Hisashi Onoue

Can Transcranial Ultrasonication Increase Recanalization Flow With Tissue Plasminogen Activator

Background and Purpose— In thrombolytic therapy for acute ischemic stroke, it is essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To develop a new technique of thrombolysis for acute ischemic stroke, the effect of transcranially applied ultrasound (TUS) on thrombolysis was examined. Methods— An occlusion model of rabbit femoral artery was produced with thrombin after establishment of stenotic flow and endothelial damage. After stable occlusion was confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490 kHz, 0.13 W/cm2) was applied through a piece of temporal bone (TUS group; n=9). The control group received mtPA alone (tissue plasminogen activator [tPA] group; n=12). To verify the efficacy of TUS, femoral artery flow was measured during the procedure. Results— The recanalization ratio was 16.7% (2 of 12) in the tPA group and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group was higher than that in the tPA group (P =0.03). Patency flow ratio, which was defined as recanalization flow divided by baseline flow, of the TUS group (44.6±13.9%) was significantly greater than that of the tPA group (9.9±6.8%) at 60 minutes (P =0.025). Patency flow ratio became higher in the TUS group than in the tPA group between 20 and 30 minutes from the start of thrombolysis. Conclusions— Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit femoral artery occlusion model. This technique should be clinically useful for thrombolysis in acute ischemic stroke.

Imaging intracranial haemangiopericytomas: study of seven cases

Imaging features of intracranial haemangiopericytomas are similar to those of meningiomas. Preoperative identification of these tumours is important because of their aggressive nature, high rate of local recurrence and propensity for late metastasis. We reviewed the CT, MRI and angiographic findings in seven pathologically proved haemangiopericytomas, to determine if imaging characteristics might distinguish them from meningiomas. None showed hyperostosis or tumour calcification. All showed marked enhancement. Five had prominent internal signal voids, suggesting feeding arteries. On angiography, one had only pial-cortical supply but six also had meningeal supply; all showed a persistent stain. Only one had multiple “corkscrew” feeding vessels.

Effective and safe conditions of low-frequency transcranial ultrasonic thrombolysis for acute ischemic stroke: neurologic and histologic evaluation in a rat middle cerebral artery stroke model.

Background and Purpose— Transcranial ultrasound (TUS) enhances thrombolysis and is expected to be useful for the treatment of ischemic stroke. However, neither its effectiveness in improving neurologic outcome nor its safety in living tissue has been fully established. We examined the efficacy and safety of low-frequency TUS under appropriate conditions of ultrasound for thrombolytic treatment in a rat middle cerebral artery stroke model. Methods— Sixty-five male Wistar rats were used. Rats with right middle cerebral artery stroke exhibiting left hemiparesis were blindly selected and randomly assigned to 1 of 3 groups: (1) control, no therapy; (2) tPA, intravenous administration of tissue plasminogen activator 3 hours after middle cerebral artery stroke, or (3) TUS, tPA administration and application of TUS (490 kHz, continuous wave, at an intensity of 0.8 W/cm2). Twenty-four hours after the onset of stroke, neurologic improvement was evaluated and brains were then removed. Thrombolysis at the origin of the right middle cerebral artery was examined. Thrombolysis ratio, cerebral infarct ratio, and rate of histologic evidence of hemorrhage were compared in the 3 groups. Results— Significantly better neurologic improvement (P=0.008), a higher thrombolysis ratio (P=0.041), and a reduction of cerebral infarct volume (P=0.047) were obtained in the TUS group compared with the tPA group, without an increase in hemorrhagic transformation. Conclusions— Our findings suggest that thrombolytic treatment with low-frequency TUS under appropriate conditions could be an effective and safe method of treatment for ischemic stroke.

Two undesirable results of wrapping of an intracranial aneurysm.

This article presents a rare case in which we experienced two undesirable results following wrapping of an internal carotid artery aneurysm. First, a muscle piece used for wrapping was absorbed completely and, therefore, could not prevent enlargement of the aneurysm. And second, muslin gauze wrapping induced a foreign-body granuloma at the site (parasellar region), and resulted in development of oculomotor palsy.

