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BACKGROUND Normal posterior inferior cerebellar artery (PICA) anatomy is highly variable, but bihemispheric PICA crossing the midline to supply the vascular territory of bilateral cerebellar hemisphere is rare. Herein, the authors reported a rare case of ruptured aneurysm that was associated with bihemispheric PICA and successfully treated endovascularly. OBSERVATIONS A 46-year-old woman presented with sudden headache and loss of consciousness because of an intraventricular hemorrhage due to a ruptured aneurysm that was associated with the bihemispheric PICA. Angiography revealed that the aneurysm was located at the bifurcation between the bihemispheric PICA and the bilateral distal PICA. The ruptured aneurysm was successfully occluded using coil embolization, which preserved the parent artery with no procedural-related complication. LESSONS To the best of the authors’ knowledge, this was the first report of a ruptured aneurysm associated with bihemispheric PICA being successfully treated endovascularly. Aneurysm formation may be accelerated by hemodynamic stress and vascular fragility. For neurosurgeons and neurointerventionalists, it is important to understand the anatomical variation of PICA, especially bihemispheric PICA, which is a potential risk factor for a fatal stroke.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

We report a 55-year-old man with Cryptococcus neoformans meningitis who showed refractory deterioration twice with an increased cerebrospinal fluid cryptococcal antigen titer during the course of treatment. Although the initial deterioration was temporarily improved by placement of a ventriculoperitoneal shunt, he experienced deterioration again. However, he improved after administration of systemic corticosteroids. The present case suggests that systemic corticosteroid can be a choice of treatment to rescue immunocompetent patients with Cryptococcus neoformans meningitis and severe deterioration, even if cerebrospinal fluid analysis shows an increased cryptococcal antigen titer.

Astroblastoma is extremely rare brain tumor which mostly arise in cerebral hemisphere of children and young adult. Limited data exists on its clinical feature and molecular analysis. We recently experienced two female patients with astroblastoma in the cerebrum. Case 1 is three-year-old girl. She developed left hemiparesis. CT and MRI revealed large supratentorial mass with cystic component and calcification. Gross total removal was achieved. She is well without recurrence on MRI one year after surgery. Case 2 is 42-year-old lady. She developed partial seizure. CT and MRI revealed a mass with ring-enhancement in the left temporal lobe. Gross total removal was achieved under awake craniotomy. She is well without recurrence on MRI six months after surgery. Pathologic examination of both patients showed pseudorosette formation of tumor cells around vasculature. Molecular analysis revealed rearrangement of MN-1 in case 1 but not in case 2. Case 2 showed BRAF V600E mutation and loss of CDKN2A/2B. Both patients received no adjuvant therapy. Prognosis of astroblastoma varies and standard of treatment is not established. Gross total resection is associated with increased survival, but the role of adjuvant chemotherapy and radiation therapy are controversial. Advances in molecular analysis will lead to establish molecular classification and risk-adapted treatment strategy.

【目的】急性期脳梗塞に対するrt-PA静注療法の中で，われわれは，特に高齢者へのrt-PA投与において症候性頭蓋内出血と転帰に関して検討した．【方法】2007年1月から2010年12月までに当院に入院した脳梗塞患者1263例のうちrt-PA静注療法を行った患者130例を対象とした．そのうち80歳未満の72例(以下80歳未満群と略)と80歳以上の58例(以下80歳以上群と略)を比較検討した．rt-PA投与後，CTおよびMRIで頭蓋内出血の有無を検索した．【結果】症候性頭蓋内出血は80歳未満群で5例(7.1%)，80歳以上群で4例(6.9%)認め，両群間に有意差は認めなかった(オッズ比1.21; 95%CI 0.04–2.39; P=0.6174)．3カ月後のmodified Rankin Scale (mRS) 0–1は80歳未満群が30.0%に対し，80歳以上群は8.8%で，80歳未満群の方が有意に高く(オッズ比7.20; 95%CI 6.05–8.34; P=0.0009)，mRS 6(死亡)は80歳未満群が9.0%に対し，80歳以上群は19.3%で，80歳以上群の方が有意に高かった(オッズ比6.52; 95%CI 5.39–7.65; P=0.0015)．【結語】症候性頭蓋内出血に年齢因子の関与は有意なものとはいえなかった．転帰には年齢因子が関与することが示唆された．

