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J C Grotta

Publications and source records attributed to J C Grotta.

At least 19 recordsLinked to original sources
PubMed1999

Neurofilament proteolysis after focal ischemia; when do cells die after experimental stroke?

To determine the occurrence and time-course of presumably irreversible subcellular damage after moderate focal ischemia, rats were subjected to 1, 3, 6, 9, or 24 hours of permanent unilateral middle cerebral and common carotid occlusion or 3 hours of reversible occlusion followed by 3, 6, or 21 hours of reperfusion. The topography and the extent of damage were analyzed with tetrazolium staining and immunoblot using an antibody capable of detecting breakdown of neurofilament. Neurofilament proteolysis began after 3 hours in the infarct core but was still incomplete in penumbral regions up to 9 hours. Similarly, tetrazolium-staining abnormalities were observed in the core of 50% of animals after 3 hours of ischemia. At 6 hours of permanent ischemia, infarct volume was maximal, and further prolongation of occlusion to 9 or 24 hours did not increase abnormal tetrazolium staining. In contrast to permanent ischemia and in agreement with the authors' previous demonstration of "reperfusion injury" in this model, prolongation of reperfusion from 3 hours to 6 and 21 hours after 3 hours of reversible occlusion gradually augmented infarct volume by 203% and 324%, respectively. Neurofilament proteolysis initiated approximately 3 hours after ischemia was quantitatively greatest in the core and extended during reperfusion to incorporate penumbra with a similar time course to that of tetrazolium abnormalities. These data demonstrate that, at least as measured by neurofilament breakdown and mitochondrial failure, extensive cellular damage is not present in penumbral regions for up to 9 hours, suggesting the potential for rescuing these regions by appropriate and timely neuroprotective strategies.

Animals↗
PubMed1999

Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke.

BACKGROUND AND PURPOSE: Five pretreatment variables (P<0.1 univariate analysis), including serum glucose (>300 mg/dL), predicted symptomatic intracerebral hemorrhage (ICH) in the National Institute of Neurological Disorders and Stroke rtPA trial. We retrospectively studied stroke patients treated <3 hours from onset with intravenous rtPA at 2 institutions to evaluate the role of these variables in predicting ICH. METHODS: Baseline characteristics, including 5 prespecified variables (age, baseline glucose, smoking status, National Institutes of Health Stroke Scale [NIHSS] score, and CT changes [>33% middle cerebral artery territory hypodensity]), were reviewed in 138 consecutive patients. Variables were evaluated by logistic regression as predictors of all hemorrhage (including hemorrhagic transformation) and symptomatic hemorrhage on follow-up CT scan. Variables significant at P<0.25 level were included in a multivariate analysis. Diabetes was substituted for glucose in a repeat analysis. RESULTS: Symptomatic hemorrhage rate was 9% (13 of 138). Any hemorrhage rate was 30% (42 of 138). Baseline serum glucose (5.5-mmol/L increments) was the only independent predictor of both symptomatic hemorrhage [OR, 2.26 (CI, 1.05 to 4.83), P=0.03] and all hemorrhage [OR, 2.26 (CI, 1.07 to 4.69), P=0.04]. Serum glucose >11.1 mmol/L was associated with a 25% symptomatic hemorrhage rate. Baseline NIHSS (5-point increments) was an independent predictor of all hemorrhage only [OR, 12.42 (CI, 1.64 to 94.3), P=0.01]. Univariate analysis demonstrated a trend for nonsmoking as a predictor of all hemorrhage [OR, 0.45 (CI, 0.19 to 1. 08), P=0.07]. Diabetes was also an independent predictor of ICH when substituted for glucose in repeat analysis. CONCLUSIONS: Serum glucose and diabetes were predictors of ICH in rtPA-treated patients. This novel association requires confirmation in a larger cohort.

Acute Disease↗
PubMed1999

Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy.

