diagnostic categorization was compared with each of the 4 physicians' baseline assignments. For the 5 collapsed subtypes, the algorithm-based and physician-assigned diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the abstracted data and/or its interpretation. The use of an operations manual designed to guide data abstraction improved the reliability subtype assignment (kappa=0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data were identified, and the manual was revised accordingly. Reliability with the use of the 5 collapsed groupings then improved for both interrater (kappa=0.68; 95% CI, 0.44 to 0.91) and intrarater (kappa=0.74; 95% CI, 0.61 to 0.87) agreement. Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstraction. CONCLUSIONS: Ischemic stroke subtype based on published TOAST classification criteria can be reliably assigned with the use of a computerized algorithm with data obtained through standardized medical record abstraction procedures. Some variability in stroke subtype classification will remain because of inconsistencies in the medical record and errors in data abstraction. This residual variability can be addressed by having 2 raters classify each case and then identifying and resolving the reason(s) for the disagreement.

Potential effects of common drugs on stroke recovery.

Studies in laboratory animals clearly show that the rate and extent of functional recovery after focal brain injury can be modulated by drugs affecting certain neurotransmitters in the central nervous system. Preliminary clinical studies suggest that similar drug effects occur in humans recovering from stroke. Understanding these pharmacological effects is important because several of the classes of drugs that impair recovery in laboratory experiments are used to treat coincident medical problems in patients who have had a stroke.

Interrater reliability of the NIH stroke scale.

The interobserver reliability of a rating scale employed in several multicenter stroke trials was investigated. Twenty patients who had a stroke were rated with this scale by four clinical stroke fellows. Each patient was independently evaluated by one pair of observers. The degree of interrater agreement for each item on the scale was determined by calculation of the kappa statistic. Interobserver agreement was moderate to substantial for 9 of 13 items. This rating system compares favorably with other scales for which such comparisons can be made. However, the validity of this system must be established.

Common drugs may influence motor recovery after stroke. The Sygen In Acute Stroke Study Investigators.

Studies in laboratory animals indicate that certain centrally acting drugs (eg, the antihypertensives clonidine and prazosin, neuroleptics and other dopamine receptor antagonists, benzodiazepines, and the anticonvulsants phenytoin and phenobarbital) impair behavioral recovery after focal brain injury. Even single doses may have long-term harmful effects. To determine whether these medications have a similar negative impact in humans, we analyzed the recoveries of control patients who were enrolled in the Sygen in Acute Stroke Study, a multicenter study of the effects of GM1 ganglioside after ischemic stroke. Motor impairments were measured by the motor subscores of the Toronto Stroke Scale at baseline and 7, 14, 21, 28, 56, and 84 days after stroke. Using these data, we compared motor recovery between patients with initial motor deficits who received at least one of the drugs that interfere with recovery in laboratory studies ("detrimental" drug group, n = 37) and patients who did not receive these drugs ("neutral" drug group, n = 59). The groups were well balanced with regard to the frequency of comorbid conditions and other prognostic factors. For upper-extremity motor function, repeated-measures ANOVA showed a significant interaction between drug group and time after stroke [F(6,528) = 2.38; p = 0.03], with a significant (p < 0.001) difference between the groups beginning 7 days after the stroke. A similar trend was present for the lower extremity, but the overall difference between the groups was not significant [ANOVA F(6,498) = 1.22; p = 0.29]. Drug group did influence the degree of independence in activities of daily living as measured with the Barthel Index.(ABSTRACT TRUNCATED AT 250 WORDS)

Physician prescribing patterns following hospital admission for ischemic cerebrovascular disease.

Functional recovery after brain injury in laboratory animals is influenced by a variety of drugs. Yet, the impact of currently prescribed drugs on recovery after human stroke remains largely unexplored. From the Duke-VA Stroke Registry, we found 77% of patients admitted to either the university hospital or the Veterans Administration hospital with cerebral infarction were taking medications at the time of their stroke. Ninety-five percent of these patients were receiving medication at the time of discharge. Antihypertensives were the most commonly prescribed agents in the study population, and platelet antiaggregants were second. Sixty-four percent of patients had a change in their antihypertensive regimens. The number of patients prescribed sedative-hypnotic agents doubled over the first 48 hours after hospital admission. The choice of a therapeutic agent for a given clinical indication may have important implications for rehabilitation of the stroke patient.

Clinical carotid endarterectomy decision making: noninvasive vascular imaging versus angiography.

