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Objective To investigate healthcare resource utilization and changes in functional status in stroke patients during hospitalization in an acute hospital and a rehabilitation hospital. Design Retrospective cohort study. Setting One acute and one rehabilitation hospital in Japan. Participants Patients who were admitted to the acute hospital due to stroke onset and then transferred to the rehabilitation hospital ( n = 263, 56% male, age 70 ± 12 years). Main outcome measures Hospitalization costs and functional independence measure (FIM) were evaluated according to stroke subtype and severity of disability at discharge from the acute hospital. Results Median (IQR) costs at the acute hospital were dependent on the length of stay (LOS) and implementation of neurosurgery, which resulted in higher costs in subarachnoid hemorrhage [$52 413 ($49 166–$72 606) vs $14 129 ($11 169–$19 459) in cerebral infarction; and vs $15 035 ($10 920–$21 864) in intracerebral hemorrhage]. The costs at the rehabilitation hospital were dependent on LOS, and higher in patients with moderate disability than in those with mild disability [$30 026 ($18 419–$39 911) vs $18 052 ($10 631–$24 384)], while those with severe disability spent $25 476 ($13 340–$43 032). Patients with moderate disability gained the most benefits during hospitalization in the rehabilitation hospital, with a median (IQR) total FIM gain of 16 (5–24) points, compared with a modest improvement in patients with mild (6, 2–14) or severe disability (0, 0–5). Conclusions The costs for in-hospital stroke care were substantial and the improvement in functional status varied by severity of disability. Our findings would be valuable to organize efficient post-acute stroke care.

Cerebral aneurysms causing visual symptoms before surgery are relatively rare. We have experience with 17 cases of such aneurysms and report their clinical features and surgical outcome. The locations of aneurysms presenting with visual dysfunction in our series are as follows: internal carotid (IC)-cavernous aneurysms in six of 29 total cases, 21%; IC-ophthalmic aneurysms in nine of 36 total cases, 25%; and anterior communicating artery (A com A) aneurysms in two of 217 total cases, 1%. The size of the aneurysms, the period between the onset of symptoms and surgical treatment, the pre- and post-operative visual function, and the surgical methods used to treat the aneurysm were analyzed. All the visually symptomatic cases featured large (15-24 mm) or giant (> 25 mm) aneurysms. Visual symptoms occurred before aneurysmal rupture in all cases but one. The type of visual field defect and the degree of reduced visual acuity were highly variable, without a typical clinical presentation. Five out of six IC-cavernous aneurysms were treated surgically with common carotid artery (CC) ligation or IC ligation with superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis. Three of these cases showed improvement of visual symptoms after surgery. Six out of nine IC-ophthalmic aneurysms were treated surgically (CC ligation or direct clipping), with four cases showing improvement of visual symptoms after surgery. One case of an A com A aneurysm featured a ruptured aneurysm that had physically penetrated the optic chiasm, while the other case was a giant unruptured aneurysm. The interval between the onset of symptoms and surgical treatment was the only factor identified which affected the clinical outcome of the aneurysms presenting with visual dysfunction. All cases that were determined to show improvement of visual function were treated surgically within 3 months of the onset of symptoms. Cerebral aneurysms presenting with visual dysfunction before surgery are most commonly large or giant, and unruptured. Recovery of visual function can most often be expected when surgical treatment is performed expeditiously, before the visual dysfunction becomes irreversible.

Only small amounts of superoxide dismutase (SOD) are present in the extracellular space to scavenge excess amounts of superoxide anions (02-) released after traumatic brain injury (TBI). Experiments were performed in rats with cerebral contusion produced by weight-drop technique. We investigated the effects of exogenous lecithinized SOD (PC-SOD) on accumulation of 02- produced in our model, by measuring the level of SOD activity (using the NBT-reducing method) and the expression of copper, zinc-SOD (Cu, Zn-SOD) mRNA (by Northern blot analysis). As determined by tissue-specific gravity, administration of PC-SOD reduced brain edema in the periphery of the lesion 6 h after contusion. SOD activity increased in the peripheral region at 30 min after contusion, but returned to normal levels at 6 h after TBI. Administration of PC-SOD increased SOD activity up to 6 h after TBI. The expression of Cu, Zn-SOD mRNA increased in the core region, peripheral portion, and contralateral hemisphere up to 6 h after TBI, then was suppressed in all three regions by PC-SOD. Our results confirm the important role of 02- in the development of brain edema after TBI and indicate that PC-SOD diminishes brain edema through a protective effect against 02-.