BACKGROUND AND PURPOSE: Ischemic changes identified on CT scans performed in the first few hours after stroke onset, which are thought to possibly represent early cytotoxic edema and development of irreversible injury, may have important implications for subsequent treatment. However, insecurity and conflicting data exist over the ability of clinicians to correctly recognize and interpret these changes. We performed a detailed review of selected baseline CT scans from the NINDS rt-PA Stroke Trial to test agreement among experienced stroke specialists and other physicians on the presence of early CT ischemic changes. METHODS: Seventy baseline CT scans from the NINDS Stroke Trial were read and classified for the presence or absence of various early findings of ischemia by 16 individuals, including NINDS trial investigators, other neurologists, other emergency medicine physicians, and radiology or stroke fellows. CT scans included normal scans and scans from patients who later developed symptomatic intracranial hemorrhage, as well as scans on which the NINDS rt-PA Stroke Trial neuroradiologist identified clear-cut early CT changes. For each CT finding, kappa-statistics were used to assess the proportion of agreement beyond chance. RESULTS: kappa-Values (95% confidence interval [CI]) ranged from 0.20 (-0.20, 0.61) (fair agreement) to 0.41 (0.37, 0.45) (moderate agreement) among the 16 viewers, and the kappa-value was only 0.39 (0.29, 0.49) (fair) in answer to the question "do early CT changes involve more than one third of the MCA [middle cerebral artery] territory?" There was substantial variability within each specialty group and between groups. kappa-Values were only fair to moderate even among physicians experienced in selecting and treating acute stroke patients with rtPA. Observed agreement ranged from 68% to 85%. Physicians agreed on the finding of early CT changes involving >33% of the MCA territory 77% of the time, although the kappa-value of 0.39 suggested only moderate agreement beyond chance. CONCLUSIONS: There is considerable lack of agreement, even among experienced clinicians, in recognizing and quantifying early CT changes. Improved methods of recognizing and quantifying early ischemic brain damage are needed.

Cerebrovascular Disorders↗
PubMed1999

Yield of transcranial Doppler in acute cerebral ischemia.

BACKGROUND AND PURPOSE: The objective of this study was to evaluate the yield of emergent transcranial Doppler (TCD) for the evaluation of acute cerebral ischemia. METHODS: We performed urgent bedside non-contrast-enhanced TCD in patients with acute cerebral ischemia before or immediately after baseline CT scanning. A fast-track scanning protocol (</=15 minutes) and detailed diagnostic criteria were developed for portable single-channel TCD testing. TCD results were compared with angiography. RESULTS: Of 130 consecutive patients studied, 36 were eligible for thrombolytic therapy; 46 with ischemic strokes and 48 with transient ischemic attacks were not eligible for thrombolysis. TCD identified occlusions in 69% of thrombolysis-eligible patients, compared with 24% and 0% of patients with strokes and transient ischemic attacks, respectively, not eligible for thrombolysis (P<0.01). Stenosis was present in 17%, 33%, and 35%, and normal vessels were found in 14%, 43%, and 65% in the respective patient subgroups. TCD also identified abnormal pulsatility of flow (12 patients), abnormal flow velocities (12), microembolic signals (5), or early recanalization (5) (34 of 130; 26%). In 65% of all patients, TCD was compared with angiography (digital subtraction angiography, MR angiography, or CT angiography). Despite a 15% rate of absent temporal windows, TCD had 88% accuracy for abnormal (occlusion and stenosis) versus normal vessels: sensitivity 87.5%, specificity 88.6%, positive predictive value 87. 5%, and negative predictive value 88.6%. CONCLUSIONS: A proximal occlusion on TCD was found in 69% of thrombolysis-eligible patients. In 26% of all patients, TCD provided further relevant information that, in addition to angiography, helped to refine the severity of a stenosis and determine stroke pathogenesis. Emergent TCD is both sensitive and specific in determining arterial occlusion and stenosis in acute cerebral ischemia.

Acute Disease↗
PubMed1998

Ischemic stroke.

Acute ischemic stroke is a neurological emergency that requires ultra-rapid intervention. Stroke teams and stroke protocols can be devised to expediate evaluation and treatment. In carefully selected patients, thrombolytic therapy offers a significant benefit but must be initialized within 3 hours of stroke onset. Emerging alternative strategies for reperfusion and neuroprotection must also be initiated during the hyperacute period. The role of more traditional therapies, such as antiplatelet agents and anticoagulants, have been better defined through several recent major clinical trials.