OBJECTIVE: Carotid endarterectomy (CEA) is frequently performed based solely on noninvasive vascular imaging (NVI) results (duplex ultrasound, DU; magnetic resonance angiography, MRA; CT angiography, CTA). The authors determined how often intra-arterial contrast angiography (ANGIO) alters a CEA decision as compared to NVI in clinical practice. METHODS: Reports of all NVI studies in 569 consecutive patients undergoing ANGIO at an academic medical center (AMC, n = 360) and a community hospital (CH, n = 209) over 3 years were reviewed. Patients were classified as to whether CEA was indicated based on each study. Misclassification rates, sensitivities, specificities, positive (PPV) and negative (NPV) predictive values were calculated. RESULTS: CTA was performed infrequently (2.5%) and not considered further. Misclassification rates for CEA based on DU in the AMC and CH were similar. The misclassification rate for DU alone was 28% (95% CI: 24,32), and for MRA alone was 18% (95% CI: 11,25). Both NVI were done in 11% of patients, with a misclassification rate of 7.9% (95% CI: 0,16) when the two were concordant (76% of studies). DU had a sensitivity of 87% (95% CI: 83,91), specificity 46% (95% CI: 38,54), PPV 73% (95% CI: 68,78) and NPV 68% (95% CI: 60,77). MRA had a sensitivity of 75% (95% CI: 63,87), specificity 88% (95% CI: 80,96), PPV 84% (95% CI: 73,95) and NPV 80% (95% CI: 70, 90). The sensitivity of concordant NVIs was 96% (95% CI: 88,100), specificity 85% (95% CI: 65,100), PPV 93% (95% CI: 81,100) and NPV 92% (95% CI: 76,100). CONCLUSION: These data suggest that surgical decisions should be made with caution if based on the results of noninvasive studies, particularly DU performed alone. Concordant DU and MRA results in a lower misclassification rate than either test used alone.

Improving patient selection for coagulopathy testing in the setting of acute ischemic stroke.

To improve patient selection for specialized coagulation testing in the setting of ischemic stroke, the authors sought to identify factors associated with the presence of hypercoagulable states. Of 208 patients with ischemic stroke tested, undetermined stroke subtype was significantly associated with the presence of coagulopathy, but only 60% were treated with warfarin. The frequency of coagulopathy in selected patients with ischemic stroke (5%) is low, and establishing the diagnosis did not uniformly influence treatment.

Comparison and meta-analysis of randomized trials of endarterectomy for symptomatic carotid artery stenosis.

OBJECTIVE: Comparison and meta-analysis of randomized trials of carotid endarterectomy for symptomatic stenosis of the extracranial carotid artery. BACKGROUND: Randomized trials (North American Symptomatic Carotid Endarterectomy Trial [NASCET], the European Carotid Surgery Trial [ECST], and the VA Cooperative Study [VACS]) each show that carotid endarterectomy improves outcomes in selected symptomatic patients with high-grade extracranial carotid artery stenosis. Direct comparisons among the studies have not been possible because of differing methodologies, endpoints, and formats of data reporting. DESIGN/METHODS: Data for specified endpoints and corresponding person-years at risk were obtained for each trial. The rates of nonfatal stroke, nonfatal myocardial infarction, or death for surgically or medically treated patients in the perioperative period (30 days) and thereafter were compared (both including and excluding perioperative events) and then combined using meta-analytic techniques. Data from NASCET and ECST were also analyzed for differences in outcomes by sex. RESULTS: Event rate estimates (with 95% confidence intervals [95% CI]) for the first 30 days (events per person-year, primarily nonfatal stroke) for medically treated patients were 0.44 (0.22 to 0.76) for NASCET, 0.15 (0.04 to 0.38) for ECST, and 0.27 (0.03 to 0.96) for VACS. For surgically treated patients, the corresponding rates (per person-year) were 0.78 (0.49 to 1.19), 0.63 (0.41 to 0.94), and 1.27 (0.58 to 2.43). Event rates per year after 30 days were higher for medically treated patients (0.20 [0.16 to 0.25] versus 0.08 [0.05 to 0.11] for NASCET; 0.12 [0.10 to 0.15] versus 0.07 [0.06 to 0.09] for ECST; and 0.15 [0.07 to 0.25] versus 0.07 [0.03 to 0.16] for VACS). There were no significant differences among the trials, with an overall benefit for surgical therapy (risk ratio estimate, RR = 0.67, 95% CI = 0.54 to 0.83). There were no significant sex-based differences between NASCET and ECST and the overall benefit was not significantly different for men and women (RR = 0.58, 95% CI = 0.45 to 0.74 for men; RR = 0.84, 95% CI = 0.57 to 1.25 for women). CONCLUSIONS: Adjusting for primary endpoints and duration of follow-up, carotid endarterectomy has a similar benefit for symptomatic patients across trials and a similar benefit for men and women.

