Early decompressive surgery after combined intra-venous thrombolysis and endovascular stroke treatment.

BACKGROUND AND PURPOSE: The prognosis of malignant middle cerebral artery infarctions (MCA) is poor. The poor prognosis is attributable to the severe cerebral edema that causes a brain herniation and death. Decompressive surgery reduces mortality and may further improve patient outcomes. However, the safety and effectiveness of decompressive surgery in patients who underwent combined intravenous (IV) thrombolysis and endovascular stroke treatment are not certain. Moreover, the evidence on the timing of decompressive surgery is lacking. METHODS: The purpose of the open, prospective and non-randomized study was to compare the outcome and complication rates of patients with malignant MCA strokes who underwent early decompressive surgery after combined intravenous thrombolysis and endovascular treatment with those of decompressive surgery patients without prior recanalization treatment strategy. All patients underwent decompressive surgery within 24h of symptom onset. RESULTS: Thirty patients were included in the study. Twelve of the 30 patients were treated with combined IV thrombolysis and endovascular approach and 18 patients received standard treatment. The proportion of patients with a modified Rankin score ≤3 at the sixth month follow-up was 33% in the standard group and 44% in the combined treatment group (p=0.712). Mortality, and major and minor complications including symptomatic intracerebral hemorrhage after decompressive surgery did not differ between the two groups (p>0.05). CONCLUSION: Early decompressive surgery can be safely performed in patients who received combined IV thrombolysis and endovascular treatment and there was no difference in outcome of these patients compared with patients who did receive the standard medical treatment before early decompressive surgery.

The neuroprotective effect of acute moderate alcohol consumption on caspase-3 mediated neuroapoptosis in traumatic brain injury: the role of lysosomal cathepsin L and nitric oxide.

Our aim in this study was to investigate the effect of moderate acute alcohol administration on cysteine protease mediated neuronal apoptosis and nitric oxide production in the traumatic brain injury. A total of 29 adult Sprague-Dawley male rats weighing 250-300 g were used. The rats were allocated into four groups. The first group was the control (sham-operated) group in which only a craniotomy was performed, the others were alcohol, trauma and trauma+alcohol groups. Caspase-3 enzyme activity in the trauma group increased significantly in comparison with the control group. The alcohol given group showed a decreased caspase-3 enzyme activity compared to the trauma group. The level of caspase-3 enzyme activity in the alcohol+trauma group decreased in comparison to the trauma group. SF/FEL ratio of cathepsin-L enzyme activity in the trauma group was significantly higher than in the control group. Our results indicate that moderate alcohol consumption may have protective effects on apoptotic cell death after traumatic brain injury. Protective effects of moderate ethanol consumption might be related to inhibition of lysosomal protease release and nitric oxide production.

Erythropoietin prevents nitric oxide and cathepsin-mediated neuronal death in focal brain ischemia.

We examined the preventive effect of human recombinant erythropoietin (HrEPO) on nitric oxide (NO)-mediated toxicity to neurons and cysteine protease release into cytoplasm, which is attributed to neuronal death in brain ischemia. Focal cerebral ischemia was induced by permanent occlusion of middle cerebral artery in two sets of rat. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. A group in both set was administered human recombinant erythropoietin (HrEPO). NO content, cathepsins B and L activity increased significantly in the post-ischemic cerebral tissue (p<0.05). HrEPO treatment reduced NO concentration and cathepsin activity to control level (p>0.05). A significant increase in the number of necrotic and apoptotic neurons was observed in the post-ischemic cerebral cortex (p<0.05). HrEPO treatment was markedly lowered both of these (p<0.05). It is concluded that HrEPO prevents neuronal death by protecting neuronal liposomes from NO-mediated toxicity and suppressing the release of cathepsins.

Spontaneous acute subdural hematoma and chronic epidural hematoma in a child with F XIII deficiency.