Anticoagulants↗
PubMed1998

Intravenous tissue plasminogen activator for acute ischemic stroke: feasibility, safety, and efficacy in the first year of clinical practice.

BACKGROUND AND PURPOSE: The feasibility, safety, and efficacy of intravenous tissue plasminogen activator (t-PA) for patients with acute ischemic stroke in clinical practice need to be assessed. METHODS: We initiated a prospective open-label study at a university hospital and two community hospitals in Houston, Tex, immediately after the publication of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA study. A total of 30 patients, age 32 to 90 years, were treated with 0.9 mg/kg of intravenous t-PA (maximum dose, 90 mg) within 3 hours of acute ischemic stroke between December 1995 and December 1996. RESULTS: Six percent (6%) of all patients hospitalized with ischemic stroke received intravenous t-PA at the university hospital and 1.1% at the community hospitals. The rates of total, symptomatic, and fatal intracerebral hemorrhage were 10%, 7%, and 3%. Thirty-seven percent (37%) of patients recovered to fully independent function. The average time from stroke onset to emergency department arrival was 57 minutes; emergency department arrival to computed tomography scan 41 minutes; and computed tomography scan to administration of treatment 59 minutes. CONCLUSIONS: When treatment guidelines are carefully followed in an urban hospital setting, intravenous t-PA for acute ischemic stroke is feasible and shows safety and efficacy comparable to the results of the NINDS study.

Activities of Daily Living↗
PubMed1998

tPA-associated reperfusion after acute stroke demonstrated by SPECT.

PURPOSE: The aim of our study was twofold: to determine the frequency and magnitude of perfusion defect in stroke patients who qualify for rtPA therapy within 3 hours of stroke onset and to determine the ability of rtPA to improve perfusion by 24 hours. SUBJECTS AND METHODS: Patients with suspected hemispheric stroke who fulfilled entry criteria into the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study and also had pretreatment injection of (99m)Tc-HMPAO, with single-photon emission computed tomography (SPECT) performed using a triple-head camera at baseline and 24 hours, were included. RESULTS: All 12 patients who qualified for rtPA therapy had perfusion defects on baseline SPECT (SPECT graded scale [SGS] score range, 16 to 79). Mean+/-SD perfusion defect was comparable in rtPA (n=4)versus placebo (n=5) groups (SGS score, 36+/-18 versus 39+/-12; NS) despite earlier injection time in the rtPA group (98+/-24 versus 141+/-21 minutes; P=.02). Total SPECT scanning time was 20 to 25 minutes. At 24 hours, reperfusion was greater in rtPA patients compared with the placebo group (SGS score, 7+/-9 versus 29+/-17; P=.05), with relative improvement in the region-of-interest scores of 87+/-16% after rtPA compared with 28+/-30% with placebo (P=.01). CONCLUSIONS: A substantial perfusion defect exists in stroke patients with larger hemispheric infarcts who meet NINDS criteria for rtPA therapy, and rtPA is better able than placebo to rectify this defect. SPECT is feasible for clinical trials and should be evaluated as a substituted end point in stroke therapeutic trials.

Cerebrovascular Disorders↗
PubMed1998

Clinical features of moyamoya disease in the United States.

BACKGROUND AND PURPOSE: We report the clinical features and longitudinal outcome of the largest cohort of patients with moyamoya disease described from a single institution in the western hemisphere. Moyamoya disease in Asia usually presents with ischemic stroke in children and intracranial hemorrhage in adults. METHODS: Our study population included all patients with moyamoya disease evaluated at a university hospital in Houston, Texas from 1985 through 1995 (n = 35). We used Kaplan-Meier methods to estimate individual and hemispheric stroke risk by treatment status (medical versus surgical). Predictors of neurological outcome were assessed. RESULTS: The ethnic background of our patients was representative of the general population in Texas. The mean age at diagnosis was 32 years (range, 6 to 59 years). Ischemic stroke or transient ischemic attack was the predominant initial symptom in both adults and children. Of the 6 patients with intracranial hemorrhage, 5 had an intraventricular site of hemorrhage. The crude stroke recurrence rate was 10.3% per year in 116 patient-years of follow-up. Twenty patients underwent surgical revascularization, the most common procedure being encephaloduroarteriosynangiosis. The 5-year risk of ipsilateral stroke after synangiosis was 15%, compared with 20% for medical treatment and 22% overall for surgery. CONCLUSIONS: Our observations indicate that moyamoya disease may have a different clinical expression in the United States than in Asia, and may demonstrate a trend toward a lower stroke recurrence rate and better functional outcome after synangiosis.

