Baseline computed tomography changes and clinical outcome after thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke.

OBJECTIVE: Intravenous recombinant tissue plasminogen activator (rt-PA) is the only therapy of proven value for patients with acute ischemic stroke (AIS). Controversy exists with regard to the prognostic significance of early computed tomography (CT) changes in patients receiving rt-PA for AIS. The authors retrospectively reviewed all cases of AIS who received intravenous rt-PA for AIS in University of South Alabama hospitals between January 1996 and May 1999. A neuroradiologist, blinded to clinical outcomes, reviewed all baseline CT scans for the presence of the following signs: hyperdense middle cerebral artery (HMCA), loss of gray-white differentiation (LGWD), insular ribbon sign (IRS), parenchymal hypodensity (PH), and sulcal effacement (SE). Modified Rankin Scale (mRS) score was recorded 90 days after thrombolysis, and clinical outcome was dichotomized as favorable (0-1) or unfavorable (2-6). The authors performed both univariate and multivariate analyses to investigate the relationship between early CT signs, baseline clinical variables, and functional outcome as measured by the 90-day mRS scores. Any one early CT finding was detected in 23(64%) patients. The frequency of specific findings were as follows: SE in 13 patients (36%), LGWD in 12 patients (33%), PH in 9 patients (25%), HMCA in 4 patients (11%), and IRS in 3 patients (8%) patients. There was no statistically significant association between the occurrence of these imaging findings and subsequent functional outcome after thrombolysis. The data suggest that the presence of subtle acute CT changes in AIS patients is not predictive of clinical outcome following administration of rt-PA as per National Institute of Neurological Disorders and Stroke protocol.

A randomized efficacy trial of citicoline in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Citicoline (cytidine-5'-diphosphocholine; CDP-choline) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects. METHODS: The current trial was a 33-center, randomized, double-blind, efficacy trial in 394 patients comparing placebo (n=127) with citicoline (n=267) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up period. Patients with acute (24 hours) ischemic strokes clinically assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale (NIHSS) > or = 5 were enrolled. RESULTS: Mean time to treatment was 12 hours, and mean age was 71 for placebo and 70 for citicoline. Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS <8 (34% vs 22%; P<0.01). The incidence and type of side effects were similar between the groups. The planned primary analysis (logistic regression: 5 categories Barthel) failed the proportional odds assumption and was rendered unreliable. There were no between-group differences seen on the planned secondary assessment analyses at 90 days, including the Barthel Index > or = 95 at 12 weeks (last observation carried forward: placebo 40%; citicoline 40%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS > or = 8 found that citicoline-treated patients were more likely to have a full recovery (Barthel > or = 95): placebo 21%; citicoline 33%; P=0.05; whereas no difference was seen in patients with baseline NIHSS<8 (placebo 77%; citicoline 69%; P>0.1. CONCLUSIONS: The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial. Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit.

Cluster headache: Horton's cephalalgia revisited.

BACKGROUND: Cluster headache (CH), though not fully characterized until this century, is a relatively common primary headache disorder. METHODS: We reviewed pertinent literature on CH and related cephalalgias. RESULTS: We found that CH typically occurs in middle-aged men and has a characteristic cyclic temporal pattern. During the cluster cycle, CH paroxysms last from 15 to 180 minutes and are manifested by excruciating periorbital or upper facial pain. Associated autonomic symptoms such as lacrimation, rhinorrhea, conjunctival injection, and Horner's syndrome are common in CH. Its pathophysiology is not entirely understood, though it may include a complex cascade of autonomic, immunologic, and vascular phenomena. CONCLUSIONS: Although its pathophysiology is still not completely understood, we present the most recent evidence regarding the underlying anatomic and biochemical basis for CH. We also present an update on the modern management of CH, including the appropriate use of standard and novel abortive and prophylactic agents, as well as more invasive treatment.

Intravenous t-PA for acute ischemic stroke: therapeutic yield of a stroke code system.