Background and Purpose Although it has been suggested that collagen plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no constructive research to prove it directly. In this study we stopped the transcription of the procollagen type I gene by introducing antisense oligonucleotides for its mRNA in a rat femoral artery model of vasospasm induced by blood and assayed the changes in the vasoconstrictive activity of the vessel and expression of the procollagen mRNA. Methods We applied antisense, sense, or missense oligonucleotides, located at the carboxyl propeptide region for α1(I) procollagen mRNA, onto the femoral artery in a rat femoral artery model of vasospasm. The diameter of the artery was measured by angiography. The transcription level of the procollagen gene in the arterial tissue was assayed by use of reverse transcription–polymerase chain reaction. Morphological change in the artery was observed with aldehyde-fuchsin-Masson-Goldner staining. Results In the model, when the artery was exposed to antisense oligonucleotides in pluronic gel for 5 days to prevent arterial contraction, the contraction was inhibited at a significant level (76.0%±5.6) when compared with that in control experiments using sense oligonucleotides (64.0%±2.4), missense oligonucleotides (63.5%±3.5), or gel alone (62.1%±5.8). The application of antisense oligonucleotide resulted in a marked decrease in α1(I) procollagen mRNA expression as determined by polymerase chain reaction, indicating that the collagen reduction by antisense oligonucleotides occurred at the transcription level. Histological staining suggested that collagen accumulation at the site in the artery where antisense oligonucleotide had been administered was indeed less than that in the control artery. Conclusions The results indicate that the induction of procollagen type I could cause pathogenesis of the arterial contraction induced by blood in a rat femoral vasospasm model.

We performed co-grafts of adrenal medulla and peripheral nerve into the bilateral caudate nuclei of a 43-year-old patient with advanced Parkinson's disease who showed severe daily motor fluctuations before surgery. There were no postoperative complications, and a 2-year follow-up result is presented. The patient showed a gradual and significant amelioration of the parkinsonian symptoms starting 2 weeks after transplantation. The alleviation of akinesia during "off" periods was the most apparent clinical improvement and continued for 2 years after surgery. The dosage of L-dopa/benserazide was significantly reduced after surgery compared with that before surgery. The results indicate that co-grafts of adrenal medulla with peripheral nerve may be useful for the treatment of Parkinson's disease in the long term.

✓ Meningiomas arising from the falcotentorial junction are extremely rare. The authors describe the clinical features, neuroimaging studies, and results of surgical treatment of meningiomas of the falcotentorial junction and clarify the characteristics of this lesion based on a review of the literature and seven patients treated at their institution. The most common symptoms resulted from intracranial hypertension. Upward-gaze palsy appeared in only one patient. Computerized tomography (CT) showed no specific findings, but there was no evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a round, smooth-bordered mass with a peritumoral rim, without edema, and showing marked contrast enhancement. The multiplanar capability of MR imaging delineated the relationship between the tumor and adjacent structures better than did CT. Detailed knowledge of the vascular structures, especially evidence of occlusion of the galenic venous system and the development of collateral venous channels, is critical for successful surgery; stereoscopic cerebral angiography is necessary to achieve this aim. The seven patients described developed five types of collateral venous channels: through the basal vein of Rosenthal to the petrosal vein, through the veins on the medial surface of the parietal and occipital lobes to the superior sagittal sinus, through superficial anastomotic veins, through veins of the posterior fossa to the transverse or straight sinus, and through the falcian veins to the superior sagittal sinus. The first three types mainly developed after occlusion of the galenic system. The tumors were removed through the occipital transtentorial approach with a large window at the posterior part of the falx. A favorable prognosis for patients undergoing surgical treatment of falcotentorial junction meningiomas can be expected if detailed neuroimaging studies and microsurgical techniques are used.

