Human interferon-beta therapy for cerebral primitive neuroectodermal tumors--two case reports.

A 5-year-old girl and a 2-year-old boy presented with recurrent cerebral primitive neuroectodermal tumor (PNET) and were treated with intravenous administration of human fibroblast interferon (HuIFN-beta) which was continued as outpatient maintenance therapy. Both patients showed a partial response and were still alive 14 months and 2 years after diagnosis. Our results suggest that HuIFN-beta is an effective therapy for PNET, and can be used as long-term maintenance therapy without serious side effects.

[Japan coma scale in the prediction of outcome after early surgery for aneurysmal subarachnoid hemorrhage].

The value of the 10-grade Japan Coma Scale (JCS) as a means of evaluating patients undergoing early aneurysm surgery was assessed in terms of its relationship to surgical outcome. The 13-grade Glasgow Coma Scale (GCS) was also assessed, and comparisons were made between the two. A series of 765 patients who underwent aneurysm surgery within 7 days after hemorrhage were evaluated both by JCS and GCS immediately prior to surgery, and outcome was assessed by the Glasgow Outcome Scale (GOS) 6 months postoperatively. Both the JCS and GCS scores were significantly correlated with surgical outcome (JCS vs GOS: rs = 0.586, GCS vs GOS: rs = 0.615, p < 0.001). There was no significant difference between the correlation coefficients for outcome of the JCS and GCS. In general, the better the JCS or GCS score was, the better the surgical outcome was, however, outcome among those with a JCS score of 3 was poorer than among those with a score of 10, 20, or 30. The results of this study indicate that both JCS and GCS are useful in predicting surgical outcome, but the GCS may be better than the JCS because of the problem with the score of 3 in the latter.

Growth suppression and astrocytic differentiation of glioma cells by interleukin-1.

The effect of recombinant human interleukin-1 (rHuIL-1) derivatives on human glioma cell lines was examined in vitro. Five glioma cell lines, U-251 MG, U-373 MG, U-87 MG, A-172, and T98G, were incubated in medium containing 1% fetal calf serum and various concentrations of different type of rHuIL-1: OCT-43 (rHuIL-1 beta), OCT-7000 (rHuIL-1 alpha), and OCT-8000 (rHuIL-1 alpha). The high-affinity IL-1 receptors were expressed in the U-251 MG and U-373 MG cell lines, and rHuIL-1 was found to suppress cell growth and to induce morphological differentiation of these cell lines. Growth inhibition occurred in a dose-dependent manner in concentrations or rHuIL-1 ranging between 1 and 100 ng/ml. Interestingly, rHuIL-1 induced a transient growth of glioma cells shortly after administration, then suppressed cell growth with accompanying elongation of cytoplasmic processes. This unique process of transient growth stimulation followed by growth suppression was parallel to the efficacy of bromodeoxyuridine uptake in the rHuIL-1-treated cells. Concomitantly, accumulation of glial fibrillary acidic protein and cyclic adenosine monophosphate contents was observed in four glioma cell lines. Continuous rHuIL-1 treatment for longer than 30 days elicited irreversible astrocytic terminal differentiation. These results indicate that IL-1 is an effector on the growth regulation of glioma cells, resulting in astrocytic differentiation in vitro.

[A case of malignant lymphoma in the skull base].

A case of malignant lymphoma located in the clivus, sella and cavernous sinus is reported. A 46-year-old female was hospitalized with a 3-week history of diplopia. Neurological examination showed left oculomotor, trochlear, abducens and hypoglossal nerve palsy. Improvement of cranial nerve palsy was achieved with the administration of prednisolone but it was only transient. Laboratory studies and endocrinological examination showed almost no abnormal findings. Skull x-ray film revealed a widely damaged base. MR studies showed a homogeneously enhanced mass lesion in the clivus, sella and bilateral cavernous sinus. Partial removal of the lesion was performed via the transsphenoidal route. The histopathological diagnosis of the mass was consistent with diffuse, medium sized cell, B-cell type malignant lymphoma. A postoperative systemic evaluation by tumor scan with 67Ga disclosed no abnormal uptake except in the skull base. Postoperatively, the patient was treated with radiation, a total of 50 Gy, followed by chemotherapy every 3 week consistent of cyclophosphamide, vincristine, pirarubicin, bleomycin, procarbazine and prednisolone. The cranial nerve symptoms disappeared during radiation therapy. The MR studies after three courses of chemotherapy revealed almost complete remission. The patient died of acute progression of pneumonia without any evidence of the recurrence of malignant lymphoma 10 months after the operation. Skull base involvement of malignant lymphoma is unusual. Five cases of malignant lymphoma invading the skull base have been reported since 1987. In most cases, the lesion originated from paranasal sinuses and was usually accompanied with intradural extensions. In the case we have reported there was no intradural invasion of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vasospasm and its outcome after early surgery for ruptured cerebral aneurysms: changing pattern of its incidence and outcome during this 9-year period].

