Impulsivity and inhibitory control in deficit and non-deficit schizophrenia.

BACKGROUND: There is conflicting evidence on impulsivity and its potential relationship with inhibitory control in schizophrenia. This study therefore aimed to identify differences in impulsivity and cognitive and motor inhibition between patients with deficit (DS) and non-deficit (NDS) schizophrenia and healthy controls (HC). We also explored the relationships between impulsivity and different dimensions of inhibitory control in all studied groups. METHODS: The sample comprised 28 DS patients, 45 NDS patients, and 39 age-matched HC. A neuropsychological battery was used. RESULTS: DS patients scored lower in venturesomeness, while those with NDS scored higher in impulsiveness compared to HC. In addition, both groups of patients scored higher on measures of cognitive and motor inhibition, including those relatively independent of information processing speed (although the results were slightly different after adjusting for IQ and/or years of education). Correlations between impulsivity and cognitive inhibition emerged in DS patients, while links between impulsivity and motor inhibition were observed in HC. CONCLUSIONS: Our results suggest the presence of deficits in experimentally assessed inhibitory control in schizophrenia patients, with predominant impulsivity in the NDS population. In addition, impulsivity may affect the cognitive control of inhibition in deficit schizophrenia. Nevertheless, due to the preliminary nature of these findings, they require further empirical verification in future research.

Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review.

Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.

Changes in cervical sagittal balance following anterior cervical discectomy with fusion.

INTRODUCTION: Change in the sagittal balance after anterior cervical discectomy with fusion (ACDF) is a phenomenon that has not yet been sufficiently studied. The aim of this study was to assess such changes. MATERIAL AND METHODS: 28 patients who underwent ACDF for cervical spondylosis were examined. The study was divided into three stages: preoperative, early postoperative, and late postoperative. Sagittal alignments were analysed based on X-ray AP and lateral images: angles C1-C7, C2-C7, C1-C2, C1-C4, C4-C7 and cervical sagittal vertical axis (cSVA). RESULTS: The cervical lordosis C2-C7 decreased by 13% in early monitoring, after which it increased by 60% in the late postoperative phase. Post hoc analysis showed that the measured values between early and late postoperative monitoring differed significantly. Cervical sagittal vertical axis (cSVA) increased by 23% in early control and then decreased by 18% in the late postoperative phase. Post hoc analysis showed that the measured values significantly differed between preoperative and early postoperative monitoring, and between early and late postoperative monitoring. CONCLUSIONS: We have shown that the long-term effect of ACDF is correction of the sagittal balance of the cervical spine. Immediately after the procedure, a disturbance in the cervical spine curvature to the morphology of the entire spine is observed.

Does SARS-CoV-2 Affect Human Semen? A Systematic Review and Meta-Analysis.

Contradictory results have been reported regarding effects of the SARS-CoV-2 upon human semen. A timely and up-to-date systematic review with meta-analysis appears necessary. This study aimed to deliver pooled prevalence (PP) of SARS-CoV-2 in semen and pooled semen parameters as compared with the uninfected. The relevant databases were scanned by two authors for observational studies reporting analysis of semen in COVID-19 patients. The SARS-CoV-2-infected were assigned to group A (exposed arm), whereas the uninfected to group B (unexposed arm). Newcastle-Ottawa Scale was used to address the risk of bias. PRISMA guidelines were adopted. In case of homogenous studies, fixed-effects model was followed, whereas for heterogenous studies random-effects model was used. Of 990 studies, 24 were eligible involving 1589 subjects (947 in group A and 642 in group B). The "comparability" domain was biased the most. SARS-CoV-2 RNA was detected in three studies among 8 individuals producing the PP of 1.76% (95% CI 0.72-3.21). Sperm concentration was reduced significantly (WMD = -16.23 [95% CI -25.56 to -6.89], as well as total sperm in ejaculate (WMD = -34.84 [95% CI - 43.51 to -26.17]) and sperm volume (WMD = - 0.48 [95% CI - 0.59 to - 0.36] in group A as compared with controls. There was a non-significant effect upon progressive motility and leukocyte presence in semen. SARS-CoV-2 RNA in semen among the infected individuals is detected infrequently. By this token, sexual transmission through semen is of low probability and little concern for public health. However, significant decrease in sperm volume, sperm concentration, and total sperm in ejaculate has been noted. The current data, though, are limited, and more studies with longer follow-up are needed to evaluate the further impact.

