Teruaki Kawano

Expression of Vascular Endothelial Growth Factors and Their Receptors in and around Intracranial Arteriovenous Malformations

OBJECTIVE The precise mechanisms responsible for the development and growth of intracranial arteriovenous malformations (AVMs) remain unclear, but it has been hypothesized that vascular endothelial growth factors (VEGFs) might be involved in their pathogenesis. The aim of this study was to examine immunohistochemically the presence of the VEGF family (VEGF-A to -D) and their receptors (Flt-1, Flk-1, and Flt-4) in the surgically resected AVM nidus. METHODS The AVM nidus was surgically obtained from 31 patients with AVMs (mean age, 40.5 yr, range 13–73 yr). The mean size of the nidus was 31.6 mm (range, 15–60 mm). Formalin-fixed, paraffin-embedded specimens were stained immunohistochemically by the labeled streptavidin-biotin method with antibodies against VEGF-A to -D, as well as Flt-1, Flk-1, and Flt-4. RESULTS Positive staining for VEGF-A to -D was observed in the endothelial cells of the abnormal vessels involved in the AVM nidus and in the cytoplasm of astroglia surrounding it. Samples from 30 (96.8%) of 31 patients stained positive for VEGF-A, 4 (9.7%) for VEGF-B, 17 (54.5%) for VEGF-C, and 16 (51.6%) for VEGF-D. Flt-1, Flk-1, and Flt-4 were also positive chiefly, but not exclusively, in the cytoplasm of vascular endothelium and smooth muscle cells of the vascular wall. With regard to VEGF receptors, it was found that among the 31 patients studied, 19 (61.3%) were immunohistochemically positive for Flt-1, 6 (19.4%) for Flk-1, and 19 (61.3%) for Flt-4. A comparison of mean nidus size and average age at operation revealed significant differences between patients positive for VEGF-C, VEGF-D, Flt-1, or Flt-4. In contrast, there were no significant differences in nidus size and age in patients positive for VEGF-A, VEGF-B, and Flk-1. CONCLUSION These results strongly suggest a possible contribution of the VEGF–VEGF receptor system to the growth of intracranial AVMs.

Malignant transformation of meningeal melanocytoma: a case report.

Intracranial meningeal melanocytoma is an uncommon tumor that is considered benign. We formerly reported an intracranial meningeal melanocytoma. Here we report a extremely rare case of malignant transformation of this tumor. A 49-year-old man complained of a headache. Magnetic resonance scanning revealed a mass in the left frontal region. The patient underwent gross total removal of the tomor in 1994. The histological findings showed a meningeal melanocytoma. In 1998, he underwent γ-knife surgery for local recurrence. An additional operation was performed in 1999 became tumor growth was not stopped. The tumor was partially excised by left frontal craniotomy. Histopathological examination revealed a malignant melanoma originating from a melanocytoma. The tumor was composed of a proliferation of severely atypical melanocytoid cells with slightly irregular nuclei and prominent nucleoli, associated with necrosis and hemorrhage. Mitotic figures were encountered occasionally. After six months, he died from cerebrospinal fluid dissemination of this tumor. To our knowledge, this is the first report of malignant transformation of an intracranial meningeal melanocytoma.

Epidemiological survey of Moyamoya disease in Korea

To both clarify the current clinico-epidemiological features of Moyamoya disease in Korea as well as compare these cases with Japanese patients, 451 cases were collected from 26 Korean major neurosurgical institutes and 296 definite cases were analyzed statistically. Although the Korean age distribution patterns of Moyamoya disease showed two peaks, similar to Japanese patients, the Korean pattern was shifted to the right thus indicating Korean adult population to be 20% higher than that of Japanese patients. The female/male ratio was 1:3, which was slightly less than that for Japanese. The family occurrence rate in Koreans was 1.8%. The incidence of cerebral infarction and bleeding in Koreans was higher while transient ischemic attack (TIA) and seizure were less than that of Japanese. The incidence of infarction in children and of hemorrhage in children and adults were also statistically higher in Koreans. The incidence of hemorrhage was higher in females than in males. Both the age at onset and sex affected the disease type. Single encephalo-duro-arterio-synangiosis (EDAS) was performed on 87.6% of all surgical cases. Although the incidence of bleeding was higher in Korea, the outcomes of the patients were similar to that of the Japanese patients. Although Korean Moyamoya disease showed a relatively higher incidence of hemorrhage and adult onset, the overall clinical background was similar to that of Japanese patients.

Clinical features of probable Moyamoya disease in Japan

To clarify the current clinical features of probable Moyamoya disease in Japan, 180 cases were analyzed based on the cases collected by the Research Committee on Spontaneous Occlusion of the Circle of Willis of the Ministry of Health and Welfare, Japan. Although the age distribution patterns of probable Moyamoya disease showed two peaks similar to that of definite cases, the pattern shifted to the right thus indicating a reversed children versus adult ratio. The female/male ratio was 1.65, which was not significantly different from that observed in definite cases. The family occurrence rate was 6.7%. The incidence of cerebral infarction and bleeding in probable cases was higher than that in definite cases. The incidence of hemorrhage was higher in females than in males. Angiographically probable cases were at earlier stages in comparison to definite cases. The rebuild-up phenomenon in electroencephalograms was less detectable than in definite cases. Surgical procedures were performed in 63.3% of all cases and approximately 81% of them underwent bypass surgery. Single encephalo-duro-arterio-synangiosis, direct bypass and combined bypass procedures were performed in 35, 40 and 25% of all surgical cases, respectively. Although the incidence of bleeding was higher in the probable cases, the outcomes of the patients were similar to that of the definite cases except for mortality. Approximately 7% of the probable cases developed into definite type within an average 6.6 year follow-up period. The majority of probable Moyamoya disease cases thus seems to have somewhat different clinical characteristics from the definite disease cases.

