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Sesquiterpenes, such as zingiberene, β-elemene, α-bergamotene, β-caryophyllene and (E,E)-α-farnesene were identified as volatile organic compounds (VOCs) from the leaves of Polygonum longisetum treated with jasmonic acid (JA) exogenously. Sesquiterpenes were emitted with 1 μM JA, and their amounts and relative proportions altered according to the concentration. Experiments with silver thiosulfate (STS) suggested that ethylene might be involved in the JA-inducible emission of sesquiterpenes, but the responses of sesquiterpenes against STS were different among them. The conjugate of JA and 1-aminocyclopropane-1-carboxylic acid (JA-ACC) was also active in emitting sesquiterpenes, while conjugates of JA and amino acids, such as Leu, Ile and Val, were inactive. Mevastatin suppressed almost all the sesquiterpenes, but zingiberene and β-elemene were not fully suppressed. It was suggested that JA might stimulate both the mevalonate and methylerythritol pathways in P. longisetum.

This study reports for the first time the appearance, extent and duration of auditory neuron apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine angle cistern with intraoperative recordings of auditory nerve compound action potentials to ensure highly reproducible results. Rats were killed between days 0 and 14 after compression, and apoptosis of spiral ganglion cells (SGCs) was evaluated quantitatively and qualitatively. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from days 1 to 5, and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. These results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the cerebellopontine angle.

Although apoptotic changes in auditory neurons induced by injury to peripheral processes (dendrites) have been intensively studied, apoptotic changes in auditory neurons induced by injury to central processes (axons of spiral ganglion cells, SGCs) have not been reported previously, probably due to lack of an experimental model. The present study reports for the first time the appearance, extent, and time course of SGC apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine (CP) angle cistern with intraoperative recordings of auditory nerve compound action potentials (CAPs) to ensure highly reproducible results. Rats were killed between day 0 and day 14 after compression and apoptosis of SGCs was evaluated quantitatively as well as qualitatively by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, anti-activated caspase-3 immunostaining, Hoechst 33342 staining, and electron microscopy. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from day 1 to day 5 and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. The results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the CP angle.

A female infant was born with a left-sided glioblastoma that manifested clinically with weakened crying and feeding on day 1 of life, fever and bulging anterior fontanel on day 4, and right hemiparesis by day 10. Preoperative magnetic resonance imaging showed hemosiderin intensity indicating that hemorrhage had occurred during the prenatal period. Radical surgical removal of the tumor was performed on the 22nd postnatal day. Postoperatively, the right hemiparesis did not worsen and the patient did not have any new neurological deficits. The right hemiparesis gradually improved after her initial surgery, and she was able to stand by herself at 18 months of age. Adjuvant chemotherapy and radiation were administered. This patient survived for 27 months following birth, which is a relatively long time for glioblastoma cases. Radical removal at the first operation with reliance on the plasticity of infant cerebral function was the key point in the long survival.

Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal sub-arachnoid hemorrhage (SAH) are still controversial and uncertain. Experimental and clinical investigations of cerebral microcirculation after SAH were performed. Experimental SAH was produced by a canine two-hemorrhage method, and the dogs were perfusion-fixed at 3, 7 and 14 days after SAH. Specimens of the anterior sylvian gyri and pons were produced by three methods. Microvascular corrosion casts produced by arterial injection of polyester resin were examined by scanning electron microscopy (SEM). Sectioned slices parallel to the brain surface were examined by SEM and by light microscopy with morphometric analysis of the luminal diameter and wall thickness of the small arteries. Corrosion casts showed tapered narrowing in the arterioles and irregular width with folds in the perforating arteries 3 to 7 days after SAH. Sectioned slices showed increased wall thickness and decreased internal diameter of the arterioles and the perforating arteries 3 to 7 days after SAH. In cases with aneurysmal SAH, regional cerebral blood flow (rCBF) and digital subtraction angiography (DSA) were performed. Also, cerebral circulation time (CCT) obtained by analyzing the time–density curve of the contrast media on DSA images was evaluated in association with rCBF and angiographic vasospasm. In addition to correlation between the degree of angiographic vasospasm and rCBF, CCT showed strong inverse correlation with rCBF, and even in mild angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF. These results suggest that intraparenchymal small arteries decrease their caliber, which results in increased small-vessel resistance and affects cerebral ischemia during cerebral vasospasm.

Intraoperative monitoring of brainstem auditory evoked potentials (BAEP) has been widely utilized to reduce the incidence of postoperative hearing disturbance due to cerebellopontine angle manipulations. The prolongation of wave V of BAEP is usually used as a criterion to warn the surgeons to modify their surgical maneuvers. However, it is not known whether all neuropathological changes are avoided if BAEP latency intraoperatively returns to the baseline level or some neuropathological changes 'silently' occur even if BAEP normalizes. The aim of this study was to experimentally clarify this point that would be important for the long-term prognosis of patients' hearing. The cerebellopontine angle portion of the auditory nerve was quantitatively compressed in the rats and reversible prolongation of BAEP latency was reproduced just as it occurs during surgery in humans. Twenty-four hours after the compression, the auditory nerve was removed for beta-APP immunostaining to investigate the degree of axonal injury. The results of the present study disclosed that axonal injury occurred even in the cases where the intraoperative normalization of prolonged wave IV (equivalent to wave V in humans) latency had been obtained. Therefore, the interpretation of BAEP changes based only on the prolongation of the latency of BAEP was not enough to prevent the auditory nerve from developing morphological changes. Changes in the amplitude of wave V of BAEP appears to be more sensitive than its latency change as an intraoperative indicator for axonal injury in the auditory nerve.