Penetrating brain injury(PBI)is very rare in Japan. Because there is a very wide variety of pathological condition of PBI, the guideline for the treatment of PBI has not been established yet. We report the unique case of PBI caused by a steel wire piece completely embedded in the brain parenchyma. A 75-year-old man was brought to the emergency department due to ocular injury caused by a steel wire piece. Neurological examination revealed only left visual disturbance. CT scan revealed a steel wire piece located intraparenchymally between the left frontal lobe and the ventricles, but digital subtraction angiography showed no significant vascular injury in the surrounding structures. We performed an open surgery and removed the steel wire piece. Because the steel wire piece was completely embedded in the brain, we used intraoperative X-ray fluoroscopy to choose a less invasive approach for the brain. The patient suffered no additional neurological deficit and no sign of cerebral infection or seizure after surgery. He was discharged after a 4-week administration of antibiotics. In most cases of PBI caused by low velocity injury, foreign bodies are not completely embedded in the brain except for remnants after surgical removal. This is the first report of low velocity PBI caused by a foreign body completely embedded in the brain.

We examined the effects of mild to moderate hypothermia and the influence of rewarming on electrophysiological function using somatosensory evoked potentials (SEPs) in transient focal ischemia in the brain. Nineteen cats underwent 60 min of left middle cerebral artery occlusion under normothermic (36 degrees-37 degrees C, n = 6) or hypothermic (30 degrees -31 degrees C, n = 13) conditions followed by 300 min of reperfusion with slow (120 min, n = 6) or rapid (30 min, n = 7) rewarming. Whole-body hypothermia was induced during ischemia and the first 180 min of reperfusion. SEPs and regional cerebral blood flow were measured before and during ischemia and during reperfusion. The specific gravity of gray and white matter was examined as the indicator of edema. During rewarming, SEP amplitudes recovered gradually. After rewarming, SEPs in the normothermic and rapid rewarming groups remained depressed (20%-40% of pre-occlusion values); however, recovery of SEPs was significantly enhanced in the slow rewarming group (p0.05). Hypothermia followed by slow rewarming reduced edema in gray and white matter. Rapid rewarming did not reduce edema in the white matter. The recovery of SEPs correlated with the extent of brain edema in transient focal ischemia. Rapid rewarming reduced the protective effect of hypothermia.

Sinonasal neuroendocrine carcinomas (NECs) are rare tumors. We present a rare case of intracranial invasion of sinonasal small-cell NEC. A 61-year-old woman with nasal obstruction and bleeding was referred to our hospital. Computed tomography showed a polyp-like tumor occupying her left nasal cavity and extending to the paranasal sinuses and anterior cranial fossa. The tumor was removed using a transfacial approach by otolaryngologists and a bifrontal cranial approach by neurosurgeons. In histopathological analyses, we found that the tumor presented with both an epithelial and neuroendocrine nature, and was diagnosed as a small-cell NEC. Post-surgery, she received localized radiation therapy and chemotherapy, and is alive, 18 months after diagnosis. In cases where it is difficult to perform a differential diagnosis of tumors arising from the frontal cranial base and extending to the nasal and cranial sides, NEC should be considered as a possibility.

Primary leptomeningeal lymphoma(PLML)is a neoplastic meningitis of lymphomatous origin without parenchymal central nervous system(CNS)disease or a systemic tumor. We report a case of PLML that presented with epileptic seizure, and review relevant literature. A 27-year-old man was brought to the emergency department with an epileptic seizure. Two months later, he was again brought to the emergency department with an epileptic seizure. MRI showed enhanced lesions on the surface of the right cerebellar hemisphere, right parietal sulci, and interhemispheric surface of the frontal lobes. We performed an open biopsy and diagnosed the patient with diffuse large B-cell lymphoma of the leptomeninges on the basis of histological findings. The patient was initially treated with chemotherapy including high-dose methotrexate(MTX). Because remission was not achieved by chemotherapy, the patient was treated with whole-brain radiation therapy. After onset, the patient survived for 2 years without recurrence. PLML is a particularly rare type of primary CNS lymphoma. The outcome of PLML, compared with general primary CNS lymphoma, is reported to be very poor because chemotherapy including MTX is ineffective.