We carried out a time course study of cerebral superoxide scavenging activity using a modified microdialysis technique. Twelve cats were divided into two groups; six were the reperfusion injury models, and six were cold injury models. In the reperfusion injury model, dialysates were collected during 60 minutes of middle cerebral artery occlusion and at 300 minutes during reperfusion. In the cold injury model, dialysates were collected 240 minutes after the injury. Regional cerebral blood flow on the injured side decreased during occlusion in the reperfusion injury model and 60 minutes after injury in the cold injury model. In the reperfusion model, superoxide scavenging activity, as determined with electron spin resonance, increased in the first 30 minutes and decreased 300 and 330 minutes after occlusion. In the dialysate, albumin increased 180 minutes after cold injury, which may show the progress of vasogenic edema. An increase in water content was observed on the injured side of both models, and a correlation between water content and superoxide scavenging activity was found in the reperfusion injury model. By this technique, a method of detecting the alteration of superoxide scavenging activity in the extracellular space of the brain was established.

To determine the effect of hypothermia on superoxide injury after cerebral contusion, the induction of Cu,Zn-superoxide dismutase was examined 6 h after contusion in rats using Northern blotting. Cu,Zn-superoxide dismutase gene expression increased at the periphery of the contusion, which may indicate the severity of the superoxide stimulus. This increase was preserved after contusion under hypothermia, which may show that superoxide injury is still severe although brain edema is decreased.

Nerve growth factor (NGF) concentration in the distal stump of the transected peripheral nerve has been shown to increase more than 20 times one day after transection. We performed adrenal medullary alone grafts or cografts of adrenal medulla and acutely transected or pretransected (24 h before) sciatic nerve into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and compared the survival of chromaffin cells and the recovery of the host-intrinsic dopaminergic fibers using tyrosine hydroxylase immunocytochemistry and high-performance liquid chromatography. We also performed peripheral nerve alone grafting (acutely transected or pretransected) for comparison. Adrenal medullary chromaffin cells cografted with pretransected sciatic nerve survived better than those in adrenal grafts alone or those cografted with acutely transected sciatic nerve. Host dopaminergic fiber recovery was also most prominent in mice cografted with pretransected peripheral nerve. Animals receiving grafts of peripheral nerve alone showed limited recovery of host dopaminergic fibers and the degree of recovery was lower than that of animals receiving cografts of adrenal medulla with pretransected peripheral nerve. We conclude that pretransected peripheral nerve enhanced the survival of cografted chromaffin cells and this increased survival led to promote the recovery of host-intrinsic dopaminergic fibers. This grafting procedure might be promising in application to patients with Parkinson's disease.

We report the magnetic resonance features of meningiomas at the falcotentorial junction in six patients. Three tumors showed several characteristics on magnetic resonance images. They demonstrated hypo- or isointensity on T1-weighted images and iso- or hyperintensity on T2-weighted images. The degree of contrast between tumor and brain parenchyma, however, was less marked. The tumors often had a mottled appearance on T2-weighted images owing to their hypervascularity. All of the tumors had a peritumoral rim, and no edema was seen in adjacent brain parenchyma. With the injection of gadolinium, the tumors in all patients markedly enhanced; the adjacent dura was enhanced in four patients.

Using the electron spin resonance (ESR) spin-trapping method and a high molecular cut-off membrane, we measured the superoxide scavenging activity in dialysates obtained from microdialysis. The activity in the dialysates of the Cu,Zn-superoxide dismutase (SOD) solution and feline serum were measured in vitro, and the recovery rate was calculated to be 12.88 ± 0.9% in Cu,Zn-SOD solution and 21.52 ± 4.38 in feline serum, which was significantly different. This difference was believed to originate from the higher osmotic pressure due to proteins in the serum and substances other than Cu,Zn-SOD that acted as antioxidants in the serum. In an in vivo study, microdialysis probes were implanted into the cerebral hemispheres in 6 cats. The sequential changes of superoxide scavenging activity were measured for 16 h and during induced cardiac arrest. No significant difference was observed and the microdialysis technique itself did not seem to cause the significant alteration of the activity in the extracellular space, although at cardiac arrest, the activity varied widely. This method can be used to study the reaction against superoxide injury in further experiments involving brain insult.

Accumulation of nerve growth factor (NGF) has been reported to occur at the distal stump of pretransected peripheral nerve. We performed adrenal medullary grafts or cografts of adrenal medulla and distal stump of pretransected peripheral nerve into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated young or aging mice. We subsequently compared the survivability of chromaffin cells and the degree of host dopaminergic (DA) fiber recovery in relation to host age. In both young and aging hosts, adrenal medullary chromaffin cells cografted with pretransected peripheral nerve survived better than those in adrenal grafts alone. Host DA fiber recovery, however, showed less recovery and more restriction around the grafted site in aging compared with young hosts. We conclude that pretransected peripheral nerve can enhance the survivability of cografted chromaffin cells both in young and in aging hosts, but that DA fiber recovery is more limited in aging hosts compared to young hosts.