Factor XIII (F XIII) deficiency is a rare autosomal recessive congenital disorder that can cause spontaneous subdural or epidural hematomas. Due to its low incidence, F XIII deficiency may well be under-diagnosed. A 7-year-old girl with no history of medical problems presented with progressive headache of 3 days. Cerebral computed tomography (CT) scans revealed a large right acute parietooccipital subdural hematoma with a significant midline shift. After an emergent parietooccipital craniotomy and evacuation of the subdural hematoma, a screening test for factor XIII was performed. The results of the test were abnormal. She had full recovery and was discharged with a follow-up treatment of monthly transfusion of fresh frozen plasma as the replacement and prophylactic therapy. Ten months later, she was referred to our center with headache after a minor head trauma. Her medical history revealed that she had not received fresh frozen plasma for the last 2 months. CT scan showed a chronic right parietal epidural hematoma beneath the craniotomy flap. The present case indicates that although its incidence is very rare, F XIII deficiency can cause acute or chronic subdural and epidural hematomas. Therefore, in acute or chronic subdural and epidural hematomas with no underlying cause, the presence of a potential F XIII deficiency should be suspected as a cause of hemorrhagic diathesis.

Evaluation of the size and area of the corpus callosum with the Osiris method in Alzheimer's disease.

BACKGROUND/OBJECTIVE: Significant corpus callosum (CC) atrophy has been demonstrated in patients with Alzheimer's disease (AD). The aim of this study is to evaluate the size and the area of the CC with the Osiris method. The correlation between the CC measurements and Mini-Mental Status Examination (MMSE) scores in AD patients was also investigated. METHODS: The results of the topographic measurements included the cross-sectional area of entire CC, body, rostral portion of the genu and splenium from a midsagittal magnetic resonance imaging section. The results of the topographic measurements of CC on MRI with the Osiris method were compared between AD (n = 29) and control subjects (n = 27). RESULTS: In AD patients the mean value of the splenium was 9.2 +/- 1.5 mm, the width of the CC body was 3.9 +/- 0.2 mm, the rostral portion of the genu was 7.9 +/- 0.2 mm, and the total CC area was 47.2 +/- 0.9 mm(2). In the control group the mean values were 12.2 +/- 2.1 mm, 5.9 +/- 0.2 mm, 11.2 +/- 0.2 mm and 56.1 +/- 0.6 mm(2), respectively. Significant reduction was detected in the splenium, the CC body and the rostral part of the genu and CC area in AD patients. The MMSE score was 18.9 +/- 4.5 in the AD patients and 29.1 +/- 0.9 in the control subjects. A significant positive correlation between the MMSE scores and each CC measurement was seen in the AD patients. CONCLUSION: The results of this study suggest that callosal atrophy in AD may suggest the severity of the disease. The Osiris method for CC measurements may be used as an easy and reliable technique to assess the severity of the disease.

Symptomatic foraminal extradural meningeal cyst.

The authors described the case of a 39-year-old man with Klippel-Trénaunay syndrome, who had an extradural meningeal cyst expanding into intervertebral foramen of lumbar 2 and 3 vertebrae. The patient suffered from low back pain radiating to the left lower extremity. Magnetic resonance imaging revealed a huge extradural meningeal cyst growing through intervertebral foramen far laterally. A widened neural foramen of L2 and L3 vertebrae was observed on his plain radiography. The cyst was totally excised after tying the ostium connecting the subarachnoid space of the dural sac. This case supports the congenital theory in the pathogenesis of spinal cysts because the Klippel-Trénaunay syndrome is a congenital disorder including a mesodermal abnormality which may be the causative factor for a congenital defect in dura.

Efficacy of prognostic factors on survival in patients with low grade glioma.

AIM: In this report, we aim to determine the prognostic factors influencing the length of survival in patients with low-grade gliomas. MATERIAL AND METHODS: In a retrospective evaluation, we have reviewed fiftythree patients who had been operated between the years of 1980 and 2006. The diagnoses of the patients were histopathologically verified as low-grade glioma(LGG). The medical records of the patients were reviewed for age, gender, tumor locations, extent of resection, and presence of seizure, the neurological status as defined by the Karnofsky Performance Scale (KPS) and radiotherapy treatment after surgery as possible prognostic factors. RESULTS: Median cumulative survival time for all the patients with LGG was 141+/-14.83 months. Median survival time was 216+/-78.52 months for astrocytoma Grade I; 115+/-8.22 months for astrocytoma Grade II, and 242+/-76.36 months for oligodendroglioma. Young age, histology subtype (oligodendroglioma) and preoperative KPS were determined to have positive influence on survival according to Log Rank Test. In contrast, age, histology type and the extent of resection remained independent prognostic factors upon survival when Cox Regression Backward Stepwise (Wald) method was performed. CONCLUSION: It can be concluded that surgery seems to be an appropriate first step option in the treatment of LGG.

