Hemorrhagic colloid cyst with sudden coma.

BACKGROUND: Third ventricle colloid cysts are regarded as benign lesions. They may, however, present with dramatic and rapidly deteriorating neurological signs, leading to sudden death. Although the exact cause of this clinical course is unknown, acute hydrocephalus caused by occlusion of Monro's foramina has been suggested. This, in turn, may be the result of acute cyst swelling, which can exceptionally be due to an intralesional hemorrhage. CASE REPORT: This report illustrates the case of a young patient who deteriorated to sudden coma and was found to have a hemorrhagic colloid cyst of the third ventricle. This was removed via a purely endoscopic technique. Although the radiological results were excellent, the clinical outcome was poor. CONCLUSIONS: This case suggests once again the importance of the early recognition of colloid cysts of the third ventricle for appropriate treatment before potentially irreversible neurological deterioration sets in.

Epidermoid cysts of the cerebellopontine angle with extension into the middle and anterior cranial fossae: surgical strategy and review of the literature.

Epidermoid cysts are tumours, which contain keratin, cellular debris and cholesterol, and lined with stratified squamous epithelium. Clinically, epidermoid cysts behave like benign, slow-growing lesions. We present a 63 year-old man with a 6-month history of right periorbital pain and hypaesthesia in the area of the first and second branch of the trigeminal nerve. MRI revealed an epidermoid cyst of the cerebellopontine angle extending into the middle and anterior cranial fossae. Radical surgical removal of epidermoid cysts should be attempted, but a less aggressive surgical strategy should be considered if there is strong adherence to the surrounding brain tissue, particularly in eloquent areas. In this case, complete tumour removal was achieved via a suboccipital retrosigmoid approach.

Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: a series of 33 cases.

AIMS: In this study we present a series of 33 patients with primary CNS lymphomas (PCNSL), many presenting with acute signs of increased intracranial pressure due to large space occupying lesions. METHODS: A series of 32 PCNSL patients for a total of 33 tumours treated from 1986 to 2000 in the Neurosurgical Department were reviewed. RESULTS: Radiotherapy and chemotherapy improved survival. No benefit could be demonstrated for the role of surgery. CONCLUSIONS: Our data confirm previous reports about the role of radiation and chemotherapy in the treatment of PCNSL's. Surgery might have a role in a selected subset of patients presenting with large single space occupying lesions and deteriorating neurological status.

The prognostic value of progesterone receptor status in meningiomas.

BACKGROUND: Meningiomas are known to recur frequently, and their longterm management remains controversial. Previous studies indicate that progesterone and its receptors can play a role in the recurrence of meningiomas, but the correlation between the presence of these receptors and patients' outcome is unclear. AIM: To conduct a retrospective analysis to investigate the prognostic relevance of progesterone receptor (PR) expression in meningiomas. METHODS: Five hundred and eighty eight meningiomas operated on over a period of 10 years were examined immunohistochemically to determine the PR status using monoclonal antibodies. Several factors including recurrence (mean follow up of 65 month), sex, tumour tissue consistency, location, vascularity, and en plaque appearance were analysed. RESULTS: PR status showed comparable values for men and women. World Health Organisation (WHO) grade II and III tumours had significantly fewer receptors than benign meningiomas. There was no significant correlation between PR status and recurrence rates in WHO grade I totally removed meningiomas. However, a combination of PR status and proliferation indices was shown to predict recurrence reliably. CONCLUSIONS: Together with routine histological evaluation, PR status can help to describe the biological behaviour of meningiomas. Only a combination of clinical and biological features can describe the behaviour of meningiomas, predict their recurrence, and help to devise more effective follow up strategies.

A model for intratumoural chemotherapy in the rat brain.

