Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Resource use and quality of care for Medicare patients with acute myocardial infarction in Maryland and the District of Columbia: analysis of data from the Cooperative Cardiovascular Project.

This study sought to evaluate the quality of care rendered to Medicare beneficiaries with acute myocardial infarction by establishing the use patterns of well-proven therapies in this population. We analyzed the quality of care rendered to 4300 Medicare beneficiaries seen at Maryland and District of Columbia hospitals with retrospectively confirmed acute myocardial infarction by evaluating the use of proven therapies. The proportion of patients ideal for therapies ranged from 10% for reperfusion to 100% for smoking cessation counseling. For ideal patients the following therapies were implemented: aspirin (87%), reperfusion therapy (64%), beta-blockers on discharge (60%), and smoking cessation counseling (41%). A substantial proportion of Medicare patients with acute myocardial infarction has one or more relative or absolute contraindications to standard regimens and therefore are not ideal therapeutic candidates. In the group of ideal patients, those with no therapeutic contraindications, a significant proportion do not receive these treatments.

The empowering potential of quality improvement data.

Data are being used to redefine, transform, and empower the roles of providers, payers, and patients. The empowering potential of data on these three groups, and their changing roles are reviewed. The use of data to transform care and increase equality is not new, yet the comprehensive application of principles of continuous quality improvement to the delivery processes is just beginning. The approach to the quality improvement processes employed by peer review organizations includes idea capture, development of intuitively appealing quality indicators, formulating the intervention, formalizing the research architecture, and quantifying the impact of the interventions. The multifaceted interventions for improvement are discussed. The future of medicine includes a greater use of data and the quantitative sciences to inspire improvement across the health care delivery continuum.

Cognitive dysfunction in a patient with long-term occupational exposure to ethylene oxide. Role of ethylene oxide as a causal factor.

This case illustrates a comprehensive approach to assessing causality in a woman with apparent cognitive dysfunction, as measured by neuropsychological testing, and a 10-year history of occupational exposure to ethylene oxide. The analysis included a multidisciplinary examination of the patient, which took place several years after the termination of her exposure. In addition, all of the patient's prior medical and psychiatric records were reviewed, as were the records of her employer to ascertain her exposure history. Our evaluation revealed a pattern of neuropsychological findings not consistent with nervous system damage secondary to an organic effect of ethylene oxide. A more likely causal hypothesis is adopted: the patient's apparent cognitive dysfunction had a psychiatric etiology. This case also illustrates the potential impact of a patient's involvement in legal proceedings related to claims of neurocognitive dysfunction.

Epileptic aphasia. First onset of prolonged monosymptomatic status epilepticus in adults.

Epileptic aphasia in adults is a rarely described syndrome. Its occurrence in individuals without a clear-cut history of seizures raises diagnostic difficulties with important therapeutic implications. Two such cases are reported in which the diagnosis was confirmed by EEG with a dramatic therapeutic response to anticonvulsant medication. The EEG criteria leading to detection of the epileptic nature of the syndrome are detailed. Maintaining a high index of suspicion in cases with fluctuating symptoms remains crucial for early diagnosis and management, especially in terms of differentiating epileptic aphasia from transient ischemic phenomena.

Comparison of ketamine and pentobarbital anesthesia in the Mongolian gerbil.

The clinical course of pentobarbital and ketamine anesthesia are compared following a single injection of each and as anesthesia for carotid ligation in the Mongolian gerbil. Induction time to pinprick insensitivity was found to be the same for each agent; however, ketamine allowed earlier emergence and, moreover, observation of peripheral motor activity during the operative procedure.

Modification of cerebral ischemic damage by anesthetics.

The yield of infarcted hemispheres following unilateral carotid ligation in gerbils under ketamine anesthesia substantially exceeded that occurring under pentobarbital anesthesia. In addition to increasing the gerbil stroke model's efficiency, ketamine provided a shorter recovery period, thus allowing earlier observation of clinical signs of brain injury. These results support the contention that anesthetic agents may modify the response of central neuronal tissues to acute ischemia.

Sedative drug surveys in coma: how reliable are they?

Routine blood tests of comatose patients for drugs that depress the CNS are highly desirable, but techniques of analysis are not well standardized and the results do not correlate well with clinical condition. Determining the role of sedative drugs in coma requires a high degree of suspicion and sound clinical judgment.

Primate model of cerebral hematoma.

Using specific anesthetic agents, permanent segmental occlusion of the proximal middle cerebral artery (MCA) causes ischemic infarction limited to the putamen and other deep hemispheral structures in primates. Using this model, 25 rhesus monkeys were subjected to acute arterial hypertension before, during and up to 5 days after onset of MCA occlusion in order to reevaluate the possible role of the ischemic process in pathogenesis of cerebral hemorrhage. Norepinephrine infusion induced prompt rapid rise in mean arterial pressure (MAP) and intracranial pressure (ICP) limited to the duration of infusion. This procedure produced acute ischemic lesions which were totally bland but topographically more extensive than untreated controls; in chronic lesions, however, deep nuclear masses showed hemorrhagic infarction. Animals given 5% CO2 air had slowly progressive elevation in ICP and MAP. Acute specimens showed intact, widely-dilan hypercarbia was induced 5 days after MCA occlusion, animals developed intracerebral hematoma involving putamen, external capsule and claustrum, occasionally dissecting through to ipsilateral ventricle. In acute cerebral ischemia, elevated MAP produced only quantiative changes in lesion size. In the vasoproliferative stages of mature infarction, MAP elevation induced by a cerebral vasoconstrictor caused hemorrhagic infarctions while cerebral vasodilation caused intracerebral hematomas.

Respirator brain. Report of a survey and review of current concepts.

Because of renewed public and scientific interest in the concept of brain death and its diagnostic criteria, an opinion survey was undertaken, polling the membership of the American Association of Neuropathologists, regarding the definition, gross and microscopical features, and pathogenesis of the syndrome popularly designated the "respirator brain." Of the 191 respondents who completed the questionnaire, 174 (91%) indicated that the term respirator brain is properly used to describe a specific pathological entity, and 160 (84%) considered the characteristics of respirator brain to be distinct from those of late fixation. Of the 174 respondents who accepted the designation, 148 (85%) regarded a history of respiratory dependency as essential, and a vast majority (95%) agreed that extensive tissue necrosis occurs with little inflammatory cell reaction; other criteria were more controversial. Microscopical changes that suggest a pathogenetic mechanism attracted a number of informative, limiting, or qualifying remarks. Nonetheless, 54% thought that impaired cerebral blood flow contributed to pathogenesis.

Clinicopathological validation of a primate stroke model.

A method recently developed in our laboratory has been evaluated for clinical and pathological reliability and validity. Intracarotid injection of a silicone polymer molded into an elastic cylinder regularly caused segmental occlusion of the middle cerebral artery in sedated but conscious rhesus monleys. Clinical changes were quantitatively monitored continuously from onset through acute and chronic phases and precise correlations made with postmortem vascular and parenchymal pathology. Minor anatomical variations in the size and branching patterns of the middle cerebral artery in this primate species paralleled those in man. Uniformity in patterns of the acute natural history and specificity in clinical pathological correlations substantiate the utility of this stroke model for tests of therapeutic efficacy.