Subsequent to publication of the NINDS t-PA Stroke Study results, we sought to determine the proportion of patients eligible for and receiving intravenous tissue plasminogen activator (t-PA) at an active acute stroke treatment center. Over a 12-month period there were 185 stroke code activations. Of these, 134 involved patients with ischemic stroke, and 48 of these (36%) were potentially eligible for treatment with t-PA by the time criterion (i.e., interval from stroke onset to hospital presentation < 3 hours). Nine of the 48 potentially eligible patients (19%) and 9 of 134 ischemic stroke patients (7%) overall received t-PA. In our patient population only a small proportion of all patients with acute ischemic stroke presently are eligible for treatment with t-PA.

Accuracy of paramedic diagnosis of stroke.

BACKGROUND AND PURPOSE: Accurate prehospital diagnosis of acute stroke may lead to fewer delays in hospital presentation. In addition, prehospital personnel soon may be administering therapies to patients with presumed stroke. We sought to determine the sensitivity and positive predictive value (PPV) of paramedic diagnosis of stroke in Mobile, Alabama, and to evaluate the impact of an educational program on paramedic diagnostic capability. METHODS: We collected data from all paramedic-diagnosed stroke patients transported to a University of South Alabama hospital by Mobile Fire Medics. Final diagnosis was determined by a neurologist and classified as stroke or nonstroke (i.e., PPV). Paramedic diagnoses for all hospitalized stroke patients transported by Mobile Fire Medics were also reviewed (i.e., sensitivity). Sensitivity and PPV were calculated for the period 6/13/95 to 3/13/97. In addition, both indices were calculated for the period before (6/13/95 to 5/5/96) and after (6/25/96 to 3/13/97) an 8-week intensive educational program. RESULTS: Seventy-one hospitalized stroke patients were transported by Mobile Fire Medics during the study period. Paramedics correctly identified 67 patients in total (94% sensitivity), 29 during the pre-education period (91% sensitivity), and 29 during the posteducation period (97% sensitivity; P=.33). Twenty-five patients were incorrectly diagnosed with stroke (73% PPV), 15 during the pre-education period (66% PPV), and 9 during the posteducation period (76% PPV; P=.30). CONCLUSION: Although paramedics in Mobile misdiagnose few patients with acute stroke, there is a tendency toward overdiagnosis. An educational intervention resulted in a trend toward improved accuracy of diagnosis, but this did not reach statistical significance.

Implementation of a stroke code system in Mobile, Alabama. Diagnostic and therapeutic yield.

BACKGROUND AND PURPOSE: There is now therapy of proven benefit for acute ischemic stroke. Successful interventional therapy for stroke patients requires implementation of a system that facilitates rapid triage and diagnostic evaluation. METHODS: We initiated a 24-hour, 7-day-per-week stroke code system at the University of South Alabama Hospitals and prospectively collected data from the first 100 patients whose clinical presentations triggered this system. RESULTS: Seventy-eight patients (78%) had acute ischemic stroke. Of the remaining 22, 9 had evidence of intracerebral hemorrhage. The most common nonstroke diagnosis was seizure (n = 5). Forty-eight of the 87 stroke patients (55%) presented within 6 hours of stroke onset (40/78 = 51% of the ischemic stroke patients), and 35 of the 87 (40%) presented within 3 hours of onset (28/78 = 36% of the ischemic stroke patients). Thirty-one (31% of the group overall; 40% of the ischemic stroke patients) were eligible for acute therapy. Twenty-five of these eligible patients were entered into a treatment study, 4 declined participation, and 2 were treated with open-label tissue plasminogen activator. CONCLUSIONS: Implementation of a stroke code system may result in a high yield of patients with acute stroke and relatively few "stroke mimickers." A significant proportion of all cases generated will be eligible for acute treatment under current experimental protocols or with tissue plasminogen activator, but the majority will not.

Thermoregulatory vasococonstriction and shivering impede therapeutic hypothermia in acute ischemic stroke patients.

