Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: integrated analysis of pooled data from double-blind phase III clinical studies.

PURPOSE: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial-onset seizures. METHODS: Data from 1,049 patients enrolled from 125 centers, in 23 countries, in three phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2-week titration period, ESL was administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. KEY FINDINGS: Seizure frequency was significantly reduced with ESL 800 mg (p < 0.0001) and 1,200 mg (p < 0.0001) compared to placebo. Median relative reduction in seizure frequency was, respectively, 35% and 39% (placebo 15%) and responder rate was 36% and 44% (placebo 22%). ESL was more efficacious than placebo regardless of gender, geographic region, epilepsy duration, age at time of diagnosis, seizure type, and number and type of concomitant antiepileptic drugs (AEDs). Incidence of adverse events (AEs) and AEs leading to discontinuation were dose dependent. AEs occurred mainly during the first weeks of treatment, with no difference between groups after 6 weeks. Most common AEs (>10% patients) were dizziness, somnolence, and headache. The incidence of AEs in ESL groups compared to placebo was generally consistent among different subpopulations. SIGNIFICANCE: Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy and safety end points. Results were independent of study population characteristics and type and number of concomitant AEDs.

Neurological outcomes in patients with ischemic stroke receiving enoxaparin or heparin for venous thromboembolism prophylaxis: subanalysis of the Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study.

BACKGROUND AND PURPOSE: The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression. METHODS: Acute ischemic stroke patients aged >or=18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (>or=4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage. RESULTS: Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression. CONCLUSIONS: The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared with UFH.

The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison.

BACKGROUND: Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke. METHODS: 1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805. FINDINGS: In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015). INTERPRETATION: Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.

Progressive myopathy with a combined respiratory chain defect including Complex II.

Biochemical defects in the respiratory chain are mostly associated with deficiencies in Complexes I, III and IV, caused by nuclear or mitochondrial DNA mutations. Combined defects including Complex II have been reported very rarely and have muscular symptoms as the main manifestation, including muscle weakness, exercise intolerance and myoglobinuria. We report a patient with a fatal progressive myopathy and muscle biopsy showing diffuse reduction in succinate dehydrogenase activity, ragged red fibers and intense lipid accumulation. Cytochrome c oxidase (COX) histochemistry demonstrated 30% of fibers with increased subsarcolemmal staining while 27% were COX negative. Western blotting analysis showed reduction in the expression of the 39 kDa subunit of Complex I, subunit II of Complex IV and the 70 kDa subunit of Complex II. Our findings suggest that the patient had a complex pattern of mitochondrial dysfunction affecting multiple respiratory chain complexes (I, II and IV) and fatty acid metabolism. This report adds a new histological pattern associated to combined deficiencies of respiratory chain with involvement of Complex II and shows that this disease may be fatal with a rapid progression.

Age-related mitochondrial DNA point mutations in patients with mitochondrial myopathy.

Mutations in the control region (D-loop) of mitochondrial DNA (mtDNA) have been described in normal old individuals and it is suggested that they originated from oxidative damage. Respiratory chain defects may lead to increased free radical generation, increased susceptibility to oxidative damage and further increased accumulation of age-related mutations. The objective of this study was to verify whether patients with a mitochondrial disease are more predisposed to accumulate the A189G and T408A mutations in the D-loop and confirm their age-associated nature. We evaluated the presence and levels of heteroplasmy of these two mutations in muscle DNA of 52 individuals with different ages (21 age-matched controls and 31 patients with single or multiple mtDNA deletions). The frequency of both mutations was significantly increased with age, but no differences were observed comparing the group of patients with their age-matched controls. We could not observe correlation of levels of heteroplasmy with age. Our results confirm the age-related nature of the A189G and T408A mutations in the D-loop in controls and patients with mitochondrial disease, but do not suggest that patients are more predisposed to the development of age-related point mutations.

Andersen syndrome: an association of periodic paralysis, cardiac arrhythmia and dysmorphic abnormalities.