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: The Kagawa prefecture is the region of Japan with the highest utilization rate of intravenous (i.v.) rt-PA treatment per 100,000 people over the age of 65. We retrospectively reviewed patient characteristics and results of this therapy for seven stroke centers in the Kagawa prefecture over the last three years. Methods: 273 patients received i.v. rt-PA treatment between January 1, 2009 and December 31, 2011. Stroke subtype, NIHSS at admission, mRS (modified Rankin Scale) at discharge, mRS by each obstructed artery, incidence of symptomatic intracranial hemorrhage (sICH), and location at the onset were recorded for all patients. Results: The mean age was 73.9 years and male/female ratio was 1.55. The proportion of cardioembolic stroke was 53.1%. The mean baseline NIHSS was 13.8 points. Excellent outcome (mRS 0 to 1) at discharge was present in 19.2%, favorable outcome (mRS 0 to 2) in 31.4%, and poor outcome (mRS 5 to 6) in 31.0%. The overall mortality (mRS 6) was 11.4% and sICH occurred in 5.1%. Cardiogenic infarction had less favorable outcomes than other stroke subtypes. Excellent outcome was achieved in 29.0% of M2 occlusions, 9% in Ml occlusions and 5.9% in ICA occlusions. Patients with ICA occlusion had the worst prognosis with poor outcome in 55.9% compared to 43.3% for Ml occlusion and 18.4% for M2 occlusion. The mortality of ICA occlusion was 35.3%. Conclusions: Our patient background and safety characteristics (such as incidence of sICH and mortality) are comparable to the Japanese J-MARS post-marketing surveillance study. However, our outcomes are less favorable than those in previous reports. Cardiogenic infarction and major artery occlusion (such as Ml or ICA) are particularly poor prognostic factors. Sixteen neurological institutes can administer i.v. rt-PA treatment in Kagawa, all with access to MRI scanners 24/7. Despite this excellent medical environment, problems remain related to regional and topographic factors such as patients living on islands and mountainous areas. In this study, we report the challenges, treatment strategies and results for the treatment of acute stroke in the Kagawa prefecture.

✓ 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.

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.

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.

Patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutation respond remarkably well to tyrosine kinase inhibitors of the EGFR (EGFR-TKI). We examined the relation of the EGFR mutation and the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer.Forty-one patients with brain metastases from lung cancer were treated in our hospital from January 2007 to October 2010. Among them, 9 patients were examined on their EGFR mutation of tumors using the PNA-LNA PCR clamp method, and were treated with gefitinib, given orally at a daily dose of 250 mg. The drug efficacy for brain tumors was evaluated with MRI and CT.Seven patients had EGFR mutation (4 in exon 19, and 3 in exon 21). Five patients showed partial response, 3 remained stable, and one had progressive disease. All 5 patients who showed partial response had EGFR mutation. One patient who had progressive disease had no EGFR mutation. Three patients (case 1, 2 and 6) among 5 patients who showed partial response were well controlled only with gefitinib (without radiation).This study suggests that the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer is related to the EGFR mutation of tumor.

Twelve patients with facial nerve neurinoma have been treated at The National Hospital, Queen Square, London, during the last 20 years. Nine tumours lay in the middle fossa arising from the area of the geniculate ganglion, two lay in the posterior fossa arising from the segment of the facial nerve in the internal auditory canal, and one tumour arose from the vertical segment of the facial nerve with extracranial extension through the stylomastoid foramen. Two patients had neurofibromatosis. The clinical and radiographic features of those tumours, the operative approaches employed, and the postoperative outcome are described. Complete tumour excision was achieved in all patients; all 12 remain free of recurrence 3-80 months after surgery. Facial nerve function was restored at least in part in all cases by transposition with end-to-end anastomosis, placement of a cable graft from the sural nerve or hypoglosso-facial anastomosis. The major determinant of the outcome of facial nerve function was the duration of preoperative facial paralysis, the results being invariably poor when this was of long duration.

Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection by JC virus and presents with progressive demyelinating lesions in the central nervous system. A 59-year-old man with a history of alcoholic liver dysfunction presented with progressive weakness of his left leg over a period of one month. MRI showed multiple white matter lesions that were of low intensity on the T1 image and high intensity on the T2 image, heterogeneously high intensity on the diffusion image, and were not enhanced with contrast media. The patient underwent open biopsy of the right parietal lesion. The histological findings were the demyelination and the enlargement of nuclei of oligodendrocytes. Electron microscopic examination showed numerous viral particles in the nuclei of the oligodendrocytes. Infection by JC virus in the central nervous system was diagnosed with the polymerase chain reaction (PCR) products sampled from the cerebrospinal fluid. The incidence of PML has significantly increased in immunosuppressive patients, such as AIDS (acquired immunodeficiency syndrome). We presented the first case of PML in an immune-compromised state with alcoholic liver dysfunction.

