Gene expression profiling of blood in ruptured intracranial aneurysms: in search of biomarkers.

The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate 1%, absolute fold change 1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH.

Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation?

BACKGROUND AND PURPOSE: Mechanisms underlying development and rupture of intracranial aneurysms (IA) are poorly recognized. The majority of studies on human tissue have focused on predefined pathways. We sought to analyze global gene expression patterns of ruptured IA, unruptured IA, and control vessels. METHODS: Transcription profiles were studied in human ruptured (n=8) and unruptured (n=6) IA, as well as in control intracranial arteries (n=5), using oligonucleotide microarrays. Real-time reverse-transcription polymerase chain reaction was used for confirmation. Functional analysis for determination of over-represented ontological groups among gene expression profiles was also performed. RESULTS: The expression of 159 genes differed among the studied groups. Compared to the controls, 131 genes showed common directions of change in both IA groups. The most impacted biological processes for IA are: (1) the muscle system; (2) cell adhesion (downregulation); and (3) the immune system and inflammatory response (upregulation). Ruptured and unruptured IA differed in genes involved in immune/inflammatory processes; expression was reduced in ruptured IA. CONCLUSIONS: Decreased expression of genes related to muscle system and cell adhesion is important for the development of IA. The role of immune/inflammatory processes is unclear. Inflammation may participate in the healing process within IA while playing a protective role against IA rupture.

Decreased levels of interleukin-10 and transforming growth factor-beta 2 in cerebrospinal fluid of patients with high grade astrocytoma.

OBJECTIVE: Glioma cells can produce anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) which inhibit T cell and monocyte function. It is unknown if production of these cytokines is limited to the site of tumor or these molecules are also released to cerebrospinal fluid and blood. The goal of our study was to determine if patients with astrocytoma have increased levels of IL-10 and TGF-beta 2 in cerebrospinal fluid (CSF) and serum. METHODS: CSF and serum samples were taken from 16 patients with astrocytoma of grade III or grade IV according to the WHO classification and from 28 age- and gender-matched controls (patients with normal pressure hydrocephalus or with lumbar disk herniation). Cytokine concentrations were measured using ELISA methods. RESULTS AND DISCUSSION: There was no difference in serum levels of IL-10 and TGF-beta 2 between groups. Patients with astrocytoma had decreased levels of IL-10 (0.9 +/- 1.2 versus 3.5 +/- 9.2 pg/ml, p=0.01) and TGF-beta 2 (0.0 +/- 0.0 versus 5.4 +/- 9.4 pg/ml, p=0.05) in CSF compared to controls. Because serum IL-10 and TGF-beta 2 levels are similar in patients with astrocytoma and in controls, these cytokines are probably not directly involved in peripheral monocyte and T cell deactivation.

Stereotactic biopsy in surgically inaccessible tumors with the use of "P.N." type frame.

INTRODUCTION: Stereotactic biopsy is unquestionably regarded as the gold standard for histopathological diagnosis of surgically inaccessible tumors. Tissue samples can be obtained by minimally invasive technique. Histopathological examination opens the door to oncological treatment of patients. Such procedures have been performed in the Neurosurgery Department, Jagiellonian University in Krakow since February 2003. The aim of this study is to evaluate the use of "P.N." type Frame (Tatramed, Slovakia) in verification of surgically inaccessible tumors. MATERIAL AND METHODS: Surgically inaccessible diffuse, deep-seated or located in eloquent areas tumors of cerebral hemispheres were diagnosed in 36 patients. In these cases 56 stereotactic biopsies were performed. The specimens of tumors were obtained with the aspiration method, according to coordinates derived from CT scan. The procedure was performed under local anesthesia in 17 patients and in 19 cases, it was performed under general anesthesia. The lesion was located in 13 cases in cerebral hemisphere infiltrating basal ganglia, in 13 cases tumors were diffused within one of the hemisphere but without involvement of basal ganglia, in 7 cases tumors were localized in eloquent areas, in 1 case in posterior commissure, in 1 case it was a tumor of corpus callosum and third-ventricle and in 1 case a tumor was multifocal. RESULTS: Material from the stereotactic biopsy has been examined neuropathologically. Astrocytomas II degree WHO were diagnosed in 8 cases, Astrocytomas III degree WHO in 12 cases, and Astrocytomas IV degree WHO in 10 cases. Metastatic Adenocarcinoma was diagnosed in 3 cases and in 3 cases a neoplasm was not found. The definite histopathological diagnosis was confirmed (in relation to the "intraoperational" one) in 91.7%. In 3 cases the increased intracranial pressure produced by tumor cyst was reduced by the use of biopsy. Patients with gliomas of III degree and IV degree WHO were treated by irradiation. Stereotactic biopsy in 11 cases (that is 44% of all cases) made the oncological treatment possible. CONCLUSIONS: Stereotactic biopsy with the use of "P.N." type frame is a very safe and precise method making the histopathological diagnosis of inaccessible tumors possible. The size of tissue sample acquired with the use of "P.N." frame makes the use of standard histopathological techniques possible. Stereotactic diagnosis of some tumors made oncological treatment possible whenever there were no contraindications for the adjuvant treatment.

Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the alpha1-antichymotrypsin, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein. SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH compared with healthy controls. METHODS: A total of 180 patients with aneurysmal SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. SERPINA3 polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. RESULTS: The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH.

II genotype of the angiotensin-converting enzyme gene increases the risk for subarachnoid hemorrhage from ruptured aneurysm.

BACKGROUND AND PURPOSE: Evidence exists in support of a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (SAH) in humans. Meta-analysis of 2 previous studies showed that the I allele of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism was a weak, but significant, risk factor for aneurysmal SAH. Moreover, a recent study has shown that the local renin-angiotensin system (RAS) is involved in the development of intracranial aneurysm. The aim of this study was to investigate the association between ACE I/D polymorphism and a risk for aneurysmal SAH in a Polish population. METHODS: Ninety patients with aneurysmal SAH (mean age: 48.9+/-14.0 years) and 128 healthy controls matched for age and sex were genotyped for the ACE I/D polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography and/or lumbar puncture and digital subtraction angiography. ACE gene polymorphism was detected by polymerase chain reaction amplification of the intron 16-specific I/D fragments, 490-bp and 190-bp, respectively. RESULTS: The ACE genotype distribution in patients with aneurysmal SAH (II, 52.2%; ID, 15.6%; DD, 32.2%) differed significantly from controls (II, 23.4%; ID, 50.8%; DD, 25.8%) (P<0.001). A logistic regression model showed that the II genotype of ACE gene was independent from female sex and smoking as a risk factor for aneurysmal SAH (OR, 4.57; 95% CI, 2.35 to 8.90). CONCLUSIONS: Here we report that II genotype of ACE gene is a risk factor for aneurysmal SAH.

[Asymptomatic recurrent neurenteric cyst of the thoracic spinal cord: case report]. / Bezobjawowa nawrotowa cysta enterogenna piersiowego odcinka rdzenia kregowego. Opis przypadku.

We describe a patient with a congenital neurenteric cyst located in the upper thoracic region of the spinal cord. Corrective surgery was performed but total excision was not possible due to the cyst's location. The patient remained asymptomatic during a 10-year follow-up, leading a normal life despite recurrence of the cyst.

[Prognostic value of epileptic seizures in patients with cerebral gliomas]. / Znaczenie prognostyczne padaczki u chorych na glejaki pólkul mózgowych.

INTRODUCTION: Epileptic seizures as the only or one of the symptoms of a brain tumor are useful for prognostication and represent a factor influencing survival rate and quality of life in patients with high-grade and low-grade gliomas. MATERIALS AND METHOD: A retrospective analysis of 189 patients was carried out between 1981 and 1997. The shortest follow-up period was 2 years, the longest 8 years. Epileptic seizures were present in 43% of the patients before operation. Correlations between localization of glioma and type of seizure were studied. The Statistica software was used to analyze histopathology findings according to seizure frequency and its influence on survival rate. RESULTS: Survival rates in patients with low-grade glioma (WHO II) and high-grade glioma (WHO III) suffering from seizures before operation were higher (p = 0.0306) than in patients without seizures. This relationship did not apply to WHO IV gliomas. There was no association between seizure frequency and histological type of tumor. CONCLUSION: Simple partial seizures are usually associated with low-grade supratentorial gliomas, whereas generalized seizures were present in high-grade gliomas.

