Saburo Sakaki

Evaluation of risk of hemorrhagic transformation in local intra-arterial thrombolysis in acute ischemic stroke by initial SPECT.

BACKGROUND AND PURPOSE Thrombolytic therapy was carried out on patients with acute ischemic stroke, and the risk of hemorrhagic transformation was evaluated from the residual cerebral blood flow (CBF) by pretherapeutic single-photon emission-computed tomography (SPECT). METHODS Local intra-arterial thrombolytic therapy was carried out using urokinase or recombinant tissue plasminogen activator (rt-PA) within 6 hours from the onset in 34 patients in whom no hypodensity areas were observed on the initial computed tomography examination. In the 20 patients with carotid territory occlusion who underwent 99mTc-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT, the residual CBF of the ischemic region was evaluated semiquantitatively by calculating two parameters: the ischemic regional activity to cerebellar activity ratio (R/CE ratio) and asymmetry index (AI). RESULTS The occluded vessels could be recanalized in 22 (92%) of the 24 patients in the urokinase group and in all 10 of the patients in the rt-PA group. Hemorrhagic transformation appeared in 4 patients in the urokinase group and 3 patients in the rt-PA group. Among the 20 patients who underwent SPECT before the treatment, the residual CBF was lower in the 5 patients who developed hemorrhagic transformation than in the 15 who did not (P < .05). Hemorrhagic transformation occurred in all patients with R/CE ratio of less than 0.35 and AI of more than 1.5. CONCLUSIONS The risk of hemorrhagic transformation after recanalization of occluded vessels by local intra-arterial thrombolytic therapy was considered to be high when the pretherapeutic residual CBF was markedly reduced.

Outcome in Acute Stroke with Successful Intra-Arterial Thrombolysis and Predictive Value of Initial Single-Photon Emission-Computed Tomography

This study investigates retrospectively, in selected patients, the ischemic outcome (reversible ischemia, infarction, and hemorrhage) and neurologic outcome of acute stroke treated with intra-arterial thrombolysis and the predictive value of pretreatment single-photon emission-computed tomography (SPECT). Thirty patients with complete recanalization within 12 hours were analyzed. The extent of ischemia was outlined on SPECT, and two CBF parameters were calculated: the ratio of ischemic regional activity to CBF in the cerebellum and the asymmetry index. Reversible ischemia, infarction, and hemorrhage were identified by comparing SPECT and follow-up computed tomography. Nine patients (30%) had no or small infarction, 14 (47%) had medium or large infarction, and seven (23%) had hemorrhage. Forty-two lesions were identified (22 reversible ischemia, 13 infarction, and 7 hemorrhage). Duration of ischemia, urokinase dose, disease type, and occlusion site were nonsignificant factors, whereas neurologic outcome and CBF parameters were significant among the three patient groups and three types of ischemic lesions. Ischemic tissue with CBF greater than 55% of cerebellar flow still may be salvageable, even with treatment initiated 6 hours after onset of symptoms. Ischemic tissue with CBF greater than 35% of cerebellar flow still may be salvageable with early treatment (less than 5 hours). Ischemic tissue with with CBF less than 35% of cerebellar flow may be at risk for hemorrhage within the critical time window. Pretreatment SPECT can provide useful parameters to increase the efficacy of thrombolysis by reducing hemorrhagic complications and improving neurologic outcome.

Evaluation of prognostic factors following expansive laminoplasty for cervical spinal stenotic myelopathy

BACKGROUND Expansive laminoplasty of several types has been proposed for patients with cervical multisegmental stenotic myelopathy to reduce postlaminectomy complications. Its effectiveness has not been fully explored by evaluating long-term results and magnetic resonance imaging (MRI) findings before and after surgery. METHODS We conducted a 5-year follow-up study of 22 patients with cervical spondylotic myelopathy and/or ossification of the posterior longitudinal ligament surgically treated with expansive laminoplasty. The operative results were examined using the Japanese Orthopedic Association (JOA) disability scale, with reference to the findings of MRI, computed tomography, and radiography. RESULTS Postoperative improvement was observed in 18 (81.8%) of the 22 patients. In 11 patients the percentage recovery of the JOA score was higher than 50% (average: 83.1%), while in the remaining 11 patients it was lower than 50% (average: 20.1%). Factors contributing to incomplete recovery appear to be related mainly to cord degeneration with atrophy (depicted as a T2-high intensity area) and to specific factors such as long symptom duration, age higher than 70 years, deterioration due to trauma, severe cord compression, radiculopathy, and kyphotic cervical curvature. CONCLUSIONS In cervical myelopathy, patients with multisegmental stenosis, expansive laminoplasty can be expected to provide a favorable outcome by providing sufficient cord decompression and stabilization of the cervical spine, when the stenotic cervical canal is enlarged to the normal range (over 12 mm residual anteroposterior diameter and 200 mm2 residual canal area). The efficacy can be restricted by various factors, especially irreparable cord degeneration.