Brain surface elastance, defined as the pressure needed to compress the cortex 3 mm, was measured using the ophthalmodynamometer in six cats using three burr holes (frontal, parietal, and occipital) on each side. An intracranial mass was then used to compress the right side for 3 hours, and cardiac arrest was induced after the mass was removed. Elastance was measured four times: before insertion of the mass, 10 and 70 minutes after removal of the mass, and 60 minutes after cardiac arrest. The results showed that: brain surface elastance does not change between sides, but varies among regions with the parietal region having the highest elastance; elastance increases after compression by an intracranial mass, but not after cardiac arrest; and stiff brain tends to restore poorly. Elastance is apparently increased by the formation of edema. Measuring brain elastance may be useful in predicting brain restoration subsequent to removal of mass lesions.

We evaluated the magnetic resonance images of the patients with intention tremor. Five patients out of seven had some atrophic structures or changes in signal intensity in the cerebello-rubral thalamic tract. Moreover, the T2-weighted images of the patients group detected the dentate and red nuclei more poorly than those of our control group. From these results, the etiological significance of the tract was confirmed and the mechanism of the intention tremor onset was discussed.

This report describes the long-term operative outcome of 72 patients with spina bifida cystica. The period of follow-up was between 4 and 20 years. In our series, 17 patients died, with the mortality rate increasing as the lesions were more rostral. All cases involving only a meningocele are living without handicap. The cases of spina bifida cystica with hydrocephalus had higher morbidity and mortality when compared to those without hydrocephalus. We conclude that the rostro-caudal location, the content of the sac, and whether there is associated hydrocephalus are important factors influencing the long-term prognosis of spina bifida cystica.

Pretransected peripheral nerve has been demonstrated to enhance the survival of cografted adrenal medullary chromaffin cells and the recovery of host dopaminergic (DA) systems in animal models of Parkinson's disease. In the present study, we examined the effect of donor age on survival of cografted chromaffin cells. Adrenal medulla and pretransected peripheral nerve from young (1-month-old) or aging (12-month-old) donors were cografted into the striatum of MPTP-treated young (2-month-old) C57/BL mice. Although chromaffin cell survivability was increased by cografting with pretransected peripheral nerve despite donor age, survivability of chromaffin cells from aging donors was less than that using young donors. Image analysis of striatal DA fibers and chemical analysis of striatal DA showed that cografting with pretransected peripheral nerve enhanced the recovery of striatal DA systems more prominently than adrenal grafting alone. However, this effect was less in mice receiving aging donor tissues compared with mice receiving young donor tissues.

We report the results of a statistical analysis of the long-term outcome of 54 patients with 72 unruptured cerebral aneurysms, and identify the factors for predicting subsequent ruptures. Twenty-two patients died during the observation period, which averaged 43.7 months. The 5-year survival rate was 56%. Aneurysms ruptured in 11 patients (20.4%), 10 of whom died without undergoing surgery. The annual bleeding rate was 1.92%. The average size of the 11 ruptured aneurysms was 13.1 mm. In 4 patients, however, bleeding occurred in unruptured cerebral aneurysms of 4 and 5 mm, which suggests that leaving unruptured cerebral aneurysms of less than 10 mm in size untreated is hazardous. According to the Cox proportional hazards model, the shape and location of the aneurysm and the presence of hypertension were the most important factors for predicting a subsequent rupture. Our data suggest that unruptured cerebral aneurysms arising from the vertebrobasilar and middle cerebral arteries of 10–19 mm size and of multilobes had a statistically high probability of subsequent bleeding. Although 20 patients with 28 unruptured cerebral aneurysms were followed through repeated examinations, we could not correlate the risk of subsequent bleeding with changes in the size of the aneurysm.