Andersen syndrome (AS) is a rare disease characterized by the presence of periodic paralysis (PP), cardiac arrhythmia and dysmorphic abnormalities. We report herein the first Brazilian patient presenting AS who also had obesity, obstructive sleep apnea (OSA) and daytime sleepiness. Clinical and genetic evaluation of six family members demonstrated that four had dysmorphic abnormalities but none had PP or cardiac arrhythmia. Sequencing of KCNJ2 revealed the R218W mutation in the index patient and her 6-year-old daughter, who presented dysmorphic abnormalities (micrognathia, clinodactyly of fourth and fifth fingers, short stature) and OSA. Three relatives had clinodactyly as the only manifestation but the R218W mutation was absent, suggesting that this characteristic may be influenced by another gene. OSA accompanied by dysmorphic features may be related to AS.

Visual Attention in Children With Migraine: The Importance of Prophylaxis.

This study aimed to compare the visual attention performance of children newly diagnosed with migraine, children undergoing migraine prophylaxis, and a healthy control group. Eighty-two children aged 8 to 12 years were divided into 3 groups: untreated migraine (n = 30), migraine prophylaxis (n = 22), and control (n = 30). All were subjected to a visual attention assessment with the Trail Making Test parts A and B, Letter-Cancellation Test, and the Brazilian Visual Attention Test 3rd edition. Although performance in attention tasks was within the normal range in all groups, children with untreated migraine performed significantly worse in some visual attention tests than did the control children or children undergoing migraine prophylaxis. The migraine prophylaxis group performed as well as the control group. The deregulation of the neurochemical mechanisms underlying the physiopathology of migraine might induce visual attention deficits, but an effective prophylactic treatment might reverse migraine symptoms.

Frequency of duplications in the D-loop in patients with mitochondrial DNA deletions.

Small duplications (miniduplications) of the D-loop of human mitochondrial DNA (mtDNA) have been described in patients with mtDNA deletions, mtDNA point mutations and in normal aged tissues. The origin of these miniduplications is still unknown but it is hypothesized that they could be formed after oxidative damage. The respiratory chain (RC) is the main source of free radicals in mitochondria and it is believed that a defect in RC increases free radical generation. If miniduplications are originated by oxidative damage, it is expected that they are more abundant in patients with a defect in the RC. We studied the frequency of miniduplications of D-loop in patients with a RC defect due to mtDNA deletions and in controls. We show that four types of miniduplications could be detected with a higher prevalence than in previous studies and that patients with mtDNA deletions did not have higher proportions or increased number of miniduplications, which is against the hypothesis that miniduplications are generated more abundantly in patients with RC defects. We also clearly demonstrate the age-related nature of these miniduplications by a carefully controlled study regarding the age of subjects, which was not considered in other studies on patients with a mitochondrial disease.

MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas.

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) measurements derived from perfusion-weighted imaging (PWI) may be useful to evaluate angiogenesis and preoperatively estimate the grade of a glioma. We hypothesized that rCBV is correlated with vascular endothelial growth factor (VEGF) expression as marker of the angiogenic stimulus in presumed supratentorial low-grade gliomas (LGGs). METHODS: From February 2001 to February 2004, we examined 20 adults (16 men, four women; mean age 36 years; range, 23-60 years) with suspected (nonenhancing) supratentorial LGG on conventional MR imaging. Preoperative MR imaging used a dynamic first-pass gadolinium-enhanced, spin-echo echo-planar PWI. In heterogeneous tumors, we performed stereotactic biopsy in the high-perfusion areas before surgical resection. Semiquantitative grading of VEGF immunoreactivity was applied. RESULTS: Nine patients had diffuse astrocytomas (World Health Organization grade II), and 11 had other LGG and anaplastic gliomas. In patients with heterogeneous tumors on PWI, the high-rCBV focus had areas of oligodendroglioma or anaplastic astrocytoma on stereotactic biopsy, whereas the surgical specimens were predominantly astrocytomas. Anaplastic gliomas had high rCBV ratios and positive VEGF immunoreactivity. Diffuse astrocytomas had negative VEGF expression and mean rCBV values significantly lower than those of the other two groups. Three diffuse astrocytomas had positive VEGF immunoreactivity and high rCBV values. CONCLUSION: Our results confirmed the correlation among rCBV measurements, VEGF expression, and histopathologic grade in nonenhancing gliomas. PWI may add useful data to the preoperative assessment of nonenhancing gliomas. Its contribution in predicting tumor behavior and patient prognosis remains to be determined.

