Development of a novel, weighted, quantifiable stroke scale: Japan stroke scale.

BACKGROUND AND PURPOSE: Several stroke scales are available for estimation of the severity of stroke, but none of them provides information regarding the relative weights of the observed variables. To define an integrated severity of stroke, we developed a quantifiable stroke scale with weighted variables that apply conjoint analysis to calculate the relative weight of each item. METHODS: We selected 10 variables (consciousness, language, neglect, hemianopsia, gaze, pupillary abnormality, facial palsy, plantar reflex, sensation, and weakness) based on the multivariate analysis of the Keio Stroke Patient Database Battery. The variables were categorized and evaluated for their distribution and sensitivity. The categorizations were then modified and rechecked. The procedure was repeated until the appropriate categorization was obtained from 198 patients. A temporary stroke scale without weight was then formulated, and the reliability of the scale was examined and revised with 80 new stroke patients. As a next step, 150 neurologists were asked to rank a set of 27 virtual patients, each with a different combination of variables, according to severity. From these rankings, conjoint analysis was used to derive utility scores (weights) for each factor level. RESULTS: The relative weights of each of the factors were as follows: consciousness 49.8%, language 9.9%, weakness of lower extremity 7.3%, pupillary abnormality 6.8%, gaze palsy 5.6%, weakness of arm 4.3%, weakness of hand 3.7%, neglect 3.7%, facial palsy 2.4%, plantar reflex 2.2%, hemianopsia 2.2%, and sensory impairment 2.1%. The total score for a patient could be calculated from the sum of the scores for each of the variables ranging from -0.38 to 27.86. Scoring of 100 patients with acute stroke was carried out, and the changes in scores were followed for validation. Longitudinal clinical monitoring of the patients correlated well with the scores in each patient. The interrater and intrarater reliabilities of the scale were excellent (weighted kappa 0.83; Cronbach's alpha 0.998). CONCLUSIONS: The Japan Stroke Scale is a parametric stroke scale that provides a quantitative measure of the severity of stroke. Each of the variables of the scale has a relative weight according to the severity of stroke. Reliability and responsiveness were proved to be excellent. The present data revealed a potentiality for the Japan Stroke Scale to be a universally accepted and reliable standardized system from the clinimetrical point of view.

Local cerebral blood flow values as estimated with diffusible tracers: validity of assumptions in normal and ischemic tissue.

A theoretical assessment is made of the validity of assumptions underlying the theory for estimating local cerebral blood flow with diffusible tracer in the tissue under normal and ischemic conditions. First, Kety's derivation of equations that have commonly been used for calculating local cerebral blood flow values is examined in order to define the problems and assumptions. Second, the brain:blood partition coefficient of diffusible tracer, lambda, and the diffusion-limited factor, m, under normal and ischemic conditions are reviewed. An examination of the literature suggested that contrary to common belief, lambda appears to change very little in ischemia if the tissue constituents remain unchanged, whereas m does change with ischemia if the diffusible tracer used is greatly diffusion-limited in the exchange between brain and blood. Even when a gas with an m value close to unity is used as the diffusible tracer, the prolonged mean transit time of blood through the ischemic tissue would make it difficult to maintain the exponential assumptions. As part of the ischemic tissue became infarcted, which is the case with most stroke patients, so the assumptions of homogeneous perfusion would become invalid. This inevitably renders it difficult to estimate local cerebral blood flow with diffusible tracer in ischemic tissue containing an infarcted mass.

Autoradiographic analysis on second-messenger systems and local cerebral blood flow in ischemic gerbil brain.

Alterations of the second-messenger systems, adenylate cyclase (AC) and protein kinase C (PKC), and local cerebral blood flow (lCBF) were evaluated during experimental cerebral ischemia in gerbils employing a quantitative autoradiographic method, which permitted these three parameters to be measured in the same brain. Ischemia was induced by occlusion of the right common carotid artery for 6 h. Animals attaining more than 5 in their ischemic scores were utilized for further experiments. At the end of ischemia, lCBF was measured by the [14C]iodoantipyrine method. The AC and PKC activities were estimated by the autoradiographic technique developed in our laboratory using [3H]forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu), respectively. The lCBF fell below 10 ml/100 g/min in most cerebral regions on the ligated side. The greatest reduction in FK binding was noted in the olfactory tubercle, caudate-putamen, and globus pallidus, followed by the hippocampus and cerebral cortices. The FK binding tended to be low at lCBF less than 20 ml/100 g/min in the cerebral cortices. However, the PDBu binding was relatively well preserved in each cerebral structure, and no significant correlation between lCBF and PDBu binding was noted in the cerebral cortices. The AC system may thus be vulnerable to ischemic insult over extensive brain regions, while the PKC system may be relatively resistant to ischemia.

