Evaluation of brain metabolism in steno-occlusive carotid artery disease by proton MR spectroscopy: a correlative study with oxygen metabolism by PET.

UNLABELLED: Carotid occlusive diseases may cause ischemic changes in both the gray matter and the white matter as a result of hemodynamic compromise. To validate the use of proton magnetic resonance spectroscopy (MRS) in evaluating the carotid occlusive diseases, we compared changes in peaks of choline, in the sum of creatine and phosphocreatine, and in N-acetyl-aspartate (NAA) of the white matter with cortical oxygen metabolism measured by PET. METHODS: Eleven patients with unilateral steno-occlusive carotid artery disease underwent PET and MRS. Ten age-matched healthy volunteers underwent MRS. No subjects had cortical infarction. MRS was performed bilaterally in the centrum semiovale. Regional blood flow, regional metabolic rate of oxygen (rCMRO2), and regional oxygen extraction fraction (rOEF) of the cerebral cortex were measured by the steady-state method with 15O gas. RESULTS: The asymmetry index of the ratio of NAA to the sum of creatine and phosphocreatine (NAA/Cr) correlated positively with the asymmetry index of rCMRO2 (r = 0.77; P < 0.01). Because rCMRO2 is a marker of tissue viability, the NAA/Cr of the centrum semiovale may reflect viable neuronal cells. The asymmetry index of the ratio of choline to the sum of creatine and phosphocreatine (Cho/Cr) showed a significant positive correlation with the asymmetry index of rOEF (r = 0.65; P < 0.05). All but 1 patient with an increased Cho/Cr (>1.03) showed an increase in rOEF of the ipsilateral cortex (>0.56). This finding may indicate membrane damage caused by ischemia, because the centrum semiovale is the deep watershed zone. CONCLUSION: The metabolic changes in the centrum semiovale detected by proton MRS reflect a hemodynamically compromised state and are useful in evaluating tissue viability.

Abnormal magnetization transfer ratios in normal-appearing white matter on conventional MR images of patients with occlusive cerebrovascular disease.

BACKGROUND AND PURPOSE: Chronic hypoperfusion may cause ischemic insult in the deep white matter. The magnetization transfer phenomenon is associated with the amount and constitution of myelin. The purpose of this study was to assess the usefulness of the magnetization transfer ratio (MTR) for detecting vasculometabolic abnormalities on positron emission tomography (PET) studies in patients with unilateral severe stenosis of the internal carotid artery (ICA). METHODS: MTR maps and PET data-including regional cerebral blood flow (rCBF), regional cerebral metabolic rate of oxygen (rCMRO(2)), and regional oxygen extraction fraction (rOEF)-were investigated in 13 patients with unilateral severe stenosis of the ICA. The same regions of interest were selected in the white matter both on MTR maps and PET scans. The areas were classified into three groups based on MTR values (group 0, MTR >47.22%; group 1, MTR = 45.77% to 47.22%; group 2, MTR <45.77%), and the relationship between MTR and PET data was analyzed by means of both absolute values and asymmetric index (AI). RESULTS: Abnormal values could not be detected in the areas classified as group 0. The areas classified as group 1 were characterized by absolutely normal values of rCMRO(2) and increased rOEF with AI, which was assessed as viable and reversible on the PET study. The areas classified as group 2 showed decreased rCMRO(2) with absolute values, which was considered irreversible in PET. A significant overall linear correlation was found between MTR and rCMRO(2) values. CONCLUSION: Using the MTR technique to classify ischemic damage into three groups (normal, reversible, and irreversible), we found a significant correlation between the reduction of MTR and that of rCMRO(2) in white matter with ICA stenosis. We believe that the MTR technique may partly replace PET data in the assessment of ischemic injury.

Growth-inhibitory effect of prostaglandin D2 on mouse glioma cells.