Stereotactic biopsy guidance in adults with supratentorial nonenhancing gliomas: role of perfusion-weighted magnetic resonance imaging.

OBJECT: The. diagnosis of low-grade glioma (LGG) cannot be based exclusively on conventional magnetic resonance (MR) imaging studies, and target selection for stereotactic biopsy is a crucial issue given the high risk of sampling errors. The authors hypothesized that perfusion-weighted imaging could provide information on the microcirculation in presumed supratentorial LGGs. METHODS: All adult patients with suspected (nonenhancing) supratentorial LGGs on conventional MR imaging between February 2001 and February 2004 were included in this study. Preoperative MR imaging was performed using a dynamic first-pass gadopentate dimeglumine-enhanced spin echo-echo planar perfusion-weighted sequence, and the tumors' relative cerebral blood volume (rCBV) measurements were expressed in relation to the values observed in contralateral white matter. In patients with heterogeneous tumors a stereotactic biopsy was performed in the higher perfusion areas before resection. Among 21 patients (16 men and five women with a mean age of 36 years, range 23-60 years), 10 had diffuse astrocytomas (World Health Organization Grade II) and 11 had other LGGs and anaplastic gliomas. On perfusion-weighted images demonstrating heterogeneous tumors, areas of higher rCBV focus were found to be oligodendrogliomas or anaplastic astrocytomas on stereotactic biopsy; during tumor resection, however, specimens were characterized predominantly as astrocytomas. Diffuse astrocytomas were associated with significantly lower mean rCBV values compared with those in the other two lesion groups (p < 0.01). The rCBV ratio cutoff value that permitted better discrimination between diffuse astrocytomas and the other lesion groups was 1.2 (80% sensitivity and 100% specificity). CONCLUSIONS: Perfusion-weighted imaging is a feasible method of reducing the sampling error in the histopathological diagnosis of a presumed LGG, particularly by improving the selection of targets for stereotactic biopsy.

Temporomandibular joint and masticatory muscle involvement in myotonic dystrophy: a study by magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to evaluate the masticatory muscles and the temporomandibular joint (TMJ) by magnetic resonance imaging (MRI) in myotonic dystrophy (MD) patients. STUDY DESIGN: MRI of the masticatory muscles and TMJ was performed in 15 MD patients, 11 male and 4 female, aged 16 to 53 years (mean, 31 years). Many of them had dental malocclusion, especially Angle class III and anterior open bite, and 3 complained of recurrent TMJ dislocation. TMJ and masticatory muscle pain was not observed, and joint sounds were noted in only 1 patient. RESULTS: The analysis of MRI scans showed masticatory muscle involvement in 13 patients (86.6%). In 11, the involvement was moderate to intense. The main abnormalities observed were increased intramuscular tissue signal on T1 (fatty infiltration) and volumetric reduction of muscles. Regarding the TMJ, articular disk displacement was seen in only 1 patient, but abnormalities of disk shape were common. Mild bone abnormalities were frequently observed, including changes of shape and contour of bone surface, and sclerosis of bone marrow. In 4 patients the condyle moved anterior to the eminence with the mouth opened fully (condylar hyperexcursion). CONCLUSIONS: This study shows that masticatory muscles are frequently and intensively affected in MD patients. Bone changes are the most consistent abnormalities observed in the TMJ. It is possible that remodeling is caused by biomechanical changes in the jaw as a result of masticatory muscle involvement.

The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil.

UNLABELLED: Peripheral neuropathy is a common neurological complication occurring in asymptomatic and symptomatic stages of HIV infection. The most common syndromes are distal symmetric polyneuropathy, inflammatory demyelinating polyneuropathy, poliradiculopathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. PURPOSE: To evaluate the frequency of peripheral neuropathy in a group of HIV seropositive outpatients in São Paulo, Brazil. METHOD: Over a period of 17 months, 49 HIV+ patients where evaluated clinically. Laboratory analysis and electroneuromyography were requested to all patients. RESULTS: >Thirty four (69.4%) of the 49 patients had the diagnosis of peripheral neuropathy established on clinical grounds. The most common sign was impairment (97.1%) of sensibility. Thirteen (33.3%) of the 39 that were subjected to electroneuromyography had features of peripheral neuropathy, being a sensitive-motor axonal neuropathy the most common. No abnormalities were found in the laboratory analysis performed in 42 patients, except in four who had VDRL positive. CONCLUSION: A peripheral neuropathy was frequently found upon clinical examination in our group of HIV positive individuals.