This report describes long-term operative outcome of 24 cases with occipital encephalocele. The follow-up periods are between 4 and 20 years. Of the 24 patients with occipital encephalocele, two have died. Of the 22 living patients, 16 are living without neurological deficit, while six are disabled mentally and/or physically. Four cases of encephalocele developed hydrocephalus, and two of them died while the other two are still living with severe handicap. The presence of gross brain tissue in the sac of encephalocele and the size of the sac were also unfavorable factors for the prognosis. We conclude that the size and the content of the sac and associated hydrocephalus are the important factors that influence the long-term prognosis of occipital encephalocele.

Two cases of acute carbon monoxide poisoning are presented in this paper. Sequential magnetic resonance (MR) images of the brain showed abnormal lesions in the bilateral globus pallidus and/or in the subcortical white matter. The MR images disclosed that the severity of the white matter lesions correlated with the prognosis in acute carbon monoxide poisoning. However, they did not always correspond to the neurological condition in the acute and subacute stages.

Six patients with haemorrhage into intracranial neuromas were studied by computed tomography (CT) and magnetic resonance imaging (MRI) at 0.5 T with spin-echo pulse sequences. The nature of the tumour and the presence of a haematoma were confirmed by surgery and microscopic examination in all cases. Four neuromas arose from the acoustic nerves and two from the trigeminal. Four of the six patients suffered from sudden onset or rapid worsening of symptoms including headache, vertigo and/or hemifacial motor and sensory disturbances. CT in the acute stage revealed a hyperdense area or a fluid-fluid level (FFL). The hyperdense area disappeared on CT repeated in the chronic stage. On MRI in subacute and chronic stages the haemorrhage showed hyperintensity on both T1 and T2 weighting in five cases examined between 16 and 46 days after the onset, and isointensity on T1 weighting and an FFL on T2 weighting in one case examined 12 days after the onset of symptoms. A well-defined low intensity rim indicating prior haemorrhage was observed on T2-weighted images in three cases. MRI was more effective than CT in detecting haemorrhage into the tumours and in staging it.

Massive intratumoral or subarachnoid hemorrhage from neurinomas is very rare. The authors report on six patients, four men and two women, with neurinomas that presented as spontaneous intratumoral hemorrhage. The average age of the patients was 56.8 years (range, 31-74 years). Neurinomas originated from the acoustic nerve in four patients and from the trigeminal nerve in two. Four cases were accompanied by the sudden occurrence of clinical symptoms such as headache, double vision, and hemisensory or motor disturbance. The maximum diameter of the tumors ranged from 2.8 to 3.8 cm (average, 3.1 cm). Histological examinations showed massive hemorrhage and increased vascularity, with dilated, thin-walled vessels, in all cases. The size of the tumor and the increase in vascularity with dilated, thin-walled vessels within neurinomas are important pathogenetic factors of hemorrhage. When sudden onset of symptoms or rapid worsening of chronic symptoms occurs in neurinomas, intratumoral or subarachnoid hemorrhage should be considered as a possible cause, and magnetic resonance imaging can be an important tool in obtaining correct diagnosis.

Unruptured cerebral aneurysms accompanied by ischemic CVD in 16 patients were analyzed and their managements are discussed. Unruptured aneurysms of 8 patients with mild or no clinical symptoms and small low density areas on CT were treated surgically. There was no operative mortality, but postoperative complication occurred in two patients. Both were operated on through the ipsilateral side of ischemic lesions shortly after the onset of ischemic symptoms. Eight patients who had severe neurological deficits due to ischemic lesions and large low density areas on CT did not receive aneurysmal operation. When unruptured aneurysms are accompanied by ischemic CVD, the treatment should be determined by the severity of neurological deficits caused by ischemic CVD. If an unruptured aneurysm was the source of emboli resulting in the ischemic lesion, it should be operated. Careful manipulation is required during surgery, especially from the ipsilateral side of ischemic lesion.

The authors report a case of cerebellopontine angle epidermoid presenting as typical hemifacial spasm. A 33-year-old male had experienced intermittent right hemifacial spasm for 2 years. Cranial nerve examination was otherwise normal, including auditory and trigeminal nerve functions. Metrizamide computed tomographic cisternography and magnetic resonance imaging demonstrated a characteristic epidermoid tumor. The tumor was totally removed. Postoperatively, no facial spasm or other facial nerve dysfunction was noted.