Atrial natriuretic polypeptides elevate the level of cyclic GMP in the rat choroid plexus

We studied the effect of synthetic rat alpha-atrial natriuretic polypeptide (1-28) (ANF-(99-126)) and related atrial natriuretic polypeptides on the accumulation of cyclic GMP (cGMP) in isolated rat choroid plexus in vitro, the objective being to determine whether ANF-(99-126) binding sites are physiologically active receptors. One microM of ANF-(99-126) increased the level of cGMP within 30 s and the accumulation reached the maximum level 5 min after adding of ANF-(99-126) to the incubation media. Significant increase in the level of cGMP depended on concentrations of the ANF-(99-126), ANF-(101-126) and ANF-(103-125), with a range of 10.0 nM to 10.0 microM. These data indicate that binding sites for ANF-(99-126) in the rat choroid plexus may be physiologically active receptors, possibly linked to the production of cerebrospinal fluid.

Striatal dopamine in acute cerebral ischemia of stroke-resistant rats.

We devised the present experiments to assess the effects of ischemia on the production of dopamine in the caudate nucleus of spontaneously hypertensive stroke-resistant rats. Ringers solution was continuously perfused at a rate of 10 microliters/min through 0.2-mm-diameter dialysis tubing implanted in the rats caudate nucleus. After bilateral occlusion of the common carotid artery, perfusate was collected at 20-minute intervals for 120 minutes and was analyzed for monoamines and their metabolites using high-performance liquid chromatography and an electrochemical detection system. The extracellular concentration of dopamine increased abruptly approximately 3 minutes after the ischemic insult, reached a maximum at between 20 and 40 minutes after the insult, and subsequently decreased. During the 120 minutes, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole-3-acetic acid concentrations decreased significantly, whereas 5-hydroxytryptamine was not detected. Our results indicate that during cerebral ischemia a large increase in extracellular dopamine concentration in the caudate nucleus occurs, probably as a result of energy failure of the cell membranes. This leakage of dopamine may be a causal factor in the neuronal damage associated with cerebral ischemia.

Meningeal melanocytoma in the left frontal region

We report a rare case of meningeal melanocytoma in the left frontal region. A 45-year-old man complained of a headache. Magnetic resonance (MR) scanning showed characteristic patterns: a slightly high signal intensity mass in the left frontal region on the T1-weighted image and a low signal intensity on the T2-weighted image. The patient underwent gross total removal of the tumor. The postoperative course was uneventful. After two years, there was a small local recurrence. The histological finding of the tumor showed meningeal melanocytoma. To our knowledge, this is the second published report of a meningeal melanocytoma in the supratentorial region.

α-Atrial natriuretic peptide binding sites in the rat choroid plexus are increased in the presence of hydrocephalus

Specific alpha-rat atrial natriuretic peptide(1-28) [ANF-(99-126)] (rANP) binding sites in the choroid plexus of rats with kaolin-induced hydrocephalus were analyzed following incubation of related tissue sections with 125I-rANP, then using autoradiography and an image analysis coupled with computer-assisted micro-densitometry. The number of 125I-rANP binding sites in the choroid plexus of these rats was significantly higher, as compared to findings in the control rats, whereas no differences in the binding affinity were observed, 3 days and 3 weeks after the intracisternal injection of kaolin. The possibility that atrial natriuretic peptide may play a significant role in the function of cerebrospinal fluid production by interacting with specific, high affinity receptors in the rat choroid plexus has to be considered.

Non-bifurcating cervical carotid artery

Three cases of an extremely rare anomaly of the carotid artery are described herein. In these patients, the common carotid arteries, without bifurcation in the cervical portion, supplied multiple arterial branches, which are more commonly branches of the external carotid artery. The non-bifurcating carotid artery continued into the cranium as a normal internal carotid artery. This anomaly can be attributed to a maldevelopment of the vascular network during embryogenesis.

Parinaud's syndrome in hydrocephalus due to a basilar artery aneurysm

A 65-year-old woman appeared with a progressive dementia, gait disturbance, and Parinauds syndrome. A computed tomography scan, an angiogram of the vertebral artery, and metrizamide ventriculography demonstrated a marked hydrocephalus. A giant aneurysm at the termination of the basilar artery projected into the third ventricle producing partial obstruction of the aqueduct. The symptoms were resolved by a ventriculoperitoneal shunt; but after a month, the patient again showed the upward-gaze palsies concomitant with occurrence of shunt malfunction. The possible mechanisms of Parinauds syndrome observed in the patient are discussed.