External validation of the Chicago Chiari Outcome Scale in adults with Chiari malformation type I.

OBJECTIVE: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients. METHODS: The authors retrospectively analyzed the medical records of symptomatic patients with CM-I who underwent posterior fossa decompression between 2010 and 2018 in six neurosurgical departments. Each patient was clinically assessed at the latest available follow-up. Gestalt outcome was determined as improved, unchanged, or worsened compared with the preoperative clinical state. Additionally, the CCOS score was calculated for each patient based on the detailed clinical data. To verify the ability of the CCOS to determine clinical improvement, the area under the receiver operating characteristic (AUROC) curve was evaluated. A logistic regression analysis using all four components of the CCOS (pain symptoms, nonpain symptoms, functionality, and complications) was performed to establish predictors of the improved outcome. RESULTS: Seventy-five individuals with a mean age of 42 ± 15.32 years were included in the study. The mean follow-up duration was 52 ± 33.83 months. Considering gestalt outcome evaluation, 41 patients (54.7%) were classified as improved, 24 (32%) as unchanged, and 10 (13.3%) as worsened. All patients with a CCOS score of 14 or higher improved, while all those with a CCOS score of 8 or lower worsened. The AUROC was 0.986, suggesting almost perfect accuracy of the CCOS in delineating clinical improvement. A CCOS score of 13 showed high sensitivity (0.93) and specificity (0.97) for identifying patients with clinical improvement. Additionally, a meaningful correlation was found between higher CCOS scores in each component and better outcomes. Patient stratification by total CCOS score showed that those categorized as improved, unchanged, and worsened scored prevalently between 13 and 16 points, 10 and 12 points, and 4 and 9 points, respectively. CONCLUSIONS: In this adult cohort, the CCOS was found to be almost perfectly accurate in reflecting postoperative clinical improvement. Moreover, all four CCOS components (pain symptoms, nonpain symptoms, functionality, and complications) significantly correlated with patient clinical outcomes.

External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort.

PURPOSE: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales. METHODS: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year. RESULTS: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively. CONCLUSION: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.

Effective Balloon Pulmonary Angioplasty in a Patient with Chronic Thromboembolic Complications after Ventriculoatrial Shunt for Hydrocephalus in von Hippel-Lindau Disease.

Von Hippel-Lindau (VHL) disease along with chronic thromboembolic pulmonary hypertension (CTEPH) is a unique and unusual severe complication of ventriculoatrial (VA) shunt implantation in the treatment of hydrocephalus. To the best of our knowledge, this can be the first reported case of an effective treatment with balloon pulmonary angioplasty in a patient with VHL after VA shunt placement. The patient underwent six balloon pulmonary angioplasty procedures. All invasive procedures resulted in haemodynamic and functional improvement.

Risk of the high-riding variant of vertebral arteries at C2 is increased over twofold in rheumatoid arthritis: a meta-analysis.

