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Patients with laterocollis or rotatory type torticollis tend to show abnormal contraction of the levator scapulae muscle and the scalene muscles. These muscles are innervated from the anterior branches of the cervical spinal nerves. Because of this, the traditional Bertrand operation dealing with posterior branches does not adequately affect the symptoms of laterocollis. The authors report selective denervation of the levator scapulae muscle in three patients and discuss its rationale. All the three patients underwent denervation of both the C1-C6 posterior spinal rami and the branches from the C3 and C4 anterior rami to the levator scapulae muscle. We added myotomy of the scalene muscle in one patient, and denervation of the omohyoid muscle which is innervated from the ansa cervicalis and the descending branch of the hypoglossal nerve. The pre/post-operative Tsui scores were 12/4, 15/1, and 14/3 respectively. There were no complications. We conclude that selective peripheral denervation of the levator scapulae muscle is safe and effective in the treatment of laterocollic type torticollis.

A 32-year-old female presented with about a week's history of dull pain in the head and neck pain. On the day of admission, she experienced a sudden onset of severe pain, extending from the occipital to the lower back region and hypesthesia and paresthesia of the right C8-Th3 dermatome. On admission, she was alert but there was a band of hypesthesia and paresthesia at the level of C8-Th3. Cervical X-ray, computed tomography scan (CT) and magnetic resonance images (MRI) of the head revealed no definite abnormalities. The peripheral blood picture was normal, and the bleeding and clotting times were in the normal range. The cerebrospinal fluid (CSF) was bloody and the CSF pressure was 220 mm H2O. An emergent 4-vessel intracranial angiography disclosed no abnormal findings. MRI and myelography revealed an intradural extramedullary lesion extending from the Th2 to the Th5 levels, ventral to the spinal cord. A T1-weighted MR image showed iso-low intensity and a T2-weighted MR image showed low intensity at these lesions. Spinal angiography revealed no abnormal vessels. In one month, spinal compression cleared gradually without surgery and her clinical symptoms disappeared about 40 days after admission. Spontaneous spinal subdural hematoma is uncommon and only 28 cases have been reported. 15 cases have been treated with surgical procedure, but spinal compression cleared spontaneously in this case. This spontaneous recovery is such a rare event that only 3 such cases have been reported in the literature. However, with the prevailing MRI, this disease will be detected more frequently in the future.

The ischemic area surrounding the cerebral infarction in the eloquent area was salvaged by STA-MCA bypass surgery. Both the misery perfusion area evaluated by positron emission tomography (PET) using the [15O] gas inhalation steady-state method and clinical symptoms improved within a year after surgery. To confirm the ischemic area and select the suitable recipient artery was important for successful bypass surgery, because only an artery covering the ischemic area is expected to have low resistance. In this case a large ischemic area with disturbed, vasodilatation by Diamox was detected on the SPECT. However, PET clearly exposed the localized misery perfusion area in the overestimated ischemic area by SPECT. We describe our experience and discuss the technique and efficacy of PET for STA-MCA anastomosis surgery.

A drug delivery system using copoly (lactic/glycolic acid) was developed for the intrathecal administration of nicardipine. This system was tested to determine its efficacy in preventing cerebral vasospasm in dogs. A rod-shaped implant (1-mm diameter, 10-mm long and which contained approximately 10% of nicardipine) was prepared by a heat compression method. In in vitro studies, 8% of the actual nicardipine loaded was released during day 1, 17% within day 2, 62% within day 4, and 96% within day 10. In in vivo studies, 12 dogs were assigned to two groups: the placebo group and the group treated with nicardipine. Angiography before the experiment was performed followed by right craniectomy and induction of subarachnoid hemorrhage by the placement of a clot in the Sylvian fissure. Eight pellets, either containing 8 mg of nicardipine or without nicardipine were placed in the cistern. On day 7, the angiography was repeated and cerebrospinal fluid was removed from the cisterna magna. The animals were then sacrificed, and the brain and blood clot were taken out. Cerebral vessels were measured three times with a calibrated optical micrometer, and the mean value was obtained. Average reduction of vessel diameters on the clot side in the placebo and nicardipine groups were -37% and -10% on the internal carotid (IC), -48% and -3% on the middle cerebral (MC), and -28% and -1% on the anterior cerebral artery (AC), respectively. There were significant differences in vessel diameters of IC (p0.05), MC (p0.005), and AC (p0.05) between these groups. No vasospasm was found in the left side. The nicardipine concentration in the clot was determined by high performance liquid chromatography. The mean concentration of nicardipine in the clot was 1.5 x 10(-4)M, at which concentration sufficient relaxation is evoked in vitro. The pellets did not last beyond day 7. Regarding the histological findings, there was a marked difference in vessel diameters between the placebo and the nicardipine treated groups. The arteries were surrounded with red blood cells and inflammatory cells. There were no specific changes related to the pellets and no sign of meningoencephalitis. A prolonged-release preparation of nicardipine that can be implanted intracranially at the time of surgery prevented vasospasm significantly in dogs. These results suggest that this new drug delivery system might be put into effect favorably in patients suffering from vasospasm due to subarachnoid hemorrhage.