Ligation of the carotid artery remains an accepted treatment for unclippable giant carotid artery aneurysms. Post-operative evaluation is commonly made subsequently by CT scan and angiography, the latter involving an invasive procedure. This paper describes the magnetic resonance (MR) appearance of a traumatic giant terminal carotid artery aneurysm treated by common carotid ligation. MR appears to be the imaging technique of choice for follow-up of giant aneurysms of the terminal carotid artery treated by carotid ligation, the accuracy of delineation of the aneurysm and its content surpassing that of the CT scan.

We report a rare case with polycystic kidney disease (PKD) having an intracranial internal carotid artery aneurysm associated with extracranial occlusion of the ipsilateral internal carotid artery. A 55-year-old man with chronic renal failure due to PKD presented with headache. CT scan and MRI showed no abnormal findings. MRA showed cervical occlusion of the right internal carotid artery and an ipsilateral intracranial carotid aneurysm. At surgery, the saccular aneurysm protruded anterolaterally at the C2 portion of the right internal carotid and was clipped. Hemodynamic stress of the blood flow through the posterior communicating artery and the fragility of arteries because of PKD were considered to be two main causes of aneurysmal formation in this case.

Background The protective effect of excitatory amino acid antagonists for CA3 hippocampal neuronal loss has been well documentated. From a clinical point of view, however, alternative therapies should also be explored because excitatory amino acid antagonists have relatively deleterious side effects. Administration of lecithinized superoxide dismutase (PC-SOD) has recently been demonstrated to reduce brain edema after traumatic brain injury (TBI) in the cerebral cortex. In this study, we investigated the effectiveness of PC-SOD on CA3 hippocampal cell loss by examining hematoxylin and eosin-stained sections. Methods Rats were divided at random into three groups. The first group received 1 mL of saline (contusion + saline group, n = 5). Rats of the second group were treated with 3000 IU/kg of PC-SOD (contusion + SOD 1 group, n = 5), while the third group received 5000 IU/kg of PC-SOD (contusion + SOD 2 group, n = 5). All agents were administered intraperitoneally 1 minute after traumatic insult and every 24 hours until 2 or 3 days post-TBI. Animals were sacrificed 3 or 7 days after contusion injury. Results PC-SOD prevented CA3 neuronal loss 3 days after TBI, and increased the number of surviving CA3 neurons 7 days after TBI. Conclusion Our findings suggest that PC-SOD may serve as a pharmacological agent in the treatment of neuronal loss after TBI.

The authors present three cases of refractory chronic subdural hematoma (CSDH) treated by embolization of the middle meningeal artery (MMA) after several unsuccessful drainage procedures. The patients were initially treated by the usual method of burr hole and irrigation of the hematoma. After recurrence, several percutaneous puncture and drainage procedures were unable to prevent re-collection of the hematoma. Then the authors embolized the MMA which was thought to be the feeding artery of the outer membrane of the hematoma cavity. No enlargement of the hematoma was seen after embolization and, gradually, complete resolution of the hematoma was obtained. The outcome of the patients was excellent in all three cases. This new therapeutic approach to recurrent CSDH is discussed.

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.

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 analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic injury, the expression of Cu,Zn-SOD mRNA was examined after contusion in rat using Northern blotting. As determined by specific gravity, lecithinized SOD decreased brain edema. The expression of Cu,Zn-SOD mRNA increased at the core, peripheral and contralateral hemisphere of injury. These increases were then suppressed by lecithinized SOD. Our results support the hypothesis that superoxide may play an important role in edema formation after contusion, and that lecithinized SOD appears to prevent brain edema through a protective effect against superoxide injury.

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 used a microdialysis technique to establish a method to detect sequential changes in disruption of the blood parenchymal border. Twelve cats were divided into two groups; one group underwent occlusion of the middle cerebral artery for 60 minutes, the other a cold injury model. Microdialysis probes were implanted bilaterally into the white matter, and dialysates were collected successively at 30 minute intervals for 6 hours in the occlusion model and 4 hours in the cold injury model. Regional cerebral blood flow was measured simultaneously using the hydrogen clearance method. The water content of the white matter was measured using specific gravity. The proteins in the dialysate were analyzed using electrophoresis with silver stain, and, with densitometric analysis, the density of the 66.2 kDa band was quantified as albumin. The ratio of this density to the preoperative density was defined as the“albumin index.”On the side of the lesion in the cold injury model, this index significantly increased 3 hours after the cold injury compared with the contralateral side, and a correlation between the water content and this index was observed. The albumin index was believed to indicate the severity of disruption of the blood parenchymal border.