The occurrence and outcome of vasospasm (VS) were analyzed in 240 patients who had aneurysm surgery within 7 days of a hemorrhage during 9-year period (1981-89). Occurrence of VS was evaluated by the appearance of ischemic symptoms, (A) with or (B) without CT evidence of infarcts. The surgical outcome was assessed by the Glasgow Outcome Scale 6 months postoperatively. The results in the first and the latter halves of the period were compared. The overall incidence of VS (A+B) was 34.8% (A: 23.5%, B: 11.3%) and 33.6% (A: 15.2%, B: 18.4%) in the first and the latter halves, respectively. Thus, VS leading to infarction showed a tendency to decrease in the latter half of the period, though the overall incidence of VS itself was almost identical in both the first and second halves of the period. The results were also analyzed according to preoperative grading based on the Glasgow Coma Scale (GCS). The tendency toward decreased severity of VS in the latter term was most remarkable in patients with GCS total scores between 14 and 13. The decreased incidence of severe VS proved to be reflected in decreased mortality and in increased rate of good outcome in the latter half of the period. In order to confirm whether the results obtained in our clinic are universal, we applied the same analysis for control groups in four cooperative double-blind clinical trials performed during this period in Japan. The study again showed that the rate of infarction has decreased significantly over the decade, resulting in the improved surgical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vasospasm and its outcome after early surgery for ruptured cerebral aneurysms: relationship with the clinical grade based on the Glasgow Coma Scale].

Over a 9 year period, 270 patients who had early aneurysm surgery within 7 days after subarachnoid hemorrhage were analyzed regarding occurrence of vasospasm (VS) and its outcome. Occurrence of VS was recognized by ischemic neurological deterioration, with or without CT evidence of infarcts. Surgical outcome was assessed by the Glasgow Outcome Scale 6 months postoperatively. The results were correlated with age, aneurysm site, day of surgery, and preoperative clinical grade evaluated by the Glasgow Coma Scale (GCS). Thirty patients with the GCS sum score of less than 6 were excluded from the analysis of VS. Eighty two patients (34%) developed VS, of which 36 patients (15%) showed ischemic symptoms only, and 46 (19%) had infarct on CT. The incidence of symptomatic VS was 12% in GCS 15 group (117 patients), 23% in GCS 14-13 group (70 patients), and 11% in GCS 12-7 group (53 patients). That of VS with infarct was 14%, 23%, and 26% in GCS 15, GCS 14-13, and GCS 12-7 groups, respectively. Thus, there was a close correlation between the clinical grade based on the GCS and the incidence of VS, especially with infarct. The grade was also useful in predicting the surgical outcome. VS was more common in the older age group. The site of aneurysm or the day of surgery had no apparent influences on the incidence of VS or its outcome. Overall, the incidence of poor outcome due to VS proved to be 12%, which accounted for one-third of the cases in which there was poor outcome due to various causes.

[Acute aneurysm surgery and the Glasgow Coma Scale: relationship with 6-month outcome].