The authors evaluated the results of selective peripheral denervation (SPD) of posterior rami of the cervical spinal nerves and/or the accessory nerve for spasmodic torticollis. Five patients underwent seven operations in total and the results were evaluated with the modified Tsui's score which was used in the clinical trial of botulinum toxin (BTX) for torticollis in Japan. The preoperative score was 10.8 +/- 2.2 (mean +/- S.D.) and the postoperative score was 1.4 +/- 1.7. The score changes indicated the effects of the operation as "excellent" in four cases and "good" in one case. These results indicate that SPD is superior to BTX in terms of control of symptoms in spasmodic torticollis. After the initial operation, however, two patients showed the so-called "mole-hitting game phenomenon" in which normal muscles develop abnormal contraction after denervation of abnormal muscles. This forced us to perform the second operations. Although this phenomenon was first described in botulinum toxin treatment, this is probably the first report in surgically denervated cases.

A 23-year-old male with splenius type torticollis underwent selective denervation of C1 and C2 roots and C3-C6 spinal posterior rami, with excellent results. Based on this experience, we stress the importance of dynamic EMG and thorough review of video recording for identifying the involved neck muscles. In the operative procedures, the nerve rami are identified under the semispinalis muscle. To dissect the correct plane under the semispinalis muscle, the key point to keep in mind is to follow the great occipital nerve to the proximal part. An ultrasonic blood flow meter is useful to locate the vertebral artery in the spaces between the occiput and the C1 lamina and between C1-C2 laminae. Because fine nerve branches run in the soft tissues over the laminae, to avoid transient neuroapraxia, dissection around the C1, C2 arches should not be carried out under the periosteum, as is usually done in case of laminectomy. Dissection of C1 and C2 rami as far as the very medial part is rather difficult because of bleeding from the venous plexus and the presence of the vertebral artery. Therefore, the intradural approach might be easier for sectioning the C1 and C2 roots. We would like to add these points to the original description by Bertrand.

The chemotherapy for malignant brain tumors creates two major problems to be solved viz systemic toxicity and interference by the blood brain barrier. The interstitial chemotherapy with sustained release of anticancer drugs has been widely investigated to overcome these problems. The Mitomycin C (MMC) - contained fibrin glue might be a promising candidate for use in local chemotherapy of malignant brain tumors. We investigated pharmacokinetics of the MMC-contained fibrin clot in vitro, activity of the MMC for the cultured glioma cell line, and its effect on the normal mouse brain. The MMC concentration in saline was measured up to 96 hours after the placement of fibrin glue into 5, 10 and 15 ml of saline. Then we periodically replaced the saline to keep the concentration difference of the MMC between the saline and the fibrin clot and evaluated the dissolution of the MMC for 288 hours. The potency of the MMC to suppress the rat glioma cell line was measured after being dissolved from the MMC-contained fibrin clot. The effects of the MMC-contained fibrin clot were histologically evaluated. The MMC-contained fibrin glue, the MMC solution and the fibrin glue were separately injected into the mouse brains. Mice were sacrificed 24, 72, 168 and 336 hours after the injection and brains were examined with photomicroscopy. The MMC was released into the saline rapidly within 24 hours then gradually released until 96 hours had elapsed. Total amounts of the dissolved MMC were proportional to the amounts in the saline.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report a case of an intracavernous internal carotid artery aneurysm associated with a persistent trigeminal artery variant (PTAV). A 47-year-old-woman developed a subarachnoid hemorrhage due to the rupture of aneurysm and underwent direct clipping operation. PTAV is basically an anomalous anastomosis between the internal carotid artery and the anterior inferior cerebellar artery. In this patient, the PTAV originated from the C4 portion of the right internal carotid artery and distributed in the territory of the hemispheric branch of the posterior inferior cerebellar artery. There have been only three reported cases of the internal carotid artery aneurysms arising from the crotch of PTAV. It is also unusual that rupture of such a small aneurysm in the cavernous sinus causes subarachnoid hemorrhage. Embryological development of PTAV and possible mechanism of subarachnoid hemorrhage from the intracavernous aneurysm are discussed.

Giant aneurysm arising from the distal segment of the anterior cerebral circulation is extremely rare, and only 14 cases of anterior cerebral circulation aneurysms have been reported in the literature. This report describes two cases of giant intracranial aneurysms, one arising from the distal segment of the middle cerebral artery, and the other from the azygos anterior cerebral artery. Although both of the patients started with intracranial hemorrhage, their surgical outcomes were good. The growth mechanisms of each aneurysm are discussed based on the clinical and pathological findings. Since the wall of the middle cerebral artery aneurysm showed granulomatous changes with infiltration of many inflammatory cells, the aneurysmal enlargement is considered to have resulted from chronic inflammation of the wall. In the case of anterior cerebral artery aneurysm, hemodynamic stress through the azygos artery may have caused the giant aneurysm. Operative indication for giant intracranial aneurysm is controversial. Since the surgical outcomes of reported cases are definitely better than those of the patients with proximal giant aneurysm, we conclude that giant aneurysm arising from the distal segment of the cerebral artery should be treated surgically.

