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.

Cilostazol stroke prevention study: A placebo-controlled double-blind trial for secondary prevention of cerebral infarction.

Cilostazol, an antiplatelet drug that increases the cyclic adenosine monophosphate (AMP) levels in platelets via inhibition of cyclic AMP phosphodiesterase, has been used in chronic arterial occlusive disease. The purpose of the present study was to examine the effects of cilostazol on the recurrence of cerebral infarction using a multicenter, randomized, placebo-controlled, double-blind clinical trial method. Patients who suffered from cerebral infarction at 1 to 6 months before the trial were enrolled between April 1992 and March 1996. Oral administration of cilostazol (100 mg twice daily) or placebo was randomly assigned to the patients and continued until February 1997. The primary endpoint was the recurrence of cerebral infarction. In total, 1,095 patients were enrolled. An analysis based on 1,052 eligible patients (526 given cilostazol and 526 given placebo) showed that the cilostazol treatment achieved a significant relative-risk reduction (41.7%; confidence interval [CI], 9.2% to 62.5%) in the recurrence of cerebral infarction as compared with the placebo treatment (P=.0150). Intention-to-treat analysis of 1,067 patients also showed a significant relative-risk reduction (42.3%; CI, 10.3% to 62.9%, P=.0127). No clinically significant adverse drug reactions of cilostazol were encountered. Long-term administration of cilostazol was effective and safe in the secondary prevention of cerebral infarction.

Prognostic value of admission blood pressure in patients with intracerebral hemorrhage. Keio Cooperative Stroke Study.

BACKGROUND AND PURPOSE: Patients with acute stroke on admission to the hospital are often found to have high blood pressure. The purpose of the present study was to investigate the prognostic value of admission blood pressure in patients with acute intracerebral hemorrhage, including putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage. METHODS: A total of 1701 patients with intracerebral hemorrhage of the putamen (n = 776; mean +/- SD age, 58 +/- 14 years) thalamus (n = 538; 63 +/- 12 years), subcortex (n = 153; 61 +/- 16 years), cerebellum (n = 110; 64 +/- 11 years), and pons (n = 124; 59 +/- 13 years) were examined. The mean blood pressure on admission in patients with a fatal outcome was compared with that in patients who survived. RESULTS: The mean age in each patient group (putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage) with fatal outcome was older than that with nonfatal outcome, while ANCOVA indicated no correlation between age and blood pressure on admission or age and volume of hematoma. The mean arterial blood pressure on hospital admission was 126.9 +/- 25.8 mm Hg (+/-SD) in cases of putaminal. 127.4 +/- 22.6 mm Hg in thalamic, 116.4 +/- 20.6 mm Hg in subcortical, 123.5 +/- 23.9 mm Hg in cerebellar, and 133.0 +/- 26.0 mm Hg in pontine hemorrhage. The mean blood pressure on admission in patients with a fatal outcome among those with putaminal (136.0 +/- 36.3 mm Hg) and thalamic (133.2 +/- 22.1 mm Hg) hemorrhage was significantly higher than that in those with a nonfatal outcome (123.8 +/- 20.6 mm Hg for putaminal, 101.6 +/- 22.5 mm Hg for thalamic) (P < .01). No correlation between mean blood pressure and outcome was observed in the patients with subcortical (116.5 +/- 22.2 mm Hg for nonfatal, 114.9 +/- 22.0 mm Hg for fatal outcome), cerebellar (125.2 +/- 22.2 mm Hg, 116.9 +/- 28.8 mm Hg), and pontine (129.9 +/- 23.8 mm Hg, 136.0 +/- 27.7 mm Hg) hemorrhage. The volume of hematoma on admission in patients with fatal outcome with putaminal (58.2 +/- 24.4 mL), thalamic (27.0 +/- 13.1 mL), subcortical (32.9 +/- 14.4 mL), and cerebellar (31.4 +/- 28.6 mL) hemorrhage was greater than that in those with nonfatal outcome (20.8 +/- 11.4 mL, 7.1 +/- 4.8 mL, 18.3 +/- 10.6 mL, and 8.1 +/- 4.2 mL, respectively; P < .01), while no correlation between volume of hematoma and outcome was observed in patients with pontine hemorrhage. CONCLUSIONS: The above data suggest that an increased mean blood pressure and volume of hematoma on admission in putaminal and thalamic hemorrhage were related to increased mortality, while in patients with subcortical, cerebellar, and pontine hemorrhage, the mean blood pressure was not related to the clinical outcome.