The effects of prostaglandin D2 (PGD2) on the growth of mouse malignant glioma cells were studied in vitro and in vivo. The in vitro studies consisted of various concentrations of prostaglandins (PG's) being added to cultures of mouse glioma cells. At concentrations above 2.5 micrograms/ml, PGD2 strongly inhibited the proliferation of glioma cells, whereas PGE2 had no effect at the same value. Exposure to 5.0 micrograms/ml PGD2 for more than 2 hours resulted in inhibition of glioma cell proliferation. This growth-inhibitory effect of PGD2 was related to the inhibition of DNA synthesis of the cells. The in vivo studies were performed with a subcutaneously transplanted mouse glioma model. Injection of 0.5 mg/kg PGD2 into the tumor was more effective than the same concentration given by intraperitoneal injection. In mice with intracranially transplanted glioma, daily intraperitoneal injection of 0.5 mg/kg PGD2 had no significant effect on survival time.

Intra-arterial ACNU therapy for malignant brain tumors. Experimental studies and preliminary clinical results.

The authors examined the growth rate of mouse 203 glioma cells in vitro and found it to be markedly inhibited after exposure to ACNU for 5 minutes at a drug concentration of 100 micrograms/ml. Rats that had undergone intracranial implantation of T1 neurogenic tumor were treated by 5 mg/kg of ACNU administered either intravenously or intra-arterially. The median survival times for the control animals and the animals undergoing intravenous or intracarotid administration of ACNU were 23, 29, and 46 days, respectively. The difference in survival time between the intravenous and intracarotid administration groups was statistically significant (p less than 0.01) when examined by the Cox-Mantel test. In a clinical trial, 17 patients with glioblastoma were treated by ACNU, eight intravenously and nine by the intra-arterial route. The drug was given in doses of 2 to 3 mg/kg at least twice before and twice after a course of postoperative radiotherapy. Intra-arterial administration was performed over a period of 5 minutes under local anesthesia. The median postoperative survival time for the patients in the intra-arterial group was 12.5 months, compared with 9.0 months for those in the intravenous group. The survival rate for the intra-arterial group was slightly higher, although statistically not significant, probably because the number of cases was small. The degree of thrombocytopenia due to ACNU tended to be less marked in the intra-arterially treated patients. The theoretical advantages of the intra-arterial administration of ACNU are discussed.

Deep Sylvian meningiomas.

A case of deep Sylvian meningioma in a 35-year-old woman was precisely diagnosed preoperatively with the aid of computed tomography and stereoscopic cerebral angiography. On reviewing the literature, it appears to be the first case that has been accurately diagnosed preoperatively and successfully treated by a total excision without serious complication. We report this case in detail together with another, similar case which we had encountered previously.

Ruptured aneurysm of the distal posterior inferior cerebellar artery in a neonate--case report.

A 34-day-old male presented with a rare neonatal ruptured aneurysm of the distal posterior inferior cerebellar artery manifesting as a 10-day history of enlargement of head circumference. Magnetic resonance imaging revealed hydrocephalus and a round infratentorial enhanced lesion which compressed the medulla. Left vertebral angiography demonstrated an aneurysm on the telovelotonsillar segment of the left posterior inferior cerebellar artery. Ventriculoperitoneal shunt emplacement and proximal artery clipping were performed. The cerebrospinal fluid was bloody, suggesting aneurysm rupture had caused hydrocephalus. His postoperative course was uneventful, and neurological and developmental findings were normal 7 months later. Present neuroimaging, surgical, and neuro-anesthesiology techniques allow successful surgical intervention in cases of neonatal ruptured aneurysm.

Recurrent malignant histiocytosis with cerebrospinal involvement--case report.