Effects of a stable enkephalin analogue, (D-Met2,Pro5)-enkephalinamide, and naloxone on cortical blood flow and cerebral blood volume in experimental brain ischemia in anesthetized cats.

The effects of intracarotid injection of the stable enkephalin analogue (D-Met2,Pro5)-enkephalinamide (ENK) and intravenous administration of naloxone on the cerebrocortical blood flow (dye dilution method) and cerebral blood volume (CBV) (photoelectric method) were investigated during unilateral brain ischemia in anesthetized cats. Both parameters were measured simultaneously in the intact and ischemic (middle cerebral artery occluded) hemispheres. An intracarotid injection of ENK 0.5 mg/kg induced a significant increase in cortical vascular resistance and a -87% decrease in cerebrocortical blood flow from 25 +/- 3 to 4 +/- 3 ml/100 g/min, without CBV alteration in the ischemic hemisphere. Naloxone (1 mg/kg i.v.), on the other hand, induced a marked two-fold increase in cerebrocortical blood flow and a significant elevation of CBV from 5.9 +/- 0.5 to 7.4 +/- 0.7 vol% in the ischemic hemisphere. No change in cerebrocortical blood flow or CBV was observed in the intact hemisphere either after ENK or after naloxone administration. Arterial blood gases and hematocrit remained unchanged. On the basis of the present findings, we conclude that besides other factors, endogenous opioid mechanisms may also participate in ischemic cerebrovascular reactions and the cerebral circulatory effects of naloxone probably reflect its opiate receptor blocking property and not simply its other non-opiate-related actions.

Comparison between the photoelectric method and H2 clearance method for measuring cerebrocortical blood flow in cats.

The photoelectric method using carbon black as a nondiffusible tracer of blood was compared with the hydrogen clearance (H2) method in nine anesthetized cats. A photoelectric apparatus and H2 electrode were applied to a small region of the cerebral cortex (left ectosylvian gyrus) for simultaneous measurement of the regional CBF. The values of CBF(H2) and CBF(photoelectric) were 50.7 +/- 19.2 and 52.1 +/- 14.5 ml.100 g-1.min-1, respectively. CBF(H2) and CBF(photoelectric) were found to correlate well (r = 0.588, p less than 0.01) when changes in CBF were induced by CO2 inhalation, exsanguination, hyperventilation, and occlusion of the middle cerebral artery. The correlation between CBF(H2) and CBF(photoelectric) was much better in the case of intraindividual comparisons (r = 0.957, p less than 0.01). In addition to its merits in common with the H2 clearance method, such as handiness, low cost, and strict regionality, the photoelectric method displayed the following advantages: time-to-time measurements of CBF (less than 20 s), immediate display of the microcirculatory flow pattern, and simultaneous monitoring of cerebral blood volume. However, measurements from deep structures of the brain are better performed by the H2 method despite the disadvantage of the use of a potentially explosive gas.

Blood flow velocity in the pial arteries of cats, with particular reference to the vessel diameter.

The blood flow velocity and diameter of feline pial arteries, ranging in diameter from 20 to 200 microns, were measured simultaneously using a newly developed video camera method under steady-state conditions for all other parameters. There was a linear relationship between blood flow velocity and pial artery diameter (y = 0.340x + 0.309), the correlation coefficient being 0.785 (p less than 0.001). The average values for blood flow velocity in pial arteries less than 50 microns, greater than or equal to 50 but less than 100 microns, greater than or equal to 100 but less than 150 microns, and greater than or equal to 150 microns in diameter were 12.9 +/- 1.3, 24.6 +/- 3.4, 42.1 +/- 4.7, and 59.9 +/- 5.3 mm/s, respectively. Blood flow rate was calculated as a product of the cross-sectional area and the flow velocity. The blood flow rate increased exponentially as the pial artery diameter increased (y = 2.71 X 10(-4) x2.98). The average values for blood flow rate in pial arteries less than 50 microns, greater than or equal to 50 but less than 100 microns, greater than or equal to 100 but less than 150 microns and greater than or equal to 150 microns in diameter were 12.8 +/- 1.5, 122.1 +/- 24.8, 510.2 +/- 74.8, and 1524.2 +/- 174.4 10(-3) mm3/s, respectively. Hemorheological parameters such as the wall shear rate and Reynolds' number were also calculated. The data obtained provide a useful basis for further investigations in the field of cerebral circulation.