Neurologic complications after heart transplantation.

OBJECTIVE: Neurologic complications are known as important cause of morbidity and mortality in orthotopic heart transplantation. Our aim was to identify the frequency and outcome of neurologic complications after heart transplantation in a prospective observational study. METHOD: From September 93 to September 99, as part of our routine heart transplantation protocol all patients with end-stage cardiac failure were evaluated by the same neurologist before and at the time of any neurologic event (symptom or complaint) after transplantation. RESULTS: Out of 120 candidates evaluated, 62 were successfully transplanted (53 male; median age 45.5 years, median follow-up 26.8 months). Fifteen patients (24%) had ischemic, 22 (35%) idiopathic, 24 (39%) Chagas' disease and 1 (2%) had congenital cardiomyopathy. Neurologic complications occurred in 19 patients (31%): tremor, severe headache, transient encephalopathy and seizures related to drug toxicity or metabolic changes in 13; peripheral neuropathy in 4; and spinal cord compression in two (metastatic prostate cancer and epidural abscess). No symptomatic postoperative stroke was observed. CONCLUSIONS: Although frequent, neurologic complications were seldom related to persistent neurologic disability or death. Most of the complications resulted from immunosuppression, however, CNS infection was rare. The absence of symptomatic stroke in our series may be related to the lower frequency of ischemic cardiomyopathy.

[Arteriovenous malformation-glioma association: study of four cases]. / Associação de malforma o vascular e gliomas: estudo de quatro casos.

We reviewed the clinical presentation, imaging and histopathologic findings in 4 patients with the diagnosis of arteriovenous malformation associated with glioma that were operated on from 1991 to 2000 in our institution. Four patients (2 males; age between 15 and 52 years) presented with progressive headache with clinical evidence of intracranial hypertension (in 3) and partial seizures (in 1). CT scan showed a brain tumor without any detectable pathologic vessels. Histologic examination revealed astrocytic tumors associated with arteriovenous malformation. No patient presented the vascular component intermixed with the tumor. The arteriovenous-glioma association is rare and must be identified by a clear demarcation between the malformation and the tumor.

Diffusion tensor imaging of the cervical spinal cord of patients with Neuromyelitis Optica.

BACKGROUND: Previous studies have demonstrated a correlation between Expanded Disability Status Scale (EDSS) and Diffusion Tensor Imaging (DTI) metrics, but the conclusions were based on evaluations of the entire cervical spinal cord. OBJECTIVES: The purpose of this study was to quantify the FA and MD values in the spinal cord of NMO patients, separating the lesion sites from the preserved sites, which has not been previously preformed. In addition, we attempted to identify a correlation with EDSS. METHODS: DTI was performed in 11 NMO patients and 11 healthy individuals using a 1.5-T MRI scanner. We measured the FA and MD at ROIs positioned along the cervical spinal cord. The mean values of FA and MD at lesion, preserved and spinal cord sites were compared with those of a control group. We tested the correlations between the mean FA and MD with EDSS. RESULTS: FA in NMO patients was significantly reduced in lesion sites (0.44 vs. 0.55, p=0.0046), preserved sites (0.46 vs. 0.55, p=0.0015), and all sites (0.45 vs 0.55, p=0.0013) while MD increased only in lesion sites (1.03×10(-3)mm(2)/s vs. 0.90×10(-3)mm(2)/s, p=0.009). The FA demonstrated the best correlation with EDSS (r=-0.7603, p=0.0086), particularly at lesion sites. CONCLUSIONS: The results reinforce the importance of the FA index and confirm the hypothesis that NMO is a diffuse disease.

Long-term safety and efficacy of eslicarbazepine acetate as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy: results of a 1-year open-label extension study.