Adolescent↗
PubMed1998

Hypertension and its treatment in the NINDS rt-PA Stroke Trial.

BACKGROUND AND PURPOSE: We examined the frequency, course, and treatment of hypertension in the NINDS rt-PA Stroke Trial. METHODS: Blood pressure (BP) was measured at the time of admission, at randomization, and then 36 times during the first 24 hours after randomization. Patients with a systolic BP of >185 mm Hg and a diastolic BP of >110 mm Hg at admission were defined as hypertensive before randomization, and those with a systolic BP of >180 mm Hg or a diastolic BP of >105 mm Hg within the first 24 hours after randomization were defined as hypertensive after randomization. Standardized clinical assessments were conducted at 24 hours and at 3 months. Post hoc analyses were conducted to evaluate the association of antihypertensive therapy with clinical outcomes. RESULTS: Of the 624 patients, 121(19%) had hypertension on admission and 372 (60%) had hypertension in the 24 hours after randomization. The use of antihypertensive therapy before randomization (tPA 9%, placebo 9%) and after randomization (tPA 24%, placebo 29%) was similar between placebo- and tPA-treated patients. No adverse effects of prerandomization antihypertensive therapy on 3-month favorable outcome were detected for either the placebo- or tPA-treated groups. For placebo patients with hypertension in the 24 hours after randomization, clinical outcome measures were similar for those patients who did and did not receive antihypertensive therapy after randomization (P > or = 0.26); antihypertensive therapy was not associated with declines in BP (P = 0.44) or with abrupt declines (P = 0.14). Those tPA patients who were hypertensive after randomization and received antihypertensive therapy were less likely to have a favorable outcome at 3 months (P < 0.01) than those who were hypertensive and did not receive antihypertensive therapy. CONCLUSIONS: The frequency of hypertension and the use of antihypertensive therapy were similar between the tPA and placebo groups in the NINDS rt-PA Stroke Trial. In the placebo group, antihypertensive therapy was not associated with less favorable outcomes at 3 months; postrandomization antihypertensive therapy was associated with less favorable outcomes for the tPA patients who were hypertensive. However, because of the nonrandomized use of antihypertensive therapy and the many post hoc comparisons leading to type 1 errors, the significance of this observation is unclear. Careful attention to BP and gentle management remain warranted for stroke patients treated with tPA.

Antihypertensive Agents↗
PubMed1998

Neurologists' attitudes regarding rt-PA for acute ischemic stroke.

We studied the attitudes of 238 Texas neurologists regarding the use of recombinant tissue plasminogen activator (rt-PA). The results show that 38 (16%) had treated stroke patients with rt-PA, and 97% of these would do so again. In the group that had not treated patients, 60% would treat if a suitable candidate presented. We conclude that soon after FDA approval of rt-PA, two-thirds of survey respondents were using or were planning to use this therapy. Those neurologists who have used rt-PA for stroke report a positive experience.

Health Care Surveys↗
PubMed1998

Hemopericardium and cardiac tamponade after thrombolysis for acute ischemic stroke.

Hemorrhage is the major complication of IV recombinant tissue plasminogen activator (rt-PA) treatment for stroke. We report three patients with mild or indistinct cardiac symptoms prior to thrombolysis in whom hemodynamically significant cardiac tamponade occurred after treatment with rt-PA. Acute ischemic stroke patients may have undetected myocardial or pericardial disease that may pose a risk for hemopericardium and life-threatening tamponade after treatment with rt-PA.