A 61-year-old male presented with recurrent malignant histiocytosis of the brain manifesting as nausea and headache. Malignant histiocytosis is a disorder of proliferating histiocytes characterized by a rapidly progressive and fatal course, but central nervous system involvement is relatively rare. Magnetic resonance (MR) imaging demonstrated cerebrospinal fluid (CSF) dissemination of histiocytes as a low-intensity area on the T1-weighted image with marked gadolinium-diethylenetriaminepenta-acetic acid enhancement and a high-intensity area on the T2-weighted image. CSF cytological examination revealed an increased level of atypical histiocytes. Brain and spine irradiation, and intrathecal methotrexate and prednisolone administration induced remission. MR imaging is particularly useful for the diagnosis of meningeal dissemination of malignant histiocytosis.

Transient ischemic attack due to dissection of the middle cerebral artery--case report.

A 57-year-old man presented with a transient ischemic attack due to dissection of the middle cerebral artery. He suffered total aphasia and clouding of consciousness for several minutes. On admission, he was alert without neurological deficit. Magnetic resonance (MR) angiography and conventional angiography depicted irregularity and double lumen of the left middle cerebral artery. The diagnosis was dissection of the middle cerebral artery. After 1 month, he left our institute with no neurological deficit. Transient ischemic attack associated with dissection of an intracranial artery is unusual. The source images of MR angiography are useful for the essential follow up of dissection.

[Transportation of cefotiam from serum to cerebrospinal fluid (author's transl)].

Cefotiam (1 g) was administered by one-shot intravenous injection to the patients proceeding a brain surgery. The cerebrospinal fluid (CSF) and serum were taken as a specimen, and the concentration CTM was assayed by agar-well method using Proteus mirabilis ATCC 21100. The most high concentration of CTM was 2,273 micrograms/ml in serum, and 2.3 micrograms/ml in CSF, respectively. The concentration of CTM in serum, CSF, and CSF/serum ration were determined at the indicated time. It appears likely that CTM can pass into CSF more easily than other cephalosporins.

[Autosensitization of neurosurgical cases by normal brain tissue antigens (author's transl)].

The leukocyte reactions of 106 neurosurgical cases, including 63 brain tumors, 10 intracerebral hematomas, 10 cerebral infarctions, 10 subarachnoidal hemorrhages, 8 cerebral injuries and 5 chronic subdural hematomas, against the extracts of gliomas and normal brain tissues were tested by capillary migration (LMI) and adherence inhibition (LAI) assays. Both tests showed specific responses with autochthonous and allogeneic glioma extracts in glioma patients. The sensitivity of LAI was superior to that of LMI, although LAI also showed adherence enhancement in the presence of weakly sensitized leukocytes or weak antigenic stimuli. Leukocytes from glioma patients showed positive inhibition with normal brain tissues from patients with glioma and intracerebral hematoma. Positive leukocyte reactions with normal brain tissues were also confirmed in patients with intracerebral hematomas, cerebral infarctions and severe cerebral lacerations, but not in those with subarachnoidal hemorrhages, minor cerebral contusions and chronic subdural hematomas. These results suggest that the leukocytes of patients with destructive brain lesions were autosensitized by normal brain antigens. The autosensitization has some advantages in that destroyed brain tissues are eliminated, but the hyperimmune state might cause postictal brain edema and should be properly controlled by steroids.

[Intracerebral picibanil injection in the rat neurogenic tumor--its histopathological changes].

Penicillin-free-Picibanil was injected into the brain of Wistar/Fibiger strain rat to investigate the histological changes. Its effect on the growth of rat schwannoma inoculated in the brain was also examined histologically. Picibanil caused the most prominent but focal lymphoreticular cell reaction around the injected site in the brain 24 to 48 hours after injection. The cells infiltrating from the blood vessels were neutrophils, monocytes, lymphocyte-like cells, histiocyte-like cells and unidentified cells. This lympho-reticular cell reaction gradually subsided in the next 4 to 5 days. Neutrophils and monocytes (macrophages)stayed till the later phase. Two weeks later, the lesion was minimal with only mild glial changes. Picibanil was however, considered to exert at the site of injection neurotoxic and glia-toxic activity at a concentration of 0.1 KE/10 microliters. The rat schwannoma (T1) cells, when inoculated without any treatment, showed vivid growth in the brain and no lympho-reticular cell reaction was observed. When the T1 tumor cells, suspended in the Picibanil solution, were inoculated into the brain, no lymph-reticular cell reaction was observed 7 and 14 days after inoculation. However, when the rat was pretreated with Picibanil into the brain 7 days before inoculation, only a mild lymphoreticular cell reaction was observed around the T1 cells till 7 days after inoculation. Accordingly, Picibanil was considered to induce nonspecific immunological in the rat brain even around the glioma.