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 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.

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.

Effects of mergocriptine on cerebral circulation and metabolism in cats.

Mergocriptine (CBM 36-733, CAS 81968-16-3) is an ergot alkaloid derivative and a dopaminergic agonist. Effects of mergocriptine on cerebral circulation and metabolism were examined by monitoring cerebral tissue oxygen and carbon dioxide tension (BrPO2, BrPCO2), cerebral blood flow (CBF) and blood pressure (BP) in 10 cats. Mergocriptine (10 micrograms/kg) infused into the carotid artery produced a significant increase in CBF during the administration followed by a decrease in BrPO2 in parallel with a significant decrease in BP.

Animal species differences in erythrocyte aggregability.

Species differences in erythrocyte aggregability were investigated employing our whole blood erythrocyte aggregometer. Blood was sampled from seven species, including humans and anesthetized (30 mg/kg pentobarbital) animals. The erythrocyte aggregation rates were the following (in s-1): cats, 0.213 +/- 0.027 (means +/- SD); dogs, 0.164 +/- 0.027; men, 0.112 +/- 0.025; rats, 0.111 +/- 0.005; domestic rabbits, 0.049 +/- 0.021; and mongolian gerbils, 0.034 +/- 0.015. Domestic fowls did not exhibit erythrocyte aggregograms like those seen in the other species. Statistical analysis revealed significant differences among the erythrocyte aggregation rates of the different species (multiple-comparisons with an overall significance level of 0.05) except between men and rats and between rabbits and gerbils. No single factor which is known to accelerate the erythrocyte aggregation rate (hematocrit, fibrinogen, etc.) was correlated with the erythrocyte aggregation rate except the globulin concentration in the blood. The failure to detect erythrocyte aggregation in domestic fowls was probably attributable to their erythrocyte shape. These results suggest that each species has its own proper tendency for erythrocyte aggregation. This factor must be taken into consideration when the blood circulation is discussed among different animal species.

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.

Cascade of cell swelling: thermodynamic potential discharge of brain cells after membrane injury.

This paper illustrates the principles of volume regulation in brain cells. Animal experiments were first performed ex vivo. Brains of gerbils were removed and incubated in 3 ml of physiological saline for 1 h. Control (0.86 g, n = 8) and swollen hemispheres (1.11 g, n = 8) were analyzed for tissue hydration, electrolytes and osmolality. The incubation media were also analyzed for gains or losses of electrolytes and water. Na+ and Cl- moved into and K+ moved out of the tissue. The ratio of Na+ influx to K+ efflux was calculated to be approximately 2:1. Water shifted into the tissue accompanying the net movements of small ions. In a simulated "cell" model constructed on the basis of the above observations with an outside saline and an inside colloid solution separated by a dialysis membrane, fluid shifts were demonstrated in the absence of (or even against) an osmotic gradient across the membrane under isobaric and isothermal conditions. Such paradoxical fluid shifts, presumably occurring in a similar manner to those in living cells, were shown to be due to the discharge of a huge thermodynamic potential accumulated by the cell as a condensation of ions outside and of proteins inside the cell membrane. We conclude that a loss in barrier function of the cell membrane ignites such a thermodynamic potential discharge causing an environmental fluid shift into the cells even under conditions of no (or even a contrary) osmotic gradient. Under such circumstances, countercotransporters and ion exchangers such as Na(+)-K(+)-2Cl- may work as modulators of the fluid shift, limiting its rate. The thermodynamic potential can explain the cascade of cell swelling (cytotoxic edema) as well as the spontaneous increase in osmolality in the ischemic cell when the cell volume increase is somehow restricted.

Magnetic resonance imaging cinecisternography in patients with white matter lesions.

1. The dynamic changes in ventricular size were computed by MRI cinecisternography. 2. The data analyzed showed that the phasic changes in size of the third ventricle and/or fourth ventricle were reduced in patients with the small multiple infarcts, with dementia, and with enlarged lateral ventricles when compared to subjects without these findings. 3. The derangement in CSF flow dynamics may be involved in the pathogenesis of vascular dementia.

