A Primary Primitive Neuroectodermal Tumor of the Central Nervous System in a 51-year-old Woman: a Case Report and Literature Review

Primitive neuroectodermal tumors are a group of rare, aggressive, and highly malignant embryonal tumors of unknown etiology of the central and peripheral nervous systems. It is a term for a group of small round cell tumors thought to be derived from fetal neuroectodermal precursor cells. Primitive neuroectodermal tumor is usually described as a tumor of children younger than 15 years and is very rare in adults. The article presents a short literature review and a rare case of a primary primitive neuroectodermal tumor of the central nervous system diagnosed in a 51-year-old woman

Importance of the putative furin recognition site 742RNRR745 for antiangiogenic Sema3C activity in vitro

Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein. Several studies have shown that the furin-mediated processing of the basic domain of Sema3F and Sema3A is critical for association with receptors. It is unclear, however, if this mechanism can also be applied to other Sema3 proteins, including the main subject of this study, Sema3C. To address this question, we generated a variant of the full-length human Sema3C carrying point mutation R745A at the basic domain at the hypothetical furin recognition site 742RNRR745, which would disable the processing of Sema3C at this specific location. The effects produced by this mutation were tested in an in vitro angiogenesis assay together with the wild-type Sema3C, Sema3A, and Sema3F proteins. Our results showed that the inhibitory effect of Sema3C on microcapillary formation by human umbilical vein endothelial cells could be abrogated upon mutation at the Sema3C basic domain within putative furin cleavage site 742RNRR745, indicating that this site was essential for the Sema3 biological activity

Signal transducer and activator of transcription 3 (STAT3) promoter methylation and expression in pituitary adenoma

BACKGROUND: Pituitary adenoma (PA) is a benign brain tumor that can cause neurological, endocrinological and ophthalmological aberrations. Till now there is a need to identify factors that can influence the tumor invasiveness and recurrence. The aim of this study was to evaluate the associations between the signal transducer and activator of transcription 3 (STAT3) promoter methylation, mRNA expression and the invasiveness or recurrence of PAs and patient clinical characteristics. METHODS: Study participants comprised of 102 subjects with a diagnosis of PA: 54 functioning and 48 non-functioning, 58 invasive and 30 non-invasive PAs and 14 relapses. The bisulfite treatment of tumor DNA and methylation-specific polymerase chain reaction (MS-PCR) method was used to determine the STAT3 gene promoter methylation. For the STAT3 mRNA expression, the first-strand cDNA was produced from total RNA by using reverse transcriptase and quantitative real-time PCR (qRT-PCR) was performed. RESULTS: In 10.78% (11/102) of PA tissues STAT3 gene promoter was methylated. A gender of male and patient group older than 60 years were significantly associated with reduced STAT3 mRNA expression (Mann-Whitney test, p = 0.025, p = 0.047, respectively). However, no more statistical differences were found between STAT3 promoter methylation, mRNA expression and patient clinical characteristics or PA invasiveness or recurrence. CONCLUSIONS: Further investigations are needed to clarify the influence of STAT3 gene promoter methylation and mRNA expression changes in PAs

Prothrombin complex concentrate for warfarin-associated intracranial bleeding in neurosurgical patients: A Single-center experience

Objective: The number of patients presenting with warfarin-associated intracranial bleeding and needing neurosurgical intervention is growing. Prothrombin complex concentrate (PCC) is commonly used for anti-coagulation reversal before emergent surgery. We present our experience with PCC use in patients presenting with coagulopathy and needing urgent craniotomy. Methods: We retrospectively identified all patients presenting with intracranial bleeding and coagulopathy due to warfarin use, requiring urgent neurosurgical procedures, from January, 2014 (implementation of 4-PCC therapy) until December, 2016. For coagulation reversal, all patients received 4-PCC (Octaplex) and vitamin K. Results: Thirty-five consecutive patients (17 men; median age 72 years) were administered 4-PCC before emergent neurosurgical procedures. The majority of patients presented with traumatic subdural hematoma (62%) and spontaneous intracerebral hemorrhage (32%). All patients were taking warfarin. Median international normalized ratio (INR) on admission was 2.94 (range: 1.20 to 8.60). Median 4-PCC dose was 2000 I.U. (range: 500 I.U. to 3000 I.U.). There was a statically significant decrease in INR (p < 0.01), PT (p < 0.01), and PTT (p = 0.02) after 4-PCC administration. Postoperative INR values were ≤3.00 in all patients, and seven (20%) patients had normal INR values. There were no 4-PCC related complications. Four (11%) patients developed subdural/epidural hematoma and 20 (57%) patients died. Mortality was associated with lower Glasgow coma scale (GCS) score. Conclusions: The 4-PCC facilitates INR reversal and surgery in patients presenting with warfarin-associated coagulopathy and intracranial bleeding requiring urgent neurosurgical intervention

Safety and efficacy of stereotactic aspiration with fibrinolysis for deep-seated spontaneous intracerebral hemorrhages: A single-center experience