[Predictability of EC/IC bypass function: a retrospective study].

Although the efficacy of extracranial/intracranial bypass for reduction of risk of ischemic stroke has been denied, we have encountered patients in whom bypass operation seems to have improved his or her clinical course. The efficacy of bypass should be evaluated not by the patency of the bypass but by the extent of collateral circulation brought about by the bypass. We retrospectively analyzed our patients to determine whether the extent of bypass flow could be predicted from the results of preoperative studies. In 18 hemispheres of 18 consecutive patients who underwent extracranial/intracranial bypass surgery, correlation between the extent of bypass flow and the multiple preoperative factors including the angiographic findings were investigated. The bypass function was highly predictable in the light of preoperative studies. In all of 10 hemispheres in patients under 70 years of age and with occlusive lesions in the proximal portion of the middle cerebral artery, collateral circulation through the bypass developed to an extensive or a moderate degree. In 9 of 10 hemispheres in which an interval between the latest attack and the diagnosis of hemodynamic failure was 4 weeks or longer, collateral circulation through the bypass was shown to have developed to an extensive or a moderate degree. Our results indicate that extensive or moderate collateral circulation through the bypass can be expected only in patients under 70 years of age, with lesions in the proximal portion of the middle cerebral artery, and in whom an interval between the latest attack and diagnosis of hemodynamic failure was 4 weeks or more.

[RI cisternography in the diagnosis of brain tumors (author's transl)].

Fifteen cases of brain tumors of supratentorial location were studied by RI cisternography; Cisternographical patterns of decreased or absent radioactivity were classified into five groups as follows: Pattern I: Sharply circumscribed and localized decrease in radioactivity; Pattern II:Ill-defined and focal decrease in radioactivity; Pattern III: Areal decrease in radioactivity involving one whole or two lobes; Pattern IV: Hemispherical decrease in radioactivity and Pattern V: Total decrease in radioactivity in the head. Each pattern appears to correspond well with topographical features of brain tumors and their related pathology, such as extracerebral tumors (pattern I), intracerebral but superficially located tumors (pattern II), extracerebral tumors with surrounding edema or large intracerebral tumors (pattern III), extracerebral or intracerebral tumors with increased intracranial pressure (pattern IV), and extremely increased intracranial pressure regardless the site of tumor (pattern V). In consideration of these patterns, RI cisternography would be a more useful supplementary method in diagnosis of brain tumors to detect the area involved, to differentiate an intracerebral from an extracerebral tumor, and to find a recurrence of the tumormfurthermore, it is helpful to know the therapeutical effects of surgery and radiotherapy. RI cisternography is a simple, relatively noninvasive method which can be used more widely.

[Treatment of tuberculous meningitis: marker of cure].

A 49-year-old male with tuberculous meningitis was reported. When admitted to our hospital with mild right hemiparesis, he was alert but he developed disorientation 7 days later. A diagnosis of tuberculous meningitis was reached because of elevated levels of adenosine-deaminase at 19.6U/liter in the cerebrospinal fluid. MRI showed a marked enhancement in the basal cisterns and an enhanced intraparenchymal lesion in the brainstem. Chronological changes of MRI findings did not closely correlate with the clinical course. Slight meningeal enhancement on MRI seems to remain for a long time without active tuberculous meningitis, and absence of the meningeal enhancement on MRI is not necessarily appropriate as a marker of cure of tuberculous meningitis.

[The bone scintigraphy in eosinophilic granuloma (author's transl)].

