Corynebacterium parvum (C. parvum) or stabilized poly I: C complex (poly ICLC) was administered to C57BL/6 mice with malignant gliomas induced by 20-methylcholanthrene.
The results were as follows. 1) When C. parvum was administered intracerebrally, growth of the brain tumor was significantly inhibited compared with intraperitoneal administration. Inhibition of tumor growth was obtained in proportion to the dose of C. parvum. Natural cytotoxic (NC) activity of brain mononuclear cells against malignant glioma cells was most enhanced when C. parvum was administered intracerebrally and that of peritoneal exudate cells was most enhanced when it was administered intraperitoneally in a 15 hour ⁵¹Cr release assay. Enhanced NC activity of brain mononuclear cells was found to reach a peak 5 days after intracerebral administration, and to depend on the administered dose. 2) When poly ICLC was administered intracerebrally, tumor growth was more inhibited than when it was administered intraperitoneally. Four administrations of poly ICLC at 4-day intervals showed significant inhibition of tumor growth compared with single administration. Enhanced NC activity of brain mononuclear cells against malignant glioma cells was found to reach a peak 1 day after intracerebral administration of poly I:C, and to depend on the frequency of intracerebral administration of poly ICLC. 3) Enhanced NC cells in the brain after administration of C. parvum and poly ICLC were observed mainly in the adherent cell fraction. 4) Tumor cell growth was inhibited when tumor cells were co-cultured with 250 μg/ml of C. parvum, but poly ICLC had no influence on tumor cell growth. 5) Interferon was not induced after intracerebral administration of C. parvum. High titers of interferon were observed after single intracerebral administration of poly ICLC, but much lower titers of interferon were observed after plural administration at 4-day intervals.
From these results, it was suggested that local administration of C. parvum or poly ICLC is effective in inhibiting the growth of brain tumors, that natural cytotoxicity of brain mononuclear cells is enhanced by intracerebral administration of C. parvum or poly ICLC with little interaction of interferon, and that there is a possibility of direct cytotoxic effects of C. parvum.

View full abstract

This study was undertaken to identify the combined effect of ACNU treatment and irradiation in a rat brain tumor model. The brain tumor model was produced in CDF male rats by stereotaxic inoculation of F-98 or D-74 glioma clone cells.
In the first series using F-98, the median survival time of the controls was 38 days. ACNU alone (7 mg/kg×3) on Day 5, 6, and 7 following tumor cell inoculation resulted in 45 days (P<0.001), a single dose of irradiation alone (1, 500 rads) on Day 8 produced 45 days (P<0.001) and the combined treatment resulted in 58 days with a 28.9% increased life span (%ILS), which was significantly longer than that of the irradiation alone (P = 0.0068). In the second series using D-74, the median survival time of the control group was 20 days. ACNU alone (7 mg/kg×3) showed no significant increase in survival time. A single dose of irradiation resulted in 23 days (P<0.001) and the combined treatment in 26 days with 13.0% ILS, significantly longer than that of irradiation alone (P<0.001). The third series assessed the schedule dependence of the combined treatment effects of ACNU and irradiation using D-74. The median survival time of the controls was 21 days. A single dose of ACNU (20 mg/kg) produced no significant increase. Irradiation alone (1, 500 rads) on Day 8 resulted in 26 days (P<0.001). A combined treatment group receiving ACNU 1 hour prior to irradiation showed a significant increase (31 days with 19.2% ILS) and this was significantly longer than that of irradiation alone (P<0.001). A significant increase in survival time was also observed (P=0.0060) when ACNU was administered three days prior to irradiation (28.5 days with 9.6% ILS). Although an increase in survival time was also observed when ACNU was given 26 or 6 hours prior to irradiation as well as 6 hours following irradiation, survival times after such combined treatments were not significantly longer than those of irradiation alone. No significant difference in tumor size at the time of death was noted among any of the groups.
In conclusion, combined treatment with ACNU and irradiation may have a synergistic effect on the rat brain tumor model, and this effect depends on the combination schedule.

View full abstract

An anti-tumor proteinic antibiotic, Neocarzinostatin (NCS), was found to significantly increase macrophages when administered into the cerebrospinal fluid.
An experiment was performed on guinea-pigs, in which NCS was administered intraperitoneally, and the cellular reaction in the peritoneal fluid was studied. NCS caused significant accumulation of macrophages in the peritoneal cells in comparison with other immunopotentiators such as OK-432. An in vitro study demonstrated that the increase of macrophages in the peritoneal exsudate was not due to the chemotactic effect of NCS but to active infiltration.
It was concluded that NCS showed immunopotentiating effects by means of macrophagic infiltration, and acted synergistically with the inherent immunosurveillance system by induction of activated T-lymphocytes. Intrathecal or intracystic instillation of NCS will be particularly useful in the treatment of malignant brain tumor patients because of its immunopotentiating effects.

