Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Prevalence of Previously Undiagnosed Abdominal Aortic Aneurysms in Patients with Intracranial Aneurysms: From the Brain and Aortic Aneurysms Study (BAAS).

BACKGROUND: A relationship between intracranial and abdominal aortic aneurysms (AAA) has been appreciated through genome-wide association studies suggesting a shared pathophysiology. However, the actual prevalence of AAA in patients presenting with ruptured intracranial aneurysms is not known. Our aim was to estimate the prevalence of previously undiagnosed AAA in patients presenting with aneurysmal subarachnoid hemorrhage (aSAH) to see if it may be high enough to justify formally testing the utility of screening. METHODS: A prospective, observational inception cohort study of 81 consecutive patients presenting to Mayo Clinic Florida with aSAH was performed from August 14, 2011 to February 10, 2014. These individuals were then screened using an abdominal ultrasound technique for an AAA. Our primary end point was detection of AAA. Our secondary end points were 30-day good-to-fair functional status (modified Rankin scale < 4) and all-cause mortality. RESULTS: We detected an AAA in 10 patients (rate: 12%; 95% CI 6-22%) with aSAH. The mean diameter of these AAA was 3.4 ± 1.0 cm. Among these 10 patients, there was one death within the first month of aSAH hospitalization. There were no significant differences in demographic or clinical characteristics based on AAA detection status. Mean follow-up time was 4.7 years. The rate of good-to-fair functional status at 30-days was 79%. All-cause mortality during follow-up at 1-year was higher for patients with AAA (36%; 95% CI 0-61%) compared to patients without AAA (7%; 95% CI 1-14%) (log-rank p = 0.045). CONCLUSIONS: The co-prevalence of AAA in patients presenting with ruptured brain aneurysms may be sufficiently high such that screening for AAA among likely survivors of aSAH might be appropriate. Larger studies would be needed to establish a net clinical benefit from screening AAA and then treating newly identified large AAAs in this morbid population.

Genetic variants associated with myocardial infarction in the PSMA6 gene and Chr9p21 are also associated with ischaemic stroke.

BACKGROUND: Ischaemic stroke shares common traditional risk factors with coronary artery disease (CAD) and myocardial infarction (MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans. METHODS: Included in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single-nucleotide polymorphisms (SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic regression models. RESULTS: In Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P = 0.036) and African Americans (OR 0.31, P = 0.020). CONCLUSIONS: Our results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series.

Prevalence of Intracranial Aneurysms in Patients with Infrarenal Abdominal Aortic Aneurysms: A Multicenter Experience.

Prior studies suggest high prevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in clinical detection/treatment of IAs in AAA patients and estimated the risk of IA in patients with AAA relative to patients without AAA. We reviewed cases of vascular surgery infrarenal AAA repairs at three Mayo Clinic sites from January 1998 to December 2018. Concurrent controls were randomly matched in a 1:1 ratio by age, sex, smoking history, and head imaging characteristics. Conditional logistic regression was used to calculate odds ratios. We reviewed 2,300 infrarenal AAA repairs. Mean size of AAA at repair was 56.9 ± 11.4 mm; mean age at repair, 75.8 ± 8.0 years. 87.5% of the cases ( n = 2014) were men. Head imaging was available in 421 patients. Thirty-seven patients were found to have 45 IAs for a prevalence of 8.8%. Mean size of IA was 4.6 ± 3.5 mm; mean age at IA detection, 72.0 ± 10.8 years. Thirty (81%) out of 37 patients were men. Six patients underwent treatment for IA: four for ruptured IAs and two for unruptured IAs. All were diagnosed before AAA repair. Treatment included five clippings and one coil-assisted stenting. Time from IA diagnosis to AAA repair was 16.4 ± 11.0 years. Two of these patients presented with ruptured AAA, one with successful repair and a second one that resulted in death. Odds of IA were higher for patients with AAA versus those without AAA (8.8% [37/421] vs. 3.1% [13/421]; OR 3.18; 95% confidence interval, 1.62-6.27, p < 0.001). Co-prevalence of IA among patients with AAA was 8.8% and is more than three times the rate seen in patients without AAA. All IAs were diagnosed prior to AAA repair. Surveillance for AAA after IA treatment could have prevented two AAA ruptures and one death.

Prestroke physical activity and early functional status after stroke.

