Radiomic features of amygdala nuclei and hippocampus subfields help to predict subthalamic deep brain stimulation motor outcomes for Parkinson's disease patients.

Background and purpose: The aim of the study is to predict the subthalamic nucleus (STN) deep brain stimulation (DBS) outcomes for Parkinson's disease (PD) patients using the radiomic features extracted from pre-operative magnetic resonance images (MRI). Methods: The study included 34 PD patients who underwent DBS implantation in the STN. Five patients (15%) showed poor DBS motor outcome. All together 9 amygdalar nuclei and 12 hippocampus subfields were segmented using Freesurfer 7.0 pipeline from pre-operative MRI images. Furthermore, PyRadiomics platform was used to extract 120 radiomic features for each nuclei and subfield resulting in 5,040 features. Minimum Redundancy Maximum Relevance (mRMR) feature selection method was employed to reduce the number of features to 20, and 8 machine learning methods (regularized binary logistic regression (LR), decision tree classifier (DT), linear discriminant analysis (LDA), naive Bayes classifier (NB), kernel support vector machine (SVM), deep feed-forward neural network (DNN), one-class support vector machine (OC-SVM), feed-forward neural network-based autoencoder for anomaly detection (DNN-A)) were applied to build the models for poor vs. good and very good STN-DBS motor outcome prediction. Results: The highest mean prediction accuracy was obtained using regularized LR (96.65 ± 7.24%, AUC 0.98 ± 0.06) and DNN (87.25 ± 14.80%, AUC 0.87 ± 0.18). Conclusion: The results show the potential power of the radiomic features extracted from hippocampus and amygdala MRI in the prediction of STN-DBS motor outcomes for PD patients.

Thyroid Hormones and Health-Related Quality of Life in Normal Pressure Hydrocephalus Patients before and after the Ventriculoperitoneal Shunt Surgery: A Longitudinal Study.

OBJECTIVE: The aim of this study was to explore the serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), and to correlate the hormone levels among iNPH patients with their self-reported quality of life before and three months after the surgery. METHODS: Twenty-five patients (52% women), mean age 63.5 (SD 9.5) years, were operated on by inserting a VP shunt. Patients with FT3 level ≤3.34 pmol/L were diagnosed as having low T3 syndrome. RESULTS: The changes in thyroid hormones resulted in a U-shaped curve throughout the follow-up period. The significant changes occurred the next day after the surgery, including a decrease in TSH, FT3, and an increase in FT4. Additionally, the decrease occurred in mean FT3 for six patients with preoperative low T3 syndrome. Three months after the surgery, thyroid hormones were restored to their baseline and/or normal values. All six patients with preoperative low T3 syndrome had significant improvement in all SF-36 subscales (except for the role emotional and physical). Patients with preoperative normal high FT3 and low FT4 had increased FT3/FT4 ratio which was associated with deterioration in all SF-36 subscales 3 months after the surgery. CONCLUSION: Routine assessment of the FT3/FT4 ratio might be a simple and effective tool for the risk stratification of iNPH patients before VP shunt surgery.

Quantitative Evans index estimation using ultrasonographic measurement of the optic nerve sheath diameter in supine and upright position.