To achieve the best reproducibility in rat brain tumour models several injection techniques have been used. Although stereotactic cell injections have proved to be effective and reliable, they are expensive and time consuming. A new permanently implanted device is presented here. It allows precise cell delivery for best tumour reproducibility, and it can be left in place for future injections at the exact same location, such as intratumoural chemotherapy. A Teflon tube was mounted on a disc, inserted into the rat brain and sealed to the skull. The device was tested in two rat strains (Wistar and New Zealand Nude rats) with two different glioma cell lines (9L and C6). Rats were treated with placebo to determine if repeated treatments had an effect on the device placement, or if device-related morbidity was induced. Analysis of brain sections showed that the device path was always within the tumour. The device never moved or came off the scalp. Both Wistar rats and NZ nude rats tolerated the device well. No morbidity or mortality was observed, regardless of the presence of the device; no infections were seen. Biocompatible, non-irritating and well tolerated, such a device can be used for reproducible tumour cell injections and repeated intralesional delivery of drugs.

The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases.

BACKGROUND: Meningiomas are mostly benign tumours that can be cured by surgical resection. Because meningiomas tend to recur, long term management in patients with subtotal tumour resection remains controversial. Previous studies have shown that the proliferation potential of meningiomas by Ki-67 labelling indices (LI) might predict their natural history. The purpose of this study was to analyse the reliability of Ki-67-labelling index in predicting the behaviour of meningiomas, and to help the neurosurgeon in establishing better follow up criteria and long term management strategies for these patients. METHOD: From 1990 to 2000 1328 meningiomas have been operated in our Neurosurgical Department. A total of 600 tumours were examined immunohistochemically using the Mib-1 monoclonal antibody. Clinical charts of the patients including surgical, histological and follow up records, as well as imaging studies were analysed retrospectively. Ki-67 LI were correlated with neuroradiological findings, 3D volumetric studies, histological subtype, recurrence-free survival, grade of resection, consistency of tumour tissue, location, osseous involvement, en plaque appearance, vascularity and progesterone-receptor status. FINDINGS: Among the 600 patients analysed, there were 66% females (mean LI 3.8%) and 34% males (mean LI 5.7%), including 20 neurofibromatosis-type-2 (NF-II) patients with a mean LI of 5.2%. Histological grading revealed 91% WHO degrees I meningiomas (mean LI 3.28%), 7% WHO degrees II (mean LI 9.95%) and 2% WHO degrees III (mean LI 12.18%). Labelling indices in recurrent meningiomas increased from initial resection to a fourth local resection. A significant correlation between negative progesteron-receptor status and high tumour vascularity with high Ki-67 LI was seen. Ki67 was not a statistically significant predictor of survival time in totally excised WHO degrees I meningiomas. INTERPRETATION: Mib-1 is one important tool in addition to routine histological evaluation, but a combination of clinical factors and particularly the extent of surgical resection, along with the biological features of the tumour, should influence the decision of the neurosurgeon to the patient follow up.

A new xenograft model of primary central nervous system lymphoma.

The management of primary lymphoma of the central nervous system (PCNSL) remains controversial and patients' outcome dismal. In order to investigate new selective therapeutic strategies in a controlled system, a reproducible model of PCNSL in nude rats was developed and characterized. Human B lymphoma cells (BL2) were implanted in the brain frontal area in New Zealand nude rats through a silastic device sealed to the skull. Fifteen and 30 days post-implantation, animals were sacrificed. An autopsy was performed. Representative brain sections were cut and examined for the presence of lymphoma. Immunohistochemistry was performed for proliferation (MIB1-Ki67), a B-cell marker (L26-CD20), a T-cell marker (UCHL1-CD45RO). The analysis of the brains showed tumor growth in 88% of the rats. No mortality was observed. At autopsy no extracerebral, spinal or cerebellar metastasis were found. Microscopically the brain tumors appeared non-encapsulated, highly vascularized, with a characteristic perivascular and diffuse lymphomatous spread in the parenchyma. Immunohistochemistry showed a marked positivity of the tumor cells for L26. Tumor cells were negative for UCHL1. Mean proliferation rate was 30%. The device was well tolerated and caused no local infection. Controlled studies on PCNSL in animal models are lacking. This PCNSL model in nude rats reproduces the histology and location of human CNS lymphoma. Tumor dimensions are within the resolution limits of CT and MRI and therefore suitable for stereotactic therapy. This model provides a tool to test new chemo and radiotherapeutical strategies in a controlled fashion.

