Protein kinase Calpha and protein kinase Cdelta play opposite roles in the proliferation and apoptosis of glioma cells.

Protein kinase C (PKC) has been implicated in the proliferation and apoptosis of glial tumors, but the role of specific PKC isoforms remains unresolved. Comparing brain tumors differing in degree of malignancy, we found that malignant gliomas expressed higher levels of PKCalpha and lower levels of PKCdelta as compared with low-grade astrocytomas. Consistent with a mechanistic role for these differences, overexpression of PKCalpha in the human U87 glioma cell line resulted in enhanced cell proliferation and decreased glial fibrillary acidic protein (GFAP) expression as compared with controls. Reciprocally, overexpression of PKCdelta inhibited cell proliferation and enhanced GFAP expression. Using PKC chimeras, we found that the regulatory domains of PKCalpha and PKCdelta mediated their effects on cell proliferation and GFAP expression. PKCalpha and delta have been implicated as potential signaling molecules in apoptosis. Therefore, we examined the role of these isoforms in the resistance of glioma cells to apoptotic stimuli. In U87 cells, manipulation of PKCalpha levels had little effect on apoptosis in response to etoposide. In contrast, overexpression of PKCdelta rendered the U87 cells more sensitive to the apoptotic effect of etoposide, and PKCdelta was cleaved in these cells by a caspase-dependent process. Furthermore, the glioma cell line U373, which expresses endogenous PKCdelta, underwent apoptosis in response to etoposide, and the apoptotic response was blocked by the PKCdelta inhibitor rottlerin. Our results suggest that PKCalpha and PKCdelta play opposite roles in the proliferation and apoptosis of glioma cells.

Roles of BCL-2 and caspase 3 in the adenosine A3 receptor-induced apoptosis.

Selective A3 adenosine receptor agonists have been shown to induce apoptosis in a variety of cell types. In this study we examined the effects of adenosine receptor agonists selective for A1, A2A, or A3 receptors on the induction of apoptosis in primary cultures of rat astrocytes and in C6 glial cells. Treatment of the cells with the A3 receptor agonist Cl-IB-MECA (10 microM) induced apoptosis in both cell types. The effects of Cl-IB-MECA were partially antagonized by the A3 receptor-selective antagonist MRS 1191. In contrast, the A1 and A2A receptor agonists, CPA and CGS 21680, respectively, did not have significant effects on apoptosis in these cells. Cl-IB-MECA reduced the expression of endogenous Bcl-2, whereas it did not affect the expression of Bax. Overexpression of Bcl-2 in C6 cells abrogated the induction of apoptosis induced by the A3 agonist. Cl-IB-MECA also induced an increase in caspase 3 activity and caspase inhibitors decreased the apoptosis induced by the A3 agonist. These findings suggest that intense activation of the A3 receptor is pro-apoptotic in glial cells via bcl2 and caspase-3 dependent pathways.

Intracranial haematomas following bone marrow transplantation.

Intracranial haemorrhage (ICH) is a known grave complication of leukaemia and has been described post mortem following bone marrow transplantation (BMT). Ante mortem following BMT, the incidence and significance of ICH is not well defined. The records of 471 bone marrow transplantation recipients over 11 years at the Hadassah University Hospital Bone Marrow Transplantation Department were reviewed. The relevant data of all patients with ICH were analysed. A resolute diagnostic and treatment protocol for subdural haematomas had been employed. The indication for transplantation in 273 of the patients was leukaemia. Thirteen of these patients developed subdural haematomas within 42 days of the transplant, and nine of these haematomas were bilateral. None of the 198 patients with other malignancies or nonmalignant indications for BMT (predominantly aplastic anaemia and beta thalassaemia major) had subdural haematomas. One thalassaemia patient and three leukaemia patients had intracerebral haematomas. There was no mortality or major morbidity from the subdural haematomas, which were all successfully resolved. In contrast, all of the patients with intracerebral haematomas consequently died. Subdural haematomas occur in approximately 5% of patients with leukaemia following BMT, but the clinical outcome is relatively benign. Intracerebral haematomas are a sporadic, lethal complication following BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertrophic spinal pachymeningitis: report of two cases and review of the literature.

The cases of two patients with idiopathic pachymeningitis hypertrophica that caused progressive paraparesis are presented. Gadolinium-enhanced magnetic resonance imaging was used to demonstrate this pathological entity in one patient, and myelography was used in the other. Decompressive surgery led to significant neurological improvement. The etiology, diagnosis, and management of this disease is discussed, and the literature is reviewed. To our knowledge, this is the first report to describe the features of this rare pathological entity on magnetic resonance imaging.

Transparaspinal exposure of dumbbell tumors of the spine. Report of two cases.

The authors present a surgical technique for resection of dumbbell tumors of the spine. The transparaspinal exposure combines laminectomy and sectioning of the paraspinal muscles through a transverse incision. The procedure allows total tumor resection by means of a single posterior approach in selected patients, thus obviating the need for a combined anteroposterior operation. The advantages and disadvantages of the transparaspinal approach compared with the more extensive lateral extracavitary approach are discussed.