A series of 610 patients who had aneurysm surgery within 7 days of the hemorrhage were analyzed as to the relationship between the preoperative Glasgow Coma Scale (GCS) score and the outcome assessed by using the Glasgow Outcome Scale (GOS) at 6 months after surgery. The patient distribution in accordance with the GCS scores in descending order from 15 to 3 was as follows: 265, 109, 44, 24, 17, 20, 25, 15, 18, 12, 16, 23, and 22 cases, respectively. In general, the larger the GCS score, the better the outcome. Thus, the overall results proved to be significantly correlated with the GCS score prior to surgery (r = 0.608, P < 0.01). As for demarcation levels along the GCS axis in terms of the GOS, a significant difference in the outcome was observed at the level of GCS scores between 15 and 14 (P < 0.0001, Wilcoxon test). However, no borderlines were evident at any GCS levels other than 15/14. The problems of applying the GCS to the grading system of aneurysmal subarachnoid hemorrhage are discussed.

[Clinical significance of thrombocytopenia associated with hemorrhagic cerebrovascular diseases].

We investigated the clinical significance of thrombocytopenia (platelet counts less than 10 x 10(4)/mm3) associated with hemorrhagic cerebrovascular disease. This study was conducted in 96 patients suffering from hemorrhagic cerebrovascular diseases. We divided the clinical course into 3 stages: acute (from the 1st to 7th day), subacute (8th-21st day) and chronic (after the 22nd day). The average age of the patients with thrombocytopenia (TCP) was 60.6 years old. TCP was more frequent in men (81.3%) than in women (18.7%). TCP developed in 18.6% (8/43) of patients with subarachnoid hemorrhage (SAH) and in 15.1% (8/53) of those with intracerebral hemorrhage (ICH). Among the patients with SAH, four were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to SAH was more likely to develop in the acute and/or subacute stage. TCP due to SAH showed two peak appearances: the first was within 24 hours (n = 3), and the second was around 10 days after onset (n = 3). The cause of TCP in its late peak appearance was presumed to be the consumption of platelets due to microembolism induced by vasospasm and/or hemodilution therapy. Among patients with ICH, five cases were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to ICH was more likely to develop in the acute stage. Fifty percent (4/8) of the patients with ICH had TCP on admission. This data suggested that TCP was possibly a cause or an inducer for ICH.(ABSTRACT TRUNCATED AT 250 WORDS)

Open surgery assisted by the neuronavigator, a stereotactic, articulated, sensitive arm.

A new computed tomographic-stereotactic device that translates the operating point onto preoperative computed tomographic (CT) images, the Neuronavigator, has been developed. We have applied this system to various neurosurgical procedures to examine its usefulness. The system consists of a 6-joint sensing arm and a 16-bit personal computer. It projects the location of the arm tip onto a corresponding CT slice with a cursor that guides the surgeon toward the intracranial target during open surgery. The system also projects the location of the tip onto angiograms, and when used in conjunction with echography or a transcranial Doppler (TCD) flow meter, the surgeon's ability to navigate is enhanced. Sixty-eight patients underwent operation with the Neuronavigator. The navigation system worked as the core of a multimodal three-dimensional data base that proved to be useful during surgery. The maximum detection error was 2.5 mm, which was considered sufficient for open microsurgery. It also proved useful in designing the position of a craniotomy, in targeting deep-seated mass lesions, and in tracing the tumor edge, which had been identified on a CT scan. When the angiogram was combined with the navigator, it became easy to identify key vessels within a small operating field. The system was also combined with a TCD flow meter. This combination makes it possible to translate the measuring point of the TCD directly into CT coordinates, improving the precision of location of the TCD probe. The Neuronavigator combines various diagnostic images into one database and effectively guides the surgeon during surgery.

[Intracranial hematoma associated with acquired immunodeficiency syndrome (AIDS): case report].

The authors report a case of intracranial hematoma associated with AIDS. A male aged 21 had been treated with infusion of factor VIII to control hemophilia A. He fell down and hit his right occipital region. Immediately after the impact, he became comatose. When he was hospitalized 30 minutes after the injury, a herniation sign was recognized. CT scan revealed right acute subdural hematoma that showed mixed density. This hematoma was successfully removed with HITT (hematoma irrigation with trephination therapy) and he recovered almost completely. However he died when the intracerebral hematoma bled suddenly on the 20th day after surgery. We assumed the hematoma was related to vasculitis induced by AIDS. Three points in this case impressed us. First, HITT is very useful for treating acute subdural hematoma associated with AIDS. Second, the patient's condition may deteriorate suddenly through intracerebral hematoma originating from AIDS-related vasculitis, although the coagulation factors are well maintained. Third, a manual for management of cases of AIDS is necessary to avoid confusion among the medical staff.