To elucidate the relationship between reperfusion injuries and free radicals, we monitored the endogenous Superoxide dismutase (SOD) activity by intracerebral microdialysis. Six cats underwent a transient occlusion of the middle cerebral artery for 60 minutes after microdialysis probes were implanted bilaterally into the white matter under the ectosylvian gyms. Dialysates were collected at 30 minute intervals over the course of 5 hours after reperfusion. The SOD activity of the dialysates was measured with electron spin resonance spectrometry. Regional cerebral blood flow was measured simultaneously and the water content of the white matter was assayed at the end of the experiment. After reperfusion, SOD activity increased significantly in the first 30 minutes compared with the preoperative value, and decreased over 4-4.5 hours and 4.5-5 hours in the occluded side. The water content in the occluded side was significantly higher than that in the contralateral side. The highest SOD activity during reperfusion and the water content in the occluded side seemed to correlate, although not significantly. A leakage of intracellular SOD or a reactive increase of SOD activity in response to the reperfusion injury are possible mechanisms of increase in extracellular SOD.

Using a new devised model of dural sinus occlusion, we investigated the pathophysiology including venous hemorrhage. Sixteen cats received, the occlusion of superior sagittal sinus(SSS) and diploic veins(DV). Intracranial pressure(ICP), cerebral blood volume(CB V) and regional cerebral blood flow(rCBF) were measured for 12 hours. At sacrifice, cerebral water content was determined. Other 8 cats received the additional occlusion of cortical veins(CV). In both groups, the blood-brain barrier(BBB) permeability was evaluated with Evans blue. The SSS and DV occlusion produced a significant increase in ICP and CBV and a significant decrease in rCBF. Cerebral water content also increased significantly. However, neither extravasated Evans blue nor venous hemorrhage could be observed, when thrombus was defined within SSS. Contrarily, the additional CV occlusion produced hemorrhagic infarctions in 6 cats, where Evans blue dye extravasated. These data suggest that durai sinus occlusion led to an increase in CBV and cerebral water content resulting in intracranial hypertension, and decreased rCBF. The brain edema in this model seemed to be hydrostatic edema. The obstruction of CV might be essential in the development of hemorrhage in this model, and the BBB was disrupted in these areas.

In 7 baboons maintained under propofol anaesthesia, pyramidal tract responses were related to the corresponding peripheral EMG evoked by electrical stimulation of the motor cortex under conditions of focal cortical ischaemia. Pyramidal responses were recorded epidurally at the C5 level and the EMG was recorded from the contralateral hand or foot muscle using subdermal needle electrodes. Cortical ischaemia was produced by transorbital occlusion of the common anterior cerebral artery, and regional cortical blood flow was measured by the hydrogen clearance method. In the normally perfused brain, the later I waves of the C5 response required a lower stimulus strength to elicit them than the earlier I1 wave. It was more difficult to record the EMG from the hand than from the foot following stimulation of the corresponding cortex even though the C5 responses were always obtained in both cases. With moderate ischaemia, the later I waves were selectively abolished, leaving the D and I1 waves. EMG amplitude was significantly correlated with cortical blood flow (r = 0.88, P less than 0.005), and the threshold of cortical flow for the EMG was 10-13 ml/100 g/min. Our results indicate that changes in amplitude of the late I waves and particularly of the EMG are sensitive indicators of cortical ischaemia.

Serial measurements of auditory brainstem-evoked responses (BERs) were conducted in 15 patients with supratentorial mass lesions. Significant prolongation of the latency of wave V BERs, which originates in the inferior colliculus, occurred when the intracranial pressure (ICP) approached 30 mmHg. In four of five patients whose BERs were measured before pupillary changes, a significant lengthening of wave V latency was observed prior to clinical manifestation of uncal herniation. These results suggest that immediate medical or surgical decompression of ICP should be performed when ICP approaches 30 mmHg with significant prolongation of wave V latency.