OBJECTIVES: We aimed to quantitatively assess Evans index (EI) using ultrasonographic optic nerve sheath diameter (ONSD) measurements in supine and upright position in normal pressure hydrocephalus (NPH) patients. METHODS: Ultrasonographically ONSD was measured in a supine and upright position before and 4-5 days after the ventriculoperitoneal shunt surgery. The changes of the ONSD between supine and upright positions were calculated as ∆ONSD = sONSD-uONSD and as the variation ONSD_V = 100% × [(sONSD - uONSD)/sONSD]. Multiple linear regression analyses were conducted to assess associations between EI and the variation of ONSD. We derived the mathematical function to predict EI. Bland-Altman analysis was applied to evaluate the accuracy and precision of the EI prediction. RESULTS: Thirteen adult patients (mean age 61.8 ± 11.1 (SD) years; 6 (46%) female) undergone VP shunt implantation for NPH. The mean EI was 0.432 (95% CI, 0.393-0.471) preoperatively and 0.419 (95% CI, 0.373-0.466) postoperatively (p = 0.066). There is a decrease of the ONSD during positional changes from supine to upright position and pre- and postoperative EI correlated with preoperative variation ONSD_V1 (r = - 0.610 and - 0.648, p < 0.05). The mathematical function for preoperative EI estimation was EIpreop = 0.504 - 0.022 × ONSD_V1 + 0.101 × gender (M = 0; W = 1), (Durbin-Watson value = 1.94), and for postoperative was EIpostop = 0.487 - 0.022 × ONSD_V1 + 0.117 × gender; (Durbin-Watson value 2.23). CONCLUSIONS: Ultrasonographic ONSD measurements in supine and upright position provide a potential method to quantify EI that can be conducted at the bedside.

Serum protein triplet TGF-ß1, TIMP-1, and YKL-40 serve as diagnostic and prognostic profile for astrocytoma.

Astrocytoma is the most common glial tumour of the CNS. The most malignant form is grade IV Astrocytoma, also called Glioblastoma. Due to its heterogeneity, aggressiveness and lethal nature scientists are trying to find less invasive methods for early prediction of tumour onset, recurrence, response to therapy and patients' survival. Here, applying decision tree classification algorithm we performed astrocytoma specific protein profile analysis on serum proteins TIMP-1, active and latent form of TGF-ß1, IP-10, ANGPT-1, OPN, and YKL-40 using enzyme-linked immunosorbent detection assay (ELISA). Results have demonstrated that astrocytoma specific profile consisted of three proteins-active form of TGF-ß1, TIMP-1 and YKL-40 and was able to correctly classify 78.0% (103/132) of sample and 83.3% (60/72) of astrocytoma sample. Calculating decision tree algorithm associated with astrocytoma patient survival, prediction model reached an accuracy of 83.3% (60/72). All together these results indicate that glioma detection and prediction from patient serum using glioma associated proteins and applying mathematical classification tools could be achieved, and applying more comprehensive research further could be implemented in clinic.

Delayed intracerebral hemorrhage associated with placement of a deep brain stimulating electrode over two years prior.

INTRODUCTION AND IMPORTANCE: Most severe complications of DBS appear in the perioperative period. There are no published case reports of delayed ICH occurring more than three months from electrode implantation. The pathogenesis of delayed ICH remains unclear. CASE PRESENTATION: We present a 64-year-old male with essential tremor who sustained a delayed intracerebral hemorrhage (ICH) 2.5 years after implantation of a deep brain stimulating electrode. DISCUSSION: The patient sustained a thalamic-midbrain ICH that may have been related to the positioning of the electrode. An analysis was performed to determine the cause and risk factors that may have contributed. Based on these findings, it is possible that the proximity of the cannula or electrode may have mildly injured the wall of the superior thalamic vein during implantation, or perhaps being in contact with the vein over a longer-term having an effect, which in either of these scenarios can subsequently lead to ICH formation on the sudden rise of intracranial pressure. CONCLUSION: It emphasizes the importance of proper surgical navigation planning, image- guidance, and the use of image verification.

Association of genetic variants at CETP, AGER, and CYP4F2 locus with the risk of atrophic age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly individuals. The etiology of AMD includes environmental and genetic factors. METHODS: We aimed to determine the association between CETP (rs5882; rs708272; rs3764261; rs1800775; rs2303790), AGER (rs1800624; rs1800625), and CYP4F2 (rs1558139) gene polymorphisms and development of atrophic AMD. About 52 patients with atrophic AMD and 800 healthy control subjects were evaluated. The genotyping of single-nucleotide polymorphisms in CETP, AGER, and CYP4F2 was carried out using the real-time-PCR method. RESULTS: Genetic risk models in the analysis of CETP rs5882 revealed statistically significant variables with increased risk of atrophic AMD in the codominant (p < .001), dominant (p < .001), recessive (p < .001), and additive (p < .001) models with the highest 25.4-fold increased risk of atrophic AMD in the codominant model (p < .001). The AGER rs1800625 was associated with a highly increased risk of atrophic AMD in the codominant (p < .001), recessive (p < .001), and additive (p < .001) genetic models. CONCLUSION: We identified two polymorphisms with a higher risk of atrophic AMD (CETP rs5882 and AGER rs1800625).