View full abstract

The authors introduced a “hemodynamic profile”, a twelve angled figure in which the values of the heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), arteriovenous difference of oxygen (A-VDO₂), oxygen consumption (VO₂), left ventricular stroke work index (LVSWI), right ventricular stroke work index (RVSWI), and cardiac index (CI) were arranged clockwise from 1 to 12 o'clock respectively. The figure connecting normal values of these parameters was designed to be round. With the input of raw data sampled at the bedside, a microcomputer situated in the critical care ward began to calculate the parameters of the profile and drew it immediately with a computer-directed plotter.
During the period from January, 1981 to January, 1983, forty-nine head injured patients complicated with other major traumas (multiple injuries) were transported to the Emergency Department and “hemodynamic profiles” were made for nineteen of them. The “hemodynamic profiles” facilitated understanding of the cardiovascular conditions and systemic water balances because typical figures marking hypovolemic or overhydrative, cardiovascular suppressive, and hyper or hypodynamic conditions were depicted. It was of great use in cases of traumatic diabetes insipidus with difficulty to control fluid supplement because of other coexisting traumatic hemorrhages, in the cardiovascular suppressive state induced by barbiturate therapy, and especially in the hyperdynamic state of sepsis. The “hemodynamic profile” is the embodiment of easier understanding of systemic conditions and will be one of the powerful weapons in caring for brain failure patients.

View full abstract

The value of decompressive craniectomy as a method of treatment for massive brain edema or cerebral contusions associated with acute subdural hematoma remains controversial. In this report, the results of further experience with decompressive hemicraniectomy were described and operative indications were discussed.
The present series consisted of 31 consecutive patients with acute subdural hematoma undergoing decompressive hemicraniectomy (24 males and 7 females) whose age ranged from five to 82 years, averaging 45.7 years. They included six patients with postoperative barbiturate therapy with a mean age of 41.2 years. Glasgow Coma Scale (GCS) scores obtained before surgery were 8 or less in all patients. Intracranial pressure (ICP) was measured in the extradural space on the operated side and was monitored for 48 to 72 hours after the operation. In cases with a combination of barbiturates and surgery, 2-3 mg/kg/hour of thiopental was administered after the operation when postoperative ICP rose above 35 mmHg within several hours. The barbiturate therapy was continued for 48 to 72 hours under mechanical ventilation.
The final outcome of the present series demonstrated a 32.2% favorable outcome (good recovery and moderate disability), a 13.0% unfavorable outcome (severe disability and vegetative state) and a 54.8% mortality rate. Careful evaluation of the results, however, revealed that 80% of the less serious patients with GCS scores of 6 to 8 before the operation had a favorable outcome. On the other hand, a mortality rate of 81% was found in the more serious patients with GCS scores of 3 to 5. Preoperative ICP was higher than 40 mmHg in all patients and postoperative ICP was controlled at around 50 mmHg or below except for cases of diffuse brain swelling. In 36.4% of the patients with sustained high ICP around 50 mmHg for days after the operation, the outcome was favorable. Postoperative use of barbiturates was effective in lowering ICP by 10 to 15 mmHg and was not associated with any complications. These results indicated that limiting the operative indications according to preoperative GCS scores and use of barbiturate therapy could improve the outcome of acute subdural hematomas.

View full abstract

Twenty-two consecutive cases of chronic subdural hematoma were treated successfully by twist-drill craniostomy after Tabaddor et al. and closed system drainage. The age distribution of the patients was between 44 and 83 years (mean of 64). Three of the 22 cases were female. A case of bilateral hematoma and six cases of high density hematoma (mean CT number 63.5 H.U.) were included. The drainage tube was kept in place for 3 days. Hematoma of 137 ml in average was drained on the first day, 74 ml on the second, and 22 ml on the third. The composition of the hematoma fluid drained on the first day was similar to that of peripheral blood, while that on the third day was similar to that of hygroma. In all cases, remarkable clinical amelioration was encountered soon after drainage, and no complications occurred. CT scans showed a marked reduction of the midline shift immediately after the drainage. The subdural space disappeared within a month in 14 cases and within 5 months in all except two elderly cases. In 13 cases, the subdural pressures before and at the end of drainage were measured. Among these, seven cases recorded higher pressure measurements at the end of drainage than at the beginning. An infusion test was performed in 12 cases by a bolus saline injection (4-10 ml, 1-2 ml/sec) followed by calculation of the pressure-volume index (PVI) and compliance (Co) according to Marmarou et al. Lumbar subarachnoid pressure was recorded in 10 cases. PVI ranged from 7.71 to 37.20, and Co from 0.37 to 2.30. Two cases which had high Co values (more than 3 S.D.) showed poor brain re-expansion in follow-up CT scans. In four cases, the infusion test revealed constantly higher pressure curves in the subdural space than in the subarachnoid. This means that a difference in tightness across the tentorium exists in patients with chronic subdural hematoma and that this may contribute to some extent to the onset of clinical symptoms and signs. This method has certain advantages, i.e. less surgical insult, freedom from tension pneumocephalus, and high precision in investigations of intracranial conditions under chronic brain compression in man. Even in two cases of poor brain re-expansion, this method was safely and effectively performed.