Rheumatoid arthritis (RA) might lead to atlantoaxial instability requiring transpedicular or transarticular fusion. High-riding vertebral artery (HRVA) puts patients at risk of injuring the vessel. RA is hypothesized to increase a risk of HRVA. However, to date, no relative risk (RR) has been calculated in order to quantitatively determine a true impact of RA as its risk factor. To the best of our knowledge, this is the first attempt to do so. All major databases were scanned for cohort studies combining words "rheumatoid arthritis" and "high-riding vertebral artery" or synonyms. RA patients were qualified into the exposed group (group A), whereas non-RA subjects into the unexposed group (group B). Risk of bias was explored by means of Newcastle-Ottawa Scale. MOOSE checklist was followed to ensure correct structure. Fixed-effects model (inverse variance) was employed. Four studies with a total of 308 subjects were included in meta-analysis. One hundred twenty-five subjects were in group A; 183 subjects were in group B. Mean age in group A was 62,1 years, whereas in group B 59,9 years. The highest risk of bias regarded "comparability" domain, whereas the lowest pertained to "selection" domain. The mean relative risk of HRVA in group A (RA) as compared with group B (non-RA) was as follows: RR = 2,11 (95% CI 1,47-3,05), I2 = 15,19%, Cochrane Q = 3,54 with overall estimate significance of p < 0,001. Rheumatoid arthritis is associated with over twofold risk of developing HRVA, and therefore, vertebral arteries should be meticulously examined preoperatively before performing craniocervical fusion in every RA patient.

Management of post-traumatic craniovertebral junction dislocation: A PRISMA-compliant systematic review and meta-analysis of casereports.

Although historically considered fatal, with the advent of improved pre-hospital care, traumatic dislocation of the craniovertebral junction (CVJ) has been increasing in prevalence in neurosurgical centers. As more survivors are reported each year, a timely review with meta-analysis of their management seems necessary. PRISMA checklist was followed step by step. PubMed and Web of Science databases were searched using words "craniovertebral junction dislocation" and their corresponding synonyms. Study eligibility criteria included research studies from 2015 onwards that delineated adult and pediatric patients with confirmed post-traumatic atlantooccipital dislocation (AOD) or atlantoaxial dislocation (AAD) who survived until proper treatment. Of 1475 initial records, 46 articles met eligibility criteria with a total of 141 patients with traumatic CVJ dislocation. Of the patients, 90 were male (63.8%). Mean age of the cohort was 33.3 years (range 1-99 years). Trauma that most often led to this injury was road traffic accident (70.9%) followed by falls (24.6%). The majority of authors support posterior instrumentation of C1-C2 (45.2%) especially by means of Goel-Harms method. At mean follow-up of 15.4 months (range 0.5-60 months), 27.2% of treated patients remained neurologically intact. Of initially symptomatic, 59% improved, 37% were stable, and 4% deteriorated. Instrumenting the occiput in cases of pure AAD was associated with lower chance of neurological improvement in chi-square test (p = 0.0013) as well as in multiple linear regression (ß = - 0.3; p = 0.023). The Goel-Harms C1-C2 fusion is currently the most frequently employed treatment. Many survivors remain with no deficits or improve, rarely deteriorate. Involving the occiput in stabilization in cases of AAD without AOD might be related with worse neurological prognosis.

Prevalence of high-riding vertebral arteries and narrow C2 pedicles among Central-European population: a computed tomography-based study.

High-riding vertebral artery (HRVA) and narrow C2 pedicles (C2P) pose a great risk of injuring the vessel during C2 pedicle or transarticular screw placement. Recent meta-analysis revealed a paucity of European studies regarding measurements and prevalence of these anatomical variants. Three hundred eighty-three consecutive cervical spine CT scans with 766 potential screw insertion sites were analyzed independently by two trained observers. C2 internal height (C2InH), C2 isthmus height (C2IsH), and C2P width were measured. Kappa statistics for inter- and intraobserver reliability as well as for inter-software agreement were calculated. HRVA was defined as C2IsH of ≤ 5 mm and/or C2InH of ≤ 2 mm. Narrow C2P was defined as C2P width ≤ 4 mm. STROBE checklist was followed. At least 1 HRVA was found in 25,3% (95% CI 21,1-29,8) of patients (16,7% of potential sites). At least 1 narrow C2P was seen in 36,8% (95% CI 32,1-41,7) of patients (23,8% of potential sites). Among those with HRVA, unilateral HRVA was present in 68,0% (95% CI 58,4-77,0), whereas bilateral HRVA in 32,0% (95% CI 23,0-41,6). No difference in terms of laterality (right or left) was seen neither for HRVA nor narrow C2P. Significant differences were found between females and males for all measurements. Each parameter showed either good or excellent inter- or intraobserver, and inter-software agreement coefficients. HRVA and narrow C2P are common findings in Central-European population and should be appreciated at the planning stage before craniocervical instrumentation. Measurements can be consistently reproduced by various observers at varying intervals using different software.