Morphometrical characterization of two glioma models in the brain of immunocompetent and immunodeficient rats.

Although several glioma models exist, systematic morphometrical studies on such experimental tumors are lacking. The purpose of this study was the quantitative assessment of how rat strains, cell lines, injection techniques and location affect tumors reproducibility and histopathological features. Glioma cells were implanted in 3 brain locations, with different injection techniques (free hand, stereotactic, water-tight device), variable volumes, cell concentrations and infusion rates. Tumors were developed from 2 rat glioma cell lines (9L and C6) in immunocompetent (Wistar and Fischer 344) and immunodeficient rats (New Zealand). Animals underwent daily neurological examination. At the scheduled time the tumors were macro and microscopically evaluated and a quantitative morphometrical analysis was performed. C6 gliomas appeared very infiltrative and irregularly shaped; 9L gliomas showed, by using the same injection technique, a grossly regular shape. Margins at the tumor-brain interface were macroscopically demarcated in the immunocompetent rats. In the nude rats, 9L tumors appeared microscopically more infiltrative, although regularly shaped, with a closer morphological resemblance to human gliomas. The implantation in the frontal area, anterior to the nucleus caudatus (3 mm anterior the coronal suture) gave reproducible tumor shape and size, no hydrocephalus and no early neurological deterioration. The use of a stereotactic technique or of a water-tight device, small volume (< 10 microl) of cell suspension, low infusion rate were useful to reduce morbidity and to improve data reproducibility. No difference in morbidity and mortality were observed in immunocompetent and immunodeficient rats. The 9L glioma model with stereotactic implantation constitutes a good option for reliable morphometrical evaluation of tumor growth. We propose a location for tumor implantation anterior to the nucleus caudatus. This produced the longest symptom-free survival.

Response of postmitotic neurons to X-irradiation: implications for the role of DNA damage in neuronal apoptosis.

The molecular changes responsible for inducing neuronal apoptosis are unknown. Rat cortical neurons were treated with x-irradiation 7 d after isolation to test for the role of DNA damage in neuronal death. The response of neurons to x-irradiation was compared with that of astrocytes that had been isolated 3 weeks earlier from newborn rats. At the time of irradiation, the neurons appeared well differentiated morphologically and were predominantly (90-95%) noncycling, based on flow cytometric analysis. There was a similar, linear increase in DNA double-strand breaks with increasing radiation dose in neurons and astrocytes. However, whereas doses as low as 2 Gy induced typical apoptotic changes in neurons, including nuclear fragmentation and/or internucleosomal DNA fragmentation, doses as high as 32 Gy caused little or no apoptosis in astrocytes. Radiation-induced apoptosis of neurons started 4-8 hr after irradiation, was maximal at 12 hr, and was dependent on dose up to 16 Gy. It was prevented when cycloheximide, a protein synthesis inhibitor, was added up to 6 hr after irradiation. In addition to their distinct apoptotic response, neurons rejoined radiation-induced DNA double-strand breaks more slowly than astrocytes. Treatment with benzamide to inhibit ADP-ribosylation and strand break repair increased apoptosis; splitting the dose of radiation to allow increased time for DNA repair decreased apoptosis. These data suggest that DNA damage may induce neuronal apoptosis, that the extent of damage may determine the degree of apoptosis induced, and that slow repair of damage may play a role in the susceptibility of neurons to apoptosis.

Accuracy of single-energy quantitative computed tomography in the assessment of bone mineral density of cervical vertebrae.