Object. It has been empirically recognized that the cochlear nerve is highly vulnerable to traumatic stress resulting from surgical procedures; therefore, careful manipulation of the cochlear nerve is mandatory in preventing trauma-induced hearing loss during cerebellopontine angle (CPA) surgery. There is, however, no precise knowledge about the temporal pattern of cochlear nerve degeneration following trauma. This study was performed to determine the temporal pattern of injury that occurs after cochlear nerve trauma, knowledge of which is indispensable not only to neurosurgeons but also to all those who manage lesions involving the cochlear nerve. Methods. Right suboccipital craniectomies were performed in groups of rats with the aid of a surgical microscope, and the seventh and eighth cranial nerve trunks were identified at the internal auditory meatus. The cochlear nerve was quantifiably compressed while compound action potentials of the cochlear nerve were monitored and recorded. Following injury, one group of rats was killed for histological examination at the end of each week for 4 weeks. Data from this study disclosed that the degeneration of the compressed cochlear nerve progressed in a relatively rapid manner and was complete within 1 week after the insult. The main pathophysiological mechanisms responsible for cochlear neuronal death in this experimental setting appeared to be necrosis, and an apoptotic mechanism seemed to play a subsidiary role. Conclusions. Accurate knowledge about the temporal profile of trauma-induced cochlear nerve degeneration is closely linked with the problem of the therapeutic time window. The results of the present study indicated that any measures to ameliorate cochlear nerve degeneration following trauma should be started as early as possible (within 1 week) after an injury.

Object. Subarachnoid hemorrhage (SAH) caused by the rupture of a dissecting aneurysm of the internal carotid artery (ICA) has been considered rare. Based on data from cooperatively collected cases, the clinical features of patients with dissecting aneurysms of the ICA who presented with SAH were examined. Methods. Data from 18 patients with dissecting aneurysms of the ICA who presented with SAH diagnosed on the basis of clinical signs, neuroradiological findings, and intraoperative findings from 41 institutions were collected during a 5-year period between 1995 and 1999. The authors found that 0.3% of all cases of SAH and 3.1% of cases of SAH of unverified cause were attributable to a dissecting aneurysm of the ICA. Eleven patients (61%) were middle-aged women, and eight patients (44%) had hypertension. Rebleeding before admission was demonstrated in 13 patients (72%), and intraoperative bleeding was exhibited in half of the patients who underwent surgery during the acute stage. Postoperative growth of an aneurysm bulge or recurrent SAH was seen in five of 10 patients who had undergone wrapping or clipping of the aneurysm bulge in the acute phase. Trapping with or without bypass, which resulted in no postoperative recurrence, was performed in three patients in the acute stage and in two patients in the chronic stage. Twelve patients (67%) had a poor prognosis, primarily attributed to intraoperative bleeding and postoperative recurrence. Conclusions. Generally, dissecting aneurysms of the ICA are not thought of as frequent causes of SAH. Nonetheless, the presence of these aneurysms should be considered when dealing with SAH because they have a susceptibility to bleeding that can lead to a poor prognosis. Careful surgical planning is necessary to decrease intraoperative bleeding and to avoid postoperative recurrence.

Object: Despite their benign characteristics, meningiomas are often accompanied by perifocal brain edema. The aims of this study are to determine what kind of characteristics on magnetic resonance (MR) image are indicative of a meningioma that produces brain edema and to investigate the mechanism responsible for brain edema accompanying meningiomas. Methods: Fifty-one patients with meningioma were examined by magnetic resonance imaging (MRI), and tumor size, tumor location, shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2-weighted image (T2WI) were compared and correlated with the presence versus absence of brain edema. Surgical histopathology was also examined and correlated with the MRI findings and brain edema. Results: Shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2WI correlated with brain edema on multivariate analyses. Conclusion: Invasive pattern of brain–tumor interface and hyperintensity on T2WI were indicative factors of meningiomas producing brain edema.

Background and Purpose — Clinical features of nontraumatic dissecting aneurysms of intracranial carotid circulation remain unclear because investigation of this disease has been limited to case reports. The aim of this study was to investigate the clinical features of this disease through the use of cooperatively collected cases. Methods — The cases diagnosed as dissecting aneurysms of intracranial carotid circulation on the basis of clinical signs and neuroradiological findings in 46 stroke centers from 1995 through 1999 were collected, and their clinical features were analyzed. Results — Forty-nine cases of dissecting aneurysms of intracranial carotid circulation were collected. Thirty-two patients presented with subarachnoid hemorrhage (SAH), and 17 presented with cerebral ischemia. The ratio of this disease to all intracranial dissecting aneurysms treated in the same institutes for the same period was 19.1%, and the ratio of SAH resulting from this disease to SAH of unverified origin treated in the same institutes for the same period was 6.2%. The predominant site of lesion was the internal carotid artery in 18 of 32 patients (56%) with SAH and the anterior cerebral artery in 13 of 17 patients (76%) with cerebral ischemia. The predominant angiographic findings were that stenosis with dilatation occurred in 20 of 32 patients (63%) with SAH and stenosis without dilatation was seen in 11 of 17 patients (65%) with cerebral ischemia. Poor prognosis was seen in 21 of 32 patients (66%) with SAH, which was due largely to rebleeding seen preoperatively, during operation, and even postoperatively when clipping or wrapping of the aneurysmal bulge was performed. Conclusions — Nontraumatic dissecting aneurysm of intracranial carotid circulation is not as rare as expected. It seems to be one of the important causes of SAH of unverified origin.