A 42-year-old man suffered from numbness in his right leg in May, 1989, and was admitted to another hospital for examination. Computed tomography and magnetic resonance imaging revealed thoracic intramedullary tumor and multiple intracranial tumors in the right frontal convexity, the right lower surface of the tentorium and the right parietal parasagittal region. In December, he underwent craniotomy and the right frontal tumor was totally removed. It was diagnosed histologically as meningioma. Because of continuing numbness in his right leg, he visited a neurologist at our university and was referred to us for removal of the spinal tumor on April 25, 1990. Neurological examination on admission revealed mild weakness of his right leg and exaggerated right knee jerk. Though he complained of numbness in his right leg, no sensory disturbance was demonstrated objectively. His bladder-bowel function was normal. There were no café au lait spots or subcutaneous neurofibromas. He and his mother were positive for anti-HTLV-1 (human T-lymphotrophic virus type 1) antibody. On May 1, laminectomy was performed at Th-7 to Th-9, and a yellowish brown tumor was found occupying the right posterolateral portion of the cord and extending to the surface. The dorsal root of Th-9, which was involved in the tumor, was cut and the tumor was subtotally removed. Histological examination showed interlacing bundles of spindle cells and loose areolar region. Immunohistochemically, the tumor was positive for S-100 protein and negative for GFAP. From these findings, the tumor was diagnosed as neurinoma. The postoperative course was uneventful, numbness disappeared, and the patient was discharged without neurological deficits.

Twelve infants with choroid plexus tumors were reviewed retrospectively. Enlarging head circumference, bulging fontanelle, and vomiting were the major symptoms and signs appearing 2 to 5 weeks (mean = 3.7 weeks) before diagnosis. The average age at diagnosis was 7.7 months. Total removal was performed in 11 patients with choroid plexus papilloma, and partial removal was achieved in 1 patient with a choroid plexus carcinoma. A cerebrospinal fluid (CSF) diversionary shunt was placed temporarily in 6 infants and permanently in 4. Of the two patients not requiring CSF diversionary shunt, 1 needed a subdural-peritoneal shunt postoperatively. Histologically, 11 of 12 tumors were choroid plexus papillomas, and one was a choroid plexus carcinoma. All 12 patients were followed up for 4 months to 11 years (mean = 5.6 years). Eleven of 12 patients were alive at the time of their last check-up. All 11 survivors had normal psychomotor and neurological development. The treatment and outcome of choroid plexus tumors and management of associated hydrocephalus are discussed.

The authors report a case of partially thrombosed giant aneurysm which was secondarily infected with purulent meningitis. The relationship between the infection of the aneurysm, the rapid growth of the aneurysm and the development of severe cerebral edema was discussed. A 53 year-old man was admitted on September 1, 1986, with a diagnosis of bacterial meningitis. On his admission, his body temperature was 39 degrees C, and he showed mental confusion but no neurological deficits. Laboratory data revealed signs of infection in white blood cell count, CRP, and erythrocyte sedimentation rate. Computerized tomographic (CT) scan and magnetic resonance (MR) imaging showed a massive round mass with perifocal edema measuring 40mm in the maximum diameter in the left paramedian frontal region. T1 weighted MR image also showed the presence of pus accumulation in the left ventricle. Cerebral angiography demonstrated a giant aneurysm at the distal portion of the azygos anterior cerebral artery, and irregular narrowing of both the supraclinoid segment of the carotid artery and its main branches indicating arteritis due to purulent meningitis. The patient was treated with ventricular drainage and administration of antibiotics. Culture of the purulent CSF was negative. The patient's lab data, CSF finding and neurological status improved progressively. However, follow-up CT scan and angiogram a month later showed enlargement of the aneurysm, dilatation of the patent lumen and perifocal edema. On October 8, the patient suddenly became comatose with anisocoria. A CT scan showed massive edema with marked midline shift. Emergency bifrontal craniotomy was carried out, and clipping was completed after removal of the thrombosed portion of the aneurysm, and thromboendarterectomy of the aneurysmal neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Head injury patients often complicate facial and/or multiple injuries other than cranio-cerebral insults and perplex the emergency staffs. The authors used Brighton epistaxis balloon for such patients with massive nasal bleeding and reported the utility of the balloon not only in such state of emergency but also for a few days to control the hemorrhage mostly caused by craniobasal fractures or rupture of the adjacent vessels. One hundred and twenty-nine patients were transported and hospitalized in Department of Emergency Medicine, University of Tokyo Hospital, Tokyo, Japan during the period from October, 1981 to January, 1983. Nasal bleeding was noted in 29 cases of them and the balloon was used in 10 cases, who were from 19 to 76 years of age, all males and suffered from basal fractures or craniofacial injuries. Six cases of them were also accompanied with fractures in the extremities or pelvis, hemopneumothorax and/or intra-abdominal bleeding and could not but put on "Military anti-shock trousers" for the management of hypovolemic shock, hence the nasal bleeding should be managed immediately in the emergency room. In these situations the balloon was inserted into both nasal cavities in all the patients, to control successfully the nasal hemorrhages one of which contaminated cerebrospinal fluid and three of which were sure to be pulsatile due to arterial injury. The Brighton epistaxis balloon is to be removed within twelve or twenty-four hours, but in the authors' cases the mean duration for the hemostasis was 58.9 hours for 6 survivors and 49.6 hours for all 10 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

