Impact of 12 Weeks of Vitamin D3 Administration in Parkinson's Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status.

The current study aimed to investigate whether a 12-week Body Mass Index (BMI)-based (the higher the BMI, the higher the dosage) vitamin D3 administration may affect both the kynurenine pathway (KP) and the inflammatory state in Parkinson's disease (PD) patients with deep brain stimulation (DBS) and may be useful for developing novel therapeutic targets against PD. Patients were randomly assigned to two groups: supplemented with vitamin D3 (VitD, n = 15) and treated with vegetable oil (PL, n = 21). Administration lasted for 12 weeks. The isotope dilution method by LC-MS/MS was applied to measure KP and vitamin D metabolites. Serum concentrations of cytokines such as IL-6 and TNF-α were measured using ELISA kits. After administration, the serum concentration of TNF-α decreased in PD patients with DBS. Moreover, in KP: 3-hydroksykynurenine (3-HK) was increased in the PL group, picolinic acid was decreased in the PL group, and kynurenic acid tended to be higher after administration. Furthermore, a negative correlation between 3-HK and 25(OH)D3 and 24,25(OH)2D3 was noticed. Our preliminary results provide further evidence regarding a key link between the KP substances, inflammation status, and metabolites of vitamin D in PD patients with DBS. These findings may reflect the neuroprotective abilities of vitamin D3 in PD patients with DBS.

Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and <10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology.

Effect of 12-Week BMI-Based Vitamin D3 Supplementation in Parkinson's Disease with Deep Brain Stimulation on Physical Performance, Inflammation, and Vitamin D Metabolites.

Parkinson's disease (PD) is the second most common neurodegenerative disease. To manage motor symptoms not controlled adequately with medication, deep brain stimulation (DBS) is used. PD patients often manifest vitamin D deficiency, which may be connected with a higher risk of falls. We administered a 12-week vitamin D3 supplementation based on BMI (with higher doses given to patients with higher BMI) to investigate its effects on physical performance and inflammation status in PD patients with DBS. Patients were randomly divided into two groups: treated with vitamin D3 (VitD, n = 13), and supplemented with vegetable oil as the placebo group (PL, n = 16). Patients underwent functional tests to assess their physical performance three times during this study. The serum 25(OH)D3 concentration increased to the recommended level of 30 ng/mL in the VitD group, and a significant elevation in vitamin D metabolites in this group was found. We observed significant improvement in the Up and Go and the 6 MWT in the VitD group. In inflammation status, we noticed a trend toward a decrease in the VitD group. To conclude, achieving the optimal serum 25(OH)D3 concentration is associated with better functional test performance and consequently may have a positive impact on reducing falling risk in PD.

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.

WHO CNS5 2021 classification of gliomas: a practical review and road signs for diagnosing pathologists and proper patho-clinical and neuro-oncological cooperation.

The 5th edition of World Health Organization (WHO) Central Nervous System (CNS) tumours classification has transformed the pathological diagnosis of gliomas from purely histological to the multilayered integrated one with molecular biomarkers necessary for proper classification, risk stratification, and prognostic-predictive clinical purposes. Because of deep and important changes in taxonomy and diagnostic approach to gliomas, this manuscript is a review of WHO CNS classification 5th edition with general testing guidance for pathologists and clinicians working in neuro-oncology.

The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe.

Background: People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients' well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods: An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results: Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion: We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents' opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Minimally invasive lateral occipitocervical fixation: case series and technique description.