Video camera method for simultaneous measurement of blood flow velocity and pial vessel diameter.

A new method for the simultaneous measurement of blood flow velocity and pial vessel diameter is described. The system consists basically of a high-sensitivity vidicon camera, camera control, width analyzer, video densitometer, TV monitor, desktop computer, and multi-pen recorder. The pial vessels are visualized through a cranial window at 25-200x magnification on the TV monitor. The diameter of three target vessels can be recorded simultaneously on the recorder by adjustment of controllable video signal gates using the width analyzer. At the same time, the optical densities of two targets at points upstream and downstream of the pial vessel are measured continuously with video densitometers, and their outputs are recorded on the polygraph and analyzed by the computer. The time difference in the two peaks of time--concentration curves, produced very 2-3 s at the highest frequency by the injection of a small amount of saline through the lingual artery, is measured on-line using the computer. The flow velocity in the vessel is calculated from the time difference and the distance between the two targets. The system was shown to be stable, reliable, and rapid in response. This method may provide a useful tool for research in the field of blood circulation in the brain or any other organ.

Effects of lesioning of the substantia innominata on autoregulation of local cerebral blood flow in rats.

Recently, accumulated data have suggested that the nucleus basalis magnocellularis, i.e., the substantia innominata (SI), may represent the primary source of central cholinergic innervation in the rat cortical vasculature. We therefore examined the effects of unilateral lesion of the SI on the autoregulation of local CBF (lCBF) during induced hypotension in rats. Male Wistar rats were divided into three groups. The animals of groups 1 and 2 received an injection of 5 micrograms of ibotenate into the right SI stereotaxically. At 7 days after the injection, the lCBF was measured by the [14C]iodoantipyrine technique in the awake state. Group 1 was used as the normotensive group (MABP = 113.1 +/- 12.2 mm Hg). Group 2 formed the hypotensive group, and the lCBF was measured during hypotension (MABP = 80.0 +/- 5.5 mm Hg) induced by hemorrhage. Group 3, the sham-operated normotensive group, received vehicle injection into the right SI at 7 days prior to the lCBF measurement. In group 1, lCBF was significantly lower in the frontal, parietal, temporal, and striate cortices on the lesioned side compared to that on the contralateral side. In group 2, lCBF was significantly decreased in the cortices on the lesioned side, but there was no significant difference in magnitude of the lCBF reduction between groups 1 and 2. Group 3 exhibited no hemispheric asymmetries in lCBF. These findings suggest that the SI exerts an influence on cortical lCBF, but does not play a role in the autoregulation of lCBF during hypotension.

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions.

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels in cats.

To elucidate the fundamental actions of endogenous opioids and naloxone on the cerebral circulation, the effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels were investigated in cats. Pial arteries (165.7 +/- 24.9 microns) were found to dilate after the intravenous administration of 1 mg/kg of (D-Met2,Pro5)-enkephalinamide, and a definite dilatation of 7.1-7.6% persisted for 15 min. Pial veins (100.6 +/- 20.2 microns) also dilated but to a lesser degree. The MABP (118.7 +/- 10.5 mm Hg) decreased by 20 mm Hg immediately after the injection, but gradually returned to the initial value 15 min later. The observed cerebral vasodilatation may be attributable to sympathetic inhibition mediated either by the presynaptic opiate receptors of the cerebral vessels or by the opiate receptors in the brainstem. After the intravenous administration of 1 mg/kg of naloxone, pial arteries (122.0 +/- 17.2 microns) showed a slight but significant dilatation of 2.3-5.3%. There were no significant changes in pial veins (87.0 +/- 12.4 microns). MABP (130.4 +/- 12.3 mm Hg) was slightly increased after the injection. Although the mechanism involved was unclear, the cerebral vasodilatation occurring after the administration of naloxone may contribute to its ameliorating effect on the neurological symptoms following cerebral ischemia.

Noradrenergic nervous activity in migraine.