The continuous intracranial pressure monitoring has been widely applied in intensive or critical care, but there are various kinds of methods for its monitoring at present. One hundred and forty-one cases mostly with severe head injury were subject to the intracranial pressure recordings in the critical care ward in Department of Emergency Medicine, University of Tokyo Hospital, from October, 1980 through May, 1983, and in Neurosurgical Unit, Showa General Hospital, in April and May, 1984. The authors made several methodological trials for the monitorings in them and compared with one another from the aspect of clinical practice. The subarachnoid catheter was inserted into the subarachnoid or sometimes into the subdural spaces by way of the burr hole in 112 cases and proved not to demonstrate in some cases the intracranial pressure waves clearly due to so called damping phenomenon but to indicate the reliable values, or trustworthy mean pressures in all the cases except for impending brain dead patients with swollen hemispheres and least cerebrospinal fluid remained in intracranial subarachnoid spaces. The ventricular fluid pressure was monitored in nine cases and was most dependable as well as the subarachnoid pressure. The ventricular cannulation and its maintenance were, however, difficult when the ventricles were compressed or deviated, which were often experienced in acute severe head injury and also in impending brain death just because of the same above mentioned reasons. These demerits were attempted to be conqured with epidural pressure monitorings such as the fiberoptic sensor (Ladd) in 17 cases, the intracranial catheter tip pressure transducer (Gaeltec) in nine cases and the sensor of bioimplantable polymer (Plastimed) in three cases.(ABSTRACT TRUNCATED AT 250 WORDS)

In the management of malignant brain tumors, it is important to know the extent and viability of tumors. However, an ordinary CT scan with iodine enhancement has only a limited ability to distinguish the tumor from surrounding normal tissue. Since the blood flow in tumor tissue was found to be relatively high in a previous experimental report, we have investigated the blood flow in a tumor and the surrounding brain. The Xenon enhanced CT method has several advantages over the conventional isotope method and enables us to evaluate rCBF with the same resolving power as with the CT scan. We evaluated rCBF in 15 brain tumor cases and obtained the following results. Mean rCBF value of the tumor is a little lower than that of gray matter and higher than that of surrounding edema. Our Xe-CT method enables us to distinguish the demarcation between the tumor area and the surrounding edematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumor which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumors. rCBF value and lambda value are important elements to know the uptake rate of anticancer drugs into the brain tumors. And to evaluate these value in each brain tumor is useful in the selection of chemotherapeutic agents.

The combined one-stage operations, STA-MCA anastomosis and internal carotid artery (ICA) ligation (or trapping) were carried out in 11 cases (Age): 18-79 yrs, Av.: 45.8 yrs) of ICA aneurysms which were inaccessible for a direct operation because of their locations and sizes. First the STA-MCA anastomosis was performed under general anesthesia. Then the patient was awaken and thereafter under local anesthesia the ICA was temporarily clamped for 30 min. under induced hypotension to check whether any ischemic signs appeared. This was followed by proximal ICA ligation when no ischemic signs were observed. In all 11 cases, the anastomosis was patent. The aneurysms disappeared. Neither cerebral ischemia nor rebleeding from the aneurysms was seen during the long follow-up. The mean value of the bypass flow was 119 m/min which was twice as much as that in the cases of other occlusive cerebrovascular diseases and which was about one third of the blood flow of the ICA. Cerebral blood flow measurements through 133Xe inhalation method revealed that there was no difference in rCBF values between the operated and non-operated sides and that their values were within normal limits. The postoperative blood pressure was unchanged in 42% of our 11 cases, temporarily elevated and thereafter normalized in 33% and persistently elevated in 25%. Ophthalmodynamometry showed that the pressure of the central retinal artery decreased postoperatively in a degree of 5-10% in comparison to the non-operated side. No visual impairment was observed postoperatively (except case 3, see the text). These combined operations, STA-MCA anastomosis and ICA ligation were beneficial in preventing the potential postoperative cerebral ischemia. Intra-arterial pressure measurements of the STA and MCA suggested that the one-stage operations of these two procedures are better than the two-stage operations for the patency of the anastomosis because the pressure gradient between the donor and recipient vessels is increased (from 10.3 mmHg to 49.3 mmHg) by this technique. Temporary ICA clamp for 30 min. under induced hypotension in local anesthesia is useful to check whether the one-stage operations can be tolerated or not. EC/IC bypass with an interposed saphenous vein graft is a more beneficial surgical technique than a routine STA-MCA anastomosis, because an immediate and larger amount of bypass flow can be obtained.

It has been known that various derangements in ionic homeostasis develop following neural trauma. In particular, potassium efflux out of and calcium influx into the cells are thought to play important roles in causing cell damage. Concomitantly we have previously reported that increased extracellular potassium per se provoked by head injury induces convulsive seizure such that the sustained high extracellular potassium leads to animal death. The purpose of the present study was further to examine the beneficial effect of drugs which could inhibit such detrimental ion movements in experimental head injury. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 gm dropped from a height of 17.6 cm above the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in about 70% and death in about 30% of animals. The severity of consciousness disturbance was evaluated by a pair of indices in time interval; time required for the recovery of righting reflex (RR) and for the recovery of spontaneous movement (SM). Ethacrynic acid, a loop diuretics, blocks carrier-mediated chloride transport into astroglia associated with sodium and water in the presence of high extracellular potassium. Animals were treated with either 0.5-1.0 mg/kg or 2.0-4.0 mg/kg of ethacrynic acid administered via tail vein 10 min before injury. In the other group of animals, a calcium entry blocker, flunarizine was injected intraperitoneally in doses 5, 10 and 20 mg/kg one hour pre-insult.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors previously reported the effect of preoperative factors affecting the reduction of chronic subdural hematoma. In this report, we evaluated some operative factors, including operative methods, duration of drainage, and residual air volume, with newly developed CT volumetry technique. As described before, the hematoma volume reduces exponentially. An exponential curve was fitted to the reduction curve using the least square method, and its half reduction days (HRD) was calculated. This HRD represents a mathematical indicator of the reduction rate of CSDH. Using this technique, the relationship between this HRD and operative method, the duration of drainage and the volume of the postoperative residual air were examined in 61 patients. Operative method (burr hole or small craniotomy) has no correlation with HRD. The duration of drainage also has no correlation. However, the volume of the residual air was highly correlated with the reduction rate of hematoma (r = 0.430; p less than 0.01). These results suggest that the residual air in the hematoma cavity may delay the reduction rate of the hematoma. Based on these results, the authors pay attention to the following points; 1) Less invasive burr hole method should be selected. 2) Patient's head position should be controlled to make the burr hole at the highest level in the operative field. 3) Hematoma cavity should be filled with saline as much as possible. 4) The inner membrane should never be injured, as it may cause tension pneumocephalus. Moreover, the drainage of cerebrospinal fluid may reduce the counter pressure and it leads to the delay of the hematoma reduction.