The significance of bone scintigraphy using 99mTc-polyphosphate or 99mTc-diphosphate in the diagnosis of eosinophilic granuloma was discussed on the basis of our experience with four cases. The summary is following: 1. On diagnostic procedure of eosinophilic granuloma, it was found that abnormal RI accumulation in the bone scintigram was more marked than that in the ordinary brain scintigram. 2. The bone scintigram of eosinophilic granuloma showed more accurately the extent of skull involvement of cellular infiltration than the plain skull X-rays or brain scintigram. Accordingly, the bone scintigram was helpful for neurosurgeon in planning the operative procedure and determining the extent of removal of the involved skull. 3. The plain skull X-rays show the size of skull defect, and the brain scintigram reveals the size of the size of granuloma per se, as well as soft tissue involvements. We can conjecture the stage of the diseases by comparison between the findings of bone scintigram and those of above procedures: plain skull X-rays and brain scintigram. Viz, the bone scintigram showed more extensive areas of RI accumulation including the surrounding cellular infiltration in the acute stage, but the same size of the lesions shown by the ordinary brain scintigram and plain skull X-rays is chronic stage. Furthermore, we discussed the possibility of the differential diagnosis between eosinophilic granuloma and other neoplastic bone diseases, such as intracranial metastatic tumors and multiple myelomas etc., by further experience with the bone scintigram.

[A case of chondroblastoma with intracranial extension].

A case of chondroblastoma with intracranial extension from middle cranial base is reported here. Chondroblastomas usually arise from the epiphysis of long bone. Intracranial chondroblastomas are very rare and only 14 cases have been reported. Histological feature of this tumor is to have numerous multinucleated giant cells resembling the giant-cell tumor. But this case has the typical features of chondroblastoma in the histological, immunohistochemical, and electron microscopical studies.

[Localization of the pyramidal tract in the internal capsule: relationship between CT classification of thalamic hemorrhage and motor weakness].

To better understand the pyramidal tract of the internal capsule, we evaluated the relationship between the localization of thalamic hemorrhage and motor weakness. On an axial CT scan at the level of the pineal body, two lines were drawn as follows: line-a between the lateral edge of the anterior horn and the lateral edge of the trigone, line-b vertical to the sagittal line and passing the midpoint of the third ventricle. The location of the hematoma was classified into three types according to localization of the center of the hematoma and lateral extension beyond line-a as follows: type A (anterior), type P (posterior) and type PL (postero-lateral). Discrepancy of motor weakness between upper extremities and lower extremities was higher in patients with hematoma of type P and type PL (p < 0.05) than in those with hematoma of type A. Improvement of motor weakness on discharge was higher in patients with type P (p < 0.01) than in those with type A. We concluded that most of the pyramidal tract fibers were located in the third quarter of the posterior limb of the internal capsule but a small number of pyramidal tract fibers were located in the anterior two-thirds of it. A greater number of cortico-spinal fibers to the upper extremities than to the lower extremities occupy the third quarter of the posterior limb of the internal capsule.

[A case of successful acute revascularization using a long vein graft].

We experienced a case of successful acute revascularization using a long vein graft. A 68-year-old man was admitted to our department due to transient ischemic attack of the left hemiparesis. CT scan showed no infarction, but PAO-SPECT revealed moderate hypoperfusion in the right ACA and MCA area. Cerebral angiography demonstrated right IC occlusion at its origin and moderate collateral circulation via leptomeningeal anastomosis from the PCA area, and via the external carotid system, especially directly from STA. But the STA was very narrow. Three days after admission, left hemiparesis appeared again and deteriorated severely. This time the hemiparesis persisted. Although MRI demonstrated little infarction in the right frontal lobe, we decided to carry out revascularization on the same day. Right saphenous vein was harvested for a graft because of the narrow STA. The facial artery and angular artery was selected as a donor and a recipient respectively, to avoid a clamp of the EC and a craniotomy of the STA running area. Finally we performed a facial artery-vein graft-angular artery (M4) bypass. The patient showed no complication and the left hemiparesis improved enough to allow the patient to walk by himself. Revascularization using vein graft is dangerous for acute ischemia due to the possibility of a complication such as brain edema and hemorrhagic infarction. The usual style of vein graft bypass is an EC-vein graft-M2 or M3 bypass. Using this style, high pressure inside the EC is carried intracranially.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of brain tumors with anticancer pellet--experimental and clinical study (author's transl)].