Angioplasty after Intra-Arterial Thrombolysis for Acute Occlusion of Intracranial Arteries

BACKGROUND AND PURPOSE The purpose of this study was to report our experience with percutaneous transluminal angioplasty (PTA) of intracranial arteries in acute stroke patients who were resistant to intra-arterial thrombolysis alone. METHODS PTA was performed within 6 hours from symptom onset in 13 acute stroke patients in whom no hypodensity areas were observed on initial CT. PTA was classified into 3 categories: immediate (3 patients), delayed (3 patients), and rescue (7 patients) angioplasty. Treatment results in the PTA group for 9 cases of middle cerebral artery (MCA) occlusion were compared with those in the thrombolysis alone group for 12 cases of thrombotic MCA occlusion. RESULTS Technical success rates for immediate, delayed, and rescue angioplasty were 100%, 100%, and 71%, respectively, and that of angioplasty for the MCA was 100%. Ten patients (77%) showed improvement in the National Institutes of Health (NIH) stroke score after treatment. Improvement in NIH stroke scores in the PTA group for MCA occlusion was greater than that in the thrombolysis alone group (P<0.01). Nine patients (69%) had an excellent, good, or fair outcome 3 months after treatment. In 9 patients who had follow-up angiography 1 month after treatment, no restenosis or reocclusion was demonstrated. There were no symptomatic complications during or after treatment. CONCLUSIONS This limited study demonstrates the technical feasibility of angioplasty for intracranial arteries in acute ischemic stroke and suggests that angioplasty may be an effective option for improving the success rate of recanalization and preventing reocclusion of the MCA. The present results encourage us to perform further clinical trials in a larger number of patients to assess the efficacy of this procedure.

Multivariable Analysis of Predictive Factors Related to Outcome at 6 Months After Intra-Arterial Thrombolysis for Acute Ischemic Stroke

BACKGROUND AND PURPOSE Recent reports have suggested that a rapid assessment of pretreatment residual cerebral blood flow (CBF) could be used to optimize selection criteria for thrombolysis in patients with acute ischemic stroke to improve clinical outcome. We investigated retrospectively residual CBF and other clinical factors related to outcome at 6 months after intra-arterial thrombolysis by using multivariable analysis. METHODS Seventy-six patients received intra-arterial thrombolysis within 6 hours of symptom onset. The multiple regression method was used to analyze associations between the modified Rankin scale (MRS) at 6 months after treatment and clinical factors including age, infarction type, duration of ischemia, dose of urokinase, degree of recanalization, hemorrhage, National Institutes of Health Stroke Scale score (NIHSSS), and residual CBF evaluated by pretreatment single-photon emission-computed tomography; these values were assessed with the use of the regional-to-cerebellar activity (R/CE) ratio of ischemic region to cerebellum and asymmetry index. RESULTS MRS at 6 months was good (0 to 3) in 65% and poor (4 to 6) in 35%. Factors significantly related to MRS at 6 months were R/CE ratio (P<0.0001), NIHSSS at baseline and the following day (P<0.0001), cardioembolic infarction (P=0.0014), age (P=0.0074), and recanalization grade (P=0. 007). NIHSSS of >20, R/CE ratio of <0.35, cardioembolic infarction, incomplete recanalization (grade <3), and older age (>75 years) were determined to be significant independent predictors of poor outcome. CONCLUSIONS The residual CBF, neurological score at baseline and the following day, age, and recanalization grade correlated significantly with long-term outcome. The NIHSSS of >20 and R/CE ratio of <0.35 were determined to be significant independent predictors of poor outcome by multivariable analysis.

Neuroprotective nitric oxide synthase inhibitor reduces intracellular calcium accumulation following transient global ischemia in the gerbil

By observing the ultrastructural intracellular Ca2+ distribution with Ca(2+)-oxalate-pyroantimonate method, we examined whether the protective mechanism of the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (LNNA), involves change of the intracellular Ca2+ movement in delayed neuronal death (DND) in gerbil hippocampal CA1 neurons following 5-min forebrain ischemia. In the group intraventricularly administered 5.0 mg/ml LNNA, 15 min after reperfusion the intracellular Ca2+ deposits and the mitochondrial Ca2+ uptake index increased to levels similar to those in the control group administered only artificial cerebro-spinal fluid, but by 180 min after reperfusion they had returned to the preischemic level. By 15 min after reperfusion Ca2+ deposits in the endoplasmic reticulum (ER) had almost disappeared in both groups, but at 180 min of reperfusion, the ER in only the LNNA group showed Ca2+ deposits. It is suggested that the neuronal toxicity of NO involves the dysfunction of the intracellular Ca2+ transport system including the mitochondria and ER.