The authors reported a case of pneumocephalus induced by bromocriptine (Bc) treatment for a recurrent invasive prolactinoma. The patient was a 38-year old man, who had been treated for 12 years, with three times of craniotomies and two times of irradiation therapies. CT scan showed the recurrence of the tumor, which extended into bilateral middle fossa, left orbit and left cerebellopontine angle. Serum prolactin levels elevated to 35,200 ng/ml. Then Bc was administered in a dose of 5 mg/day. Serum PRL concentration fell to 2,090 ng/ml one month after the initiation of the treatment, when he complained of headache, nausea and vomiting. Since these symptoms were considered as the side effects of Bc, the dose was reduced to 2.5 mg/day. Three weeks later, plain craniograms showed marked pneumocephalus, while no tumor was found on CT scan. The administration of Bc was stopped and he was prescribed a complete rest for a month. The air was collected again when he began to walk around. Therefore, the transsphenoidal operation was performed in order to pack the sella turcica and sphenoid sinus with muscle pieces. Since the pneumocephalus could not be cured, the muscle, taken from the thigh, was spread throughout the left middle fossa by the front-temporal craniotomy. When Bc reduces the size of the invasive prolactinomas, the intra- and extra-cranial spaces may be communicated. The greatest care should be taken for pneumocephalus, CSF rhinorrhea and/or meningitis during the Bc treatment of prolactinomas.

In order to investigate the pathological changes of prolactinomas induced by the treatment with bromocriptine, 12 cases of prolactinoma were studied using immunocytology and electronmicroscopy. Eight cases were treated with bromocriptine, 5 mg/day, for a few days before surgery, while 4 cases were given for several months. 1) Cases of the short-term administration All of the adenomas except one appeared to be eosinophilic by H-E stain. Electronmicroscopically, abundant secretory granules, measuring 100-350 nm, were found throughout the cytoplasm, while exocytosis, frequently seen in the common type of prolactinomas, could not be observed. With immunostains, prolactin was diffusely positive in the cytoplasm of most adenoma cells, though the intensity of immunostaining for prolactin was relatively faint compared with that of normal prolactin cells or usual prolactinomas. Immunoreactive prolactin was demonstrated on accumulated secretory granules, while it was negative in the Golgi apparatus and rough endoplasmic reticulum (ER). 2) Cases of the long-term administration The tumors corresponded to chromophobe adenomas and the immunoperoxidase techniques revealed the absence of prolactin in the cytoplasm. Electronmicroscopically, secretory granules, measuring about 100 nm, were infrequent and lined up along the cell membrane. Marked shrinkage of the Golgi apparatus and ER was noted with various stages of degenerative changes in adenoma cells. In conclusion, bromocriptine not only inhibits the release of prolactin, but also suppresses the synthesis of it at the initial phase. With a long-term administration of bromocriptine, the cell organelles related to the hormone production, such as the Golgi apparatus and ER show gradual shrinkage under the prolonged tonic inhibition for prolactin release and synthesis. This might be the mechanism by which bromocriptine leads prolactinomas to the shrinkage.

We have been studying the therapeutic effect of anticancer drugs such as ACNU and vincristine in human glioma-bearing nude mice models and this time, the effect of interferon was also evaluated. Since 1980, the phase 1, 2 clinical trials on Hu-Interferon (IFN) have been studied in the neurosurgical field and the effect is now regarded to be not as pronounced as previously expected. It is difficult to compare the effect of IFN with other anticancer drugs in an in-vivo study, because of the species specificity of IFN, and only a few studies have so far been reported. With respect to evaluating the therapeutic effect of IFN, the nude mouse model is thought to be useful. The anticancer activity of beta-IFN in nude mice, receiving subcutaneous transplants of human brain tumors (6 strains) was compared with that of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, alpha-IFN, beta-IFN, poly ICLC, the tumor reduction rates were evaluated by Battelle's method. Although in 2 out of 6 glioma strains, the tumor reduction rate (treated/control values) treated with beta-IFN was evaluated as effective, the effectiveness of beta-IFN was inferior to that of ACNU and vincristine. Therefore, further studies are indicated to evaluate the efficiency of the drug at higher dosage levels and to determine its tolerance dose. The combined modality treatment such as chemotherapy and radiation are issues that are still to be settled by further studies.