PURPOSE: Occipitocervical junction (OCJ) instability is commonly treated with fixation via open posterior approach. The use of intraoperative navigation allows us to perform occipitocervical fixation via minimally invasive approach. We report a series of patients treated with percutaneous occipitocervical fixation, describing the surgical procedure in detail and discussing the technique. METHODS: We prospectively enrolled 8 patients affected by OCJ instability secondary to trauma and rheumatoid arthritis. Traumatic patients were preoperatively evaluated with CT scan and MRI scan if needed. Rheumatoid arthritis group was evaluated with both CT and MR. Patients underwent percutaneous occipitocervical fixation with the assist of intraoperative 3D imaging and navigation. All patients were functionally and radiologically evaluated pre-, at 6 weeks, and at 1 year postoperatively. RESULTS: Percutaneous occipitocervical fixation was successfully performed in all of the patients. 33 screws were placed. 29 (87.88%) were placed without any pedicle breach. In 3 (9.09%) screws we observed a minor; and in 1 (3.03%) screw we observed a major pedicle breach. We did not have any postoperative complications. CONCLUSIONS: Described method of occipitocervical fixation is a minimally invasive method that has a similar outcome to the open technique. It requires the experience in open techniques and the assist of intraoperative 3D imaging and navigation to be performed efficiently.

Content Quality and Audience Engagement Analysis of Online Videos for Anterior Lumbar Interbody Fusion.

OBJECTIVE: For the majority of patients, the Internet constitutes the first source of health information influencing their medical decision-making. We aimed to assess the quality of the online videos regarding anterior lumbar interbody fusion (ALIF). METHODS: YouTube database was searched using 3 different phrases: "anterior lumbar interbody fusion", "ALIF", and "ALIF surgery". The first 50 videos for each phrase were selected. Video content was evaluated by 3 independent researchers using the DISCERN instrument. Qualitative data, quantitative data, and the source of upload were analyzed. RESULTS: A total of 24 videos were included. The mean DISCERN score was 38.21, indicating the poor quality of ALIF videos on YouTube. Video duration was positively correlated with DISCERN score (r = 0.71, P < 0.001) but not with the video power index (VPI). A negative correlation between time since upload and DISCERN score (r = -0.8 P < 0.001) was found. Furthermore, videos containing surgical complications, risk factors, and postoperative prognosis had a significantly higher DISCERN score. Neither DISCERN score nor a VPI correlated with the presence of intraoperative recordings. Videos including the explanation of the spine anatomy had a significantly higher number of likes (P = 0.018). CONCLUSIONS: Despite the increasing educational value of ALIF videos over time, the overall quality of YouTube videos on ALIF remains poor. However, the majority of videos can be recommended to the patient as an informative source of basic knowledge on the surgical details of the ALIF procedure. Longer video duration increases its quality without simultaneous negative influence on its popularity.

COVID-19 - neuropathological point of view, pathobiology, and dilemmas after the first year of the pandemic struggle.

This article constitutes a summary of the knowledge on the involvement of the nervous system in COVID-19, concerning its general pathobiology, clinical presentation and neuropathological features as well as the future directions of investigation. Variable definitions, selection bias, mainly retrospective analyses of hospitalized patients and different methodologies are implemented in the research of this new disease. Central nervous system (CNS) pathology presents most frequently features of non-specific neuroinflammation with microglial activation and lymphoid infiltrations, ischemic/hypoxic encephalopathy, acute cerebrovascular disease, and microthrombi. Some brain specimens remain unaffected or show only non-specific changes of the critical status. Interpretations of the neuropathological findings are not always balanced in a clinical context and discrepant in consequence. Designing of longitudinal neuropathological studies, more frequent autopsies, and building of COVID-19 brain banks, together with neuroimaging analyses is essential. Genetic predispositions or immunological factors corresponding to the disease profile as well as cerebrospinal fluid (CSF) or serum biomarkers of COVID-19, the impact of different virus variants and influence of the therapy need to be identified. The mechanisms causing neuroCOVID and cognitive impairment - whether they are infectious, toxic, vascular or metabolic - create other aspects under research. There are also many existential questions about post-COVID and delayed sequelae of the infection. The fight with pandemic is a challenge for the global society, with neuropathologists and neuroscientists as important allies in struggle for understanding and conquering COVID-19.

Vitamin D Supplementation Improves the Effects of the Rehabilitation Program on Balance and Pressure Distribution in Patients after Anterior Cervical Interbody Fusion-Randomized Control Trial.