Clinical and Biological Correlates of Preoperative Cognitive Functioning of Glioma and Meningioma Patients.

OBJECTIVES: This study aimed to investigate the association of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations with cognitive functions of glioma and meningioma patients. METHODS: 177 brain tumor patients awaiting for brain tumor surgery participated in the study. Patients were assessed preoperatively, using neuropsychological tests for verbal memory, psychomotor speed, mental flexibility, and verbal fluency. The functional status of patients was evaluated using the Karnofsky Performance Index. Blood samples were drawn for evaluation of serum hsCRP and NT-proBNP concentrations upon hospital admission. RESULTS: The highest NT-proBNP concentration was observed in meningioma patients. Glioma and meningioma patients did not differ in hsCRB concentration. Patients in the highest hsCRP tertile were older and more frequently reported cardiovascular comorbidity. Patients in the highest NT-proBNP tertile were older, more frequently with cardiovascular comorbidity, females, and diagnosed with a meningioma. hsCRP was significantly related to slower psychomotor speed in high-grade glioma patients (rho = 0.30, p < 0.05). In meningioma sample, NT-proBNP correlated with decreased psychomotor speed (rho = 0.38, p < 0.01), mental flexibility (rho = 0.33, p < 0.01), worse cumulative learning (rho = -0.27, p < 0.05), and delayed recall (rho = 0.30, p < 0.01). However, the relationship between the NT-proBNP and cognitive functions became nonsignificant when demographic and clinical covariates were included into analysis. Higher hsCRP concentration remained significantly related to slower psychomotor speed (p = 0.02) and worse mental flexibility (p = 0.05) in glioma patients, independently from demographic and clinical covariates. Preoperative cognitive functioning was also predicted by older age, gender, side and location of the tumor, and tumor malignancy, and general functional status of a patient. CONCLUSIONS: NT-proBNP was not associated with memory, language, and attention/executive cognitive domains of glioma and meningioma patients. Increased hsCRP was related to slower psychomotor speed and worse mental flexibility in glioma patients, indicating that inflammation processes are important for cognitive functioning in glial tumors.

Neuropsychiatric complications and neuroimaging characteristics after deep brain stimulation surgery for Parkinson's disease.

Psychiatric complications after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease patients are common. The aim of this study was to evaluate a possible role of cortical thickness, cortical and subcortical volume for neuropsychiatric complications after STN-DBS implantation surgery. Twenty-two Parkinson's disease patients underwent STN-DBS. Control group consisted of 18 healthy volunteers who were matched by age and gender. All Parkinson's disease patients and control subjects underwent neuropsychological assessment and brain MRI. Control group subjects had normal MRI and neurocognitive testing results. Seven (31.8%) Parkinson's disease patients developed neuropsychiatric complications (psychosis and delirium) after STN-DBS implantation surgery with full recovery in short follow up. Two Parkinson's disease patients were excluded from further analysis, because they did not match image processing and analysis quality control. Volumetric analysis showed significant differences in cortical thickness between STN-DBS patients with and without postoperative neuropsychiatric complications in 13 gyruses on the right hemisphere (superior frontal, caudal middle frontal, pars triangularis and opercularis, temporal lobe, superior and inferior parietal, supramarginal) and in 7 gyruses on the left hemisphere (caudal middle frontal, inferior and middle temporal, pre and postcentral, superior parietal and supramarginal). White matter volume analysis showed also its reduction in the left caudal middle frontal area. Moreover, white matter volume and surface area reduction implicating that this area can be the most important for postoperative neuropsychiatric complication risk. Study results suggest that neuropsychiatric complications are common in Parkinson's disease patients after STN-DBS implantation and can be associated with excitation of frontal-striatum-thalamus and temporal-parietal circuits.