Use of specialized coagulation testing in the evaluation of patients with acute ischemic stroke.

OBJECTIVE: To investigate the use and appropriateness of specialized coagulation tests in the evaluation of patients with acute ischemic stroke and identify factors that influence test ordering. BACKGROUND: Coagulation abnormalities are a rare but recognized cause of ischemic stroke. METHODS: Patient demographics, stroke risk factors, history of venous thrombosis or miscarriage, family history of stroke, and the results of specialized tests for coagulation disorders were recorded for a consecutive series of ischemic stroke patients over age 18 admitted to an academic medical center over 3 years (n = 674). Factors associated with testing were identified with univariate analyses in a random sample of two-thirds of the patients (n = 450). Multivariate logistic regression modeling was then used to identify variables independently associated with testing and then validated in the remaining patients (n = 224). RESULTS: Of the 31% of patients (n = 208) tested for coagulopathies, 29% (n = 60) were tested when the result was unlikely to influence therapeutic decisions. Historical factors associated with an increased incidence of a coagulopathy, such as history of venous thrombosis or miscarriage, were not commonly documented. The absence of small-artery atherosclerosis (OR 0.36, 95% CI 0.17 to 0.76) and younger age (OR 0.89 per year, 95% CI 0.87 to 0.92) were independently related to the frequency of specialized coagulation testing. CONCLUSIONS: One-third of specialized coagulation tests were ordered when the test results were unlikely to affect therapeutic decisions. Age was the only clinical factor increasing the likelihood of a coagulopathy that appeared to influence ordering of specialized coagulation tests.

Low rate of complications of cerebral angiography in routine clinical practice.

OBJECTIVE: The use of cerebral angiography (ANGIO) to select patients for carotid endarterectomy (CEA) has been limited by concern about the risk of complications of the procedure. The authors sought to determine the rate of neurologic complications at both an academic medical center (AMC) and a community hospital (CH). METHODS: The authors reviewed the records of 569 patients undergoing ANGIO. Any documentation of stroke, transient neurologic event, myocardial infarction, or death occurring in the 24 hours after the procedure was recorded. The rate of neurologic complications at the AMC and CH were compared to published studies. RESULTS: The overall complication rate was 0.5% for stroke and 0.4% for TIA. There was no difference between the AMC and CH. One of the strokes was of moderate severity and four of the five patients with complications subsequently underwent endarterectomy. CONCLUSIONS: The rate of major neurologic complications due to ANGIO may be lower than expected, even when performed in a non-academic setting. Awareness of local ANGIO complication rates is important when selecting patients for CEA.

Hormone replacement therapy and ischemic stroke severity in women: a case-control study.

OBJECTIVE: To investigate whether ischemic stroke severity differed among women who were receiving hormone replacement therapy (HRT) as compared with those who were not receiving these drugs. BACKGROUND: Estrogen has a neuroprotective effect in animal models of ischemic stroke, but data reflecting the impact of HRT on ischemic stroke severity in humans are lacking. METHODS: All women receiving HRT at the time of admission for acute ischemic stroke to an academic medical center over 3 years were identified by medical record review (n = 58). HRT users were matched with 116 HRT nonusers by age and number of stroke risk factors. Stroke severity was assessed retrospectively with the Canadian Neurological SCALE: Data were analyzed with nonparametric univariate tests (Spearman rank and chi(2) tests) and linear regression modeling using nonparametric matched-pair analysis. RESULTS: History of congestive heart failure or coronary artery disease (p = 0.01), atrial fibrillation (p = 0.02), and African American race (p = 0.04), were significantly associated with greater stroke severity in the univariate analysis. There was a nonsignificant trend toward lesser stroke severity in HRT users (median Canadian Neurological Scale score, 10, vs 9.5 in non-HRT users, p = 0.08). Multivariate analysis showed no independent effect of HRT use on stroke severity (F = 1.24, p = 0.17). CONCLUSIONS: There was no significant effect of HRT status on stroke severity. Because this was a retrospective analysis, prospective studies are also needed to further elucidate any potential neuroprotective effect of hormone replacement.