Locus coeruleus stimulation exerts different influences on the dynamic changes of cerebral pial and intraparenchymal vessels.

The present experimental study was undertaken to investigate the effects of locus coeruleus stimulation on the dynamic changes of intraparenchymal vessels and pial vessels. Twelve cats were anaesthetized with alpha-chloralose and urethane. For stimulation of the locus coeruleus, a concentric stainless-steel needle electrode was inserted stereotaxically. During the stimulation, volumetric changes of the intraparenchymal vessels were monitored by a photoelectric method for estimating the cerebral blood volume (CBV) (6 cats), and the diameters of pial arteries were measured continuously using a video camera system (6 cats). The CBV followed a decreasing course during the stimulation of the locus coeruleus. The decrease in CBV from the control value (6.3 vol%) was 0.14 +/- 0.04 vol% at 80 s (p less than 0.05), 0.15 +/- 0.05 vol% at 100 s (p less than 0.05), and 0.15 +/- 0.03 vol% at 120 s (p less than 0.01). After cessation of the stimulation, CBV showed a gradual recovery. On the other hand, the diameters of the pial arteries did not change during or after the stimulation of the locus coeruleus. The above results suggest that the locus coeruleus has a vasoconstrictive effect on the intraparenchymal vessels, although it exerts no apparent influence on the pial arteries.

Inhibition of nitric oxide synthesis induces a significant reduction in local cerebral blood flow in the rat.

The effect of intravenous administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg), a specific inhibitor of nitric oxide synthesis, on local cerebral blood flow (lCBF) was examined in the rat using the [14C]iodoantipyrine autoradiographic method. L-NMMA induced a statistically significant reduction in lCBF in the cerebral cortices as well as in various deep structures of the brain. This reduction in lCBF was accompanied by a clear increase in mean arterial blood pressure, suggesting that the cerebral resistance vessels constricted significantly beyond the autoregulatory response following L-NMMA administration. These findings indicate that the basal cerebral circulation may be closely related to nitric oxide production.

Evidence for in vivo cerebrovascular neurogenic vasodilatation in the rat.

To determine the function of cerebrovascular parasympathetic nerves, the calibre of rat pial arteries was continuously measured when the nerves (the postganglionic fibres originating from the sphenopalatine ganglion) were electrically stimulated in vivo. The pial arteries (72.3 +/- 2.8 microns) dilated immediately after electrical stimulation (5 V, 10 Hz, 0.5 ms, 1 min duration). Their diameter increased 4.7 +/- 0.1% (p less than 0.01), 6.3 +/- 1.7%, 5.1 +/- 0.3% (p less than 0.05), 6.3 +/- 1.4%, at 15, 30, 45 and 60 s after initiation of stimulation, respectively. No significant change was observed in systemic arterial blood pressure or the expiratory carbon dioxide content during stimulation. This is the first direct demonstration of in vivo cerebrovascular neurogenic vasodilatation in the rat.

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 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.

Effects of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine on cerebral circulation and metabolism in cats.

Effects of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) on cerebral circulation and metabolism were examined measuring cerebral oxygen and carbon dioxide tension (BrPO2, BrPCO2) and mean arterial blood pressure (MABP) in cats. KC-404 (100 micrograms/kg) infused into the carotid artery produced no significant changes in BrPO2, BrPCO2 and MABP. 300 micrograms/kg of KC-404 infused into the femoral vein produced significant decrease in MABP, whereas BrPO2 remained constant. It is suggested that a large dose of KC-404 causes preferential cerebral vasodilation and maintenance of constant blood flow despite marked reduction in MABP.

Stroke in systemic lupus erythematosus.

We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti-deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman-Sacks endocarditis are closely associated with occlusive cerebrovascular disease.

Normal pressure hydrocephalus associated with cauda equina neurinoma.

A 65-year-old woman with normal pressure hydrocephalus experienced improved gait and hydrocephalus following surgical resection of a cauda equina neurinoma. Fibrinogen, detected in the cerebrospinal fluid, may be involved in the pathophysiological process of normal pressure hydrocephalus.