Oncosuppressive Role of RUNX3 in Human Astrocytomas.

BACKGROUND: Gliomas are the most common and aggressive among primary malignant brain tumours with significant inter- and intratumour heterogeneity in histology, molecular profile, and patient outcome. However, molecular targets that could provide reliable diagnostic and prognostic information on this type of cancer are currently unknown. Recent studies show that certain phenotypes of gliomas such as malignancy, resistance to therapy, and relapses are associated with the epigenetic alterations of tumour-specific genes. Runt-related transcription factor 3 (RUNX3) is feasible tumour suppressor gene since its inactivation was shown to be related to carcinogenesis. AIM: The aim of the study was to elucidate RUNX3 changes in different regulation levels of molecular biology starting from epigenetics to function in particular cases of astrocytic origin tumours of different grade evaluating significance of molecular changes of RUNX3 for patient clinical characteristics as well as evaluate RUNX3 reexpression effect to GBM cells. METHODS: The methylation status and protein expression levels of RUNX3 were measured by methylation-specific PCR and Western blot in 136 and 72 different malignancy grade glioma tissues, respectively. Lipotransfection and MTT were applied for proliferation assessment in U87-MG cells. RESULTS: We found that RUNX3 was highly methylated and downregulated in GBM. RUNX3 promoter methylation was detected in 69.4% of GBM (n=49) as compared to 0 to 17.2% in I-III grade astrocytomas (n=87). Weighty lower RUNX3 protein level was observed in GMB specimens compared to grade II-III astrocytomas. Correlation test revealed a weak but significant link among Runx3 methylation and protein level. Kaplan-Meier analysis showed that increased RUNX3 methylation and low protein level were both associated with shorter patient survival (p<0.05). Reexpression of RUNX3 in U87-MG cells significantly reduced glioma cell viability compared to control transfection. CONCLUSIONS: The results demonstrate that RUNX3 gene methylation and protein expression downregulation are glioma malignancy dependent and contribute to tumour progression.

Common genetic variations of deiodinase genes and prognosis of brain tumor patients.

BACKGROUND: Thyroid hormone (TH) metabolism can have prognostic significance in brain tumors. We studied the association of common variations in three deiodinase gene single-nucleotide polymorphisms (SNPs) with circulating TH concentrations and prognosis of brain tumor patients. METHODS: Patients admitted for glioma and meningioma surgery between January, 2010 and September, 2011 were evaluated for functional status (Barthel Index or BI) and circulating free tri-iodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) concentrations. Ten common SNPs in the DIO1 gene; five SNPs in the DIO2 gene; and one SNP in the DIO3 gene were genotyped. Follow-up continued until November, 2017. RESULTS: In glioblastoma patients, the DIO1 SNP rs2235544 CC genotype was associated with significantly lower risk of death at 2 years when compared to AA + CA genotypes after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, and extent of resection (HR = 0.34, 95% CI: 0.13-0.84, p = 0.019). The TT genotype vs. CC + TC genotypes of the DI02 SNP rs12885300 was associated with increased mortality risk after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, extent of resection, and FT3/FT4 (HR = 3.13, 95% CI: 1.20-8.16, p < 0.019). The C-allele of the DI01 SNP rs2235544 was related to increased circulating free T3/ free T4 ratio in glioma and meningioma patients, indicating greater T4 to T3 conversion. CONCLUSIONS: SNPs of DIO1 gene (rs2235544) and DIO2 gene (rs12885300) have independent prognostic significance in glioblastoma patients. The C-allele of the DIO1 (rs2235544) is associated with greater T4 to T3 conversion.

RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702, rs4351379, and rs4351376), COL8A1 (rs13095226), and COL10A1 (rs1064583) Gene Variants with Predisposition to Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of a central part of the neural retina (macula) and a leading cause of blindness in elderly people. While it is known that the AMD is a multifactorial disease, genetic factors involved in lipid metabolism, inflammation, and neovascularization are currently being widely studied in genome-wide association studies (GWAS). The aim of our study was to evaluate the impact of new single nucleotide polymorphisms (SNPs) in RAD51B, TRIB1, COL8A1, and COL10A1 genes on AMD development. METHODS: Case-control study involved 254 patients diagnosed with early AMD, 244 patients with exudative AMD, and 942 control subjects. The genotyping of RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702, rs4351379, and rs4351376), COL8A1 (rs13095226), and COL10A1 (rs1064583) was carried out using TaqMan assays by a real-time polymerase chain reaction (RT-PCR) method. RESULTS: Statistically significant difference was found in genotype (TT, TC, and CC) distribution of COL8A1 rs13095226 between exudative AMD and control groups (60.2%, 33.6%, and 6.1% vs. 64.9%, 32.3%, and 2.9%, respectively, p = 0.036). Also, comparing with TT+TC, rs13095226 CC genotype was associated with 3.5-fold increased odds of exudative AMD development (OR = 3.540; 95% CI: 1.415-8.856; p = 0.007). CONCLUSION: Our study revealed a strong association between a variant in COL8A1 (rs13095226) and exudative AMD development.

Preoperative verbal memory problems and their clinical prognostic value in meningioma patients: A prospective study.

This study aimed to evaluate clinical utility of The Hopkins Verbal Learning Test-Revised (HVLT-R) for assessment of preoperative memory function in meningioma patients and to investigate prognostic value of memory assessment in predicting outcomes after meningioma excision surgery. A total of 93 meningioma patients were assessed 2-3 days preoperatively using HVLT-R, and EORTC QLQ-30 and QLQ-BN20. Functional outcome at discharge was evaluated using The Glasgow Outcome Scale. A sample of 95 healthy controls was matched to patients according to age, gender, and education. Meningioma patients demonstrated impaired working memory, delayed recall and recognition, flatter learning slope, and less effective acquisition. Location of meningioma was not related to any of the studied memory scores. Patients with left sided meningiomas more often produced false positive recognitions and demonstrated worse delayed recall when compared to patients with right sided, but not bilateral meningiomas. Verbal memory impairment was not associated with perceived health status. Functional outcome at discharge was predicted by tumor side, global health status score, and HVLT-R Cumulative learning score. Cumulative verbal learning impairment was associated with greater risk for poor functional outcome, indicating that cognitive impairment has added prognostic value beyond established prognostic indicators of meningioma patients.

SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, LIPC rs10468017, rs493258 and LPL rs12678919 genotypes and haplotype evaluation in patients with age-related macular degeneration.

OBJECTIVE: Age-related macular degeneration (AMD) is the leading cause of blindness in elderly individuals in the developed countries. The etiology of AMD is thought to be multifactorial, including environmental and genetic factors. Our purpose was to determine the genotype frequencies of six different SNPs in genes that encode proteins involved in AMD-related molecular changes (SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, LIPC rs10468017, rs493258 and LPL rs12678919) for evaluation of haplotype risk in patients with AMD. METHODS: The study cohort consisted of 652 AMD patients and 829 healthy controls. The genotyping was carried out using the RT-PCR. RESULTS: TT genotype of the LIPC rs493258 polymorphism was associated with decreased odds of early AMD development under the codominant and recessive models (OR = 0.446; 95% CI: 0.258-0.772; p = 0.004 and OR = 0.455; 95% CI: 0.274-0.756; p = 0.002, respectively) after Bonferroni correction, (p > 0.05/6, since we analyzed 6 different SNPs). The haplotype containing the two minor alleles T-T in rs10468017-rs493258 were significantly (p = 0.034) associated with early AMD development decreasing. There were no associations found with atrophic AMD development. CONCLUSION: The study showed that LIPC rs493258 gene and haplotype containing the two minor alleles T-T in rs10468017-rs493258 may decrease AMD development.

Incidence and clinical significance of postoperative delirium after brain tumor surgery.