The authors present a case of central neurocytoma in a 34-year-old female who had experienced intermittent headaches over a 10-year period. On computed tomographic (CT) scans and magnetic resonance images, the tumor appeared as a large, calcified mass occupying both lateral ventricles. A right parieto-occipital craniotomy was performed and the tumor was totally removed. While the light microscopic findings suggested a diagnosis of oligodendroglioma, electron microscopic examination demonstrated clear vesicles, microtubules, and synaptic structures within the abundant cytoplasmic processes of the tumor cells. Immunohistochemical examination showed the tumor cells to be strongly positive for neuron-specific enolase, sparsely positive for S-100 protein, and negative for glial fibrillary acidic protein. The final histological diagnosis was central neurocytoma. The postoperative course was uneventful and no further treatment was administered. She has no neurological deficits and CT has shown no evidence of recurrence during the 2 years since her surgery. Central neurocytoma is a rare tumor arising in the lateral ventricle, and the diagnosis is mainly based on electron microscopic findings. Since central neurocytoma appears to have a good prognosis following total removal alone, it is very important to distinguish between this and other ventricular tumors.

CSF rhinorrhea is a common complication of acoustic neurinoma surgery via the suboccipital route. In this paper we present our incidence of CSF rhinorrhea and our surgical techniques for reducing the risk of this post-surgical complication. Following removal of the acoustic neurinoma, the drilled posterior wall of the internal auditory canal is covered with bonewax, muscle or fat pieces, and fibrin-glue, while the previously reflected dura is sutured in place keeping the packing material in position. Bone chips removed during the craniectomy are then mixed with fibric glue and are used for a cranioplasty. Although we routinely perform aggressive drilling of internal auditory canal to facilitate total removal of the acoustic neurinoma, only 1 out of 94 consecutive cases (1%) showed postoperative CSF rhinorrhea. Since previous reports mention the rate of this complication following acoustic neurinoma surgery varies between 4% and 27%, we believe that our methods may be useful in helping reduce the incidence of postoperative rhinorrhea.

Polymer-encapsulated dopamine-secreting cell grafting is one of the most promising approaches for the treatment of Parkinson's disease. We microencapsulated dopamine secreting PC12 cells into agarose/poly(styrene sulfonic acid) complex and grafted them into the xenogeneic brain without immunosuppression. Dopamine secretion from the encapsulated cells was confirmed by high-performance liquid chromatography (HPLC) analysis before grafting. A large number of encapsulated PC12 cells survived in the brain 1 mo after transplantation and these cells were immunoreactive to tyrosine hydroxylase (TH) antibody, suggesting that these cells were secreting dopamine into the brain. There was no apparent immunological rejection or tumor formation. We concluded that microencapsulated PC12 cells survive in the xenogeneic brain without immunosuppression, and this grafting procedure is expected to be applied for the treatment of Parkinson's disease in the near future in combination with stereotaxic thalamotomy or pallidotomy.

To evaluate the usefulness of an MRI score for identifying tumour tissue characteristics, 41 histologically verified supratentorial astrocytic gliomas, including 13 low-grade astrocytomas (LGA) 14 anaplastic astrocytomas (AA) and 14 glioblastoma multiformes (GBM), were examined with a 0.5T superconductive MR imager. Nine MRI criteria were used: heterogeneity (HET), cyst formation or necrosis (CN), haemorrhage (HEM), crossing the midline (CM), oedema or mass effect (EM), border definition (BD), flow void (FV), degree (CE-D) and heterogeneity (CE-HET) of contrast enhancement; Gd-enhanced T1-weighted images were obtained in 32 cases (10 LGA, 10 AA, and 12 GBM). Each of the criteria was scored and analysed statistically. The mean values of LGA, AA and GBM were 0.45 +/- 0.31, 1.18 +/- 0.20, and 1.47 +/- 0.22, respectively. The MRI score increased with the pathological grades (P0.01-0.001). LGA had significantly lower values than AA in five (HET, CN, EM, BD, CE-D) of the nine criteria (55.6%) and lower values than GBM in all except HEM (88.9%). Three criteria (33.3%): HET, CN, and FV were significantly higher in GBM than AA. CE-D, HET, EM, CN, and CE-HET proved to be related to the pathological grade by a multiple regression analysis (P0.001).