Earlier studies have shown that single-energy quantitative computed tomography (SEQCT) is a reliable method for bone mineral density (BMD) measurements in thoracic and lumbar vertebrae. Moreover, SEQCT has proved to be a useful parameter in the selection of appropriate implants in cervical spondylodesis. The aim of this study was to determine the accuracy of SEQCT in cervical vertebrae BMD measurement. BMD with reference to calcium hydroxyapatite (Ca10[PO4]6[OH]2) was assessed by SEQCT in 100 human vertebral bodies of the cervical spine. Bone cylinders were then cut from the appropriate region of interest. The cylinder volume was determined by the liquid displacement technique. The density of the mineral component was measured following incineration at 1100 degrees C for 24 h. The calculated BMD was correlated with the SEQCT values, resulting in a coefficient of r = 0.79 (P < 0.01). Mean SEQCT values were significantly lower than those determined by direct density assessment (t-test for coupled sampling, P < 0.02). This result was in agreement with studies on thoracic and lumbar vertebrae. These data suggest that SEQCT can reliably measure BMD in the cervical spine.

Environmental and urinary reference values as markers of exposure to hydrocarbons in urban areas.

A study using individual dosimetry to evaluate the daily inhaled dose of sixteen aromatic and aliphatic hydrocarbons in three groups of primary school children, living in three Italian towns with 50,000 inhabitants or less, (Treviglio-Lombardy; Poggibonsi-Tuscany; Valenza-Piedmont) is presented. The simultaneous use of two passive samplers (radial diffusion) for each child, for a 24 h period, determined both the indoor and indoor + outdoor environmental reference concentrations. We measured the urinary levels of benzene, toluene, ethylbenzene and xylenes for each child and hence determined the urinary reference values for BTEX. We also considered the possibility of using benzene in urine as a biomarker of environmental exposure of the general population to this xenobiotic. We evaluated how both the environmental and biological measures were influenced by the presence of smokers in the surveyed children's houses. For the group of children living in Poggibonsi, we considered the influence of the living area and the traffic density on environmental concentrations of benzene (indoor and indoor + outdoor).

Microglial responses after focal radiation-induced injury are affected by alpha-difluoromethylornithine.

PURPOSE: The objective of this study was to quantify microglial and astrocytic cell responses after focal 125I irradiation of normal brain and to determine the effects of an intravenous infusion of alpha-difluoromethylornithine (DFMO) on those responses. METHODS AND MATERIALS: Adult beagle dogs were irradiated using high activity 125I sources. Saline or DFMO (75 mg/kg/day) was infused for 18 days, and 1 to 10 weeks later brain tissues were collected. Immunohistochemical stains were used to label phagocytes and amoeboid microglia (lectin RCA-1), astrocytes (GFAP), and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cell densities (cells/mm2) and BrdU labeling indices were quantified. RESULTS: In dogs infused with saline, increases in phagocytes and amoeboid microglia were observed at 1-2 weeks and 4 weeks, respectively. The labeling indices for phagocytes and amoeboid microglia peaked at 4 weeks with maximum values of 4.8 and 13.4%, respectively. Astrocyte cell numbers increased from 2-6 weeks following irradiation; increased labeling indices were observed after 2 weeks. An infusion of DFMO significantly suppressed BrdU labeling and delayed the increase in cell numbers for phagocytes and amoeboid microglia. In both treatment groups, the proportion of total BrdU labeling accounted for by phagocytes was maximum 1 week after irradiation and then decreased. The proportion of total BrdU labeling accounted for by amoeboid microglia and astrocytes was zero for 2 weeks and then increased. CONCLUSIONS: Microglial reactions after focal irradiation involve the phagocytic and amoeboid cell forms and are characterized by increased BrdU uptake and increased cell number. DFMO significantly alters these responses. Changes in astrocyte cell number and BrdU labeling may be related to changes in microglia. Studies of cell responses and their modification may lead to a better understanding of the pathogenesis of radiation injury, and to new strategies to optimize the use of therapeutic irradiation.

Apoptosis is induced in the subependyma of young adult rats by ionizing irradiation.