In case of chemotherapy against brain tumors, it is most important to choose suitable drugs for brain tumors, since human tumors have different drug sensitivity and growth. Heretofore, the nitrosourea-induced rat glioma cell, such as C6, or immunodeficient mice were usually used for predicting the drug sensitivity of brain tumors. We took notice of Murphy's system for the chemosensitivity test, in which a human tumor is transplanted into the chorioallantoic membrane (CAM) of a chick embryo. By modifying the conventional Murphy's system, we studied the efficiency of this system in predicting the drug sensitivity of brain tumors. First, we compared the result of a drug sensitivity test using CAM of a chick embryo with that using nude mice. Next we studied the effect of chemotherapeutic agents against brain metastasis of a chick embryo caused by the intravenous injection of mouse B16 melanoma cells. The tumor reduction rate of the sensitivity test using a chick embryo tended to agree with that using nude mice. In the drug sensitivity test against brain metastasis, ACNU was the most effective. This result supports the result of the clinical study. In conclusion, the drug sensitivity test using a chick embryo is thought to be useful and the advantages or disadvantages of this system are discussed.

A case of epidermoid carcinoma arising in an epidermoid cyst in the cerebellopontine angle is presented. Clinical features and CT appearance are discussed in comparison with those of benign epidermoid cyst. A 43-year-old man was admitted to the Department of Neurosurgery, University of Tokyo Hospital on April 14, 1983, with complaints of right facial numbness and weakness of six months' history. On neurological examination, sensation of the right half of the face was decreased in all modalities. Marked atrophy of the ipsilateral temporal muscle was also noted. Right facial paresis of peripheral type was evident. Gag reflex was decreased on the same side. Except for a slightly increased left deep tendon reflexes, there were no pyramidal tract signs. A CT without contrast material failed to show any abnormalities. A postcontrast CT demonstrated an irregular enhancement in the right cerebellopontine angle. The finding of asymmetry of the ambient cistern indicated minimum mass effect on the metrizamide CT cisternography. Suboccipital exploration of the right cerebellopontine angle was carried out on April 28, 1983. Leaving a part of the capsule indenting the pons between the roots of the fifth and the seventh nerve, we removed a white pearly tumor. Histological diagnosis was typical epidermoid cyst. He left the hospital one month later with signs of the right seventh and the eighth nerve. His postoperative course, however, was beyond our expectation. Over a few months following his discharge, left hemiparesis as well as horizontal and vertical nystagmus gradually developed. He was readmitted on November 10, 1983. A postcontrast CT revealed enlargement of the enhanced lesion filling the right ambient cistern.(ABSTRACT TRUNCATED AT 250 WORDS)

An overview of treatment of brain metastasis from lung cancer in National Cancer Center is presented with respect to T and N categories in TNM classification. To know the rate of brain metastasis, CT scan on brain was performed for all the patients with lung cancer hospitalized for surgical treatment and revealed that 3 of 87 patients had brain metastasis without any neurological signs and symptoms. On the other hand, 105 out of 320 (32.8%) lung cancer patients who had taken CT scan for some reason from 1975-1983 in this hospital had shown the brain metastasis. Therefore, it should be memorized that only 3.4% was detected to have brain metastasis from the patients without any neurological signs and symptoms. Two hundred sixty-one patients with metastatic brain tumor from lung cancer were treated in 1963-1983 at National Cancer Center in Japan. Of these, 205 patients were evaluated for the median survival and the average survival according to various therapeutic modalities. Of this 205 patients, 123 had no operation with or without other treatment--chemotherapy or radiotherapy showed median survival of 3-5 months (range 2-25 months). Eighty-two had operation on brain metastasis with or without chemotherapy showed median survival of 6-11 months (range 2-112 months). Correlation between survival time and T and N categories in TNM classification at the diagnosis of lung cancer was studied and no remarkable difference was noted either in T or N categories in the average survival time and percent number of cases survived equal or more than 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

This study reports the effect of intracisternal administration of papaverine in 15 patients with vasospasm due to rupture of aneurysm. All patients had undergone clipping of aneurysm and had neurological deterioration and decreasing level of consciousness. Bolus injection of 40 mg of 1% papaverine hydrochloride was started on day 6.3 +/- 1.7 and continued for 4.4 +/- 1.6 days. In seven cases serial angiogram after initial dose revealed dilatation of IC and/or anterior, middle cerebral arteries at 30 min and further dilatation up to 85% increase in diameter at 60 min, which continued at least 90 min. Arteries with marked vasospasm responded more to papaverine than those with less vasospasm. There was a close correlation between degree of vasospasm and vasodilatation effect (r = 0.88, p less than 0.01). In all but two cases vasodilatation tended to become prominent by repeat doses, twice a day, for two to seven days (r = 0.87, p less than 0.01). Vasodilatation was observed only in IC and proximal trunks of ACA and MCA where papaverine could make direct contact, but not in the distal branches beyond A3 or M3. Neurological examination showed improvement of paresis or level of consciousness in 7 cases but no effect in 6 cases. Intracerebral hematoma occurred in two cases (one by high concentration 4% papaverine) during the treatment. Therefore intracisternal papaverine is the treatment of choice in cases with symptomatic vasospasm with some cautions on concentration to be administered.