Molecular classification of glioblastoma based on immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins.

Glioblastoma (GBM) is the most common and most aggressive primary tumor of the central nervous system. Current GBM treatments have low effectiveness. This is mainly due to the high degree of heterogeneity of GBM tumors. Despite similarities in the classic microscopic image, these tumors differ significantly in molecular terms. The aim of the study was to classify GBM tumors into one of four molecular types based on the immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins and find the association between individual glioma molecular types and prognostic clinical and morphological parameters. From the group of 162 patients the classical molecular type of tumor was observed in 17 (10%) patients, in 23 (14%) the tumor was mesenchymal, in 32 (20%) proneural, and in 90 (56%) neural. No significant relationship was observed between the molecular type of GBM tumors and the studied clinical and morphological parameters of prognostic significance. There were also no statistically significant correlations between the GBM tumor molecular type and survival, both in terms of overall survival and relapse-free survival. Analyzing the impact of all prognostic variables and molecular type of GBM on the probability of overall survival, statistically significant relationships were found.

Global incidence of spinal perineural Tarlov's cysts and their morphological characteristics: a meta-analysis of 13,266 subjects.

BACKGROUND: Spinal perineural Tarlov's cysts (TCs) are considered incidental findings that occasionally might exert pressure upon nerve roots and correspond with patients' signs and symptoms. Purpose of this meta-analysis is to deliver global incidence and characteristics (location, size, and shape) of TCs. METHODS: Following PRISMA checklist, all major databases were searched by two authors for radiologic studies reporting incidence and morphologic features (location, size, and shape) of TCs. Anatomical Quality Assessment tool was applied for risk of bias evaluation. Meta-analysis of random-effects model was employed. Subgroup analysis for regional distribution, gender, sacral levels, age, correspondence with symptoms, and persistent genital arousal disorder (PGAD) were planned ahead. RESULTS: 22 radiologic studies of level 3 evidence involving 13,266 subjects were included. Global pooled prevalence of TCs was 4.18% (95% CI 2.47-6.30). Mean pooled sagittal diameter was 11.86 mm (95% CI 10.78-12.93). Sacral cysts strongly prevailed over the other segments. Of the sacral, S2 level was the most common (46.7% [95% CI 29.4-60.5]). Geographically, the highest incidence was found in Europe (6.07% [95% CI 1.49-13.00]), followed by North America (3.82% [95% CI 0.49-9.44]), and Asia (3.33% [95% CI 1.52-5.75]). TCs were more common in women than in men (5.84% vs 3.03%, p < 0.001, test of homogeneity, χ2). Subjects with PGAD had incidence of 37.87% (95% CI 2.45-81.75). TCs in pediatric population are rare-0.53% (95% CI 0.02-1.51). 15.59% of TCs corresponded with symptoms. CONCLUSIONS: Spinal perineural (Tarlov) cysts are found in a minority of population. S2 level of the sacral bone is affected most frequently. There is female predominance. Correspondence with symptoms is seen in less than one-fifth of TCs. Studies with stronger evidence level are needed to corroborate the results. The purported high incidence in PGAD requires confirmation in case-control studies for the risk-ratio calculation.

Changes in cervical range of motion following anterior cervical discectomy with fusion - preliminary results.