BACKGROUND: Delirium is an acute and reversible deterioration of mental state. Postoperative delirium (POD) can develop after surgical procedures and is associated with impaired health status and worse recovery. So far, there is little data about postoperative delirium after brain surgery. The aim of this study was to evaluate frequency, risk factors, and prognostic value of POD in predicting short-term postoperative outcomes after brain tumor surgery. METHODS: Five-hundred and twenty-two patients who underwent elective brain tumor surgery in 2010-2017 were included in this prospective study. Patients were monitored for POD using the Confusion Assessment Method for the ICU (CAM-ICU) for 2 to 7 days after the surgery. At hospital discharge, outcomes were evaluated using the Glasgow Outcome Scale (GOS). RESULTS: POD was diagnosed in 22 (4.2%) patients. Risk factors of POD were low level of hemoglobin, poor functional status at time of admission, low education level and older age (65 years and older). POD incidence was not associated with brain tumor laterality, location, extent of resection, histological diagnosis, or affected brain lobe. POD was associated with greater risk for unfavorable outcomes at hospital discharge (OR = 5.3; 95% CI [2.1-13.4], p = 0.001). CONCLUSIONS: POD is not a common complication after elective brain tumor surgery. Older age, poor functional status, low education level and anemia are associated with greater POD risk. Extent of surgical intervention and brain tumor location are not associated with POD risk. POD is associated with worse outcome at hospital discharge.

Brain MRI morphometric analysis in Parkinson's disease patients with sleep disturbances.

BACKGROUND: Sleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep disturbances in PD patients. METHODS: Twenty-eight PD patients (14 men and 14 women, median age 58 years) were evaluated for sleep disturbances with PDSS and underwent brain MRI. Control group consisted of 28 healthy volunteers who were matched by age and gender. Automated voxel based image analysis was performed with the FreeSurfer software. RESULTS: PD patients when compared to controls had larger ventricles, smaller volumes of hippocampus and superior cerebellar peduncle, smaller grey matter thickness in the left fusiform, parahipocampal and precentral gyruses, and right caudal anterior cingulate, parahipocampal and precentral hemisphere gyruses, as well as smaller volume of left rostral middle frontal and frontal pole areas, and right entorhinal and transverse temporal areas. According to the Parkinson's disease Sleep Scale (PDSS), 15 (53.58%) patients had severely disturbed sleep. The most frequent complaints were difficulties staying asleep during the night and nocturia. The least frequent sleep disturbances were distressing hallucinations and urine incontinence due to off symptoms. Patients who fidgeted during the night had thicker white matter in the left caudal middle frontal area and lesser global left hemisphere cortical surface, especially in the lateral orbitofrontal and lateral occipital area, and right hemisphere medial orbitofrontal area. Patients with frequent distressful dreams had white matter reduction in cingulate area, and cortical surface reduction in left paracentral area, inferior frontal gyrus and right postcentral and superior frontal areas. Nocturnal hallucinations were associated with volume reduction in the basal ganglia, nucleus accumbens and putamen bilaterally. Patients with disturbing nocturia had reduction of cortical surface on the left pre- and postcentral areas, total white matter volume decrease bilaterally as well in the pons. CONCLUSIONS: PD patients with nocturnal hallucinations had prominent basal ganglia volume reduction. Distressful dreams were associated with limbic system and frontal white matter changes, meanwhile nocturia was mostly associated with global white matter reduction and surface reduction of cortical surface on the left hemisphere pre- and postcentral areas.

Atypical Teratoid/Rhabdoid Tumor After In Vitro Fertilization: Illustrative Case Report and Systematic Literature Review.