Assessment of aspiration risk in stroke patients with quantification of voluntary cough.

BACKGROUND: Dysphagia and subsequent aspiration are serious complications of acute stroke that may be related to an impaired cough reflex. It was hypothesized that aspirating stroke patients would have impaired objective measures of voluntary cough as compared with both nonstroke control subjects and nonaspirating stroke patients. METHODS: Swallowing was evaluated by standard radiologic or endoscopic methods, and stroke patients were grouped by aspiration severity (severe, n = 11; mild, n = 17; no aspiration, n = 15). Airflow patterns and sound pressure level (SPL) of voluntary cough were measured in stroke patients and in a group of normal control subjects (n = 18). Initial stroke severity was determined retrospectively with the Canadian Neurological Scale. RESULTS: All cough measures were altered in stroke patients as a group relative to nonstroke control subjects. Univariate analysis showed that peak flow of the inspiration phase (770.6 +/- 80.6 versus 1,120.1 +/- 148.4 mL/s), SPL (90.0 +/- 3.1 versus 100.2 +/- 1.6 dB), peak flow of the expulsive phase (875.1 +/- 122.7 versus 1,884.1 +/- 221.6 mL/s), expulsive phase rise time (0.34 +/- 0.1 versus 0.09 +/- 0.01 s), and cough volume acceleration (5.5 +/- 1.3 versus 27.8 +/- 3.9 mL/s/s) were significantly impaired in severe aspirators as compared with nonaspirators. Aspirating patients had more severe strokes than nonaspirators (mean Canadian Neurological Scale score 7.7 +/- 0.7 versus 9.8 +/- 0.3). Multivariate logistic regression found only expulsive phase rise time values during cough correlated with aspiration status. CONCLUSION: Objective analysis of cough may provide a noninvasive way to identify the aspiration risk of stroke patients.

A dose escalation study of ORG 10172 (low molecular weight heparinoid) in stroke.

An intravenous infusion of a low molecular weight heparinoid, with a reduced risk of hemorrhage, may be an alternative to heparin in the management of acute ischemic stroke. To evaluate this hypothesis, we studied the safety of the heparinoid, ORG 10172, in a dose-escalation study in 26 patients. The drug was administered as a loading bolus followed by a 7-day infusion in five rates with target anti-factor Xa levels from 0.2 to 1.0 U/ml. The drug was well tolerated; no major bleeding complications or thrombocytopenia occurred. There were no deaths or hemorrhagic transformation of cerebral infarctions. The results indicate that ORG 10172 at doses to achieve a level of 1.0 U/ml or less may be used safely in management of acute cerebral infarction.

Effects of amphetamines and small related molecules on recovery after stroke in animals and man.

Drugs modulating the levels of specific central neurotransmitters may influence both the rate and amount of functional recovery after focal brain injuries such as stroke. Because such drugs may be effective long after brain injury, the "therapeutic window" may be widened beyond the first few hour after stroke and an entirely new avenue for pharmacological intervention may be possible. The impact of drugs affecting norepinephrine and gamma-aminobutyric acid have been among the most extensively studied in the laboratory, and preliminary clinical data suggest similar effects in humans.

Expression of the apolipoprotein E gene does not affect motor recovery after sensorimotor cortex injury in the mouse.

Motor recovery after unilateral sensorimotor cortex ablation or sham-injury was measured in apolipoprotein E knockout and wild-type mice by testing their abilities to traverse a narrow beam. All mice trained without difficulty. Sham-operated mice performed perfectly regardless of genotype throughout testing. There was no difference in motor scores between lesioned apolipoprotein E knockout and wild-type mice on a first trial 24h after injury (P>0.05). There was a significant overall effect of lesion on motor performance (two-way repeated measures analysis of variance F(1,42)=304, P<0.0001), a significant time effect (F(17,714)=58, P<0.0001) and a lesion by time interaction (F(17,714)=58, P<0.0001). However, there was no effect of apolipoprotein E genotype group on recovery rate (i.e. there was no lesion group by genotype group by time interaction, F(17,714)=0.33, P=1.00) and no effect of genotype on the final level of motor performance 12 days after the lesion (Kruskal-Wallis H=5.79, P=0.12). These data suggest that motor recovery after unilateral injury to the sensorimotor cortex does not vary with apolipoprotein E genotype.