Nitric oxide level and adenosine deaminase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage.

OBJECTIVE: Adenosine and nitric oxide (NO) are known as vasodilatators. We investigated adenosine deaminase (ADA) activity and NO concentration in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH). METHODS: Forty patients with SAH and 10 controls were included in the study. Nitrate level and ADA activity were measured in CSF. SAH patients were grouped according to the presence of angiographic vasospasm, Hunt and Hess grading, Glasgow Coma Scale (GCS) and Fisher Grade (FG). RESULTS: The level of NO markers in SAH patients decreased when compared to that in the control group (p < 0.05). However, NO markers in patients with vasospasm was higher than in that of patients without vasospasm (p < 0.05). ADA activity increased in patients with SAH (p < 0.01) and also patients with angiographic vasospasm (p < 0.05). ADA activity in the poor-grade SAH group was higher than that in the good-grade SAH group. The group with the lower GCS showed increased ADA activity compared to those with a higher GCS score (p < 0.01). Furthermore, patients with FG 4 had a higher level of ADA activity compared to FG 1 and 2 and FG 3 (p < 0.001 and p < 0.01, respectively). CONCLUSION: Decreased NO level may participate in the early development of vasospasm. However, the increased level of ADA activity in the SAH patients with the poor clinical and consciousness level may have resulted from the ischemic cerebral insult.

The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p < 0.05). Dexanabinol treatment reduced NO concentration and cathepsin activity to the control level (p > 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p < 0.05). However, dexanabinol treatment lowered both of these (p < 0.05). We conclude that dexanabinol might be a useful agent for the treatment of stroke patients.

Dexanabinol prevents development of vasospasm in the rat femoral artery model.

We postulated that a multi-potential agent such as dexanabinol may prevent the development of vasospasm after subarachnoid hemorrhage. We tested the effect of dexanabinol (10 mg/kg) on established vasospasm in a rat femoral artery model. Dexanabinol was given as single or repeated doses. On the 7th day after blood application, vessels were prepared for transmission electron microscopy studies, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining, and studying vessel morphology including luminal area and wall thickness. Application of blood to femoral artery caused a significant narrowing of luminal area (p<0.001) and a marked increase of radial wall thickness (p<0.001) when compared to controls. Similar to its single injection, repeated doses of dexanabinol markedly widened luminal area (p<0.001) near to control values (p>0.05) and decreased radial wall thickness significantly compared to hemorrhage (p<0.05) and vehicle-treated groups (for single p<0.05 and repetitive injections p<0.01). Both single and multiple dexanabinol injections also lowered apoptotic index (p<0.001). In conclusion, dexanabinol seems to prevent established vasospasm and endothelial cell apoptosis.

AA-861 appears to suppress leukocyte infiltration induced by traumatic brain injury in rats.

OBJECTIVE: To study the effect of 2,3,5-Trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861) on intercellular adhesion molecule 1 (ICAM-1) and P-selectin expression, leukotriene B4 (LTB4) level, and myeloperoxidase (MPO) activity 24 hours after traumatic brain injury (TBI). METHODS: This study was carried out in the laboratory of the Department of Clinical Pharmacology, Osmangazi University, Eskisehir, Turkey in 2006. Traumatic brain injury was induced in 2 sets of animals using Feeney`s weight-drop method. The first set was used to study the expression of ICAM-1, P-selectin, CD11a, and mouse anti-rat granulocyte monoclonal antibody (HIS48). The second was used to study tissue changes in LTB4 level, and MPO activity. The rats were sacrificed at 0.5, 4, 24, 48, and 72 hours post-injury. RESULTS: Intercellular adhesion molecule (p=0.000001) and P-selectin expression (p=0.00002) peaked at 24 hours, remained high at 48 hours (p=0.00012 for ICAM-1, and p=0.00002 for P-selectin), and 72 hours (p=0.000008 for ICAM-1, p=0.0011 for P-selectin). The HIS48 intensity was significantly increased at 24-72 hours (p=0.022), while the intensity of CD11a became significant only at 72 hours (p=0.040). Myeloperoxidase activity increased notably at 24 hours (p=0.00077), and peaked at 48 hours (p=0.00001). The LTB4 increased markedly at 4 hours (p=0.000004), and peaked at 24 hours (p=0.000001). Pretreatment with AA-861 considerably suppressed the expression of ICAM-1 (p=0.0053), and P-selectin (p=0.0018) on microvascular endothelium, and lowered MPO activity (p=0.0007), and LTB4 level (p=0.008) at 24 hours. CONCLUSION: The present results suggest that AA-861 might be a potential mediator in the treatment of brain inflammation in TBI.