To determine if radiation-induced apoptosis occurred in young adult brain, we exposed 2-3-month old rats to single x-ray doses of 5 or 30 Gy. Apoptosis was quantified using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method and a morphologic assessment of nuclear fragmentation. Apoptosis occurred primarily in the subependyma but also in the corpus callosum, peaking 6 h after irradiation. At 48 h there were no apoptotic nuclei observed. These data are the first to show that apoptosis occurs in the young adult rat brain after ionizing irradiation. Further studies are required to define the particular cell type(s) involved and to address the role of this process in the pathogenesis of late radiation injury.

The role of interfascicular nerve grafting after gunshot wounds. A report of 44 cases.

In this study the authors present the results of 44 patients with 49 interfascicular nerve grafting procedures necessitated by gunshot wounds. The aim was to establish the effectiveness of microsurgical interfascicular nerve grafting for war injuries. The 49 interfascicular nerve grafting procedures were performed between July 1991 and January 1993. All but one were performed within 6 months of injury. Nerve recovery was assessed independently by a neurologist. The M/S scale was used for median, ulnar and radial nerves, and the grading scale recommended by Millesi was used for the sciatic, tibial and peroneal nerves. Follow-up was for between 2.5 and 3.5 years. Patients scoring at least M3/S3+, or Grade 2 on the Millesi scale, were considered to have useful functional recovery which occurred in high median (0 out of 1), low median (4 out of 9), high ulnar (0 out of 2), low ulnar (5 out of 11), high radial (4 out of 6), low radial (2 out of 2), sciatic (5 out of 9), peroneal (4 out of 7), and tibial (2 out of 2). The extent of recovery correlated inversely with the patient's age and the length of the graft, but was independent of the time between injury and surgery and of presumed projectile energy. Our results suggest that microsurgical interfascicular nerve grafting is of value in the management of wartime nerve injuries.

Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis.

PURPOSE: The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal 125I irradiation of normal brain, and to determine the effects of an intravenous infusion of alpha-difluoromethylornithine (DFMO) on those responses. METHODS AND MATERIALS: Adult beagle dogs were irradiated using high activity 125I sources. Saline (control) or DFMO (150 mg/kg/day) was infused for 18 days starting 2 days before irradiation. At varying times up to 8 weeks after irradiation, brain tissues were collected and the cell responses in and around the focal lesion were quantified. Immunohistochemical stains were used to label astrocytes (GFAP), vascular endothelial cells (Factor VIII), polymorphonuclear leukocytes (PMNs; MAC 387) and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cellular responses were quantified using a histomorphometric analysis. RESULTS: After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. alpha-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm2 were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. CONCLUSIONS: There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury.

Effects of lateral reticular nucleus stimulation on trigeminal sensory and motor neuron activity related to the jaw opening reflex.

The effects of lateral reticular nucleus (LRN) stimulation on the responses to tooth pulp (TP) stimulation of neurons located in the trigeminal (V) sensory (39 units) and motor (33 units) nuclei were assessed in anesthetized rats. Only neurons which responded to TP stimulation with bursts of spikes that were in a constant temporal relationship with the digastric EMG signal were studied. The LRN-stimulating electrodes were positioned at optimal sites to suppress the TP-evoked jaw-opening reflex (JOR) recorded simultaneously with the neuronal activity related to it. It was found that: (1) the neurons in the V nucleus oralis responded to TP stimulation with 3-8 msec latency excitatory responses that were suppressed during LRN conditioning stimulation with a time course comparable to that of the JOR suppression, and (2) the neurons in the V nucleus motor responded to TP stimulation with 5-15 msec latency excitatory responses. This activity was suppressed during LRN-conditioning stimulation with a time course that parallels the inhibition of the activity of nucleus oralis neurons and of the JOR. However, assuming that the excitatory interneurons for the V motoneurons are located in the nucleus oralis, the suppression of this input by LRN may account for the lack of response in V motor neurons. Thus, we suggest that LRN inhibits the TP-evoked JOR by acting on the sensitive afferent limb of the reflex.