Estimation of intracranial pressure using computed tomography scan findings in patients with severe head injury.

The relationship between initial intracranial pressure and the findings of the first computed tomography scan on admission was assessed in 100 consecutive moderate-to-severe head injury patients using a method of multiple regression analysis. Intracranial pressure was measured through a slender subarachnoid catheter with a transducer. Thirty-nine checkpoints of computed tomography findings, including a shift of midline structure, the status of ventricles or cisterns, and the amount of subarachnoid hemorrhage, were investigated. The results were as follows: (1) The computed tomography findings that contributed to estimating intracranial pressure were the appearance of cisterns, the size of a subdural hematoma (number of slices), ventricular size, status of subarachnoid hemorrhage, status of cerebral contusion, magnitude of midline shift, and ventricular index, in that order. (2) Approximately 80% of predicted cases of intracranial pressure were included within the range of measured intracranial pressure +/- 10 mmHg. When the predicted intracranial pressure was less than 30 mmHg, the discrepancy between both intracranial pressures was small. It is concluded that an equation using several computed tomography findings gives a reasonably accurate intracranial pressure for the initial stage of severe head injury.

Clinical course and surgical prognosis of 33 cases of intracranial epidermoid tumors.

Thirty-three cases of intracranial epidermoid tumors treated during the past 25 years were analyzed with regard to clinical manifestations, recurrence rates related to the extent of surgery, and long-term survival rates. Epidermoid tumors caused various symptoms, especially in the cerebellopontine angle (15 cases), of which a transient remission of symptoms was observed in 4 cases (23.5%). The average time from initial symptoms to surgery was much shorter in suprasellar region and third ventricular locations (average of 11 months) than in other locations (average of 7 years). In 28 patients (84.9%), the tumor was removed totally or subtotally. Most of the patients could lead an independent and useful life after operation (93.1%). Among the 29 patients in a long-term follow-up survey, seven tumors recurred after an average interval of 8 years and 10 months (from the first to second operation) and 12 years and 6 months (from the second to third operation). Patients with recurrent tumors were successfully treated, and excellent functional prognosis was observed even after the second or third operation. The 20-year survival rate was 92.8% (Kaplan-Meier method).

[Metastatic hepatoma presenting as intracranial hemorrhage: report of two cases].

Metastasis of hepatoma to the central nervous system is rare, although hepatoma is a relatively common malignant tumor in Japan. Much rarer is metastatic hepatoma presenting as intracranial hemorrhage and there have been only 4 cases reported in the past. Here, we report two such rare cases with a literature review. Case 1 was a 26 years-old female with a history of 60% hepatic resection in the diagnosis of hepatocellular carcinoma. Later, she developed bilateral lung metastasis. She was admitted with complaints of headache, nausea and vomiting. Neurological findings were clear consciousness, right homonymous hemianopsia and bilateral papilledema. CT showed high-density mass in the left occipital lobe. Evacuation of hematoma and removal of tumor were performed. Pathological diagnosis was hepatocellular carcinoma of clear cell type. Later, two other hemorrhage occurred from different metastatic lesions in the left occipital lobe and the right occipital lobe, and the patient underwent two more surgeries. The patient died of lung metastasis, three months from neurological onset. Case 2 was a 42 years-old male who developed an intracranial tumor adjacent to the right temporal bone without a history of hepatoma. The tumor was removed, which turned out to be hepatocellular carcinoma pathologically. Three months later, on admission, the patient showed sudden neurological deterioration into deep coma. CT showed an irregular high-density mass in the right temporal lobe and evacuation of hematoma coupled with tumor removal was performed. Pathology was of trabecular type. Later, intracranial recurrence and bony metastasis to C5, L3 and the left iliac bone appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnosis of early stage of brain tumors].

There are two points to find the brain tumor in early stage; the first is cautious history taking and neurological examination, the second is to choice appropriate image diagnoses. If one recognized progressive neurological sign and symptom, mental disorder and/or epilepsy, brain tumor should be considered and be ruled out. The CT scan, especially enhanced CT, is a powerful for discovering brain tumor.

[Treatment of recurrent craniopharyngioma].

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".