Genomic alterations in low-grade, anaplastic astrocytomas and glioblastomas.

To extend our understanding of potential stepwise genetic alterations that may underlie tumor progression from low-grade astrocytomas to glioblastomas, histopathologic and comparative genomic hybridization analyses were performed on tumor specimens from 68 primary lesions, including 40 glioblastomas, 10 anaplastic and 18 low-grade astrocytomas. The number of aberrations per case increased towards the higher grade tumors (grade II: 1.66+/-1.49; grade III: 2.80+/-1.68; grade IV: 3.02+/-1.07; F=6.955, p=0.002). A gain of 7/7q was common and the most frequently seen aberration in low-grade astrocytomas, whereas loss of 10q was the most frequently seen anomaly in anaplastic astrocytomas and glioblastomas. Chromosome 7p amplification was only detected in glioblastomas. Chromosome 10/10q deletion and combination of 1p, 19q and 17p deletions were specific to high-grade astrocytic tumors. Sequences of chromosome 7 and 10 seem to have pivotal roles in the biology of human gliomas. The genomic copy deletions of chromosomes 1p and 19q might provide an alternative mechanism in the genesis of astrocytomas.

Comparison of the antiproliferative properties of antiestrogenic drugs (nafoxidine and clomiphene) on glioma cells in vitro.

The antitumoral activity of nonsteroidal antiestrogens on C6 and low passage of human glioma cells was investigated. Tamoxifen and its metabolite, 4-hydroxytamoxifen, did not influence viability of the human cells, but tamoxifen had a limited antiproliferative effect on C6 cells (IC50: 49 micromol/l). The derivatives of tamoxifen, nafoxidine and clomiphene, caused reduction of living cell number in a dose-dependent manner. These two drugs showed differences in their potency following 24-hour incubation in a humidified atmosphere with 37 degrees C and 5% CO2. Obtained from a tetrazolium-formazan growth rate assay, IC50 of nafoxidine for C6 cells was calculated as 44 micromol/l and for the human cells as 16.5 micromol/l. The calculated IC50 dose of clomiphene for C6 is 16 micromol/l and for the human cells 13 micromol/l. Compared to the other drugs we used, it is clear that clomiphene is the most efficient inhibitor of C6 and the human glioma cells. These preliminary results suggest that nafoxidine and clomiphene possess antiproliferative effect on two different sources of glioma cells and therefore, instead of tamoxifen, multiple activities of these drugs may enable their use in combination therapy of glioblastoma malignancies.

The importance of genomic copy number changes in the prognosis of glioblastoma multiforme.

Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.

Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic reperfusion injury.

The aim of the present study was to determine the potential therapeutic value of 21-aminosteroid U-74389G, on blood-brain barrier (BBB) breakdown and edema in association with the changes in synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPase activities in rat brain subjected to post-ischemic reperfusion injury. Brain ischemia was achieved by means of four-vessel occlusion model for 25 min and animals were sacrificed after 12 h reperfusion. An increase of cerebral tissue water content, blood-brain disruption and the changes of synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPases activities were evaluated. U-74389G was given intraperitoneally at two times as 5 mg/kg at 10 min prior to ischemia and at the beginning of reperfusion. Edema was determined by means of wet-dried weight method, and BBB of extravasation of Evan's blue dye. Extravasation of Evan's blue dye into brain following ischemia and reperfusion was 2.4-fold of control value and brought close to control levels by the effect of U-74389G (p<0.001). Post-ischemic reperfusion injury caused an increase of 3.7% in tissue water content of whole brain and administration of U-74389G lowered the cerebral edema (p<0.001). The loses in the Na(+)/K(+)-ATPase and Mg(2+)/Ca(2+)-ATPase activities occurred as 42.1% (p<0.01) and 65.7% (p<0.001) of control value, respectively. While Mg(2+)/Ca(2+)-ATPase activity was enhanced compared to vehicle-treated group of animals (p<0.01), Na(+)/K(+)-ATPase activity was fully recovered when compared to control by U-74389G (p>0.05). U-74389G also significantly attenuated neuronal necrosis (p<0.001) which was determined in the hippocampal CA1 subfield. Blood-brain barrier protection, attenuation of brain edema and neuronal necrosis concomitant with the stabilizing of membrane-bound enzymes brought about by the effect of U-74389G suggest that 21-aminosteroids are worthy of consideration in the acute treatment of cerebral ischemia.

