Citations

Reduced nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarbital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to be reliable.

Regional cerebral blood flow (CBF) was measured (intra-arterial injections of 133 Xe) and electroencephalograms (EEG) were recorded periodically before, for two hours during, and for one and one-fourth hours after middle cerebral artery (MCA) occlusion in 20 squirrel monkeys ( Saimiri sciureus ). A CBF-Pa co co2 response curve for these animals under barbiturate anesthesia was created from CBF values prior to MCA occlusion and during the time a steady state was being achieved. The animals were subdivided into four groups (five monkeys in each) on the basis of Pa co co2 values: 20, 36, 40, and 60 mm Hg. CBF values from this study were compared to previous results obtained with 35 Kr. The phenomenon of "look through" and the importance of recognizing this artifact and its significance in analyzing CBF results in areas of focal ischemia are discussed. The present results were correlated with cerebral ATP and lactate concentrations in ischemic regions determined in previous studies using this preparation at these Pa co co2 values and at comparable time intervals before, during, and after MCA occlusion. The EEG appears to reflect the state of ischemic brain accurately. However, CBF measured by the 133 Xe method can be misleading in regard to the true degree of ischemia resulting from occlusion of an intracranial vessel and cannot be relied on to demonstrate accurately "steal" or "reverse steal" due to changes in Pa co co2 .

The clinical findings in 64 patients with transient symptoms of unilateral carotid system ischemic disease (amaurosis fugax or transient focal cerebral ischemic attacks or both) were reviewed in an effort to determine the value of the neurovascular examination in predicting the presence and extent of roentgenographically demonstrated ipsilateral extracranial internal carotid artery disease. Amaurosis fugax seems to be a highly specific indicator of disease, being associated with 4% of normal vessels as compared to 27% for patients with transient focal cerebral ischemic attacks alone. In patients with transient symptoms, the incidence of a normal, ipsilateral carotid artery was 36% in the absence of any positive neurovascular findings, 15% in the presence of an ipsilateral carotid bruit, 6% in the presence of ipsilateral retinal embolic events, 5% in the presence of ipsilateral reduction in superficial temporal or carotid (or both) pulse, 4% in the presence of an ipsilateral reduction in retinal artery pressure, and 3% when more than one of these findings were noted. The neurovascular examination appears to be a useful adjunct in detecting the presence or absence of ipsilateral carotid disease. However, no combination of symptoms or signs would, in all cases, allow one to accurately determine whether a vessel was abnormal, stenotic, or occluded.

A previously described in vitro model for cerebral anoxia has been modified to ensure vitality of the rabbit brain slices. The oxygen or nitrogen atmosphere was provided by a continuous gas flow system. Amino acid incorporation into proteins was studied during recovery periods up to 60 minutes. An initial decrease of incorporation and subsequent recovery were observed after an anoxic period of five minutes. On the other hand, a marked decrease and only partial recovery were seen after anoxic periods of 15 minutes or longer. No consistent change was observed in acid-soluble radioactivity. This in vitro model appears to be feasible for various biochemical studies of cerebral anoxia.

The right seventh cranial nerve (n. VII) was exposed intracranially via a suboccipital approach in each of eight cats. Measurements of cerebral blood flow (CBF) were made from superficial cortex, sulcal cortex, basal cortex, the basal ganglia, and the centrum semiovale of each cerebral hemisphere of each cat by autoradiography using 14 Cantipyrine. In six cats, measurements of CBF were made during electric stimulation of n. VII; in two of these, the nerve was sectioned before stimulation. In the remaining two cats, measurements were made after exposure but without stimulation of n. VII; in these cats, there were no side-to-side differences of CBF. In each of the four cats with n. VII intact, CBF values were lower on the stimulated side. In each of the two cats with n. VII sectioned, CBF values were higher on the stimulated side. Thus, stimulation of n. VII causes regional increases of CBF only when centripetal effects of stimulation are prevented. Cerebral vasodilatation has been observed by others during stimulation of a sectioned or an intact n. VII. When an intact nerve is stimulated, vasodilatation apparently is unable to compensate for decreases of CBF mediated centripetally through brain stem structures and extracranial or basal cerebral vessels; moreover, such vasodilatation may be due in part to regulatory responses of vessels to decreases of perfusion pressure.

The effect of large dosages of dexamethasone on the edema of cerebral ischemia and infarction in the squirrel monkey after temporary occlusion of the middle cerebral artery is reported. There was no difference between the ten monkeys treated with dexamethasone and the 11 control animals in clinical course, mortality, morbidity, histological appearance, or amount of edema associated with this ischemic lesion. The differences in the electron microscopic and pathophysiological findings of the edema from ischemia secondary to single major vessel occlusion and in the edema from an intracranial mass lesion are reviewed. The possible therapeutic or pharmacological effects of steroids are considered along with available data on lysosomes in the brain. At the present time, there is no justification for the use of large doses of dexamethasone in the treatment of cerebral infarction.

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 κ 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.

Background and Purpose —The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm 3 . The volume of first-ever ischemic stroke in the population is not known. Methods —The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. Results —There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm 3 (interquartile range, 0.5 to 8.8 cm 3 ). There was a significant relation between location of lesion and infarct size ( P <0.001) and between volume and mechanism of stroke ( P =0.001). Conclusions —The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Background —Stroke is a complex genetic disorder with a variable phenotype. Investigations of heritable factors in complex genetic disorders use pedigree and genetic techniques, which pose different ethical and methodological challenges than those routinely encountered in therapeutic research. Building consensus on acceptable research practices in this field is vital to the success of multicentered collaborations. Summary of Review —We review important ethical and methodological concerns related to the collection, storage, and release of pedigree research information. The human studies aspects of pedigree research are complicated methodologically because individuals can be active or passive participants and pedigrees can be proband derived, partially validated, or fully validated. Current research ethics frameworks do not work well outside of a dyadic researcher-subject relationship. Privacy and confidentiality for family members must be considered in pedigree research. Investigators should anticipate potential conflicts of interest among family members when designing a pedigree research protocol. Conclusions —We propose a “proband-initiated contact” methodology in which the proband or the proband’s designate allows identification of potential families without breaching the privacy of individuals in the family. In situations in which family history data are collected without direct contact between researchers and individuals in the proband’s family, an Institutional Review Board may waive consent by family members after appropriate review of the protocol and application of rules for granting waivers of consent. Certificates of Confidentiality should be considered.