STUDY DESIGN: A double-blinded, randomized controlled trial. BACKGROUND: Surgery is effective in reducing pain intensity in patients with cervical disc disease. However, functional measurements demonstrated that the results have been not satisfactory enough. Thus, rehabilitation programs combined with the supplementation of vitamin D could play an essential role. METHODS: The study recruited 30 patients, aged 20 to 70 years, selected for anterior cervical interbody fusion (ACIF). The patients were randomly divided into the placebo (Pl) and vitamin D (3200 IU D3/day) supplemented groups. The functional tests limits of stability (LOS), risk of falls (RFT), postural stability (PST), Romberg test, and foot pressure distribution were performed before supplementation (BS-week 0), five weeks after supplementation (AS-week 5), four weeks after surgery (BSVR-week 9), and 10 weeks after supervising rehabilitation (ASVR-week 19). RESULTS: The concentration of 25(OH)D3 in the serum, after five weeks of supplementation, was significantly increased, while the Pl group maintained the same. The RFT was significantly reduced after five weeks of vitamin D supplementation. Moreover, a further significant decrease was observed following rehabilitation. In the Pl group, no changes in the RFT were observed. The overall postural stability index (OSI), LOS, and the outcomes of the Romberg test significantly improved in both groups; however, the effects on the OSI were more pronounced in the D3 group at the end of the rehabilitation program. CONCLUSIONS: Our data suggest that vitamin D supplementation positively affected the rehabilitation program in patients implemented four weeks after ACIF by reducing the risk of falls and improving postural stability.

Early Rehabilitation Program and Vitamin D Supplementation Improves Sensitivity of Balance and the Postural Control in Patients after Posterior Lumbar Interbody Fusion: A Randomized Trial.

BACKGROUND: The introduction of early rehabilitation exercise is the foundation of treatment post-Posterior lumbar interbody fusion (PLIF) surgery, and the search for additional sources of reinforcement physiotherapy seems to be very important. METHODS: The patients were randomly divided into the vitamin D3 (n = 15; D3) supplemented group and received 3200 IU per day for five weeks before surgery and the placebo group (n = 18; Pl) received vegetable oil during the same time. The patients began the supervisor rehabilitation program four weeks after surgery. RESULTS: The limits of stability (LOS) were significantly improved in the D3 group after 5 and 14 weeks (p < 0.05), while in the Pl group, progress was only observed after 14 weeks (p < 0.05). The LOS were also higher in the D3 group than in the Pl group after five weeks of supervised rehabilitation (p < 0.05). In the postural stability (PST) test, significant progress was observed in the D3 group after 14 weeks (p < 0.02). In addition, neither rehabilitation nor supplementation had significant effects on the risk of falls (RFT). CONCLUSIONS: Vitamin D supplementation seems to ameliorate the effects of an early postoperative rehabilitation program implemented four weeks after posterior lumbar interbody fusion. Early physiotherapy treatment after PLIF surgery combined with vitamin D supplementation appears to be a very important combination with regard to the patients' recovery process.

From magnifying glass to operative microscopy - the historical and modern role of the microscope in microsurgery.

The modern computer-assisted microscope, being a hallmark of microsurgery, has become a standard piece of equipment in the operating theatre. Its introduction enabled visualisation of fine anatomical structures, obscure to the unaided eye, and revolutionised many surgical specialties, such as neurological, ophthalmological, or vascular. These astounding achievements have been the culmination of a century of constant progress in optical engineering and microsurgery, since 1921, when a microscope was first used during surgery. Long before surgery, pathology adopted microscopes, and they have become its most prominent diagnostic tools. We traced the evolution of this important invention and discussed its present status and future prospects.

Vitamin D Deficiency Is Associated with Muscle Atrophy and Reduced Mitochondrial Function in Patients with Chronic Low Back Pain.