Eighty three patients suffering from brain tumors have been treated by anticancer pellets containing 5-FU, urokinase, mitomycin and BUdR in dimethylsiloxan (Silastic) for three years. Constant and prolonged release of the chemicals from the anticancer pellet had already been proved in vitro. The amount of daily release were 1-3/1,000 of original volume. Tissue concentration of 5-FU was measured by bioassay system using staphylococcus 209 P strain with plate dilution method. In spite of the rapid disappearance of serum 5-FU, the local high accumulation of 5-FU was demonstrated in vivo. In rat neurogenic tumor, 1.104 microgram/g was detected on 60 days after the application of anticancer pellet containing 500 mg of 5-FU. The growth of tumor was also suppressed. The clinical study consists of 83 patients, 30 of glioblastoma, 19 of metastatic brain tumor, 13 of astrocytoma, 7 of oligodendroglioma, 4 of ependymoblastoma, 4 of malignant lymphoma and 6 of others. The median survival time of gliblastoma was prolonged to 71.5 weeks by the implantation of anticancer pellet from 40 weeks of control group. However, the median survival time of astrocytoma and metastatic brain tumor were 24 and 6 months, respectively, which have no significant difference from control groups. In the patients of metastatic brain tumor, the regrowth of metastatic foci in the brain was completely suppressed. However, most of them were succumbed from the original tumors. The concentration of 5-FU in several human tissue was measured in ten patients with different time intervals after the implantation of the anticancer pellet. Although they have different histologic patterns, the concentrations of 5-FU in human brain tumors were ranged from 0.05 to 0.67 microgram/g by 14 months after the implantation of the anticancer pellet. The adjacent cystic fluids also contain from 0.62 to 4.9 microgram/ml of 5-FU for two years. These results mean that they are keeping higher level of 5-FU than the tumoricidal level of 5-FU (0.056 microgram/g) for more than two years. On the other hand, no respective accumulation was demonstrated in other tissues. None of the patients showed any adverse reactions except a continuous slight fever up to 38 degrees C.

[Clinical application of a sustained release anticancer pellet].

During a 6.5-year period from March 1978, 136 patients with brain tumors, which were diagnosed as gliomas or metastatic brain tumors during surgical operation, were treated by the application of sustained release anticancer pellets in seven institutes. Histological diagnosis disclosed that the majority of the tumors were malignant gliomas (61 cases), metastatic brain tumors (35 cases), and benign astrocytoma (17 cases). The anticancer agents (250 mg of 5FU, 1.5 mg of MMC, 250 mg of BUdR and 6,000 iu of urokinase) were sealed in a Silastic silicone tube of 6 mm in diameter, 0.25 mm in wall thickness, and 12 mm in length. The daily delivery of the drugs was (2-3)/10,000 of the original volume. This treatment was combined with surgical and irradiation therapy with or without general chemotherapy. The median survival time of patients with malignant gliomas was 545 days (18 months). The 1-year survival rate was 65.63%, and the 3-year survival rate 16.2%. On the other hand, in patients with benign astrocytomas, the median survival time was 1,500 days (4.1 years), 1-year survival rate 83.75%, and 3-year survival rate 42.84%. In those with metastatic brain tumors, the median survival time was 280 days, 1-year survival rate 43.87%, and 3-year survival rate 24.84%. The present findings revealed that the tube-type anticancer pellets cannot inhibit the growth of the brain tumors located 5 cm from the pellets.