BACKGROUND: The importance of physical activity as a modifiable risk factor for stroke in particular and cardiovascular disease in general is well documented. The effect of exercise on stroke severity and stroke outcomes is less clear. This study aimed to assess that effect. METHODS: Data collected for patients enrolled in the Ischemic Stroke Genetics Study were reviewed for prestroke self-reported levels of activity and four measures of stroke outcome assessed at enrollment and approximately 3 months after enrollment. Logistic regression was used to assess the association between physical activity and stroke outcomes, unadjusted and adjusted for patient characteristics. RESULTS: A total of 673 patients were enrolled; 50.5% reported aerobic physical activity less than once a week, 28.5% reported aerobic physical activity one to three times weekly, and 21% reported aerobic physical activity four times a week or more. Patients with moderate and high levels of physical activity were more likely to have higher Barthel Index (BI) scores at enrollment. A similar association was detected for exercise and good outcomes for the Oxford Handicap Scale (OHS). After 3 months of follow-up, moderate activity was still associated with a high BI score. No significant association was detected for activity and the OHS or Glasgow Outcome Scale at follow-up after adjustment for patient characteristics. CONCLUSIONS: Higher levels of self-reported prestroke physical activity may be associated with functional advantages after stroke. Our findings should be seen as exploratory, requiring confirmation, ideally in a longitudinal study of exercise in an older population.

Diagnosis and management of neurological sarcoidosis.

BACKGROUND: Neurological involvement is a significant cause of morbidity and mortality in patients with sarcoidosis. Detection and management of neurosarcoidosis remains problematic. Our interest in immunosuppressive agents for chronic sarcoidosis has given us experience with various agents for the treatment of sarcoidosis, including cyclophosphamide and methotrexate. METHODS: We analyzed all patients with sarcoidosis seen in our clinic during a 10-year period. Evaluation for neurological disease included routine physical examination. Magnetic resonance imaging, cerebral spinal fluid analysis, and neural tissue biopsy were performed where clinically indicated. Patients were treated with corticosteroids, methotrexate, or cyclophosphamide. RESULTS: Neurological disease was identified in 71 of 554 patients with sarcoidosis. Seventh (facial) cranial nerve paralysis was the most common manifestation identified in 39 patients. This included 24 patients with facial nerve palsy as the only manifestation of neurological sarcoidosis in whom complete recovery was seen in all but 1 patient. Forty-eight patients with disease other than facial nerve palsy received corticosteroids or other therapies. Corticosteroids benefited only 14 patients (29%). Methotrexate successfully treated 17 (61%) of 28 patients and cyclophosphamide controlled disease in 9 (90%) of 10 assessable patients. Methotrexate and cyclophosphamide were each associated with a higher response rate than corticosteroids alone (chi 2, 14.6; P < .001). CONCLUSIONS: Neurological symptoms can be significant manifestations of sarcoidosis. Facial nerve paralysis is a common, but usually self-limited form of disease. Other manifestations are usually chronic and agents other than corticosteroids appear to have increased efficacy with lower morbidity.

Time of hospital presentation in patients with acute stroke.

BACKGROUND: Stroke is a leading cause of death and disability in the United States. Although new treatments are being studied, most must be given early in the course of stroke to be effective. This study was performed to identify factors associated with early hospital arrival in patients with stroke. METHODS: As part of the National Institute of Neurologic Disorders and Stroke Tissue-Type Plasminogen Activator Pilot Study, information from patients, patients' families, or, most commonly, the medical record was gathered on all patients presenting to the hospital within 24 hours of the onset of stroke. A total of 14 hospitals participated. Three were university hospitals, and 11 were community hospitals with and without university affiliation. The main outcome measure was the time from stroke onset to hospital arrival. RESULTS: Of 2099 patients screened, adequate time data were available in 1159. Thirty-nine percent presented to the hospital 90 minutes or less after symptom onset and 59% within 3 hours. Early hospital arrival after stroke was greatly influenced by the type of first medical contact and, to a lesser degree, by the patient's location at the time of the stroke and the time of the day at which the stroke occurred. Hospital arrival was fastest in patients using 911 as their first medical contact (mean, 155 minutes; median, 84 minutes) vs their personal physician (mean, 379 minutes; median, 270 minutes; P < .0001) or a study hospital (mean, 333 minutes; median, 212 minutes; P < .0001). Time from symptom onset to arrival was longer for patients having the stroke at night compared with patients having a stroke in the morning (P < .05), in the afternoon (P < .01), or in the evening (P < .0001). Time to hospital arrival was significantly longer for patients having the stroke at home than for patients having the stroke at work (P < .01) or in an unknown place (P < .05). Gender, age, race, and presence of brain hemorrhage had no significant effect. CONCLUSIONS: As many as 50% of patients with stroke arrive at the hospital within 3 hours of symptom onset. Our data indicate that strategies to increase the use of 911 systems may have a high yield with regard to recruitment into urgent treatment protocols for stroke.