The authors examined the preoperative factors affecting the reduction of chronic subdural hematoma (CSDH). A new method was developed to calculate the reduction rate of CSDH using CT volumetry technique. Postoperative serial CT films were examined and each hematoma volume was calculated by microcomputer. A postoperative exponential decrease of hematoma volume was observed, and the log-transformation of the hematoma volume turned the curve to a linear decrease. The least square method was used to fit an exponential curve, and the half reduction date (HRD) was calculated from the fitting curve. This HRD represents a mathematical indicator of the reduction rate of CSDH. Using this technique, the relationships between this HRD and the following parameters were examined in 61 patients. The preoperative factors examined are as follows; 1) patient's age, 2) preoperative hematoma volume, 3) CT number of the hematoma, 4) time interval between the head injury and the onset of symptom, and 5) the degree of cerebral atrophy. The degree of cerebral atrophy was calculated by means of a simple approximate formula as described by one of the authors (K.N.). Patient's age and the hematoma volume were correlated with HRD, and the correlation coefficients were 0.346 (p less than 0.01) and 0.298 (p less than 0.05) respectively. On the other hand, preoperative CT findings and the duration from the trauma had no correlation with HRD. Cerebral atrophy has hitherto been thought to affect the reduction of hematoma. However, our quantitative study revealed no correlation between cerebral atrophy and the reduction of hematoma rate. This unexpected result may be attributed to the difference between cerebral atrophy and cerebral elasticity.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of high frequency jet ventilation (HFJV) on intracranial pressure (ICP) in the series of seven patients with severe head injury was studied. These patients received mechanical ventilation for respiratory failure accompanied with neural damage or circulatory shock and for ICP control by decreasing PaCO2. ICP was measured continuously by subarachnoid catheter method connected to Gould P-50 strain-gage transducer and controlled by hyperventilation and/or osmotic diuretics during acute phase. Arterial pressure, central venous pressure and intratracheal pressure were measured continuously in the same way. Arterial blood gases were analysed by BG-I of Technicon Co. Ltd. At the weaning from respirator, two methods were applied. One was conventional IMV (with PEEP) and/or CPAP by using IMV mode of Servo 900 respirator or T-piece together with PEEP valve and another was new-fashioned HFJV. Mean intratracheal pressure (mPit) was fixed at 0 mmHg (control value), 5, 10 and 15mmHg in both methods by adjusting PEEP valve or driving pressure of HFJV. The result is that in the same patients ICP was significantly lower during HFJV than IMV/CPAP when mPit was 5 and 10mmHg. Only three cases having been studied at 15mmHg of mPit because circulatory condition would not permit it, significant difference of ICP between HFJV and IMV/CPAP was not detected. PaCO2, being suspected to be the cause of lower ICP of HFJV group, was studied too. But blood gas analysis showed no significant difference neither PaCO2 nor PaO2. The fluctuation of CVP reflecting the change of intrathracic pressure was smaller in HFJV group than in IMV/CPAP group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular synchronization chemoradiotherapy was performed in 122 patients with glioblastoma and malignant astrocytoma (GrIII) registered between April 1977 and August 1982. The study was a non-randomized clinical phase II trial. The chemotherapeutic agents employed as synchronizers during the irradiation were VM26 (epipodophyllotoxin) and vincristine (VCR) as plant alkaloids and ACNU as a nitrosourea. Either VM26 or VCR was administered on D1, D2 and D3 at the dosage of 1 mg/kg (0.025 mg/kg-VCR) body weight. ACNU was administered on D2 and D3 at the dosage of 1 mg/kg body weight. The duration of the chemotherapy was eight to fourteen days at the initial induction stage and almost eight weeks at the maintenance stage. Thus, two synchronization arms of VM26 + ACNU and VCR + ACNU were employed. The regimen-VM 26 + ACNU + Radiation (Rad) could yield the initial induction of CR + PR-30%, NC-50%, and PG-15% in 58 cases. Long-term survival, calculated by the cumulative survival rate, was as follows: one year, 58%; two years, 42%; three years, 32%; four years, 30%, and five years, 25%. The regimen VCR + ACNU + Rad could yield the initial induction of CR + PR-28%, NC-49%, and PG-23% in 64 cases. The cumulative survival rate was calculated as follows: one year, 55%; two years, 42%; three years, 27%; four years, 22%, and five years, 22%. As a control, particularly for the survival rate, the data of the All-Japan Registry were revised to correspond to our study population. The survival rate of simple radiation cases thus revised was as follows: one year, 43%; two years, 23%; three years, 11%; four years, 7%, and five years, 5%. The comparison between VM 26 plus ACNU and VCR plus ACNU yielded a higher initial induction response of 35% for the former (vs. 28% for the latter), although it is difficult to make a judgement on the excellence of the regimen involving VM 26 plus ACNU, because this trial was clinical phase II. On the other hand, compared with the data from the All-Japan Registry, each regimen of cellular synchronization radiation therapy could achieve statistically more excellent responses both in the initial induction and the long-term survival (p less than 0.01). Thus, cellular synchronization radiation therapy is a hopeful therapeutic method for malignant glioma, with less side effects and statistically confirmed higher responses.(ABSTRACT TRUNCATED AT 400 WORDS)