Recent studies show that vitamin D deficiency may be responsible for muscle atrophy. The purpose of this study was to investigate markers of muscle atrophy, signalling proteins, and mitochondrial capacity in patients with chronic low back pain with a focus on gender and serum vitamin D level. The study involved patients with chronic low back pain (LBP) qualified for posterior lumbar interbody fusion (PLIF). Patients were divided into three groups: supplemented (SUPL) with vitamin D (3200 IU/day for 5 weeks), placebo with normal levels of vitamin D (SUF), and the placebo group with vitamin D deficiency (DEF). The marker of muscle atrophy including atrogin-1 and protein content for IGF-1, Akt, FOXO3a, PGC-1α, and citrate synthase (CS) activity were determined in collected multifidus muscle. In the paraspinal muscle, IGF-1 levels were higher in the SUF group as compared to both the SUPL and DEF groups (p < 0.05). In the SUPL group, we found significantly increased protein content for pAkt (p < 0.05) and decreased level of FOXO3a (p < 0.05). Atrogin-1 content was significantly different between men and women (p < 0.05). The protein content of PGC-1α was significantly higher in the SUF group as compared to the DEF group (p < 0.05). CS activity in the paraspinal muscle was higher in the SUPL group than in the DEF group (p < 0.05). Our results suggest that vitamin D deficiency is associated with elevated oxidative stress, muscle atrophy, and reduced mitochondrial function in the multifidus muscle. Therefore, vitamin D-deficient LBP patients might have reduced possibilities on early and effective rehabilitation after PLIF surgery.

The Preoperative Supplementation With Vitamin D Attenuated Pain Intensity and Reduced the Level of Pro-inflammatory Markers in Patients After Posterior Lumbar Interbody Fusion.

The aim of this experimental study was to assess whether 5 weeks of preoperative supplementation with vitamin D affects the intensity of pain and the level of inflammatory markers in patients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation. 42 patients were divided, by double-blind randomization, into two groups: supplemented (SUPL) vitamin D (3200 IU dose of vitamin D/day for 5 weeks) and placebo group (PL) treated with vegetable oil. The 10-week program of early rehabilitation (3 times a week) was initiated 4 weeks following PLIF. Measurements of serum 25(OH)D3 and CRP, IL-6, TNF-α, and IL-10 were performed. Pain intensity was measured using VAS. After supplementation with vitamin D serum, the concentration of 25(OH)D3 significantly increased in the SUPL group (∗ p < 0.005) and was significantly higher as compared to the PL group (∗ p < 0.001). A significant reduction in pain intensity was observed 4 weeks after surgery and after rehabilitation in both groups. In the SUPL group, serum CRP and IL-6 concentration significantly decreased after rehabilitation, compared with the postsurgical level (a p < 0.04). The level of TNF-α was significantly lower after rehabilitation only in the supplemented group (∗ p < 0.02). There were no significant changes in the IL-10 level in both groups during the study. Our data indicate that supplementation with vitamin D may reduce systemic inflammation and when combined with surgery and early postsurgical rehabilitation, it may decrease the intensity of pain in LBP patients undergoing PLIF. Data indicate that LBP patients undergoing spine surgery should use vitamin D perioperatively as a supplement.

Impact of Different Illness Perceptions and Emotions Associated with Chronic Back Pain on Anxiety and Depression in Patients Qualified for Surgery.

BACKGROUND: Anxiety and depression are known comorbidities of chronic back pain. Their psychological predictors are not well established in patients with chronic back pain qualified for neurosurgery. AIMS: The purpose of this study was to determine the psychological predictors of depression and anxiety in patients with chronic back pain qualified for surgery. DESIGN: This was a cross-sectional study. SETTINGS: A neurosurgical ward in Gdansk, Poland. PARTICIPANTS/SUBJECTS: All patients who were admitted to the neurosurgical ward and met the inclusion criteria were recruited for the study. Finally, 83 patients with chronic back pain waiting for surgery were recruited. METHODS: A battery of questionnaires, including Illness Perceptions Questionnaire-Revised, Multidimensional Health Locus of Control Scale, Hospital Anxiety and Depression Scale, and Brief Pain Inventory, was used in 83 spinal surgery candidates. RESULTS: Higher anxiety was predicted by stronger beliefs about negative consequences of illness (ß = .205, p < .05), worse illness coherence (ß = .204, p < .05), negative emotional representations of illness (ß = .216, p < .05), and depression (ß = .686, p < .001). Higher depression was predicted by anxiety (ß = .601, p < .001), pain interference (ß = .323, p < .01), lower personal control over pain (ß = -.160, p < .05), and lower external control of health (ß = -.161, p < .05) but, surprisingly, higher internal control of health (ß = .208, p < .01). CONCLUSIONS: Anxiety and depression commonly coexist in chronic back pain sufferers qualified for spine surgery but are derived from dissimilar beliefs. The results highlight the usefulness of advising about the disease and treatment in comprehensive care for this group of patients.

Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases.

Brain metastases are devastating complications of cancer. The blood-brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood-tumor barrier (BTB) when brain metastases form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy by limiting drug uptake. Here, we report that experimental breast cancer brain metastases of low- and high permeability to a dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic sphingosine-1 phosphate receptor 3 (S1P3) is upregulated in the neuroinflammatory response of the highly permeable lesions, and is expressed in patients' brain metastases. S1P3 inhibition functionally tightens the BTB in vitro and in vivo. S1P3 mediates its effects on BTB permeability through astrocytic secretion of IL-6 and CCL2, which relaxes endothelial cell adhesion. Tumor cell overexpression of S1P3 mimics this pathway, enhancing IL-6 and CCL-2 production and elevating BTB permeability. In conclusion, neuroinflammatory astrocytic S1P3 modulates BTB permeability.

Malignant Gliomas as Second Neoplasms in Pediatric Cancer Survivors: Neuropathological Study.

This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.

Vitamin D supplementation attenuates oxidative stress in paraspinal skeletal muscles in patients with low back pain.

PURPOSE: The aim of the study was to evaluate markers of oxidative stress and vitamin D receptor in paraspinal muscles in low back pain patients with vitamin D deficiency, with normal level of vitamin D, and after 5 weeks of vitamin D supplementation. METHODS: Patients were divided into three groups: supplemented (SUP) with vitamin D, placebo with normal concentration of vitamin D (SUF), and the placebo group with vitamin D deficiency (DEF). The concentration of serum vitamin D was measured before and after the supplementation with vitamin D (3200 IU/ day for 5 weeks). Markers of lipid and protein peroxidation, the activity of antioxidant enzymes, and protein content of vitamin D receptor was determined in multifidus muscle of patients. RESULTS: Vitamin D supplementation increased serum level of 25(OH)D3 (p < 0.001). In paraspinal muscle level of 8-isoprostanes and protein carbonyls was higher in DEF group as compared to the SUP group (p < 0.05). Antioxidant enzyme activity and vitamin D receptor in paraspinal muscle altered between the groups with different serum vitamin D concentration. The cytosolic superoxide dismutase and glutathione peroxidase activities were significantly higher in DEF group as compared to the SUP group (p < 0.05). CONCLUSIONS: An attenuation of markers of free radical damage of lipids and proteins was observed in participants supplemented with Vitamin D. Antioxidant enzyme activities in skeletal muscle differ among patients with different serum vitamin D concentration. Monitoring oxidative stress and VDR protein content might be useful for future studies on the mechanism(s) of vitamin D action in muscle.

Cerebellar liponeurocytoma with atypical histological features - a rare example of a glioneuronal tumor.

We present a case of a rare neoplasm in a 77-year-old woman with previous oncological history, who developed a rapid onset of cerebellar symptoms. The neuroimaging detected a posterior fossa tumor suspected of meningioma which was completely resected soon after. Histologically the neoplasm had two components with different immunophenotype. One constituent was lobular, composed of monotonous mitotically active round cells with a predominant neuronal profile. The second, astrocytic component contained lipomatous cells intermixed with larger gemistocytic astrocytes. Fields of geographic necrosis as well as multifocal microvascular proliferation were observed. The Ki67 proliferation index was 12%. After two years of follow-up the patient remains free of symptoms and radiologic recurrence. The presented case of cerebellar liponeurocytoma is unusual in terms of its atypical histological features and prominent astrocytic component. The authors propose that the term 'lipomatous glioneuronal tumor' seems to be more appropriate for this type of lesion, considering its histologic spectrum and possible extracerebellar location.