BACKGROUND: The biomechanics of the cervical spine after anterior cervical discectomy with fusion (ACDF), and in particular changes in its global mobility, are phenomena that have not yet been sufficiently studied. Consequently, their effect on the eventual result of treatment is not fully understood. The aim of this study was to assess changes in global and segmental mobility of the cervical spine after ACDF. MATERIAL AND METHODS: 28 patients who underwent ACDF for cervical spondylosis were examined. The study was divided into two stages: preoperative and postoperative. Range of motion (ROM) was analysed based on X-ray AP, lateral and functional images: C1-C7, C1-C2, C2-C7, C1-C4, C4-C7, and segments adjacent to the stabilisation. The patients were divided into groups depending on the length of spondylodesis and the occurrence of adjacent segment degeneration (ASDeg). RESULTS: A statistically significant difference was found in the total ROM of C2-C7, C1-C7 and C4-C7 after ACDF. The ROM of C2-C7 decreased by 23%, of C1-C7 by 20%, and of C4-C7 by 38%. These changes occurred by reducing the extension ROM C2-C7 by 33%, C1-C7 by 31%, and C4-C7 by 12%. There was a statistically significant (31%) reduction in total ROM in the segment above ACDF, a 41% reduction in extension ROM of this level in the non-ASDeg group, and a 73% increase in the segmental extension ROM above ACDF in patients with ASDeg. CONCLUSIONS: ACDF reduces the total ROM of the cervical spine in the sagittal plane. This change occurs by reducing the neck extension, and its severity depends on the length of the spondylodesis. In patients without ASDeg after ACDF, the mobility of the level above the stabilisation decreases. The occurrence of ASDeg is associated with a higher postoperative ROM of the segment located above the spondylodesis.

Diagnostic value of non-enhanced computed tomography in identifying location of ruptured cerebral aneurysm in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: In patients with SAH and multiple aneurysms, the ruptured lesion must be identified to prevent recurrent bleeding. AIM OF THE STUDY: To assess the diagnostic value of non-enhanced computed tomography (NECT) in identifying the rupture site in patients with subarachnoid haemorrhage (SAH) and multiple aneurysms. MATERIAL AND METHODS: We included patients with SAH revealed by NECT and multiple aneurysms detected on computed tomography angiography (CTA) in whom a ruptured aneurysm was identified during neurosurgery. Two radiologists predicted the location of the ruptured aneurysm based on the distribution of the SAH and location of intracerebral haematoma (ICH) by NECT. RESULTS: Eighty-three patients with a mean age of 55.7 ± 14.4 years were included. Ruptured aneurysms were significantly larger (mean size 7.7 ± 4.7 mm) than unruptured aneurysms (mean size 5.9 ± 4.5 mm; p = 0.014). Interobserver agreement was 0.86 (p < 0.001). Overall sensitivity and specificity of radiological prediction were 78.3% (95% CI, 68.6%-87.1%) and 96.4% (95% CI, 94.3%-97.8%) respectively. Overall PPV and NPV were 78.3% (95% CI, 67.6%-86.3%) and 96.8% (95% CI, 94.8%-98.1%) respectively. The sensitivity and PPV for aneurysms in the anterior communicating, anterior, and middle cerebral arteries appeared to be significantly higher than in other locations (p = 0.015 and 0.019 respectively). Analysis of independent predictive factors of correct radiological location revealed that ICH predisposes to a correct radiological diagnosis with an odds ratio of 8.57 (95% CI, 1.07-68.99; p = 0.03). CONCLUSIONS: NECT has a high diagnostic value in identifying the source of bleeding in patients with multiple aneurysms for anterior circulation aneurysms, especially with coexisting ICH. For other locations, NECT is not reliable enough to base treatment decisions upon.

Simpson-Golabi-Behmel syndrome in a 39-year-old male patient with suspected acromegaly-A case study.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic condition and is inherited in an X-linked recessive manner. The disease is caused by a change in the nucleotide sequence of an X-linked gene encoding glypican 3, a protein belonging to the heparan-sulfate membrane proteoglycan family. SGBS case studies are almost entirely restricted to the pediatric population. Scarce literature describing SGBS course in adults may be due to both the high mortality of SGBS patients in childhood and low rate of SGBS diagnosis in adults. We present a case of a 39-year-old man with an initial diagnosis of acromegaly. Genetic tests revealed a hitherto unreported deletion in the GPC3 gene. SGBS manifestations in our patient included tall stature, dysmorphic features, and central nervous system (CNS) anatomical pathology. MRI of the head visualized abnormalities of median line structures, a feature consistent with SGBS: an unclosed craniopharyngeal canal, a sellar-suprasellar cyst, dysmorphic pituitary gland, and a cyst of the septum pellucidum. Moreover, cardiomyopathy complicated by life-threatening paroxysmal ventricular tachycardia was diagnosed. Although various cardiac anomalies are often found in SGBS, their pathogenesis is unclear and may be multifactorial. We believe that the presented case contributes to a better understanding of SGBS and may help clinicians in introducing prophylaxis and treatment for its comorbidities.