View full abstract

A trivial head injury can transiently render a child lethargic or even comatose. There have been several isolated reports concerning such conditions. Critical analysis disclosed that all these reports had certain factors in common: 1) they occurred in young people, 2) after head injury, 3) with several minutes to hours of lucid period; 4) neurological signs and symptoms were transient, and 5) complete recovery was usual. On closer checking, however, these syndromes could be categorized into three groups, i.e., nonconvulsive, convulsive, and brain swelling types. A typical non-convulsive type was the juvenile head trauma syndrome (Haas et al.). Injuries were usually trivial. After a short time, nausea, vomiting, lethargy, headache, cortical blindness, hemiparesis, and/or brain stem signs occurred. Not only a similarity of the manifestations with the periodic syndrome and migraine attacks but also the presence of migraine diathesis was frequently reported. Altogether 50 cases of the convulsive type were collected from the literature. Most of them were young children with minor head injury. Some became stunned, or received skull fractures. Convulsions were mostly focal motor. The third type consisted of 23 cases of diffuse brain swelling in children with a lucid period reported by Bruce et al. Vomiting, headache, disturbed consciousness from lethargy to coma, pupillary changes, apnea, and/or convulsive seizure were noted. CT scans disclosed small ventricles and effacement of the perimesencephalic cistern. All recovered without deficits except one who died from delayed brain swelling. In the first and second types of patients, no brain swelling was documented. Two patients who, after a minor head injury, convulsed and died of severe brain swelling have been separately reported. Three cases of the first type and one case of the second type recently experienced by the authors showed normal CT scans in the acute stage. All these three types might have a common underlying mechanism and they might be collectively termed as ‘benign post-traumatic encephalopathies in young people’, modified from Guthkelch. Children and young adults must have low thresholds against external force or more specifically either to increased extracellular potassium or to cerebral vasospasm. The relationship with migraine diathesis was noted only in the first type, which probably indicates a lower threshold in such predisposed youngsters.

View full abstract

An 18-year-old female was admitted following an automobile accident. She was confused and the left pupil was not reactive to light. Plain skull films and tomograms of the skull revealed a left frontal linear, vertical, skull fracture extending to the floor of the anterior fossa and the lateral aspect of the orbit. Blindness of the left eye was found, when the patient became alert. Five days later, left third, fourth and sixth-nerve palsies were noted. The patient became aphasic and right hemiparetic. A computerized tomography scan revealed a slightly low density area in the left fronto-temporal region and a round contrast-enhancing mass in the left cavernous sinus region. A left internal carotid angiogram showed a large aneurysm, 8×9×13 mm in size, in the cavernous portion and an early venous filling in the region of the frontal branches of the middle cerebral artery. Aphasia and the right hemiparesis gradually improved. Repeated angiography demonstrated a marked enlargement of the aneurysm despite a daily, Matas test maneuver. Surgery identified a lacerated optic nerve and fracture of the planum sphenoidale. The aneurysm was partially obliterated by copper wire thrombosis. One month after surgery, paralysis of the oculomotor and abducens nerves completely recovered.

View full abstract

Three cases in which massive pneumocephalus caused a grave postoperative neurological deterioration are presented. Two of the three patients underwent suboccipital craniectomy for posterior fossa tumors. One patient developed tension pneumocephalus immediately after the surgery due to uncontrolled drainage of cerebrospinal fluid (CSF) during surgery and prolonged use of nitrous oxide for anesthesia. The other patient developed massive pneumocephalus the day after the surgery, caused by excess drainage of CSF from an epidural drain and entry of air from the ventriculostomy. The third patient developed tension pneumocephalus following surgery for large bilateral chronic subdural hematomas due to failure of re-expansion of the chronically compressed brain and plugging of the drainage tube. All three patients were successfully treated by aspiration of air under pressure and replacement of air with normal saline.
Tension pneumocephalus should be considered in the differential diagnosis of acute postoperative neurological deterioration, especially in the presence of a CSF drainage device.

View full abstract

Primary intracranial choriocarcinoma is relatively rare, and only 56 cases have been reported since the first description by Askanasy et al. Few reports are available concerning the sequential change of the human chorionic gonadotropin (HCG)-β subunit with therapeutic correlations.
The patient, a 17-year-old male, was admitted because of signs and symptoms of increased intracranial pressure, progressive worsening of right hemiparesis and generalized convulsive seizures for four years. Enhanced CT showed a small mass lesion of high density in the genu of the corpus callosum near the interventricular foramen. Hormonal studies showed an excessively high level of HCG-β in the serum, urine, and cerebrospinal fluid. Serum a-fetoprotein and carcinoenzymic antigen were negative. After irradiation, HCG-β decreased to the normal level. Three months later, he abruptly became comatose because of a tumoral hemorrhage extending into the right capsular region. The intracerebral hematoma mixed with the tumor was removed. Histopathologically, the tumor was diagnosed as choriocarcinoma. Immunohistochemical staining revealed localization of HCG in syncytiotrophoblasts. One month postoperatively, the patient remained unresponsive.
Serial evaluation of HCG-β is useful in the follow-up of choriocarcinoma. Early detection and surgical intervention combined with radio-chemotherapy may be effective against this malignant tumor.

View full abstract