Lazaroid attenuates edema by stabilizing ATPase in the traumatized rat brain.

OBJECTIVE: The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma. METHODS: Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals. RESULTS: Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1% (p<0.001) at 24h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg(2+)/Ca(2+)-ATPase activities were found as 39.5% (p<0.001) and 29.4% (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209% (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05). CONCLUSION: U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.

Detection of chromosomal imbalances in spinal meningiomas by comparative genomic hybridization.

Little is known about genetic mutations during the malignant progression of spinal meningiomas. This study investigated genomic changes across the entire genome in spinal meningioma samples to determine possible mechanism(s) of tumorigenesis. Paraffin-embedded tissue sections of 16 spinal meningiomas were analyzed by the comparative genomic hybridization (CGH) technique. Lymphocytes of the patients were evaluated as controls. Genomic change was detected in 11 samples. Complete or partial loss of chromosome 22 was the most commonly seen abnormality in eight cases. Chromosome losses on 1p, 9p, and 10q and gains on 5p and 17q were the other abnormalities. These changes are all frequently seen in meningiomas, but are mostly specific to atypical and anaplastic meningiomas. However, in the present study, copy number changes on chromosomes 9p (3 samples), 17q (2 samples), and 1p (2 samples) were seen even in the benign tumors. Our results suggest that in addition to the neurofibromatosis type 2 tumor suppressor gene, other cancer-related genes located on 1p, 9p, 10q, and 17q might be involved in the etiology of spinal meningiomas.

Comparative genomic hybridization analysis of genomic alterations in benign, atypical and anaplastic meningiomas.

BACKGROUND: Meningiomas are common tumors of the central nervous system. Although most are benign tumors, approximately 10% show a histologic progression to a higher malignancy grade similar to atypical (GII) and anaplastic (GIII) meningiomas. Monosomy 22q12 is the most frequent genetic alteration detected in these tumors, but failure of detection of 22q mutations in about 40% of tumors which are indistinguishable from meningiomas with 22q deletions with respect to clinical and histopathologic features, makes it apparent that an alternative mechanism is responsible for the initiation of meningioma. Moreover, little is known about genetic alterations during malignant progression of meningioma. PURPOSE: In order to determine the genetic pathways underlying the development of meningioma, 15 benign (WHO grade I), 7 atypical (WHO grade II) and 3 anaplastic (WHO grade III), sporadic meningiomas were screened by Comparative Genomic Hybridization (CGH). RESULTS: Statistical analysis revealed a significant correlation between the number of chromosomal imbalances and the tumor grade; the numbers of total alterations detected per tumor were 2.20 (2.24 for GI, 10.00 (1.17 for GII and 14.66 (1.15 for GIII. The most frequent abnormality seen in benign tumors was loss on 22q (47%). The second alteration was 1p deletion (33%) and this abnormality was also the common aberration in three tumors without CGH detected 22q deletion. In GII, aberrations most commonly identified were losses on 1p (6/7 cases), 22q (5/7 cases), 10q (4/7 cases), 14q and 18q (3/7 cases) as well as gains on 15q and 17q (3/7 cases). In GIII, genomic loss on 1p was the most commonly observed abnormality (3/3). Losses on 9p, 10q, 14q, 15q, 18q and 22q as well as gains on 12q, 15q and 18p were the other genomic alterations detected by CGH. Combined 1p/14q deletions were encountered in 2/15 benign, 3/7 atypical and 2/3 anaplastic meningiomas. By CGH, DNA sequences on 17q21-qter were seen to be amplified in 1/7 GII and 2/3 GIII, whereas highly amplified DNA sequences on 12q13-qter, 20q and 22q11-q12 were seen in one GII, two GII/one GIII, and one GIII, respectively. CONCLUSION: It was concluded that chromosomal deletion from 1p could play a major role in the initiation and progression of meningiomas and that 1p/14q deletions could be a primary focus of further detailed assessment of tumour genesis.