OBJECTIVE: To evaluate the long-term safety, tolerability and efficacy of once-daily eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial-onset seizures. METHODS: One-year open-label extension (OLE) study with ESL in patients who completed a randomised, double-blind placebo-controlled trial (study BIA-2093-302; Epilepsy Res. 89 (2010) 278-285). Starting dose was 800 mg once-daily, for 4 weeks; thereafter, dose could be individualised within the 400-1,200 mg range. Doses of concomitant antiepileptic drugs were to be kept stable. RESULTS: Overall, 325 patients were enrolled (intent-to-treat population); 223 (68.6%) patients completed 1-year of treatment. ESL median dose was 800 mg once-daily. Compared to the baseline period of the double-blind study completed prior to this OLE study, median seizure frequency decreased by 32% in weeks 1-4, and between 37% and 39% thereafter. The responder rate (seizure reduction ≥ 50%) was 37% during weeks 1-4 and thereafter ranged between 38% and 42% per 12-week interval. Proportion of seizure-free patients per 12-week interval ranged between 5% and 11%. Improvements from baseline in several Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and Montgomery Asberg Depression Rating Scale (MADRS) scores were observed. Adverse events (AEs) were reported by 83% of patients. AEs occurring in ≥ 10% of patients were dizziness, headache and somnolence. AEs were usually of mild to moderate intensity. CONCLUSION: In this study, ESL demonstrated a sustained therapeutic effect and was well tolerated during 1-year add-on treatment of adults with partial-onset seizures. Additionally, significant improvements in quality of life domains and depressive symptoms were observed under long-term treatment with once-daily ESL.

The role of nitric oxide in muscle fibers with oxidative phosphorylation defects.

NO has been pointed as an important player in the control of mitochondrial respiration, especially because of its inhibitory effect on cytochrome c oxidase (COX). However, all the events involved in this control are still not completely elucidated. We demonstrate compartmentalized abnormalities on nitric oxide synthase (NOS) activity on muscle biopsies of patients with mitochondrial diseases. NOS activity was reduced in the sarcoplasmic compartment in COX deficient fibers, whereas increased activity was found in the sarcolemma of fibers with mitochondrial proliferation. We observed increased expression of neuronal NOS (nNOS) in patients and a correlation between nNOS expression and mitochondrial content. Treatment of skeletal muscle culture with an NO donor induced an increase in mitochondrial content. Our results indicate specific roles of NO in compensatory mechanisms of muscle fibers with mitochondrial deficiency and suggest the participation of nNOS in the signaling process of mitochondrial proliferation in human skeletal muscle.

Pleiotrophin expression in astrocytic and oligodendroglial tumors and it's correlation with histological diagnosis, microvascular density, cellular proliferation and overall survival.

BACKGROUND: Pleiotrophin (PTN) is a secreted cytokine with several properties related with tumor development, including differentiation, angiogenesis, invasion, apoptosis and metastasis. There is evidence that PTN has also a relevant role in primary brain neoplasms and its inactivation could be important to treatment response. Astrocytic and oligodendroglial tumors are the most frequent primary brain neoplasms. Astrocytic tumors are classified as pilocytic astrocytoma (PA), diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GBM). Oligodendroglial tumors are classified as oligodendroglioma (O) and anaplastic oligodendroglioma (AO). The aim of the present study was to compare PTN expression, in astrocytomas and oligodendrogliomas and its association with the histological diagnosis, microvascular density, proliferate potential and clinical outcome. METHODS: Seventy-eight central nervous system tumors were analyzed. The histological diagnosis in accordance with WHO classification was: 13PA, 18DA, 8AA, 15GBM, 16O and 8AO. Immunohistochemistry was realized with these specific antibodies: pleiotrophin, CD31 to microvascular density and Ki-67 to cell proliferation. RESULTS: PTN expression was significantly higher in GBM and AA when compared to PA and higher in GBM compared to DA. PTN expression did not differ between O and AO. Proliferate index and microvascular density were evaluated only in high grade tumors (AA, GBM and AO) divided in three groups according to PTN expression (low, intermediate and high). These results showed no statistical difference between PTN expression and index of cellular proliferation and neither to PTN expression and microvascular density. Overall survival (OS) analysis (months) showed similar results in high grade gliomas with different levels of PTN expression. CONCLUSIONS: Our results suggest that PTN expression is associated with histopathological grade of astrocytomas. Proliferation rate, microvascular density and overall survival do not seem to be associated with PTN expression.