Aged↗
PubMed1998

Surgical treatment for intracerebral hemorrhage (STICH): a single-center, randomized clinical trial.

OBJECTIVE: To perform a single-center pilot investigation of early hematoma removal in patients with intracerebral hemorrhage (ICH). BACKGROUND: Considerable debate remains regarding the utility of surgical clot evacuation for ICH. METHODS: This was a prospective trial of open craniotomy within 12 hours of ICH symptom onset versus best medical therapy. Patients were eligible if they had a nontraumatic ICH >9 mL with significant neurologic impairment and were prepared for surgery within 12 hours of symptom onset. The study included a prospective registry of patients and a randomized trial. RESULTS: The registry group included 34 medical and seven surgical patients. The surgical group had larger hemorrhages (median, 96 mL) and a lower Glasgow Coma Scale (GCS) score (median, 10) compared with the medical group (33 mL; GCS score, 13). Six-month mortality was less in the medical group (36%) compared with the surgical group (54%). In the randomized series, median ICH volumes were similar in the surgical group (n = 17; 49 mL) compared with the medical group (n = 17; 44 mL). Median GCS score was also similar (medical, 10; surgical, 11). Mortality was lower in the surgical group (6%) compared with the medical group (24%) at 1 month, but similar at 6 months (surgical group, 17%; medical group, 24%). CONCLUSION: A trial of early surgery for ICH is feasible. This study represents the largest prospective, randomized series of surgery for ICH. A modest early mortality benefit for surgery is possible, but long-term benefit for surgery was not established in this single-center pilot investigation.

Adult↗
PubMed1998

Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis.

STUDY OBJECTIVE: This study investigated the hypothesis that modern computed tomographic (CT) imaging is sufficient to exclude subarachnoid hemorrhage (SAH) in patients with severe headache. METHODS: All 38,730 adult patients who presented to Hermann Hospital in Houston, Texas, during a 16-month period were prospectively screened to detect those with "the worst headache of my life." Two neuroradiologists blinded to the study hypothesis interpreted the CT scans. Patients with negative scans underwent comprehensive cerebrospinal fluid (CSF) analysis including cell count in first and last tubes, visual and spectrophotometric detection of xanthochromia, and CSF D-dimer assay. RESULTS: A chief complaint of headache was elicited in 455 patients, and 107 of these had "worst headache" and were enrolled in the study. CT-confirmed SAH was found in 18 of the 107 (17%). Only 2 patients (2.5%, 95% confidence interval, .3% to 8.8%) had SAH detected by CSF analysis among those with negative CT imaging result. CSF spectrophotometric detection was the most sensitive test for blood. Three patients with less than 6 red blood cells in tube 1 had positive spectrophotometric results, but in all 3, tube 4 was negative on spectrophotometric analysis, suggesting a high false-positive rate. CONCLUSION: Modern CT imaging is sufficient to exclude 97.5% of SAH in patients presenting to the ED with "worst headache" symptoms.

Adult↗
PubMed1997

Emergency identification and treatment of acute ischemic stroke.

In this review we describe the pathophysiology of cerebral ischemia and its implications for potential therapy. We summarize the results of recently completed trials of acute stroke intervention and explore some of the controversy surrounding thrombolysis for acute stroke. We also introduce the key concepts of neuroprotection and its therapeutic possibilities. Finally, we discuss the delays that may occur in the emergency evaluation and management of acute ischemic stroke and suggest some methods to expedite the process.

Brain Ischemia↗
PubMed1997

Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats.