Background and Purpose —Poly(ADP-ribose) polymerase (PARP) is important in modulating inflammation, which has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the role of PARP in vasospasm using 3-aminobenzamide (3-AB), a PARP inhibitor, in a rabbit model. Methods —Twenty-four New Zealand White rabbits were divided into 4 groups: (1) no treatment (control group, n=6); (2) blood injection without pretreatment (SAH-only group, n=6); (3) blood injection with pretreatment by vehicle (SAH+vehicle group, n=6); and (4) blood injection with pretreatment by 3-AB (SAH+3-AB group, n=6). We used the single-hemorrhage model of SAH, injecting autologous arterial blood into the cisterna magna. Angiography was performed before (baseline) and after (day 2) SAH, and the diameter of the basilar artery (BA) was measured. Animals were euthanatized after the second angiogram. After perfusion and fixation, the brains were cut into sections for hematoxylin and eosin and immunohistochemical staining for poly(ADP-ribosyl)ation. Results —In the control group, there were no differences in the BA lumen caliber between baseline and day 2 (96.8±10.4%). Cerebral vasospasm in the SAH+3-AB group (88.2±6.2%) was remarkably attenuated in comparison with that in the SAH-only group (64.9±8.0%) and the SAH+vehicle group (65.6±10.8%). The BA in the SAH+3-AB group showed less corrugation of the tunica elastica interna than that in the SAH-only and SAH+vehicle groups. Staining for poly(ADP-ribosyl)ation was markedly inhibited in smooth muscle and adventitial cells of the BA in the SAH+3-AB group compared with other groups. Conclusions —Inhibiting ADP-ribosylation attenuates cerebral vasospasm after SAH in rabbits, and PARP activation may play an important role in the development of cerebral vasospasm.

There have been controversies regarding the influence of aging on the degree of vasospasm after subarachnoid hemorrhage. Most of the previous reports are studies based upon clinical data and there have not been detailed experimental studies. Contractile responses of cerebral arteries to vasoconstricting agents have been demonstrated to be increased with age, athelosclerosis and hypertension [4]. The cause of vasospasm is considered multifactorial, thus aging might influence the degree of vasospasm. Issues related to intraarterial infusion of papaverine for the treatment of vasospasm have often been discussed 3]. However, vasodilating responses induced by papaverine in young and in old arteries have not been compared. The present study was conducted to clarify age-related differences in vasospasm and the efficacy of papaverine.

✓ The authors describe the first reported case of dissecting aneurysm presenting with hemifacial spasm. The patient was a 58-year-old woman with left hemifacial spasm of 2 years' duration. Cranial nerve examination was otherwise normal and no other clinical symptoms were observed. Vertebral angiography revealed a fusiform enlargement of the left vertebral artery and contrast medium remaining in the intramural false lumen in the venous phase. Microvascular decompression of the facial nerve with wrapping of the aneurysm resulted in complete relief of the hemifacial spasm.

Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established. The purpose of this article is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic brain injury (TBI) in rats, we studied the SOD activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern blot analysis. As determined by the specific gravity method, the administration of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr after contusion. SOD activity, without lecithinized SOD administration, increased at the peripheral portion at 30 min after contusion, but decreased to the normal level at 6 hr after TBI. By administration of lecithinized SOD, the increase of SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA increased in the core lesion, peripheral portion, and contralateral hemisphere until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD. These results support the hypothesis that superoxide anions may play an important role in the development of brain edema after TBI, and that leciyhinized SOD appears to prevent brain edema through a protective effect against superoxide anions.

The PC12 pheochromocytoma tumor cell line is derived from a rat adrenal medullary tumor and secretes dopamine. We have previously reported that grafted microencapsulated PC12 cells using agarose and poly(styrene sulfonic acid) survived in the xenogeneic brain without immunosuppression. To investigate whether unencapsulated PC12 cells form a tumor and how they provoke immunological reaction, PC12 cell suspension was implanted into the striatum of Sprague-Dawley rat (allogeneic graft) or guinea pig (xenogeneic graft) and histological analysis using Nissl stain and immunocytochemical analysis using antityrosine hydroxylase (TH) antibody were performed 1, 2, and 4 wk after transplantation. Host animals were not immunosuppressed. PC12 cells formed a mass 1 and 2 wk after transplantation both in allogeneic and xenogeneic brain. These grafted PC12 cells were immunoreactive to anti-TH antibody. Four weeks after transplantation, however, grafted PC12 cells in the allogeneic brain were only found within the restricted area near the site of implantation. In the xenogeneic brain, only the trace of grafted PC12 cells were found around the site of implantation 4 wk after transplantation. In both allogeneic and xenogeneic animals, a number of lymphocytes were found in and around the grafts at all period investigated. These findings indicate that PC12 cells could survive in the allogeneic or xenogeneic brain for 2 wk and were ultimately rejected by immunological reaction by 4 wk after transplantation. Implantation of encapsulated PC12 cells in the allogeneic or xenogeneic brain is considered a safe and effective method for delivering dopamine into the brain because PC12 cells will not form a tumor in the long-term even if capsules are damaged in some reason.