An 18-year-old male presented with a pineal region germinoma with hearing impairment as the chief complaint. Magnetic resonance image demonstrated a well-enhanced multi-cystic tumor extending into the upper fourth ventricle and wall of the bilateral lateral ventricles. Audiometry revealed bilateral mild hearing impairment in the low frequencies. Auditory brainstem response recording showed low amplitudes in all waves (IV-V/I ratio < 1) with prolong latencies (I-V and III-V) on the right but no discernable wave at 60 dB clicks on left. Hearing impairment and audiometric findings were improved after ventriculoperitoneal shunt operation. The hearing impairment appeared to be a mixed (conductive and sensorineural) type. The tumor was responsible for the sensorineural deafness because of invasion and compression of the central auditory structures. The inferior brachium was maximally compressed anterolaterally by the dilated bilateral lateral ventricles and posteromedially by the tumor. Hydrocephalus caused conductive deafness by halting or arresting the footplate of stapes movement, as a consequence of high-pressure transmission through the cochlear aqueduct.

Background and Purpose — The incidence of subarachnoid hemorrhage (SAH) has been investigated in many studies. A recent study in Izumo, Japan, indicates that the incidence of SAH is as high as that in Finland. The purpose of this study was to confirm the high incidence of SAH in Japan. Methods — The incidence rate of SAH was investigated from 1989 through 1998 in the Shimokita peninsula, which is a clearly defined closed-boundary area in northern Japan with a population of 89 991. The registration was based on the complete referral system of SAH patients. All cases suspected of SAH underwent CT scan, and the images were referred to stroke specialists. The moribund cases and dead-on-arrival cases suspected of SAH also underwent CT scan. Results — From 1989 through 1998, 198 cases were diagnosed as having aneurysmal SAH. Out of these, 26 cases were moribund or dead when the initial CT scan was performed. The age-adjusted annual incidence of SAH was 21 per 100 000 person-years. The age and sex distribution of the cases indicated that the incidence plateaued after age 45 in men and the incidence increased after age 45 and reached the peak after 75 years in women. Conclusions — The high incidence of SAH in Japan is confirmed. The incidence of SAH obtained in this study is near to that of the Izumo study, of which the size of the geographic region and denominator and diagnostic criteria were similar to this study.

The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5–3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS.

Post-traumatic invasion of macrophages into the cochlear nerve of the rat and measurement of how their invasion was modified by the administration of methylprednisolone were investigated for the first time by using a reproducible and quantifiable experimental model of cochlear nerve injury. Two weeks after precise cochlear nerve compression, a massive invasion of ED1 immunostained macrophages was observed at the compressed portion of the cochlear nerve, and this invasion of macrophages was markedly reduced in the rats to which methylprednisolone had been administered during the pre- and post-compression period. Concomitantly, the residual number of spiral ganglion cells was found to be greater in the compression+methylprednisolone group than in the control compression group. The tissue loss observed in the lesion epicenter was also significantly less in the compression+methylprednisolone group than in the control compression group. The results of our present study demonstrated the effectiveness of methylprednisolone treatment to ameliorate trauma induced cochlear nerve degeneration in the acute phase. However, these results may reflect the sum effects of methylprednisolone on macrophages, including both its beneficial effect by inhibiting the negative aspects of macrophages through attenuating macrophage recruitment to the lesion site, and at the same time an undesirable effect by sacrificing the positive aspects of macrophage function. Moreover, one reservation should be added that the protective effects of steroid to injured cochlear nerve may have operated via a pathway not related to macrophage function. Besides macrophages, various cells and factors participate in the process of CNS injury, and their effects may potentially work either positively or negatively with respect to CNS protection and regeneration at each particular time during the on-going process of CNS injury. Therefore, future investigation in CNS injury should be directed toward understanding such complex mechanisms involved in this process.

We investigated whether methylprednisolone sodium succinate can ameliorate cochlear nerve degeneration following compression injury on the cerebellopontine angle portion of the cochlear nerve, using a quantitative animal experimental model that we have developed recently. In this model, cochlear nerve degeneration after compression could be quantitatively evaluated, while cochlear ischemia induced by the compression carefully maintained below the critical limit that causes irreversible damage to the cochlea. Eleven rats were treated with methylprednisolone during the pre- and post-compression period. Two weeks after compression, the numbers of SGC were compared between the rats that received the compression without and with methylprednisolone treatment. Methylprednisolone treatment improved the survival of SGC following cochlear nerve injury statistically highly significantly in the basal turn where the traumatic stress had been less than in the other cochlear turns in our experimental setting. Although it was not statistically significant, greater survival was also observed in the other cochlear turns. The results of this experimental study indicated that at least a portion of injured cochlear nerve had been potentially treatable, and that methylprednisolone might prevent such cochlear neurons from entering into the vicious process of irreversible damaging process.

Background and Purpose —Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF). Methods —In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm. Results —Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen ( r =0.429, P =0.0006). Peripheral CCT showed strong inverse correlation with rCBF ( r =−0.767, P Conclusions —In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.