Objective: The aim of this study was to evaluate feasibility and safety of stereotactic aspiration with fibrinolysis of deep-seated intracerebral hemorrhages (ICH).Materials and methods: From March 1995 until December 2016, 58 adult patients (34 men and 24 women; mean age of 56.8 ± 11.8 years) presenting with deep-seated spontaneous supratentorial ICH were treated using a minimally invasive technique. Intracerebral hematomas were aspirated until obvious resistance to free-hand suction and subsequent clot fibrinolysis was done using either streptokinase or recombinant tissue-type plasminogen activator. CT scans were performed at intervals ranging from 24 to 72 h. At discharge, functional outcomes were evaluated using the Glasgow outcome scale (GOS). The 30-day mortality rate was evaluated in all patients.Results: The average ICH volume on initial CT scan was 34.7 ± 11.1 cm3 (range, 20–90 cm3). Mean residual hematoma volume after the treatment was 8.0 ± 5.1 cm3 (range, 3–32 cm3). There was statistically significant reduction of ICH volume after the treatment (P &lt; 0.001). Median ICH reduction rate was 5 cm3/d (range, 1.5–16.0 cm3/d) and 17.2%/d (range, 5.27– 40.0%/d). Median discharge GOS score was 3 (range, 1–4). Six (10.9%) patients died during the 30-day follow-up period. Treatment related complications were observed in three (5.5%) patients. In two patients asymptomatic increase of ICH volume occurred and one patient was diagnosed with CNS infection.Conclusions: Stereotactic clot aspiration with subsequent fibrinolytic therapy is safe and feasible treatment procedure associated with significant hematoma resolution rates and acceptable patient outcomes

The Role of CASC2 and miR-21 Interplay in Glioma Malignancy and Patient Outcome

Recently long non-coding RNAs (lncRNAs) were highlighted for their regulatory role in tumor biology. The novel human lncRNA cancer susceptibility candidate 2 (CASC2) has been characterized as a potential tumor suppressor in several tumor types. However, the roles of CASC2 and its interplay with miR-21 in different malignancy grade patient gliomas remain unexplored. Here we screened 99 different malignancy grade astrocytomas for CASC2, and miR-21 gene expression by real-time quantitative polymerase chain reaction (RT-qPCR) in isocitrate dehydrogenase 1 (IDH1) and O-6-methylguanine methyltransferase (MGMT) assessed gliomas. CASC2 expression was significantly downregulated in glioblastomas (p = 0.0003). Gliomas with low CASC2 expression exhibited a high level of miR-21, which was highly associated with the higher glioma grade (p = 0.0001), IDH1 wild type gliomas (p < 0.0001), and poor patient survival (p < 0.001). Taken together, these observations suggest that CASC2 acts as a tumor suppressor and potentially as a competing endogenous RNA (ceRNA) for miR-21, plays important role in IDH1 wild type glioma pathogenesis and patients' outcomes

The effects of sevoflurane and propofol on cerebral hemodynamics during intracranial tumors surgery under monitoring the depth of anesthesia

Hemodynamic effects during cerebral tumor resection surgery under monitoring the depth of anesthesia and during recovery in sevoflurane- or propofol-anesthetized patients have not been previously compared. Objective. To compare cerebral hemodynamic changes using transcranial Doppler sonography during sevoflurane or propofol anesthesia under state entropy (SE) monitoring, and during recovery period. Material and methods. In a randomized manner, 130 patients received sevoflurane (group T-S) or propofol (group T-P) to maintain SE at 40–50. Cerebral blood flow velocity (Vmean) in the middle cerebral artery was evaluated at baseline, after tracheal intubation, opening of the dura mater, tumor resection, skin closure, extubation, and two hours after extubation. Cerebrovascular resistance index (RAP), estimated cerebral perfusion pressure (eCPP), and cerebral blood flow index (CBFI) were calculated off-line. Results. During surgery SE was 40.6 (SD, 8.1) in the group T-S and 44.0 (SD, 7.4) in the group T-P. Blood pressure was significantly higher in the group T-P. Compared to the baseline, Vmean decreased by 16.6% and 23.5% in the groups T-S and T-P, respectively (P&lt;0.05). RAP and eCPP were higher in the group T-P versus the group T-S: 28.9% and 5.2%, respectively, above the baseline for RAP (P&lt;0.005) and 3.2% and 16.9% below the baseline for eCPP (P&lt;0.005). CBFI was below the baseline by 20.1% and 24.0% in the groups T-S and T-P, respectively (P&gt;0.05). After the extubation and 2 hours later, Vmean recovered comparably with no differences in RAP, eCPP, or CBFI between the two groups. Conclusions. At the comparable depth of anesthesia for intracranial tumors surgery and during recovery, sevoflurane had no major effect on cerebral circulation measured by transcranial Doppler sonography as compared with propofol. Our results add to current knowledge on the safety of sevoflurane in neuroanesthesia

Changes of Visual Functions in Patients With Pituitary Adenoma

Background and Objective. The aim of this study was to evaluate associations between visual functions (visual acuity, perimetry, optic nerve disc condition, and color contrast sensitivity) and pituitary adenoma (PA) diameter. Material and Methods. In the study, 20 patients with PA, which was confirmed by computed tomography or magnetic resonance imaging scans, were examined. The patients were divided into 2 groups: those with a PA diameter of ≤1 cm (14 eyes) and with a PA diameter of &gt;1 cm (26 eyes). The control group comprised 40 healthy age- and gender-matched persons (80 eyes). The diameter of PA, visual acuity, and perimetry were analyzed; the F-M 100 hue test for color discrimination was used in patients with PA. Results. Visual acuity was better in the control group as compared with both groups of patients (1.0 vs. 0.90 [SD, 0.50] and 0.64 [SD, 0.21]; P=0.01; respectively). The results of the Farnsworth- Munsell 100 hue test were also better in the control group compared with the patients with PA of ≤1 cm and &gt;1 cm (error score of 80.1 [SD, 53.0] vs. 131.8 [SD, 30.6] and 244.68 [SD, 51. 6], respectively; P=0.011). There was a very strong positive correlation between the error score of the F-M 100 hue test and PA diameter (r=0.905), but the correlation between the error score and visual acuity (r=–0.32), perimetry (r=0.21), and eye fundus changes (r=0.36) and PA diameter was weak. Conclusions. Our results showed that PA can cause the impairments of visual acuity, perimetry, and color contrast sensitivity. The computerized F-M 100 hue test can be one of the methods for an early diagnosis of chiasm damage in patients with PA