To examine the relationship between the free radicals and brain tissue damage, we investigated the intensity of brain hydroxyl (OH) radical generation and lipid peroxidation in the rat contusion injury model. A unilateral contusion was induced by a weight-drop method. All rats were decapitated six hours after the injury, and brain samples were taken from three portions (core, peripheral, and distal) to examine the specific gravity as an indicator of brain edema, generation of OH using an electron paramagnetic resonance spectrometer (EPR), and malondialdehyde (MDA) and 4-hydroxyalkenals production. Analysis of the specific gravity revealed cerebral edema on the ipsilateral side in the injured group. The signal intensity of EPR in the core and peripheral portions in the contusion group was significantly higher than that in the distal portion of the contusion group and that of all portions in the control animals.

✓ To clarify the role of endothelin-1 (ET-1) in the etiology of hemolysate-induced contraction of vessels, the authors introduced antisense oligoDNA for preproendothelin-1 (ppET-1) messenger RNA in a rat model of vasospasm. Phosphorothioate antisense oligoDNAs for ppET-1 were injected into the cisterna magna. Fluorescein isothiocyanate-labeled phosphorothioate antisense oligoDNAs were proven by fluorescence chasing to be incorporated into the vascular wall. Striking inhibitory effects of experimental vasospasm were observed in the basilar artery (BA) in which the oligoDNAs were injected. The vascular contraction was significantly inhibited by oligoDNAs after 20 minutes of hemolysate exposure, which suggested that ET synthesis started approximately 20 minutes after hemolysate stimulation. Expression of ppET-1 in the BA in which the spasm was inhibited was markedly suppressed at the transcription level. The results indicate that ET-1 may play an important role in hemolysate-induced vasoconstriction in rats. In addition, the antisense approach in the cerebrospinal fluid might be a useful tool for preventing cerebral vasospasm.

✓ A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase—immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.

We analyzed the expression of Cu,Zn-superoxide dismutase (SOD) mRNA in both contusion and cold injury. Twenty-three rats were divided into 3 groups: a control group, a contusion group, and a cold injury group. Six hours after the injury, the rats were decapitated and the gray matter was resected from 3 portions: the core of the injured cortex, its periphery, and a distal portion on the non-lesion side. Based on the specific gravity of each sample, almost the same degree of edema developed in both injury groups. The mRNA expression in the cold injury group, however, significantly decreased in all portions. The extremely low temperature associated with cold injury is a possible cause of the decrease in Cu,Zn-SOD mRNA.

We compared two- and three-point methods for phase-contrast MR angiography in vitro. The three-point method is an excellent technique by which we can measure the flow velocity of the arteries in the head and neck without careful slice selection.

We report the surgical morbidity and mortality and the results of statistical analysis based on the long-term outcome (average 50.1 months) of 69 patients with unruptured cerebral aneurysms. These patients harbored a total of 76 unruptured cerebral aneurysms, 72 larger than 3 mm in diameter. All the latter were surgically treated. There was no operative mortality. Operative morbidity occurred in 5 patients (7.2%), including hemiplegia in 2 from obliteration of perforator vessels, transient memory impairment in 2 due to brain retraction, and transient oculomotor nerve palsy in 1 patient resulting from an unknown etiology. During the observation period, 53 patients (76.8%) had a good or fair outcome, 11 (15.9%) had a poor outcome, and 5 (7.3%) died from causes unrelated to the aneurysms, such as pneumonia, gastrointestinal bleeding, and heart failure. The 5-year survival rate was 94%. Statistical analysis of the long-term outcome of all patients showed no significantly important factor influencing long-term morbidity. Prophylactic surgery of aneurysm is recommended for low-risk patients who may develop eventual rupture of an aneurysm, but perforator vessels around the aneurysm should be preserved, clips should be properly placed, and brain retraction should be minimized.