Preoperative magnetic resonance imaging localization of convexity brain lesions. Technical note.

The authors present a simple and accurate new technique for preoperative localization of convexity lesions of the brain by means of magnetic resonance (MR) imaging. This method uses measurements from the initial diagnostic MR image and provides precise intraoperative guidance to cortical and subcortical cerebral lesions.

Safety of perioperative minidose heparin in patients undergoing brain tumor surgery: a prospective, randomized, double-blind study.

OBJECT: Thromboembolic phenomena (TEPs) continue to be a significant source of morbidity and mortality in patients undergoing neurosurgery. Although the efficacy of low-dose heparin in preventing TEPs in neurosurgical patients is well established, neurosurgeons are reluctant to use it perioperatively because of concern for increased bleeding complications. To clarify this issue, the authors used a prospective, randomized, double-blind design to evaluate the safety of minidose heparin treatment in patients undergoing surgery for supratentorial brain tumors. METHODS: One hundred three patients, all 40 years of age or older, were treated with either 5000 U of heparin (55 patients) or placebo (48 patients) starting 2 hours before surgery and continuing until full mobilization or for 7 days. Both groups were well matched for sex, weight, duration of surgery, and tumor diagnosis. Subjective and objective parameters were used to estimate and calculate the perioperative bleeding tendency in all patients. Red blood cell mass loss was calculated by assessing the preoperative and postoperative hematocrit and the patient's weight. Intraoperative blood loss was determined by measuring the quantity of blood in the suction containers and subtracting the amount of irrigation fluids. Postoperative bleeding was measured by determining the amount of fluid in the subgaleal drain, and blood cell replacement was monitored during and after the procedure. Intracranial bleeding was graded according to findings on the postoperative computerized tomography scan obtained 48 to 72 hours after surgery. In addition, the senior surgeon in each case was asked to assess each patient's bleeding tendency during the operation. The results showed that perioperative administration of heparin did not significantly alter bleeding tendency by any measured parameter. The surgeon was blinded to which group individual patients had been allocated. CONCLUSIONS: Perioperative minidose heparin is safe for use in patients undergoing craniotomy for supratentorial tumors. This relatively simple and inexpensive measure is recommended as a routine regimen for the prevention of TEPs in patients undergoing neurosurgery.

Fine needle aspiration biopsy for skull tumors: technical note and two demonstrative case reports.

Fine needle aspiration biopsy was performed in two case of infiltrating skull lesions. The role played by this relatively simple procedure in avoiding a major operation is discussed.

[Tumors at the skull base].

Tumors at the skull base, usually benign, present diagnostic and therapeutic challenges. Thus they necessitate close cooperation between the departments of otolaryngology, head and neck surgery, neurosurgery, anesthesia and diagnostic radiology. We therefore set up a special team for diagnosis and treatment of such cases. 2 representative cases of benign tumors at the skull base operated through the combined middle cranial fossa--infratemporal fossa approach are presented in detail.

[Surgical approach to benign extradural lesions of the thoracic spine].

A benign epidural lesion in the thoracic spine is rare, and usually the result of intervertebral disc herniation or infection. Not long ago patients were diagnosed late in the course of their disease and the surgical results of the standard laminectomy usually performed were grave. The development of newer imaging techniques (CT and MRI) has made diagnosis much easier, so diagnosis is often earlier, when neurological deficit is minimal. Newer neurosurgical techniques and approaches to the thoracic spoine have been developed to treat these lesions, which we describe. Clinical data on 16 patients operated from January 1996 to January 1997 are presented.

[Central neurocytoma].

4 cases of central neurocytoma are reported. Sex distribution was symmetrical, average age at presentation was 29.7 years, and duration of symptoms varied from 1 day to 5 years. Headache and nausea were the most frequent symptoms; 1 patient was asymptomatic, 3 tumors were located in the left lateral ventricle and 1 in the third ventricle. 3 were operated on via an interhemispheric transcallosal route and 1 transcortically. Morbidity included symptomatic subdural effusions (2 cases), short term memory deficit (1) and transient hemiparesis with aphasia (1). There was no mortality.

[Surgery for craniopharyngioma].

We present a series of 20 patients (11 males) operated on for craniopharyngioma through a frontal craniotomy during an 11-year period. They ranged in age from 7 months to 58 years (mean 20 years). The most common symptoms were headaches, blurred vision and endocrine disorders. The perioperative mortality was 5% and morbidity 25%. 5 (25%) patients need reoperation; 13 (65%) received additional radiation therapy. In 94% visual function improved. 65% continued to have or developed endocrine problems, although all were well controlled with supplemental therapy. These results, similar to those reported from other centers, justify a combination of radical surgery and radiation therapy for this condition.

[Stereotactic brain biopsy].