During a recent 10-year period, the incidence and risk factors of aneurysmal subarachnoid hemorrhage (SAH) in Shimokita area of Aomori prefecture was investigated. A total of 195 patients were registere, and the age-adjusted annual incidence was 20.7 per 100, 000 population. The age-specific annual incidences ranged from 32 to 40 per 100, 000 population at the age of 40-79 years in men. In Women, they became higher with increasing age, and revealed a peak, which was around from 60 to 70 per 100, 000 population after the sixth decade of life. This results suggested that Japan has much high incidence of SAH compared with other countries.Case-control study was performed to evaluate the risk factors of SAH. Hypertension, cigarette smoking were a risk factor for both men and women. Alcohol consumption over 500 g/week was a risk factor for men, and familial history of SAH was a risk factor for women. The same factors can be risk factors in Japan as in other countries.

A 72-year-old man developed left facial palsy at age 14 and left-sided hearing loss at age 20. At the age of 59, he presented with gait disturbance, and a large left cerebellopontine angle tumor was detected, which had markedly destroyed the pyramidal bone. The tumor was subtotally resected, but he required two more operations at the ages of 64 and 69 because of tumor regrowth. At the present time, recurrent tumor has destroyed the occipital bone and is invading the scalp. However, even though he has several cranial nerve palsies and cerebellar ataxia, he remains in stable condition and demonstrates long-term survival. The patient's surgical specimens revealed a papillary adenoma, which was recently thought to be of endolymphatic sac origin, although the origin of this kind of tumor, whether arising from the middle ear or from the endolymphatic sac, has not been established with certainty so far. In this paper, we provide further evidence that this tumor originates from the endolymphatic sac, based on anatomical, histopathological, and embryological evidence.

OBJECTIVE Morphological and microcirculatory changes in intraparenchymal vessels after subarachnoid hemorrhage (SAH) have not yet been fully clarified. We conducted this experimental study to investigate the serial morphological changes of intraparenchymal arterioles after SAH. METHODS SAH was produced by injecting autologous arterial blood into the cisterna magna twice at 48-hour intervals in 30 dogs. The dogs were killed 3, 7, or 14 days after SAH, and then perfusion-fixed specimens of both anterior sylvian giri were obtained by using two methods. Microvascular corrosion casts produced by arterial injection of polyester resin were examined using scanning electron microscopy, and the widths of 40 arterioles of each animal were measured. Sectioned slices from the brain surface to 500 microns deep were examined by light microscopy, and external diameter, internal diameters, and wall thickness of the arterioles at depths of 50, 200, and 500 microns from the brain surface were morphometrically evaluated in 40 arterioles of each animal. In control animals receiving cisternal injections of mock cerebrospinal fluid (n = 10) and in healthy control animals (n = 10), the same examination and evaluation were performed. RESULTS Corrosion casts of arterioles showed tapered narrowing with folding after SAH, and the width of the arterioles significantly decreased 3 and 7 days after SAH (P < 0.01). Morphometric examination by light microscopy showed a significant decrease of internal diameter of arterioles associated with a significant increase of wall thickness at any depth from the brain surface 3 and 7 days after SAH (P < 0.05 or P < 0.01). These findings improved 14 days after SAH. Control animals receiving cisternal injections of mock cerebrospinal fluid showed no significant differences compared with healthy control animals. CONCLUSION These results suggest that constriction of intraparenchymal arterioles occurs after SAH and may contribute to delayed cerebral ischemia.

BACKGROUND Although dissecting aneurysm of vertebral artery is known as one of the causes of subarachnoid hemorrhage (SAH) in the posterior circulation, the best surgical treatment method remains controversial. METHOD AND RESULT This 64-year-old woman was admitted to our service with headache due to SAH caused by a ruptured vertebral dissecting aneurysm in the distal portion of the posterior inferior cerebellar artery. After confirming tolerance of parent artery occlusion by temporary balloon occlusion, both the dissection site and the proximal portion of the parent artery were occluded completely by interlocking detachable coils (IDCs) without any ischemic complications. The patient was discharged without any neurologic deficit on the 25th day after the therapy. CONCLUSION The goal of treatment for the ruptured dissecting aneurysm is isolation of the dissection site from the circulation to prevent rerupture. In our case, endovascular occlusion with IDCs was sufficient to reach the goal. In cases with difficulties in the surgical approach, embolization of the dissection site with IDCs should be considered.

Cadherins are Ca(2+)-dependent cell adhesion molecules that play an important role in tissue formation and morphogenesis in multicellular organisms. In recent years, there have been reports of cadherin involvement in tumor invasion and metastasis. Twenty-two surgical specimens and some cultured cells were studied by immunohistochemical staining. No significant difference was observed in the patients with anaplastic astrocytoma, whereas decreased expression of N-cadherin was detected at the time of recurrence in those with glioblastoma. In these groups, cerebrospinal fluid dissemination was found, and contralateral cerebral metastases and extracranial metastases were observed. We conclude that decreased N-cadherin expression at the immunohistochemically demonstrated time of recurrence correlates with tumor invasion and dissemination of cerebrospinal fluid.