OBJECTIVE: In vitro fertilization (IVF) is increasingly used for the treatment of infertile couples worldwide. The association between IVF and cancer risk in offspring is conflicting. We present a case of atypical teratoid/rhabdoid tumor (AT/RT) in a girl conceived by IVF and present results of systematic review of literature of primary intracranial neoplasms diagnosed in children conceived by IVF. METHODS: A systematic review of literature was conducted on April 12, 2017, to identify previously published reports of intracranial brain tumors in patients conceived after IVF. RESULTS: A 21-month-old girl born after IVF and uneventful pregnancy presented with progressive nausea, vomiting, irritability, and right-side weakness. Magnetic resonance imaging demonstrated large heterogeneous contrast enhancing left frontotemporoparietal tumor. The operation was aborted due to asystole after subtotal tumor removal. The patient passed away on postoperative day 3. Histologic examination demonstrated AT/RT. We identified 7 previously published case reports of intracranial neoplasms in children conceived by IVF. Patient age at brain tumor diagnosis ranged from 31st week of gestation to 3 years of age. The most common histological diagnosis was AT/RT (3 cases), followed by glioblastoma multiforme, gliosarcoma, medulloblastoma, craniopharyngioma, and choroid plexus papilloma. Three of five operated patients died during perioperative period. Outcomes were dismal in 7 patients. CONCLUSIONS: IVF-associated brain tumors are usually malignant and associated with high mortality. Future studies investigating possible causal relationship between IVF and brain tumor risk are encouraged.

Prognostic role of high sensitivity C-reactive protein and interleukin-6 in glioma and meningioma patients.

High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) can be important prognostic indicators of brain tumor patients. We investigated the association of circulating IL-6 and hsCRP concentrations with discharge outcomes and survival of glioma and meningioma patients. One-hundred and sixty-three (115 women; median age 57 years) patients admitted for meningioma (n = 94), high-grade glioma (n = 48) and low-grade glioma (n = 21) surgery were enrolled in this prospective cohort study. Serum samples were collected within 24 h of admission. Discharge outcome was evaluated using the Glasgow Outcome Scale (unfavorable outcome = score from 1 to 3). Follow-up continued until November, 2016. Elevated IL-6 (≥ 2 pg/ml) and hsCRP (≥ 1 mg/l) concentrations were present in 25 and 35% of brain tumor patients, respectively. Elevated IL-6 concentrations were associated with unfavorable outcome at hospital discharge, adjusting for brain tumor histological diagnosis, patient age and gender (OR 2.39, 95% CI 0.97-5.91, p = 0.05). Elevated hsCRP concentrations were not associated with discharge outcome (p = 0.13). In multivariate Cox regression analyses adjusted for patient age, gender, extent of tumor resection and adjuvant treatment, elevated IL-6 concentration was associated with greater mortality risk in high-grade glioma patients (OR 2.623; 95% CI 1.129-5.597; p = 0.01), while elevated hsCRP concentration was associated with greater mortality risk in meningioma patients (OR 3.650; 95% CI 1.038-12.831; p = 0.04). Elevated IL-6 concentration is associated with greater unfavorable outcome risk in brain tumor patients and with greater mortality in high-grade glioma patients, while elevated hsCRP concentration is associated with greater mortality in meningioma patients.

The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration.

BACKGROUND Age-related macular degeneration (AMD) is the leading cause of blindness in people aged 65 years and older in developed countries. The pathogenesis of AMD has been linked to mechanisms involving inflammation, oxidative stress, and basal laminar deposit formation between retinal pigment epithelium (RPE) cells and the basal membrane, caused by advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of AMD through the AGE-and receptor for AGE (RAGE) interaction, which can be altered by polymorphisms of the RAGE gene. We examined RAGE rs1800624 and rs1800625 gene polymorphisms contributing to AMD development. MATERIAL AND METHODS The study enrolled 300 patients with early AMD, 300 patients with exudative AMD, and 800 healthy controls. The genotyping was carried out using the RT-PCR method. RESULTS The analysis of two single nucleotide polymorphisms (SNPs) in the RAGE gene showed that rs1800624 was associated with a 1.6-fold decreased risk for exudative AMD under the dominant model after adjustment for age (OR=0.616; 95% CI: 0.394-0.963; p=0.034) and each copy of allele T at rs1800624 was associated with a 1.4-fold decreased risk for exudative AMD development under the additive model after adjustment for age (OR=0.701; 95% CI: 0.510-0.962; p=0.028). Analysis revealed that the rs1800625 allele G at rs1800625 was associated with a 1.5-fold increased risk for exudative AMD after adjustment for age (OR=1.545; 95% CI: 1.003-2.379; p=0.048). These results suggested that the allele G at rs1800625 was a risk-allele for exudative AMD development. In haplotype analysis, A-G haplotype was significantly more frequently observed in exudative AMD patients compared to healthy controls (3.3% versus 1.4%, p=0.035). CONCLUSIONS We revealed a significant association between RAGE gene rs1800624 and rs1800625 polymorphisms and AMD risk. We considered T allele at rs1800624 to be protective against AMD development, while allele G at rs1800625 was considered to be a marker of poor prognosis in AMD development.