Large deletion causing von Hippel-Lindau disease and hereditary breast cancer syndrome.

Patients with intragenic mutations of the VHL gene have a typical disease presentation. However in cases of large VHL gene deletions which involve other genes in the proximity of the VHL gene a presentation of the disease can be different. To investigate whether large VHL deletions that remove the FANCD2 gene have an effect on the disease phenotype, we studied a family with a 50 kb large deletion encompassing these two genes. Four patients in this family were affected by VHL-related lesions. However one carrier of the deletion also had bilateral ductal breast cancer at age 46 and 49. Both tumors were of ~2 cm in diameter. On one side lymph nodes were affected. One tumor was ER- and PR-negative (HER2 s unknown) and the second was ER- and PR-positive, and HER2-negative. Our study suggests that a deletion of FANCD2 gene, an important gene in the DNA repair pathway, may be associated with an increased risk of breast cancer, but further studies are needed in this regard.

Greater methylation of the IL-6 promoter region is associated with decreased integrity of the corpus callosum in schizophrenia.

BACKGROUND: Schizophrenia is associated with chronic subclinical inflammation and decreased integrity of the corpus callosum (CC). Our previous study showed associations between peripheral IL-6 levels and the integrity of the CC. Epigenetic studies show associations between methylation of the genes related to immunological processes and integrity of the CC. AIM: To investigate correlations between methylation status of IL-6 promotor and peripheral IL-6 levels and the integrity of the CC in schizophrenia. MATERIAL AND METHODS: The participants were 29 chronic schizophrenia patients (SCH) and 29 controls. Decreased integrity of the CC was understood as increased mean diffusivity (MD) and/or decreased fractional anisotropy (FA) in diffusion tensor imaging. Peripheral IL-6 concentrations were measured in serum samples and IL-6 promoter methylation status of 6 CpG sites was analyzed in peripheral leukocytes by pyrosequencing. RESULTS: Moderate positive correlations were found between CpG1 methylation and the MD of proximal regions of the CC (CCR1-CCR3) and between CpGmean and MD of CCR1 in SCH. Weaker positive correlations were found for CpGmean with CCR2 and CCR3 and negative correlations were found for CpG1 and FA of CCR3 in SCH. Multivariate regression showed that methylation of CpG1, type of antipsychotic treatment, and their interaction were significant independent predictors of MD of CCR1 in SCH. Methylation of CpG2 was negatively correlated with serum IL-6 in SCH. CONCLUSIONS: The methylation level of the IL-6 promotor region in peripheral leukocytes is associated with the integrity of the CC in schizophrenia and this association may depend on the type of antipsychotic treatment. Further studies are necessary to explain the mechanisms of the observed associations.

The importance of oxidative biomarkers in diagnosis, treatment, and monitoring schizophrenia patients.