脳虚血発作の22から39％は心原性の塞栓が原因と考えられているが, その診断は塞栓や塞栓形成のrisk factorの把握に限界があるためしばしば困難である.特に洞調律でtransthoracic echocardiogram (TTE) では所見が見られない症例で, 頚動脈病変を認めない症例では診断法に苦慮するのが現状である.このような脳虚血の原因が確定していない脳梗塞患者において, 本研究ではtransesophageal echocardiography (TEE) による心疾患の診断を検討している.対象は次のcriteriaを満たした30症例である.1) 神経脱落症状が24時間以上続いたcompleted ischemic stroke, 2) 洞調律, 3) TTEで心原性塞栓の発生に関連する心疾患を有しない, 4) 頚動脈狭窄病変を超音波ドップラー検査で認めない.TTEは2.5MHzまたは3.5MHzのtransducer (Interspec Apogee CX200, Acuson 128 XP/10) を用いている.TEEは5MHzのmonoplane transducer (Interspec Apogee CX) および, biplane transducer (Acuson 128 XP/10) を使用している.TTEでは30人中16人で異常 (高血圧に伴った左心室肥大が11例, 心筋梗塞の既往のある患者で部分的なwall motionの異常が4例, 弁の石灰化9例, 大動脈弁閉鎖不全2例, 僧帽弁閉鎖不全4例, 僧帽弁逸脱1例) を見ているが, 塞栓はまったく検出されていない.一方, TEEではこの30例のうち3例に左心房先端の血栓, 2例に心房中隔動脈瘤, 7例に卵円孔開存, 19例に大動脈の血栓が描出されている.左心房先端の血栓の見られた3例では, 治療法を変更し内服薬による抗凝固療法が追加されている.左心房先端の血栓が正常洞調律の患者に出来る原因としては, ホルター心電図でも検出されないような間欠的な心房細動の出現, 左心房内圧の上昇による左心房の機能不全, 凝固機能の異常などをあげている.以上よりTEEはTTEで頚動脈に明らかな脳虚血を来たす原因が認められず, しかも正常洞調律を有する脳虚血発作症例での塞栓源となる心臓内の病変を検出する有用な補助診断であることが示唆されている.従ってこの診療法により, 従来原因不明とされた脳虚血発作症例に対する治療法にも新たな情報提供も期待される.

Two cases of spontaneous rupture of cystic craniopharyngioma without chemical meningitis are described. A 70-year-old woman complained of headache and visual field disturbance in July 1993. The tumor was extirpated in November 1993 and again in December 1996. After regular periodic follow-up evaluation, she was hospitalized for reoperation because of expansion of the cyst on magnetic resonance (MR) imaging in November 1998. However, preoperative MR imaging taken 8 weeks later revealed spontaneous reduction of the cyst. A 69-year-old woman noticed deteriorating vision and bitemporal hemianopsia in November 1998. The tumor was removed in December 1998, and 50.4 Gy postoperative radiotherapy was administered. MR imaging in May 2000 demonstrated an enlargement of the cyst, so she was hospitalized again for operation. However, preoperative MR imaging taken 7 weeks later showed spontaneous reduction of the cyst. Neither of the cases of cyst rupture were accompanied by symptoms of chemical meningitis. The signal intensity of the tumors on T1-weighted MR imaging declined after cyst reduction. Thereafter, the cysts increased in size again at 7 months and 5 months. Regular follow-up on MR imaging is necessary, since the cyst size can increase rapidly, even after spontaneous rupture.

To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage.

微かな頭蓋内圧上昇及び脳室拡大によって意識状態の明らかな低下を示した高齢脳出血症例について報告し, 高齢者脳の頭蓋内圧変化への低対応性を示した.患者は76歳女性で脳室穿破を伴う脳出血後, 微かな脳室拡大によると思われる意識及び呼吸障害を来した.脳室ドレナージによって症状の改善した後, この設定圧を100mmH2Oから120mmH2Oへ上げただけで再度意識障害が出現し, 低圧チューブを用いての腰椎一腹腔シャント術によって再び意識レベルの改善を得た.本症例は高齢者脳の圧脆弱性の具体的一面を示すものと考えられた.

A comparative investigation of the pathogenetic factor in symptomatic cerebral vasospasm was made by quantitative histological and clinical studies in four patients who died immediately of symptomatic cerebral vasospasm (Cases 1-4) and in two who died without fatal cerebral vasospasm (Cases 5 and 6). Histological examination of the brain from Cases 1 and 2 found many white and fibrin microthrombi together with ischemic and infarctic changes in the territories of spastic arteries, which corresponded to the low-density areas (LDAs) observed on computed tomographic (CT) scans and the typical neurological symptoms. In Case 3, who had suffered severe vasospasms in bilateral anterior cerebral and middle cerebral arteries, bilateral LDAs were observed on CT scans and multiple fibrin thrombi were seen diffusely throughout the brain. In Case 4, extensive bilateral LDAs (lt greater than rt) were observed on CT scans, and multiple microthrombi were seen diffusely but predominantly in the left cerebral hemisphere. Only in Case 3 the possible complication of disseminated intravascular coagulation could not be ruled out. Only negligible thrombi were observed in Cases 5 and 6, whose immediate cause of death was considered to be acute hydrocephalus and aneurysmal rerupture, respectively. Distributions of microthrombi were significantly greater in the regions clinically identified to have been ischemic or infarctic.

✓ The authors describe the histopathological findings in a case involving rerupture of a recanalized aneurysm of the internal carotid artery 8 months after partial (95%) embolization with interlocking detachable coils. The aneurysm was filled with poorly organized thrombus, and its orifice was devoid of endothelial cells. It appears likely that a long period of observation may be required to confirm the complete thrombotic organization of coil-embolized aneurysms. This indicates that caution is needed because rupture may follow recanalization of the aneurysm.