Preoperative N-terminal pro-B-type natriuretic peptide concertation and prognosis of brain tumor patients: a 5-year follow up study.

Increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration predicts poor prognosis of non-CNS cancer patients. We evaluated the association of NT-proBNP concentration with disease severity, discharge outcomes and prognosis of patients undergoing craniotomy for brain tumor. From January, 2010 until September, 2011 two-hundred and forty-five patients (age 55.05 ± 14.62 years) admitted for brain tumor surgery were evaluated for NT-proBNP serum concentration. Outcome at hospital discharge was evaluated with the Glasgow Outcome Scale (GOS). Most common diagnoses were meningioma (37%) and high-grade glioma (20%). Greater NT-proBNP concentration was associated with lower Barthel index (rho = -0.305, p = 0.001) and Mini Mental State Examination scores (rho = -0.314, p = 0.001) and with greater Hospital Anxiety and Depression scale Depression score (rho = 0.240, p = 0.026). Greater admission NT-proBNP concentration was associated with lower discharge GOS score after adjusting for patient age, gender and histological brain tumor diagnosis (ß = -0.253, p < 0.001). Greater NT-proBNP concentration was also associated with greater 5-year mortality risk (HR = 1.845; 95%CI [1.166-2.920], p = 0.009) controlling for patient age, gender, history of cardiovascular disease, histological diagnosis and adjuvant therapy. In sum, greater pre-operative NT-proBNP concentration is associated with worse health status, unfavorable discharge outcome and shorter survival of brain tumor patients.

Association between psychological distress, subjective cognitive complaints and objective neuropsychological functioning in brain tumor patients.

OBJECTIVES: Psychological distress and cognitive impairment are common complications in patients with brain tumors that are associated with poor quality of life and worse prognosis. This pilot study aimed to evaluate the associations between psychological distress, subjective cognitive complaints and baseline neuropsychological performance of brain tumor patients before neurosurgery. PATIENTS AND METHODS: Sixty-two patients with various brain tumors referred for routine neuropsychological assessment 2-3days before neurosurgery participated in the study. Short neuropsychological assessment battery was used to evaluate attention and executive functions, memory and verbal fluency. Presence of cognitive complaints was evaluated during neuropsychological interview using standardized symptoms checklist. Level of psychological distress was assessed using the Hospital Anxiety and Depression Scale. RESULTS: Various attention and executive function problems were reported by 13-58% patients; memory problems by 8-63%; language problems by 10-58% of patients. 36-57% of patients scored below 5th percentile on objective memory measures; 32-45% on attention measures and 11-27% on verbal fluency. However, correlation between objective neuropsychological findings and subjective cognitive complaints was weak, ranging from 0.0 to 0.3. 45% of patients met criteria for increased psychological distress. Psychological distress was associated with subjective cognitive complaints but failed to predict objective neuropsychological findings. Brain tumor histological diagnosis, side and location were not related to neuropsychological functioning. CONCLUSION: Cognitive impairment and psychological distress are highly prevalent in BT patients before neurosurgery. Although depression and distress may adversely impact quality of life and prognosis of BT patients, our current findings do not confirm that distress has strong negative impact on objective preoperative cognitive functioning. However, it is related to worse subjective evaluation of one's cognitive abilities. Therefore, objective neuropsychological assessment of cognitive functions is highly recommended despite concern.