During a 3-year period starting in 1991, 49 patients with brain lesions underwent 50 stereotactic brain biopsy procedures. The average age was 46 years (range 4-74). Specimens were taken from various brain regions, particularly from the deep aspect of the cerebral hemispheres and midline structures. The pathologic entities included 27 gliomas (13 glioblastomas, 6 astrocytomas, 3 anaplastic astrocytomas, 1 pilocytic astrocytoma and 4 oligodendrogliomas), 5 lymphomas, 2 germinomas, 1 primitive neuroectodermal tumor, 2 metastatic tumors and 11 non-neoplastic lesions (4 demyelination, 2 infarcts, 1 hematoma, 1 brain abscess, 1 radiation necrosis, 1 Alzheimer's disease and in 1 case no diagnosis). The diagnostic success of the stereotactic brain biopsies in this series was 96% (in 98% of the patients). The mean hospital stay was 3 days. 1 patient with a multifocal bilateral glioblastoma died due to early postoperative hematoma of the basal ganglia (2%). Another 2 patients underwent craniotomy due to post-biopsy hematoma. They continued to suffer from hemiparesis after discharge. Transient Horner's syndrome was noted in 1 patient. Thus the permanent morbidity rate was 4%. We conclude that stereotactic brain biopsy can be performed relatively safely, has a high diagnostic yield, and facilitates planning of treatment.

Nystagmus as the presentation of tentorial incisure subdural haematoma.

A case of chronic subdural haematoma in the posterior fossa, secondary to anticoagulant treatment, is presented. The unusual clinical presentation of vertigo and nystagmus and the atypical CT are discussed. This seems to be the first report to describe a chronic subdural haematoma in the posterior fossa in an alive adult.

Intracranial haemorrhage from a meningioma in a patient receiving aspirin prophylaxis: a case report.

A case of acute subdural haematoma originating spontaneously from an angiomatous meningioma in a patient receiving prophylactic aspirin therapy is presented. To the best of our knowledge no comparable case and no discussion of possible complications of aspirin prophylaxis in patients with brain tumours have been published. Possible reasons and clinical significance of this complication are discussed. This observation questions the suitability of aspirin as prophylaxis for vascular disease in patients with meningiomas.

Foraminal herniation of a lumbar disc mimicking neurinoma on CT and MR imaging.

A case of a large L3-L4 intervertebral disc herniation causing a widening of the intervertebral foramen is reported. There was a soft-tissue mas within the spinal canal and intervertebral foramen. The soft-tissue mass within the spinal canal and intervertebral foramen showed marked enhancement on magnetic resonance scans after injection of a paramagnetic contrast agent (Gd-DTPA). The combination of lesion configuration and paramagnetic contrast enhancement mimicked a spinal neurinoma. There exists a degree of overlap between the imaging of herniated discs and spinal neurinomas. When this overlap involves several aspects, such as anatomic configuration, mass enhancement, and secondary foraminal dilatation, the differential diagnosis between a herniated disc and a neurinoma may be problematic.

Pudenz antisiphon device tear as a cause of shunt malfunction.

Antisiphon device (ASD) tear was found in nine patients who underwent ventriculoperitoneal (VP) shunt revision of a Pudenz three-piece system. In six cases this was the only finding, in three, there was an associated distal malfunction. Repair of ASD tear constituted 27% of our shunt revision procedures. The locus minoris resistentia of the Pudenz ASD is the attachment of the diaphragm to the cylinder. ASD tear should be suspected whenever a noninflammatory fluid collection of a CSF leak are found at the proximal extracranial section of this system.

Surgical outcome in an elderly population with intracranial meningioma.

Thirty seven patients aged 70 and over (mean = 74 years) with an intracranial meningioma who had craniotomy between the years 1978-88 were reviewed. There were 20 women and 17 men. Resection was total in 28 (76%) and subtotal in 9 (24%) cases and each tumour was histologically verified. The location of the tumours were: base of skull 11, convexity 10, parasagittal 9, falx 6, and tentorial 1. The most frequent associated diseases were: hypertension (35%), chronic ischaemic heart disease (22%) chronic obstructive pulmonary disease (19%), and diabetes (14%). The Karnofsky Scale (KS) score before surgery ranged from 30 to 90 (mean = 59). It was less than 40 in ten patients. The length of anaesthesia during the surgical procedure varied from 4 to 12 hours and was not related to the outcome. There were two perioperative deaths (mortality = 5.4%). There were major complications in 8 patients and minor complications in 7 patients. In a mean follow up period of 29 months (shortest 6 and longest 96 months) the results were: excellent (KS 90-100) 39%, good (KS 70-80) 49%, fair (KS 60) 6%, and poor (KS 40-50) 6%. The difference between the mean preoperative KS value (KS = 59) and the mean postoperative KS value (KS = 80) was statistically significant (P less than 0.001). The results support a more aggressive therapeutic approach to the elderly patient with an intracranial meningioma.