Fourteen patients with symptoms of vertebrobasilar insufficiency caused by vertebral artery stenosis in the distal first portion underwent surgical reconstruction. They ranged in age between 42 and 73 years, with a median age of 57 years. Their symptoms included vertigo, dysarthria, syncope, hemiparesis, and homonymous quadrant anopsia. The etiologies of the stenoses involved kinking in 12 cases and mechanical compression due to cervical sympathetic nerve, osteophyte, or fibrous bands in two cases. Digital subtraction angiography revealed that stenosis was maximal at systole and minimal at diastole in six of eight cases. In two of the 14 cases, stenosis was not demonstrated in the neutral position, but stenosis of the left vertebral artery appeared when the head was rotated to the right. Surgical procedures involved 13 decompressions of the vertebral artery and one subclavian artery-vertebral artery bypass using the saphenous vein. Postoperatively, 12 cases of miosis and one of asymptomatic phrenic nerve palsy were observed, but there were no serious complications. All but two patients had complete resolution of their symptoms. Stenosis due to kinking and/or mechanical compression disappeared in all cases after decompression of the vertebral artery. The effects of arterial pulse and neck rotation on vertebral artery stenosis in the distal first portion are discussed.

Fourteen patients with symptoms of vertebrobasilar insufficiency caused by vertebral artery stenosis in the distal first portion underwent surgical reconstruction. They ranged in age between 42 and 73 years, with a median age of 57 years. Their symptoms included vertigo, dysarthria, syncope, hemiparesis, and homonymous quadrant anopsia. The etiologies of the stenoses involved kinking in 12 cases and mechanical compression due to cervical sympathetic nerve, osteophyte, or fibrous bands in two cases. Digital subtraction angiography revealed that stenosis was maximal at systole and minimal at diastole in six of eight cases. In two of the 14 cases, stenosis was not demonstrated in the neutral position, but stenosis of the left vertebral artery appeared when the head was rotated to the right. Surgical procedures involved 13 decompressions of the vertebral artery and one subclavian artery-vertebral artery bypass using the saphenous vein. Postoperatively, 12 cases of miosis and one of asymptomatic phrenic nerve palsy were observed, but there were no serious complications. All but two patients had complete resolution of their symptoms. Stenosis due to kinking and/or mechanical compression disappeared in all cases after decompression of the vertebral artery. The effects of arterial pulse and neck rotation on vertebral artery stenosis in the distal first portion are discussed.

The vasopressor response (Cushing) in patients with high intracranial pressure (ICP) has been thought to be a result of lower brainstem dysfunction. This study was carried out to study the effect of stimulation of the reticular formation of the medulla oblongata on ICP and cerebral blood volume (CBV) in injured brain with increased ICP. The CBV was measured by the photoelectric method from the uni- or bilateral parietal lobe. Seventeen hours prior to the experiments, cold-induced edema was produced to increase basal ICP. In 15 cats, electric stimulation produced temporary increases in blood pressure (BP), ICP, and CBV and progressive intracranial hypertension was never observed (group A). In 9 animals, progressive increases in CBV and ICP up to 50-100 mmHg occurred after cessation of stimulation (group B). Prestimulation ICP in group B was significantly higher than that of group A (p less than 0.01). Rapid and simultaneous increases in ICP and CBV following stimulation strongly suggested that global increments of CBV secondary to loss of cerebral vasomotor tonus were responsible for producing progressive intracranial hypertension. In group B, the stimulation electrodes were invariably located at the area of the nucleus reticularis parvocellularis and gigantocellularis. Our experimental results show that under conditions of increased ICP, a stimulated or irritable condition of the medullary reticular formation will cause temporary or progressive intracranial hypertension.

In severely head-injured patients with intracranial hypertension, irregular vital signs are frequently observed indicating medullary dysfunction. This study was carried out to investigate the effects of stimulating the medullary reticular formation on brain edema and ICP in a cerebral contusion model.

The authors have reported that in patients with uncal and central herniation, lengthening of the latency and deterioration of the wave form of the auditory brain stem response (BER) wave V, which originates in the inferior colliculus, correlated well with a rostrocaudal neurological impairment after pupillary change (Nagao et al. 1983). In this study, further investigations were carried out on whether or not the changes in BER wave V are related to the development of uncal herniation before pupillary changes and to obtain objective parameters, with which to assess the effectiveness of medical decompression of ICP in the stage of uncal herniation, manifested by pupillary change (Plum and Posner 1980).