OBJECTIVES: We tested the hypothesis that vasoconstriction and shivering thresholds are sufficiently reduced by acute stroke to permit induction of therapeutic hypothermia without additional pharmacological inhibition of thermoregulatory control. METHODS: We studied eight patients 2 +/- 1 days after ischemic stroke. Forced-air cutaneous cooling was administered until the patients shivered continuously or reached a tympanic membrane (ie, core) temperature of 34 degrees C. The tympanic membrane temperatures triggering vasoconstriction and shivering identified the thresholds for each response. RESULTS: Patients had a mean age of 68 +/- 8 years and a mean National Institutes of Health Stroke Scale (NIHSS) score of 5. No patient reached the target core temperature of 34 degrees C. Vasoconstriction and shivering thresholds were 37.1 +/- 0.4 degrees C and 36.6 +/- 0.4 degrees C, respectively. CONCLUSIONS: Vasoconstriction and shivering were initiated at roughly normal temperatures in ischemic stroke patients, and these thermoregulatory responses prevented induction of therapeutic hypothermia. Pharmacological reduction of the vasoconstriction and shivering thresholds will be required if therapeutic hypothermia for stroke patients is to be induced easily by surface cooling.

Aseptic meningoencephalitis following iohexol myelography.

We report a case of aseptic meningoencephalitis complicating iohexol myelography and compare this case with previous reports of neurotoxicity from intrathecal contrast media.

Impact of race and ethnicity on ischemic stroke. The University of California at San Diego Stroke Data Bank.

BACKGROUND AND PURPOSE: As the US minority population continues to grow, increasing numbers of nonwhite citizens are at risk for stroke. A better understanding of how ischemic stroke differs in the minority populations may lead to more effective clinical management. METHODS: We prospectively evaluated 542 consecutive patients (416 whites, 71 Mexican Americans, 55 blacks) presenting to the University of California at San Diego Medical Center or the San Diego Veterans Affairs Hospital with presumed acute ischemic stroke or transient ischemic attack. RESULTS: Whites had a higher proportion of transient ischemic attacks (32% versus 18% and 17% for blacks and Mexican Americans, respectively) and had the lowest prevalence of diabetes mellitus (17% versus 29% and 40% for blacks and Mexican Americans, respectively). Mexican Americans had higher initial serum glucose levels (178 versus 133 and 131 mg/dL for whites and blacks, respectively). Blacks were youngest (average age, 56 years). There were no differences among the groups in the prevalence of prior stroke, hypertension, myocardial infarction, or smoking; initial systolic blood pressure, serum cholesterol levels, and functional deficit also were similar. Although it did not reach statistical significance, there was a trend toward relatively late presentation in the black stroke subpopulation: only 53% of blacks (compared with 73% of both Mexican Americans and whites) reached medical attention within 24 hours of stroke onset. All groups had similar diagnostic evaluations and functional outcome at 1 week. With the exception of a higher frequency of stroke of unknown cause in Hispanics, the distributions of stroke etiologies did not differ significantly among the groups. CONCLUSIONS: These data suggest that there are significant clinical differences in populations with ischemic stroke and transient ischemic attack that are related to race and ethnic origin, but in our population these differences did not include the extent of diagnostic evaluation undertaken or stroke severity.

Renal hemodynamic changes during serial seizures in rats.

Renal blood flow (RBF) and mean arterial blood pressure (MABP) were measured during serially induced seizures in anesthetized paralyzed rats to investigate possible alterations in hemodynamic responses during experimental status epilepticus. During initial seizures, MABP increased from 143 to 193 mmHg, and RBF decreased from 4.8 to 1.5 ml/min. In contrast, MABP fell from 124 to 100 mmHg and RBF dropped from 3.6 to 2.8 ml/min during late seizures. The large decreases in RBF during initial seizures were blocked by renal denervation or bilateral adrenalectomy. During the period of late seizures, both the increase in MABP and the decrease in RBF in response to intravenous boluses of norepinephrine fell to 55% of the preseizure value. Our data indicate that the marked decreases in RBF during early seizures can be mediated by either the renal nerves or the adrenal glands. Furthermore, decreased sensitivity of the vasculature to norepinephrine likely contributes to the diminution of both MABP and RBF responses during later seizures.