In the present study, the anti-edema effect of AVS [1,2-bis (nicotineamide)-propane] was evaluated using the cat MCA occlusion model with or without recirculation. In the prolonged ischemia (PI) group, cortical edema as assessed by the changes in specific gravity, developed in those cortical areas where the mean 1-CBF was less than 25-30 ml/100 g/min during MCA occlusion (4 hours). In the recirculation group (2 hours' ischemia followed by 2 hours' recirculation: RC group), the ischemic threshold for edema development was almost the same as in the PI group. In both groups, the drop in cortical specific gravity was significantly suppressed by AVS. Regarding the time-course of 1-CBF, there was no difference between the PI-AVS-treated and PI-saline-treated groups. In the RC group, however, the postischemic hypoperfusion was significantly ameliorated by AVS. Based on the present and previous data showing the antiedema effect of AVS, the mechanism of action of AVS was discussed in relation to the pathomechanism underlying ischemic brain edema. Our new concept of ischemic brain edema is briefly stated below. Related in vitro studies have shown the followings: (i) the influx of sodium not of proteins is the principal cause of ischemic brain edema: (ii) the eicosanoid synthetic capacity of the brain microvessel (MV) is increased simultaneous to edema development (iii) an elevation in the level of hydroperoxides enhances the activities of Na+, K+-ATPase as well as the arachidonate cascade of MV. These data suggest that free fatty acids and free radicals liberated following cerebral ischemia stimulate the activity of the MV-Na+, K+-ATPase, which results in increased sodium influx across the BBB. AVS was shown to scavenge hydroxyl radicals and to inhibit the stimulatory effects of a lipid hydroperoxide (15-HPAA) on the activities of Na+, K+-ATPase and the arachidonate cascade of the MV. These actions of AVS may be linked to its antiedema effect.

A 27-year-old man was admitted to the Urological Department of Tokyo University, with complaints of delayed puberty and growth retardation. At the age of 14 years, he found his skeletal growth retarded. Since then he had not shown any development of secondary sex characters, such as change of voice, appearance of public and axillary hair and development of external genital organs. He had not experienced the ejaculation and libido, while the excretion has been maintained. This feminized patient showed poorly developed external genitalia, while there was no evidence of galactorrhea or gynecomastia. Ophthalmologic examinations were normal. Endocrinological studies revealed moderate hyperprolactinemia (185-200 ng/ml) and marked disorder for GH secretion. Gonadotropins were low normal and their responses to LH-RH were moderately disturbed. Serum testosterone level was extremely low and its responses to HCG were insufficient. Under the diagnosis of prolactinoma, he was referred to the Neurological Department. Plain skull film and tomography of the sella showed a deformed and slightly expanded sella, the measurement of which were within normal limits. No supra-sellar extention was demonstrated by pneumoencephalography and CT scan. A diagnosis of PRL producing microadenoma was made, and a radical removal of the tumor was performed through the transsphenoidal route. In most tumor cells the presence of PRL was revealed by immunohistochemical stains. Postoperatively, PRL levels returned to normal, while other hormonal deficiencies remained unchanged. With the administration of testosterone, he gradually became masculine and reportedly gained normal libido and potency.

Treatment results on 48 patients with "recurrent" craniopharyngioma treated by surgery or/and radiation are analyzed. Median relapse-free survival time was 43.6 months in patients treated initially with radiation and 22.2 months without. Operative death occurred in 17% of all patients and in 3 out of six patients after total removal. The five- and ten-year survival rates were 91.7% and 66.8%, respectively, for 14 patients treated with combined surgery and radiation therapy. For 26 patients treated with surgery, the survival rates were 20.3% and 10.1%. All of 6 patients, who had received both initial and later radiotherapy, were well 1/2 to 18 years later without clinical evidence of radiation injury. These results lead us to the following conclusions: 1) A radical surgery in recurrent cases has the higher risks of mortality and morbidity than that of the first radical surgery. 2) Radiation therapy improved the survival rate of patients with "recurrent" craniopharyngioma. 3) After initial radiation therapy, additional irradiation was allowed based on the scale of nominal standard dosage and the estimation of "decay factor".

In order to establish more strict and objective indication for EC-IC bypass, a retrospective study on the surgical effect on cerebral blood flow (CBF) and neurological function was carried out in 37 cases. STA-MCA bypass was carried out on 20 cases with IC occlusion and 17 cases with MCA occlusion. Twenty-two cases with completed stroke, 9 cases with TIA and 6 cases with RIND. All patients were able to ambulate before surgery, and none of them were hemiplegic. CBF study by 133Xe inhalation method was carried out before and 2 to 4 weeks after surgery. Bypass was patent in all cases. Thirty percent of all cases showed more than 16% increase in CBF (++ group) on the side of bypass surgery and another 30% demonstrated 6 to 15% increase (+). On the other hand 30% of cases appeared to be unchanged (+/-), and 10% showed more than 6% decrease (-). The less the pre-operative CBF value was, the more the post-operative CBF was expected to be increased. Patients with pre-operative CBF less than 60% of normal value (ISI = 63 +/- 4) showed remarkable increase (++), and those with 60 to 70% showed moderate increase (+). Contrarily, cases with more than 70% of normal value showed either no change or decrease. Neurological change was evaluated as to disappearance of TIA attack and improvement of hemiparesis or mental dysfunction. Seventy-seven percent of patients in groups with (++) and (+) effect on CBF showed improvement in neurological function, whereas only 27% of patients in groups with (+/-) and (-) effect demonstrated improvement, which was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)