A case of 52-year-old female presented with dysarthria and paresis of right upper extremity 3 years after an operation and chemotherapy for uterine leiomyosarcoma. Magnetic resonance imaging showed an enhanced mass in the left corona radiata. Brain biopsy was carried out and pathological examination of the specimen showed features of a leiomyosarcoma. Uterine leiomyosarcoma is an uncommon tumor and its metastasis to the brain is rare. Only 13 other cases have been published. The patient underwent gamma-knife therapy and obtains good quality of life.

Background— Local renin-angiotensin systems (RAS) have been implicated as playing an important role in vascular remodeling. The relationship of this system to the etiology of cerebral aneurysm was investigated. Methods and Results— The aneurysmal wall from patients with a ruptured or unruptured cerebral aneurysm and the cortical cerebral artery in control patients with head trauma or a glioma were taken during surgery for study. Local RAS were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry. RT-PCR analysis revealed a significantly decreased expression of angiotensin-converting enzyme (ACE), angiotensin type 1 (AT 1 ) receptor, basic fibroblast growth factor, platelet-derived growth factor-AA, and tissue inhibitor of matrix metalloproteinases-1 mRNA in the aneurysmal wall as compared with the control cortical arterial wall. Immunohistochemistry also revealed a decreased expression of ACE, AT 1 receptor, and angiotensin II in the aneurysmal wall. Conclusion— Expression of local RAS was decreased in the aneurysmal wall, which may induce aneurysm formation caused by a lack of vascular remodeling that prevents the arterial wall from thickening under increased hemodynamic stress. This is the first report that suggests that a decreased expression of local RAS plays a part in the pathogenesis of any disease.

Cerebral microcirculatory changes are an important factor regulating cerebral blood flow. The aim of this study was to investigate the possibility of phenotypic modulation of smooth muscle cell (SMC) and vascular remodeling of intraparenchymal small cerebral arteries after subarachnoid hemorrhage (SAH). Seven to 14 days after canine experimental SAH, in intraparenchymal perforating arteries, the amount of beta-actin mRNA evaluated by Northern blot analysis increased, the structural change of the 3' untranslated region of beta-actin mRNA detected by polymerase chain reaction analysis was enhanced, and immunohistochemistry showed marked induction of the embryonal isoform of myosine heavy chain accompanied by decreased expression of smooth muscle myosin heavy chain (SM2). Histological morphometric analysis showed an increase in the area of the arterial wall without changes in the number of nuclei of SMC. This is the first report suggesting that vascular remodeling accompanied by phenotypic modulation occurs in intraparenchymal small arteries. These changes may affect cerebral blood flow after SAH by inducing increased cerebrovascular resistance.

Background and Purpose— Thrombin is activated in the cerebrospinal fluid (CSF) after a subarachnoid hemorrhage (SAH). However, the relationship between thrombin and cerebral vasospasm has not yet been fully established. The aim of this study was to investigate the possibility of thrombin as a causative factor for cerebral vasospasm and to delineate the signal transduction mechanism that results in thrombin-inducing sustained vasoconstriction in cerebral vasospasm. Methods— In the SAH group, SAH was simulated by the 2-hemorrhage rabbit model. In the treatment group, antithrombin III (AT-III) was injected into the cisterna magna just before production of the SAH. CSF samples were obtained serially to measure d -dimer with latex photometric immunoassay. On day 4, the basilar artery was excised after perfusion-fixation. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar arterial lumen, and the expression of mitogen-activated protein kinase (MAPK) in the vascular wall was examined with an immunohistochemical technique. Results— In the treatment group, the value of d -dimer on day 4 was 0.83±0.07 μg/mL, which was statistically significantly lower than that in the nontreated SAH group (2.49±0.09 μg/mL, P 5± 1.58×10 4 square pixels, which was statistically significantly larger than that in the nontreated SAH group (2.60×10 5± 2.29×10 4 square pixels; P Conclusions— Inhibition of thrombin activity leads to amelioration of cerebral vasospasm and suppression of MAPK diphosphorylation. This suggests that thrombin and its related signal transduction, including the MAPK cascade, appear to play an important role in the pathogenesis of cerebral vasospasm after SAH.

The fungal derived nitric oxide donors, (E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl]-3-pyridinecarboxamide (FR144420), were evaluated for the treatment and prevention of cerebral vasospasm induced by subarachnoid hemorrhage (SAH) by an in vitro study using rabbit basilar artery. The tension-relaxation of a 3 mm-long artery segment was carried out in a micro-tissue organ bath with a real-time recorder to record the tension-relaxation curve. Steady contraction of the specimens was induced by KCI (n = 12) and oxyhemoglobin (oxyHb) (n = 12). Sodium nitroprusside was used for comparison. Each of the agents was added in ascending concentration. Relaxation caused by FK409 and FR144420 was significantly greater (p < 0.05) than that by sodium nitroprusside. Relaxation effects of FK409 and FR144420 on the KCl-induced steady contraction were better than those on the oxyHb-induced contraction. FK409 and FR144420 have potential uses for the treatment and prevention of SAH-induced cerebral vasospasm.