The autonomic nervous function in patients with migraine was studied during headache-free intervals. The following observations were made: (1) a decrease in overshoot in Valsalva's maneuver; (2) orthostatic hypotension; (3) low levels of plasma norepinephrine in the steady state; (4) failure in elevation of the plasma norepinephrine level after head-up tilting; (5) dilatation of the pupils after instillation in the eye of 1.25% epinephrine; and (6) a long recovery time in tests by bolus injection of 0.1 microgram of norepinephrine bitartrate per kilogram. The above findings suggest that patients with migraine show sympathetic hypofunction together with denervation hypersensitivity of the iris and the arteries, and that a defective noradrenergic nervous system may play a role in the pathogenesis of migraine.

Tolosa-Hunt syndrome. Arteriographic evidence of improvement in carotid narrowing.

Diagnosis of Tolosa-Hunt syndrome was made in a 25-year-old woman on the basis of unilateral third and sixth nerve paresis and possible involvement of the first branch of the ipsilateral trigeminal nerve, accompanied by headaches and ocular pain, which responded promptly to corticosteroid administration. Irregular narrowing of the right carotid siphon and occlusion of the homolateral superior ophthalmic vein were observed. During steroid therapy this stenosis improved in association with almost complete clinical recovery, although the vein was not recanalized. Of ten reported cases with contrast radiographic abnormalities, including our own, only two showed pupillary involvement. We hypothesize that the third nerve paresis with pupillary sparing in this syndrome may be attributable to the same underlying mechanism as that of diabetic ophthalmoplegia.

Influence of cerebral venous obstruction on cerebral circulation in humans.

The influence of cerebral venous obstruction on cerebral circulation was investigated in three patients with cerebral venous and sinus thrombosis in the chronic stage. The xenon Xe 133 intracarotid injection method was used to evaluate the cerebral blood flow (CBF). Values for CBF showed a slight decrease in all patients, despite intact cerebrovascular autoregulation. In two of the three patients, hypercapnia failed to increase CBF, but hyperventilation decreased CBF normally. This phenomenon can be explained on the basis of both failure of the capacitance vessels on the venous side to dilate and an increased intracranial pressure and is not attributable to decreased carbon dioxide reactivity. Long-lasting obstruction of the venous system can lead to a slight reduction in CBF and not affect cerebral autoregulation or CO2 reactivity itself in humans.

Serum dopamine-beta-hydroxylase activity in migraine.

Serum dopamine-beta-hydroxylase (DBH) activity was measured during headache-free intervals in 17 patients with migraine and during the headache interval in 16 patients with muscle contraction headache, as well as in 40 normal subjects. The DBH activity was significantly higher in the migraine patients (46.5+/4.5 units) than in the controls (24.9+/2.4 units), whereas no significant difference was observed between the patients with muscle contraction headache (29.4+/4.5 units) and the controls.

Role of cyclooxygenase system in cerebrovascular responsiveness: different effects of indomethacin on CO2 responsiveness and dilatation by Ca(2+)-channel blocker.

To investigate roles of prostaglandins in the regulation of cerebral blood flow, we compared effects of indomethacin, a cyclooxygenase inhibitor, on the cerebrovascular CO2 responsiveness with those on the cerebrovascular dilatory action of diltiazem, a Ca(2+)-channel blocker. Fifteen adult cats were used. The cerebral tissue oxygen tension, carbon dioxide tension, pH and blood pressure were measured continuously. Indomethacin (1 mg/kg) was infused into the carotid artery. In 8 cats, 3 min inhalation of 5% CO2 in air was performed before and after the indomethacin infusion. In 7 cats, diltiazem (100 micrograms/kg) was infused into the carotid artery for 3 min before and after the indomethacin infusion. The cerebrovascular CO2 responsiveness was significantly decreased (p < 0.05) after the administration of indomethacin. On the other hand, the cerebrovascular dilatation induced by the Ca(2+)-channel blocker was significantly increased (p < 0.05) after the administration of indomethacin. It is concluded that the products of cyclooxygenase system are involved in the cerebrovascular responsiveness both to CO2 and to Ca(2+)-channel blocker, but action mechanisms of prostaglandins may be different, that is, prostaglandians may enhanced cerebrovascular responsiveness to CO2 but diminish it to Ca(2+)-channel blocker.

Midpontine tegmentum infarction with "one-and-a-half syndrome" demonstrated by magnetic resonance imaging.