During reperfusion after ischemia, deleterious biochemical processes can be triggered that may antagonize the beneficial effects of reperfusion. Research into the understanding and treatment of reperfusion injury (RI) is an important objective in the new era of reperfusion therapy for stroke. To investigate RI, permanent and reversible unilateral middle cerebral artery/common carotid artery (MCA/CCA) occlusion (monitored by laser Doppler) of variable duration in Long-Evans (LE) and spontaneously hypertensive (SH) rats and unilateral MCA and bilateral CCA occlusion in selected LE rats was induced. In LE rats, infarct volume after 24 hours of permanent unilateral MCA/CCA occlusion was 31.1 +/- 34.6 mm3 and was only 28% of the infarct volume after 120 to 300 minutes of reversible occlusion plus 24 hours of reperfusion, indicating that 72% of the damage of ischemia/reperfusion is produced by RI. When reversible ischemia was prolonged to 480 and 1080 minutes, infarct volume was 39.6 mm3 and 16.6 mm3, respectively, being indistinguishable from the damage produced by permanent ischemia and significantly smaller than damage after 120 to 300 minutes of ischemia. Reperfusion injury was not seen in SH rats or with bilateral CCA occlusion in LE rats, in which perfusion is reduced more profoundly. Reperfusion injury was ameliorated by the protein synthesis inhibitor cycloheximide or spin-trap agent N-tert-butyl-alpha-phenylnitrone pretreatment.

Animals↗
PubMed1997

African Americans and women have the highest stroke mortality in Texas.

BACKGROUND AND PURPOSE: Hispanic American (HA), African American (AA), and non-Hispanic white (NHW) populations are well represented in Texas. The Texas HA population is 95% Mexican American, affording comparison with other Hispanic populations. From risk factor profiles we expected stroke mortality to be highest in AAs and HAs. We also expected stroke mortality to be considerably higher for men than for women based on previous data. METHODS: We used International Classification of Diseases, 9th Revision, codes 430 to 438 to search Texas vital statistics data for the 5-year period from 1988 through 1992. Race/ethnic differences are presented in age- and sex-specific format to avoid masking the important interaction of age and sex with stroke mortality. RESULTS: Women constituted 61% of the 40,346 stroke deaths in Texas during this period. The ratio of stroke deaths for women versus men approximates the ratio of women to men in the population. AAs had a threefold to fourfold increased stroke mortality relative to NHWs at young ages. At older ages, when stroke mortality is the highest, the stroke mortality rate in NHWs approached the stroke mortality rate of AAs. HAs had a significantly higher rate of stroke mortality at younger ages relative to NHWs but a significantly lower rate at older ages. CONCLUSIONS: Measures to prevent stroke mortality should emphasize its predilection for young AAs and women. A rigorous surveillance project is needed to determine whether stroke mortality is underestimated in the HA population.

Black or African American↗
PubMed1997

Grading carotid stenosis with ultrasound. An interlaboratory comparison.

BACKGROUND AND PURPOSE: Carotid ultrasound had modest accuracy in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) of carotid endarterectomy in predicting severe carotid stenosis when a 250-cm/s peak systolic velocity (PSV) criterion was applied to different laboratories. We compared the performance of two independent laboratories using similar equipment (ATL-HDI Ultramark 9) but different interpretation criteria. METHODS: Consecutive patients who underwent both color-coded duplex ultrasound and intra-arterial digital subtraction angiography were studied. PSV was determined with angle correction at the site of the tightest arterial narrowing. Carotid stenosis was measured on angiograms using the North American (N) method. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values with 95% confidence intervals were calculated for each laboratory. RESULTS: In 87 patients, 174 bifurcations were imaged. A 250-cm/s criterion was the best single predictor of a > 70% N stenosis at one laboratory (sensitivity 93% [95% confidence interval, 85 to 101], specificity 86% [76 to 96], PPV 75% [62 to 87], and NPV 96% [90 to 102]) but had modest parameters at the other laboratory (50% [34 to 64], 87%, [77 to 97], 60 [44 to 76], and 91 [82 to 100], respectively). However, the diagnostic criteria routinely used in the second laboratory included different velocity values, which when applied decreased specificity by 17% but increased sensitivity by 35% (85% [74 to 96], 70% [56 to 84], 90% [81 to 99], and 77% [64 to 90], respectively). CONCLUSIONS: Despite the use of similar equipment, ultrasound grading of carotid stenosis is operator dependent and relies on different and individually validated criteria. Greater sensitivity of ultrasound screening is achieved by applying diagnostic criteria specific to each laboratory. Multicenter studies should use laboratory-specific criteria and a local validation process.

Angiography, Digital Subtraction↗