Free Radical Reaction and Biological Defense Mechanism in the Pathogenesis of Prolonged Vasospasm in Experimental Subarachnoid Hemorrhage

The relationship between free radical reactions and the defense mechanisms against them was investigated in the pathogenesis of prolonged vasospasm following experimental subarachnoid hemorrhage (SAH) in dogs. The concentration of lipid peroxides in the cerebro spinal fluid (CSF) increased markedly up to the eighth day following SAH; the concentrations also rose in the arterial wall (p < 0.01) and the gray matter of the temporal lobe where the subarachnoid blood clots were (p < 0.01). On the other hand, the activity of superoxide dismutase (SOD) decreased significantly up to the eighth day after SAH (p < 0.01), and there was a gradual increase of glutathione peroxidase (GSH-px) in the CSF. In the arterial wall, there was a slight decrease in the activity of SOD, a significant decrease in the activity of GSH-px (p < 0.01), and also a significant decrease in the concentration of glutathione (p < 0.01) up to the eighth day following SAH. In conclusion, lipid peroxidation with insufficient biological defense mechanisms against it in the arterial wall, concomitant with that in the CSF, might take part in the genesis of prolonged vasospasm following SAH.

Biological defence mechanism in the pathogenesis of prolonged cerebral vasospasm in the patients with ruptured intracranial aneurysms.

We examined the relationship between the biological protective mechanisms of scavengers and free radicals that are elicited by subarachnoid hemorrhage (SAH) in the pathogenesis of prolonged vasospasm following ruptured intracranial aneurysm. The study included 25 patients treated by early surgery (within 72 hours after SAH). Lipid peroxides concentrations and the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px) in the cerebrospinal fluid (CSF) were measured. The concentration of lipid peroxides increased significantly more (p less than 0.05) during the first 4 days after SAH in patients with symptomatic vasospasm than in those without. Patients with symptomatic vasospasm had a marked decrease in SOD activity on Days 3 and 4 followed by a gradual decrease, whereas the patients without spasm showed little change (difference between the groups, p less than 0.05). There was a significant difference in catalase activity reversal to SOD activity, but no difference in GSH-px activity. Thus, correlation was close between the increased lipid peroxides concentration and the decrease in SOD activity in CSF (p less than 0.05), suggesting an important mechanism in the pathogenesis of vasospasm.

Calcium Movement in Ischemia-Tolerant Hippocampal CA1 Neurons After Transient Forebrain Ischemia in Gerbils

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracelluar Ca2+ movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca2+ distribution and the Ca2+ adenosine triphosphatase (Ca2+-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca2+ from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca2+ deposits in these mitochondria were rapidly decreased. Plasma membrane Ca2+-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca2+ distribution and Ca2+-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca2+ sequestration and plasma membrane Ca2+-ATPase reduced Ca2+ toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.

Role of Protein Kinase C in the Pathogenesis of Cerebral Vasospasm after Subarachnoid Hemorrhage

This study investigated the role of protein kinase C (PKC) in the pathogenesis of vasospasm after experimental subarachnoid hemorrhage (SAH). PKC activation by intracisternal injection of a phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TP)] induced dose-dependent, slowly developing, severe contraction of the basilar artery. A single intracisternal injection of TP (5 × 10−9 M in the CSF) induced sustained contraction lasting over 3 days, which almost paralleled the changes of membrane-bound PKC activity in the basilar arterial wall. In a two-hemorrhage SAH model, membrane-bound PKC activity in the basilar artery increased up to day 4 and returned to the control level by day 14, whereas angiographic contraction reached a maximum on day 7 and still persisted at a moderate level on day 14. Thus, there was a discrepancy between arterial PKC activity and arterial contraction. Multiple intracisternal injections of TP produced 30–40% sustained contraction of the basilar artery lasting for more than 10 days along with sustained activation of PKC to levels compatible with that observed in the SAH model. However, TP injection caused considerably milder histological changes in the basilar artery than those noted in the SAH model. We concluded that cerebral vasospasm after SAH cannot be explained solely on the basis of activation of the PKC pathway.