[Usefulness of the "P.N." frame in biopsies and stereotactic operations on the brain]. / Przydatnosc ramy typu "P.N." do biopsji i operacji stereotaktycznych mózgu.

BACKGROUND: Stereotactic biopsy represents the gold standard for tissue diagnosis surgically inaccessible gliomas, tumors and cystic lesions. Tissue samples can be obtained by minimally invasive technique. Moreover, the combination of the neuro-endoscope with stereotactic method is possible. MATERIAL AND METHOD: 23 patients underwent 43 stereotactic biopsy procedures for diagnosis diffuse, deep-seated and eloquent site tumors at Neurosurgery Department Jagiellonian University in Krakow since February 2003. Stereotactic frame "P.N." type (TatraMed S.r.o.) was used. In one case the combined method was used for third ventriculostomy. The specimen was obtained from the target point of CT scan by the aspiration method under local anesthesia in 17 patients and under general anesthesia in 6 patients. The lesion was located in 9 cases of cerebral hemisphere and basal ganglia, in 8 cases of spreading site, in 5 cases of eloquent area and in 1 case of corpus callosum and third-ventricle. RESULTS: Material from the stereotactic biopsy has been examined neuropathologically. Astrocytoma II(o) WHO were diagnosed in 6 cases, Astrocytoma III(o) WHO in 11 cases, Astrocytoma IV(o) WHO in 3 cases, Metastatic adenocarcinoma in 1 case and in 2 cases the neoplasm was not found. The diagnosis was histologically confirmed in 91.3%. Emergency craniotomy was performed in one patient. In 3 cases the increased intracranial pressure produced by tumor cysts was reduced by the use of biopsy. CONCLUSIONS: Our data confirm that the "P.N." frame is useful in stereotactic biopsies and operations even with the use of neuroendoscope. The procedure is safe, easy to follow as a tool for patients with various tumors.

[Endovascular coiling and microsurgery of the cerebral arteriovenous malformations. Assessment of criteria of treatment and outcome]. / Embolizacja wewnatrznaczyniowa i mikrochirurgia naczyniaków tetniczo-zylnych mózgu. Ocena kryteriów stosowanych w wyborze postepowania oraz wyniki leczenia.

BACKGROUND: Three available methods of therapy of arteriovenous malformations (AVM) i.e. microsurgical resection, intravascular embolization and stereotactic radiosurgery, make possible definitive treatment in the majority of patients. During qualification to these procedures the risk of complications and efficacy of each method should be considered. OBJECTIVE: To analyze criteria of qualification, risk factors and results of embolization and surgical treatment of AVMs. PATIENTS AND METHODS: Within four years (1999-2002) 53 patients were treated for arteriovenous malformations (AVMs) in the Department of Neurosurgery of the University Hospital in Krakow (24 women and 29 men). The group of 25 patients was treated with intravascular embolization, 20 patients were operated and 8 patients were treated conservatively or were qualified to radiotherapy. We retrospectively analyzed clinical findings, criteria of qualification and results of embolization as well as microsurgical treatment of AVMs with regard to Spetzler-Martin scale. RESULTS: 25 patients qualified for embolization underwent 39 embolization procedures. Complete embolization of AVM was obtained in 4 (16%) cases. 18 patients (72%) presented very good or good condition on discharge. In 5 (20%) serious complications were noted: in 2 hemorrhagic and in 3 ischemic. Three patients (12%) died. In the group of 18 operated patients, 13 (72%) patients presented very good or good condition on discharge and 1 patient died because of hemorrhagic complications. CONCLUSIONS: 1. Spetzler-Martin scale is very useful in evaluation of operative risk of AVM operations but, in our opinion, before operation there should be considered also such factors like number and diameter of feeding arteries, exact localization of AVM and initial condition of the patient. 2. Although intravascular embolization is less invasive than neurosurgical operation, the risk of hemorrhagic and ischemic complications is present. 3. Complete AVM embolization is possible in the minority of patients. The remaining group require follow up and control radiological examinations to establish indications for further treatment.