Investigation of Postmortem Functional Changes in Human Cerebral Arteries

This study demonstrated the time-dependent changes in postmortem responses of isolated human middle cerebral artery strips to vasodilators. The relaxation induced by prostaglandin (PG) I2 or nitroglycerin remained stable for 24 h postmortem. In arterial strips precontracted with PGF2α, substance P and bradykinin both elicited relaxation that was almost completely abolished by removal of the endothelium. The endothelium-dependent response to both peptides was significantly degraded in strips obtained >12 h postmortem. These results indicate a selective functional or anatomical vulnerability of the vascular endothelium compared with that of the vasodilator mechanisms of the smooth muscle in the postmortem period. However, cerebral arteries isolated from human cadavers within 12 h postmortem should be adequate for studies of both smooth muscle and endothelial reactivity to vasodilators.

Suppression of cerebral vasodilation with endothelin-1.

We investigated the effect of endothelin-1 on relaxation responses induced by vasodilator substances in canine middle cerebral arteries to better understand regulation of cerebrovascular tone and its potential impact on mechanism of cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in helical strips of canine cerebral arteries (EC50; 4.62 x 10(-9) M). Pretreatment with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation elicited by substance P and endothelium-independent relaxations by nitroglycerin, prostaglandin I2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-independent relaxations, it did inhibit endothelium-dependent relaxation caused by substance P. A low concentration (10(-10) M) of endothelin-1 also significantly reduced endothelium-dependent relaxation of canine mesenteric arteries induced by acetylcholine. Other vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit endothelium-dependent and -independent relaxations. These results indicate that endothelin-1 not only produces cerebral vasoconstriction but also interferes with vasodilator mechanisms and that endothelium-dependent vasodilation is more sensitive to the inhibitory effect of endothelin-1 than endothelium-independent vasodiltion.

The potentiating effect of KC-404 on prostacyclin-induced vasodilation in isolated human cerebral artery

1. KC-404 (10(-9)-10(-6) g/ml) produced concentration-dependent relaxations in human middle cerebral arteries contracted with prostaglandin F2 alpha. 2. KC-404 (10(-8) and 10(-7) g/ml) has the ability to significantly potentiate prostaglandin I2-induced relaxations in human middle cerebral arteries. 3. KC-404, at least in low concentrations, may elicit human cerebral vasodilation predominantly by potentiating relaxant responses to prostaglandin I2 produced spontaneously in vascular wall. 4. KC-404 is expected to increase cerebral blood flow at least by dilation of major cerebral arteries, and this agent may be beneficial for the treatment of cerebrovascular disorders.

Role of Birth Injury in Syringomyelia

The role of birth injury was evaluated in different pathological types of syringomyelia by assessing the history of 74 patients with syringomelia. According to the intraoperative findings and magnetic resonance imaging (MRI), these syringomyelias were classified into three types; type 1; hindbrain-related syringomyelia without basal arachnoiditis (52 cases), type 2; hindbrain-related syringomyelia with basal arachnoiditis (10 cases), type 3; primary spinal syringomyelia (12 cases). As the results, 41% of patients, in type 1 had a history of difficult labor and 7 of them was due to breech delivery. In type 2, all patients with idiopathic basal arachnoiditis had a history of difficult labor and a half of them was due to breech delivery. The disturbance of cerebro-spinal fluid (CSF) circulation around the craniovertebral junction is the most important factor in the pathogenesis of hindbrain-related syringomyelia. A difficult labor may aggravate the disturbance of CSF circulation by further impaction of the cerebella tonsils due to an excessive moulding of the foetal head and/or traumatic subarachnoid hemorrhage (SAH) produced basal arachnoiditis.

Magnetic resonance cineflow imaging of cerebrospinal fluid in syringomyelia

The cerebrospinal fluid (CSF) hydrodynamics of 17 patients with syringomyelia were analysed using a Toshiba MRT-200 superconducting system (1.5 T) in 3 normal subjects. The turbulent flow of CSF in the cisterna magna which was seen in normal subjects could not be detected before operation in patients with the syringomyelia Chiari malformation complex. Moreover, the CSF in the syrinx moved actively in synchrony with pulsation in the lateral ventricles. After obstruction of the central canal by Gardner’s operation, the syrinx decreased in size and pulsatile movements of CSF within it were absent even in patients with a remaining cavity. This suggests that the pulsatile flow inside the syrinx is transmitted from the fourth ventricle through the patent central canal. The pathogenesis of syringomyelia associated with a Chiari malformation is discussed.