A modified National Institutes of Health Stroke Scale for use in stroke clinical trials: preliminary reliability and validity.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) is accepted widely for measuring acute stroke deficits in clinical trials, but it contains items that exhibit poor reliability or do not contribute meaningful information. To improve the scale for use in clinical research, we used formal clinimetric analyses to derive a modified version, the mNIHSS. We then sought to demonstrate the validity and reliability of the new mNIHSS. METHODS: The mNIHSS was derived from our prior clinimetric studies of the NIHSS by deleting poorly reproducible or redundant items (level of consciousness, face weakness, ataxia, dysarthria) and collapsing the sensory item into 2 responses. Reliability of the mNIHSS was assessed with the certification data originally collected to assess the reliability of investigators in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA (recombinant tissue plasminogen activator) Stroke TRIAL: Validity of the mNIHSS was assessed with the outcome results of the NINDS rtPA Stroke Trial: RESULTS: Reliability was improved with the mNIHSS: the number of scale items with poor kappa coefficients on either of the certification tapes decreased from 8 (20%) to 3 (14%) with the mNIHSS. With the use of factor analysis, the structure underlying the mNIHSS was found identical to the original scale. On serial use of the scale, goodness of fit coefficients were higher with the mNIHSS. With data from part I of the trial data, the proportion of patients who improved >/=4 points within 24 hours after treatment was statistically significantly increased by tPA (odds ratio, 1.3; 95% confidence limits, 1.0, 1.8; P=0.05). Likewise, the odds ratio for complete/nearly complete resolution of stroke symptoms 3 months after treatment was 1.7 (95% confidence limits, 1.2, 2.6) with the mNIHSS. Other outcomes showed the same agreement when the mNIHSS was compared with the original scale. The mNIHSS showed good responsiveness, ie, was useful in differentiating patients likely to hemorrhage or have a good outcome after stroke. CONCLUSIONS: The mNIHSS appears to be identical clinimetrically to the original NIHSS when the same data are used for validation and reliability. Power appears to be greater with the mNIHSS with the use of 24-hour end points, suggesting the need for fewer patients in trials designed to detect treatment effects comparable to rtPA. The mNIHSS contains fewer items and might be simpler to use in clinical research trials. Prospective analysis of reliability and validity, with the use of an independently collected cohort, must be obtained before the mNIHSS is used in a research setting.

Feasibility of an affected sibling pair study in ischemic stroke: results of a 2-center family history registry.

BACKGROUND AND PURPOSE: We sought to determine pedigree availability for a concordant sibling pair study of genetic risk factors in ischemic stroke. METHODS: Probands with confirmed ischemic stroke were prospectively enrolled. Family histories were obtained by systematic interview. A study neurologist prospectively assigned stroke subtype. RESULTS: Of 310 probands (median age, 75 years; range, 26 to 97 years; 48% women), 75% had at least 1 living sibling; 10%, at least 1 concordant living sibling; 2%, at least 1 concordant sibling living in the same city; and 7%, at least 1 concordant living and 1 discordant living sibling. Likelihood of having a concordant sibling increased significantly with proband age, even after adjustment for sibship size (P=0.002). Positive family history of stroke was not related to either proband stroke subtype or risk factor profile. CONCLUSIONS: Approximately 10 probands were screened to find 1 potentially concordant living sibling. A concordant sibling pair study should be multicentered and enable enrollment of siblings from diverse geographic areas.

Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA stroke trial.

BACKGROUND AND PURPOSE: We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial. METHODS: Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results. RESULTS: Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score

Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

OBJECTIVE: To develop an approach for reducing time between emergency department (ED) admission and treatment in patients with acute ischemic stroke to meet the challenge of providing tissue plasminogen activator treatment within 180 minutes. DESIGN: An observational study. SETTING: Forty trial-affiliated hospitals, including 30 community hospitals. PARTICIPANTS: A total of 17,324 consecutive patients admitted to trial-affiliated hospital EDs within 24 hours of possible stroke, from January 1991 through October 1994. INTERVENTION: Appraisal of the process of triage, evaluation, diagnosis, and treatment by means of total quality improvement techniques in each hospital. Staff participating in the process identified sources of variation and modifications by flow charting the process. MAIN OUTCOME MEASURE: Time between ED admission and treatment with study medication. RESULTS: Total quality improvement methods identified hospital-specific process improvements. Many improvements were administrative, requiring no additional resources. More than 50% of screened patients arrived too late to be treated. Only 1268 patients were admitted between 0 and 125 minutes from stroke onset with no other trial exclusion criteria; 48% were treated. Of 243 patients admitted between 126 and 170 minutes from stroke onset with no exclusion criteria, 4% were treated. Mean time from ED admission to treatment was similar in teaching and community hospitals. CONCLUSIONS: Total quality improvement methods identified ED-specific sources of process variability and reduced time between ED admission and treatment. Therefore, these methods should be considered in developing and monitoring emergent stroke treatment protocols.

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial.

BACKGROUND: Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. METHOD: To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. RESULTS: There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased (p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. CONCLUSIONS: In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.

Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study.

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. METHODS: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT-treatment interaction. Tests for OTT-treatment interactions adjusting for potential masking confounders were performed. An OTT-treatment interaction was considered significant if p < or = 0.10, implying that treatment effectiveness was related to OTT. RESULTS: For 24-hour improvement, there were no masking confounders identified and there was an OTT-treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT-treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. CONCLUSIONS: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group.

Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.

Preserved color imagery in an achromatopsic.

The loss of color vision secondary to central nervous system disease (achromatopsia) is thought to preclude visual imagery of colors. We report a patient with achromatopsia, secondary to bilateral temporo-occipital infarcts inclusive of the lingual and fusiform gyri, with preserved color imagery. Our findings, in conjunction with previous cases in the literature, are consistent with a single neural network for color processing in which a disconnection of internal activation from stored color representations produces impaired color imagery with preserved color perception, whereas a disconnection of visual input to these representations produces achromatopsia with preserved color imagery.

Adult choroidal vein of Galen malformation.

We report staged embolization and stereotactic radiation in a true adult choroidal vein of Galen malformation. Management dilemmas and their resolutions are also discussed.

Outcome of stroke patients without angiographically revealed arterial occlusion within four hours of symptom onset.

BACKGROUND AND PURPOSE: Follow-up imaging data from stroke patients without angiographically apparent arterial occlusions at symptom onset are lacking. We reviewed our Emergency Management of Stroke (EMS) trial experience to determine the clinical and imaging outcomes of patients with ischemic stroke who showed no arterial occlusion on angiograms obtained within 4 hours of symptom onset. METHODS: All patients in this report were participants in the EMS trial that was designed to address the safety and potential efficacy of combined IV and intraarterial thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. RESULTS: Thirty-five patients were randomized to receive either IV rt-PA (n = 17) or placebo (n = 18), followed by cerebral angiography. No symptomatic arterial occlusion was evident in 10 (29%) of the 34 patients. Eight (80%) of 10 patients without angiographically apparent clot within 4 hours of symptom onset had a new cerebral infarction confirmed on follow-up brain imaging. The median 72-hour infarction volume was 2.4 cc (range, 1-30 cc). Four of the 10 "no-clot" patients had a favorable 3-month outcome as assessed by Barthel Index (score, 95 or 100) and modified Rankin Scale (score, 0 or 1). The six remaining patients had 3-month Rankin Scale scores of 1 (Barthel of 90), 2, 3, 4, or 5. CONCLUSION: Acute ischemic stroke patients with a neurologic deficit but a negative angiogram during the first 4 hours after symptom onset usually develop image-documented cerebral infarction, and approximately half suffer from long-term functional disability. The two most likely explanations for negative angiograms are very early irreversible ischemic damage despite recanalization or ongoing ischemia secondary to clot in non-visible penetrating arterioles or in the microvasculature.

Hyperdense middle cerebral artery sign on CT: efficacy in detecting middle cerebral artery thrombosis.

The hyperdense middle cerebral artery sign is a CT predictor of the development of a large cerebral infarct. The limits of detectability were tested in a blinded, then unblinded analysis of CT scans from 25 acute stroke patients. In the initial blinded analysis, sign detection exhibited the following mean values: sensitivity, 78.5%; specificity, 93.4%; positive predictive value, 66%; negative predictive value, 96.4%; accuracy, 91.3%. Kappa statistics analysis indicated poor interobserver agreement (k = .38). Results of unblinded analysis were as follows: sensitivity, 69%; specificity, 94.4%; positive predictive value, 82.8%; negative predictive value, 88.7%; accuracy, 87.3%. There was fair unblinded interobserver agreement (k = .53). Unblinded analysis had a lower false-positive frequency and did not increase the number of true-positive determinations. We conclude that detection of the hyperdense middle cerebral artery sign on CT scans by multiple observers is a sensitive, accurate, and predictive indicator of middle cerebral artery thromboembolism.

Ultra-early evaluation of intracerebral hemorrhage.

The authors evaluate eight patients with intracerebral hemorrhage (ICH) who underwent computerized tomography (CT) within 2 1/2 hours after symptom onset and then again several hours later. The second CT scan was performed within 12 hours after onset for seven of the patients and 100 hours after onset for the eighth patient. In four patients, the second CT scan was obtained prospectively. The mean percentage of increase in the volume of hemorrhage between the first and second CT scans was 107% (range 1% to 338%). In each of the six patients with a greater than 40% increase in hemorrhage volume, neurological deterioration occurred soon after the first CT. A systolic blood pressure of 195 mm Hg or greater was recorded during the first 6 hours in five of the same six patients. The data from this study indicate that, in ICH, bleeding may continue after the 1st hour post-hemorrhage, particularly in patients with early clinical deterioration.