INTRODUCTION: The etiology of schizophrenia (SCZ), an incredibly complex disorder, remains multifaceted. Literature suggests the involvement of oxidative stress (OS) in the pathophysiology of SCZ. OBJECTIVES: Determination of selected OS markers and brain-derived neurotrophic factor (BDNF) in patients with chronic SCZ and those in states predisposing to SCZ-first episode psychosis (FP) and ultra-high risk (UHR). MATERIALS AND METHODS: Determination of OS markers and BDNF levels by spectrophotometric methods and ELISA in 150 individuals (116 patients diagnosed with SCZ or in a predisposed state, divided into four subgroups according to the type of disorder: deficit schizophrenia, non-deficit schizophrenia, FP, UHR). The control group included 34 healthy volunteers. RESULTS: Lower activities of analyzed antioxidant enzymes and GSH and TAC concentrations were found in all individuals in the study group compared to controls (p < 0.001). BDNF concentration was also lower in all groups compared to controls except in the UHR subgroup (p = 0.01). Correlations were observed between BDNF, R-GSSG, GST, GPx activity, and disease duration (p < 0.02). A small effect of smoking on selected OS markers was also noted (rho<0.06, p < 0.03). CONCLUSIONS: OS may play an important role in the pathophysiology of SCZ before developing the complete clinical pattern of the disorder. The redox imbalance manifests itself with such severity in individuals with SCZ and in a state predisposing to the development of this psychiatric disease that natural antioxidant systems become insufficient to compensate against it completely. The discussed OS biomarkers may support the SCZ diagnosis and predict its progression.

Gut microbiome in intracranial aneurysm growth, subarachnoid hemorrhage, and cerebral vasospasm: a systematic review with a narrative synthesis.

Intracranial aneurysms (IA) are the most common cerebral vascular pathologies. Their rupture leads to the most dangerous subtype of stroke-aneurysmal subarachnoid hemorrhage (aSAH), which may be followed by cerebral vasospasm and ischemic sequelae. Recently, an imbalance within the intestinal microbiota, referred to as dysbiosis, was suggested to play a role in the formation, progression, and rupture of IA. As no systematic review on this topic exists, considering the significance of this matter and a lack of effective prophylaxis against IA or cerebral vasospasm, we aim to sum up the current knowledge regarding their associations with intestinal microbiome, identify the gaps, and determine future prospects. Scientific databases were systematically and independently searched by two authors from inception to 1st May 2023 for original articles regarding the role of intestinal microbiota in intracranial aneurysmal growth, aSAH occurrence, as well as in cerebral vasospasm following aSAH. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist was followed in an abstraction process. The STROBE tool was applied to assess the risk of bias. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 302 records, four studies were included that fully met eligibility criteria. Studies reported (1) that the relative abundance of Hungatella hathewayi is a protective factor against aneurysm growth and rupture, resulting from the reduced inflammation and extracellular matrix remodeling in the cerebral arterial wall and from reduced metalloproteinase-mediated degradation of smooth muscle cells in cerebral vessels. (2) Relative abundance of Campylobacter ureolyticus is associated with aSAH. (3) No article has evaluated microbiota in relation to cerebral vasospasm following aSAH although there is an ongoing study. We concluded that intestinal microbiota might be a potential target for diagnostic and therapeutic tools to improve the management of cerebral aneurysms. However, more studies of prospective design are needed.

Serum Inflammatory Markers and Integrity of the Superior Longitudinal Fasciculus and the Inferior Longitudinal Fasciculus in Schizophrenia, from Prodromal Stages to Chronic Psychosis-A Cross-Sectional Study.

Chronic subclinical inflammation is believed to be an important factor in the pathogenesis of schizophrenia. Meta-analyses confirm the presence of increased levels of peripheral inflammatory markers (IM) in schizophrenia and its prodromal stages. Peripheral cytokines may affect the brain microstructure through chronic activation of microglia. Disruptions in the integrity of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) are commonly seen in patients with schizophrenia spectrum disorders. We therefore attempted to verify in a cross-sectional study whether there is a correlation between levels of peripheral IM and the integrity of these brain regions in healthy controls, from prodromal states and first episode psychosis to long-term schizophrenia. The integrity of white matter was measured using diffusion tensor imaging. Despite a broad analysis of six IM (CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ), we did not find any correlations with the integrity of the SLF or ILF in any of the analyzed groups (after correction for multiple comparisons). In conclusion, our study does not support the existence of a link between disrupted levels of peripheral IM and reduced integrity of ILF and SLF in schizophrenia spectrum disorders. However, prospective studies are needed to verify this over a long period of time.