A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas.

Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0-unmethylated and 1-weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss' Kappa statistical analyses indicated moderate agreement (Fleiss' Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss' Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.

The Significance of MGMT Promoter Methylation Status in Diffuse Glioma.

A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (<50 years) with surgically resected glioma and temozolomide (TMZ) adjuvant chemotherapy were associated with better prognosis, consistent with other studies. The methylation status depends on the chosen method and the cut-off value determination. Methylation-specific PCR (MSP) established the methylation status for 36 glioma patients (19 (52.8%) positively methylated and 17 (47.2%) unmethylated) without relevancy for the overall survival (OS) (p = 0.33). On the other side, real-time methylation-specific PCR (qMSP) revealed 23 tumor samples (54%) that were positively methylated without association with OS (p = 0.15). A combined MSP analysis, which included the homogenous cohort of 24 patients (>50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.

The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma.

Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients' gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma.

Long-lasting undetected neurocysticercosis.

Neurocysticercosis is the most common parasitic disease of the nervous system, nevertheless, it can remain undetected for a long period of time, especially if it occurs in non endemic areas and regions with low-endemicity. Inadequate diagnostic procedures and lack of clinician's dedication towards this health issue can lead to a missed diagnose. Herein, we present a case of a 51-year-old male, with a missed diagnosis of neurocysticercosis for more than two decades. A history of epilepsy had started twenty-one years earlier and was of unclear etiology. Recently, after neurological worsening and headaches, brain computed tomography and magnet resonance imaging was performed as well as Western blot immunoassay of serum and cerebrospinal fluid, surgery, and pathohistological examination of the extracted cysts. Neurocysticercosis was confirmed. Combined therapy that consisted of albendazole and prednisolone was administered for a period of four weeks. Also, antiepileptic therapy was continued. Both clinical status and brain imaging showed the apparent improvement in the patient's condition. Review of the literature was implemented in the discussion that deals with proper and adequate therapy option and outcome factors in neurocysticercosis patients. Over a long period of time, the majority of patients develop seizures as the most common symptom, which requires the administration of medications. Proper diagnostic procedures and adequate combination of surgery and conservative treatment areessential.

Spontaneous chronic subdural hematoma in elderly people - Arterial hypertension and other risk factors.

BACKGROUND: The risk factors implicated in the genesis of chronic subdural hematomas include old age, alcoholism, diabetes mellitus, arachnoid cysts, coagulopathy, anticoagulant (ACTh) and antiplatelet drugs. However, no study has reported an association between arterial hypertension (HTA) and chronic subdural hematomas. Therefore, the aim of this study was to investigate whether HTA is a risk factor for spontaneous chronic subdural hematomas (SCSDHs). METHODS: This multicenter study included patients aged over 60 years and was conducted from January 2009 to the end of 2015. One hundred and twenty-two patients with SCSDHs and 111 controls treated for other reasons with no evidence of intracranial hemorrhages on brain computed tomography were enrolled. The patients were separated into three age subgroups to provide a better insight into the role of risk factors with age. RESULTS: The average age in the SCSDH group was 74.45 ± 8.16 years, compared to 71.28 ± 6.69 years in the control group. The SCSDH group was significantly older than the control group (p = 0.0014). The patients in the 60-69 years age group diagnosed with SCSDHs had significantly higher rates of HTA (p = 0.0519), ACTh treatment (p = 0.0292) and alcoholism (p = 0.0300) than the control group. The patients in the 70-79 years age group diagnosed with SCSDHs had significantly higher rates of HTA (p = 0.0071) and ACTh treatment (p = 0.0158) than the control group. In the subgroup of patients older than 80 years, there were no statistical differences. CONCLUSION: The incidence of HTA had borderline significance in the patients aged 60-69 years with SCSDHs and statistical significance in the patients aged 70-79 years with SCSDHs. Anticoagulant therapy was the most significant risk factor. Among the patients with SCSDHs aged 60-69 years, the percentage of heavy drinkers was significantly higher than in the control group.

Factors affecting the survival of patients with glioblastoma multiforme.

PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive malignant tumor in the brain and no therapy can achieve full recovery/cure. The aim of this study was to identify which factors could improve the survival of operated patients, and to determine which kind of therapy was most successful. METHODS: The study was conducted at the Clinic for Neurosurgery in Nis, Clinical Centre Nis and the Oncology Institute, Clinical Center Nis. A cohort of patients who underwent surgery between January 2013 and December 2015 was studied and continuous monitoring of survival lasted until June 2017. RESULTS: Patients who underwent only biopsy have 3.82- fold greater chance of death than patients with complete tumor resection (HR 3,825; p=0.001). Karnofsky performance status score significantly affected survival (preoperatively and postoperatively; p<0.001). Apart from radiotherapy, three types of chemotherapy were applied: carmustine (BCNU) - 32.80% of the patients, procarbazine/lomustine/ vincristine (PCV) - 38.80% and temozolomide - 28.40%. Kaplan-Meier overall survival showed that patients treated with temozolomide had the longest survival compared to patients treated with BCNU and/or PCV chemotherapy. CONCLUSION: The best prognosis was seen in those patients who had complete tumor resection. Patients treated with temozolomide had the best survival compared with those treated with BCNU and PCV chemotherapy.