Background: Though atherosclerosis is generally regarded as a risk factor for stroke, its quantitative assessment in patients with stroke has not yet been reported. Recently, the ankle brachial index (ABI) has been receiving increasing attention as a noninvasive measurement of atherosclerosis. In this study, we investigated ABI to determine the degree of atherosclerosis in patients with stroke. Methods: ABI was measured in 114 patients who had suffered a stroke, and the significance of differences between the ABI of the stroke subgroups and that of the normal group was investigated. The correlation of ABI with the degree of cerebral artery stenosis was also investigated. Results: There was no significant difference in ABI between the hemorrhagic groups and the normal group, but in the infarction group (p = 0.0002) ABI was significantly less than the normal group. ABI was significantly correlated with the degree of stenosis in the intracranial internal carotid artery and middle cerebral artery (p < 0.0001, respectively). Conclusions: A strong relationship between ischemic stroke and atherosclerosis was demonstrated quantitatively by ABI measurement. A decrease in ABI may be a risk factor for ischemic stroke.

Two cases of spontaneous rupture of cystic craniopharyngioma without chemical meningitis are described. A 70-year-old woman complained of headache and visual field disturbance in July 1993. The tumor was extirpated in November 1993 and again in December 1996. After regular periodic follow-up evaluation, she was hospitalized for reoperation because of expansion of the cyst on magnetic resonance (MR) imaging in November 1998. However, preoperative MR imaging taken 8 weeks later revealed spontaneous reduction of the cyst. A 69-year-old woman noticed deteriorating vision and bitemporal hemianopsia in November 1998. The tumor was removed in December 1998, and 50.4 Gy postoperative radiotherapy was administered. MR imaging in May 2000 demonstrated an enlargement of the cyst, so she was hospitalized again for operation. However, preoperative MR imaging taken 7 weeks later showed spontaneous reduction of the cyst. Neither of the cases of cyst rupture were accompanied by symptoms of chemical meningitis. The signal intensity of the tumors on T1-weighted MR imaging declined after cyst reduction. Thereafter, the cysts increased in size again at 7 months and 5 months. Regular follow-up on MR imaging is necessary, since the cyst size can increase rapidly, even after spontaneous rupture.

A 32-year-old female presented with a rare case of pituitary abscess manifesting as homonymous hemianopsia. Serum prolactin level was slightly high (40.8 ng/ml). Magnetic resonance (MR) imaging showed the content of the lesion as homogeneously isointense on the T1-weighted images and hyperintense on the T2-weighted images. The capsule of the lesion, which appeared thin and smooth, was enhanced by gadolinium. Dural enhancement around the sella turcica was also recognized. Thallium-201 single photon emission computed tomography (201Tl SPECT) showed homogeneous high accumulation in the pituitary region on both the early and delayed images. The lesion was treated via a transnasaltranssphenoidal approach. The cystic lesion contained pus and the capsule consisted of normal pituitary gland with inflammatory changes. The patient was treated with antibiotics for 3 weeks and the pituitary abscess was cured completely. Pituitary abscess can be differentiated from pituitary adenoma as lesion with a homogeneous high uptake on 201Tl SPECT on both the early and delayed images, and no enhancement of the central portion on MR images.

Background and Purpose— Japan is known to have an incidence of aneurysmal subarachnoid hemorrhage (SAH) as high as that in Finland, where SAH is especially common. However, the risk factors for SAH in Japan are unknown. The purpose of this study was to identify the risk factors and then examine their possible roles in cases of SAH in Japan. Methods— Case-control data were collected in the Aomori prefecture between June 2000 and May 2001 and in the Shimokita area between 1989 and 1998. A history of hypertension, cigarette smoking, alcohol consumption, hypercholesterolemia, and diabetes mellitus were examined as possible risk factors for SAH by using stepwise logistic regression analysis. Results— Stepwise logistic regression analysis showed that a history of hypertension and current smoking increased the risk of SAH and that a history of hypercholesterolemia decreased the risk of SAH. Alcohol consumption and a history of diabetes mellitus were excluded from the model, because their log-likelihood ratios were not significant. The adjusted odds ratios, obtained by forcing matching factors, were 2.29 for a history of hypertension (95% CI, 1.66 to 3.16), 3.12 for current smoking (95% CI, 2.05 to 4.77), and 0.41 for a history of hypercholesterolemia (95% CI, 0.24 to 0.71). The prevalence of hypertension in control subjects was 27% in men and 31% in women, whereas the prevalence of cigarette smoking in control subjects was 46% in men and 9% in women. Conclusions— Hypertension and cigarette smoking seem to be independent risk factors for SAH in Japan. The high prevalence of hypertension in both sexes and the high prevalence of cigarette smoking in men in the general population might contribute to the high incidence of SAH in Japan.

A classification system for vestibular schwannomas (VSs) is proposed, whereby VSs are classified first by location, and then by extent. This system is proposed because traditional classifications of VSs do not comprehensively describe lesions that grow in different patterns after arising in regions as diverse as the cerebellopontine (CP) angle, the internal auditory canal, and the region lateral to the fundus of the internal auditory canal (labyrinth). The proposed system provides surgeons information helpful in choosing the surgical approach, in estimating the difficulty of tumor excision, and in determining whether hearing might be preserved. The system also avoids confusion and misunderstanding in discussion of treatment results because it reflects the diverse biological characteristics of VSs.