Magnetic resonance imaging (MRI) revealed a small midpontine tegmentum infarction in a patient with Fisher's one-and-a-half syndrome. The lesion was extremely restricted to the unilateral paramedian area of the midpontine tegmentum involving both the paramedian pontine reticular formation and medial longitudinal fasciculus. The typical form of this syndrome, that is, a combination of lateral gaze palsy and unilateral internuclear ophthalmoplegia, can be caused by a midpontine lesion.

Role of the sympathetic system in impairment of the cerebrovascular CO2 responsiveness during moderate hypoglycemia.

We examined the mechanism of impairment of the cerebrovascular CO2 responsiveness in moderate hypoglycemia. Twelve fasted cats were used. The brain-PO2, brain-PCO2 and brain-pH were measured continuously with electrodes placed on the brain surface. Hypoglycemia was induced with insulin. Intravenous injection of hexamethonium (a sympathetic ganglion blocker, C6; 0.1 mg/kg) was performed at the following stages: Control, hypoglycemia and recovery. Before and after the C6 administration, 5% CO2 in air was inhaled for 3 min at the respective stages. The CO2 responsiveness (cerebrovascular dilatory response to increased PaCO2) at the control stage was not altered after the ganglionic blockade. At the hypoglycemic stage, the increase in BrPO2 by CO2 inhalation was significantly less than that at the control stage. This reduction of delta BrPO2 was significantly improved after the administration of C6. At the recovery stage, the CO2 responsiveness before and after the administration of C6 was not significantly different. An impaired CO2 responsiveness in the hypoglycemic state was improved by sympathetic ganglion blockade with C6 which did not alter the reactivity during normoglycemia. It is suggested that the sympathetic activity plays an important role in impairment of the cerebrovascular CO2 responsiveness during moderate hypoglycemia.

Colloid osmotic pressure of cat brain homogenate separated from autogenous CSF by a copper ferrocyanide membrane.

The colloid osmotic pressure (oncotic pressure) of cat brain homogenate against cerebrospinal fluid (CSF) was determined using an electronic osmometer with a rigid selectively permeable copper ferrocyanide membrane. First, the basic characteristics of the membrane were examined. The relative value of the reflexion coefficient (sigma) for polyethylene glycol (PEG) became rather stable above a molecular weight of 6000 Da, below which sigma declined. The osmometer showed a linear response to sucrose concentration, whereas it revealed a non-idealistic change with respect to concentration of high molecules (PEG). The temperature effect on sigma for albumin solution was found to be large. The membrane could thus be used for measuring the relative value of the colloid osmotic pressure of protein solutions without dilution and at the same temperature as the calibrating solution. Samples of CSF and brain cortex were freshly obtained from 5 cats. The cortex was immediately homogenized and the colloid osmotic pressure of the homogenate against the CSF was measured at room temperature within 3 min after cortex removal. The mean value was 213 +/- 11 (S.D.) mm Hg with the osmometer calibrated with respect to the colloid osmotic pressure of autogenous plasma.

Creutzfeldt-Jakob disease: a case with extensive white matter degeneration and optic atrophy.

A 52-year-old woman is described, whose clinical features were typical of Creutzfeldt-Jakob disease except for the presence of optic atrophy. Serial CT scans showed rapid development of brain atrophy early in the course. Postmortem examination revealed extensive degeneration of the cerebral and cerebellar white matter and of the optic nerves in addition to the classic findings of Creutzfeldt-Jakob disease. It is suggested that both the grey and white matter may undergo a severe destructive process early in the course of the disease, and the possibility is discussed that the white matter involvement is not a result of neuronal loss.

Controlled ultraviolet irradiation generates endothelial damage without affecting the nerve terminals of the cerebral artery in cats.

The vesicles of adventitial autonomic nerve terminals were examined quantitatively under an electron microscope in controlled ultraviolet ray (UV)-irradiated cerebral vessels. Five cats whose basilar arteries were irradiated with UV (UV group) and 5 cats whose basilar arteries were irradiated with visible rays (control group) were compared. Endothelial vacuolation was observed only in the UV group. There was no statistically significant difference in the diameters of the dense-cored vesicles, related to noradrenaline, and clear vesicles, related to acetylcholine, between the two groups. It is concluded that controlled UV irradiation which generates endothelial damage does not affect the vascular adventitia ultrastructurally.