There are few reported cases of nontraumatic dissecting aneurysms of the middle cerebral artery (MCA), and their neuroradiological and clinical features have not been analysed. We looked at these aspects in a collaborative study. We reviewed 13 patients diagnosed as having a dissecting aneurysm of the MCA based on clinical signs and neuroradiological findings in 46 stroke centres between 1995 and 1999. There were four patients who presented with cerebral ischaemia, and nine who presented with bleeding. Of the former group, three were aged less than 15 years. Cerebral angiography showed extensive stenosis and a double lumen of the M1 portion in all four patients. High signal on T1-weighted images around the arterial flow void, due to intramural haematoma, was often seen in the second week. MR angiography showed findings corresponding those of intra-arterial angiography in all four cases. We saw an infarct on CT or MRI in territory of the perforating branches of the M1 segment in all four patients. In the patients presenting with bleeding, pure subarachnoid haemorrhage or a sylvian fissure haematoma was seen on initial CT, and the predominant angiographic finding was dilatation with stenosis, but the site of the lesions was not uniform. A double lumen or intimal flap was seen in about half the cases. Rebleeding occurred within 14 days of the onset in five of the nine patients, with a poor prognosis.

An 18-year-old male presented with a pineal region germinoma with hearing impairment as the chief complaint. Magnetic resonance image demonstrated a well-enhanced multi-cystic tumor extending into the upper fourth ventricle and wall of the bilateral lateral ventricles. Audiometry revealed bilateral mild hearing impairment in the low frequencies. Auditory brainstem response recording showed low amplitudes in all waves (IV-V/I ratio1) with prolong latencies (I-V and III-V) on the right but no discernable wave at 60 dB clicks on left. Hearing impairment and audiometric findings were improved after ventriculoperitoneal shunt operation. The hearing impairment appeared to be a mixed (conductive and sensorineural) type. The tumor was responsible for the sensorineural deafness because of invasion and compression of the central auditory structures. The inferior brachium was maximally compressed anterolaterally by the dilated bilateral lateral ventricles and posteromedially by the tumor. Hydrocephalus caused conductive deafness by halting or arresting the footplate of stapes movement, as a consequence of high-pressure transmission through the cochlear aqueduct.

Despite their benign characteristics, meningiomas are often accompanied by perifocal brain edema. The aims of this study are to determine what kind of characteristics on magnetic resonance (MR) image are indicative of a meningioma that produces brain edema and to investigate the mechanism responsible for brain edema accompanying meningiomas.Fifty-one patients with meningioma were examined by magnetic resonance imaging (MRI), and tumor size, tumor location, shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2-weighted image (T2WI) were compared and correlated with the presence versus absence of brain edema. Surgical histopathology was also examined and correlated with the MRI findings and brain edema.Shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2WI correlated with brain edema on multivariate analyses.Invasive pattern of brain-tumor interface and hyperintensity on T2WI were indicative factors of meningiomas producing brain edema.

Background Friction injury of cortical surface or cerebrospinal fluid leakage are the major complications of polytetrafluoroethylene (ePTFE) duraplasty because of their strong surface tension and lesser adaptability. Autologous duraplasties are also accompanied by potential donor-site complications and are inappropriate for large defects. Acellular Dermal Graft (ADG), prepared from cadaver human skin, does not have the above-mentioned drawbacks because of its human nature. Moreover, the dermal basement membrane and supporting tissues remain intact, so the rate of cellular migration and transformation to the surrounding host tissue is supposed to be excellent. We studied ADG in canine model to observe the rate of transformation into the surrounding dura mater via collagen synthesis from the invaded fibroblasts to evaluate its usefulness as a duraplasty. Methods Dural grafting surgery was performed on 6 adult mongrel dogs weighing from 8 to 12 kgs under general anesthesia. Three dogs were sacrificed after 1 month (acute) of surgery and the other three (chronic) were sacrificed after 3 months with overdose of pentobarbital sodium. Transcardiac perfusion-fixation with 4% paraformaldehyde was done. Hematoxylin-eosin and trichrome masson stains were performed to see the graft cellularity. Thickness of grafts was also assessed along the length of the histologic sections. Results Duralization, which was microscopically characterized by infiltration with regular array of collagen fibers, was observed at a few places in every high-power field in acute group. But in chronic animals, where dermal side of ADG was facing towards cranium, duralization was excellent. Conclusions Our result suggests that ADG can be considered as a useful dural substitute.

We report successful operations for a meningeal hemangiopericytoma using sufficient amounts of Preoperative Autologous Transfusion (PAT) and Hemodilutional Autologous Transfusion (HAT). A 23-year-old woman with amenorrhea and bilateral visual field disturbance was found to have a huge intracranial tumor. MRI showed a well-enhanced cystic mass in the left middle fossa, suprasellar, intrasellar, sphenoidal sinus, and cavernous sinus. Preoperatively, the tumor was thought to be a cystic pituitary tumor or meningioma. Surgical removal was planned in three steps. The first operation was carried out via the transsphenoidal approach. Total blood loss was 1348 ml and 2 MAP infusion were required to control bleeding. Histopathological diagnosis was hemangiopericytoma. After preparation of PAT 400 ml and HAT 800 ml, we carried out the second partial removal operation mainly via the interhemispheric approach. Total blood loss was 1829 ml and required autologous transfusion only. After preparation of PAT 1200 ml and HAT 400 ml, the last total removal operation was carried out mainly via the pterional and subtemporal approach. Total blood loss was 1813 ml and required autologous transfusion only. We needed 2 MAP infusion in the first operation, but were able to perform total removal successfully without homologous blood transfusion because a sufficient amount of PAT and HAT had been prepared preoperatively. Hemangiopericytoma required postoperative radiation therapy to avoid local recurrence. After successful removal of the tumor surgically, postoperative radiation therapy was able to be carried out efficiently.