Alterations of non-motor symptoms in Parkinson's disease, after of subthalamic deep brain stimulation.

The effect of subthalamic deep brain stimulation (STN DBS) on motor symptoms of Parkinson's disease (PD) has been thoroughly analyzed. The influence of STN DBS on non-motor symptoms (NMS) is still debatable. We analyzed the effect of STN DBS on NMS in PD. Materials and methods: 17 PD patients were qualified for STN DBS according to CAPSIT-PD criteria. Demographic data and clinical status according to the Hoehn-Yahr (H-Y) were recorded. The efficacy of STN DBS on NMS was measured with the NMS Scale before surgery and twelve months after surgery. Results: Global NMS Scale score decreased by 1-75 points (mean 25,67) in 12 patients. No improvement or deterioration was reported in 5 patients (29%). The mean age of the improved group was 56 years and 59,8 years in the non-improved group. The mean duration of PD in the improved group was 11 years and 21 years in the non-improved group. In the non-improved group, four patients were rated 4 and one patients 3 according to the H-Y Scale. In the improved group, two patients were rated 4, six patients 3 and four patients 2 according to the H-Y Scale The most significant improvement of the NMS Scale was recorded in the domain IV- Perceptual problems/Hallucinations- (by 77%), domain I- Cardiovascular including falls- (by 68%) and domain III- Mood/Cognition- (by 58%). Deterioration of the NMS Scale was reported in the domain IX- Miscellaneous- (by 10%) and the domain VII- Urinary- (by 6%). Conclusions: STN DBS has a positive impact on NMS among PD patients. The most important factors that influence improvement are: young age, short disease duration, and good clinical status measured with the H-Y Scale. The NMS Scale domains that tend to respond the best are the domains I, III and IV. The NMS Scale domains that might deteriorate after STN DBS are the domains VII and IX.

Periaqueductal/periventricular gray deep brain stimulation for the treatment of neuropathic facial pain.

Background: The Periaqueductal gray (PAG) and the periventricular gray (PVG) are the anatomical targets for deep brain stimulation (DBS) to treat severe, refractory neuropathic pain. Methods: Seven (four female and three male) patients were qualified for PAG/PVG DBS because of neuropathic facial pain. Frame-based unilateral implantations of DBS were conducted according to indirect planning of the PAG/PVG, contralateral to reported pain (3389, Activa SC 37603, Medtronic). The efficacy of PAG/PVG DBS on pain was measured with Numeric Pain Rating Scale (NRS) and Neuropathic Pain Symptom Inventory (NPSI) before surgery and 3, 12, and 24 months after surgery. Results: The mean age of the group at the implantation was 43.7 years (range: 28-62; SD: 12.13). The mean duration of pain varied from 2 to 12 years (mean: 7.3; SD: 4.11). Five patients suffered from left-sided facial pain and two suffered right-sided facial pain. The etiology of pain among four patients was connected to ischemic brain stroke and in one patient to cerebral hemorrhagic stroke. Patients did not suffer from any other chronic medical condition The beginnings of ailments among two patients were related to craniofacial injury. NRS decreased by 54% at the 3 months follow-up. The efficacy of the treatment measured with mean NRS decreased at one-year follow-up to 48% and to 45% at 24 months follow-up. The efficacy of the treatment measured with NPSI decreased from 0.27 to 0.17 at 2 years follow-up (mean reduction by 38%). The most significant improvement was recorded in the first section of NPSI (Q1: burning- reduced by 53%). The records of the last section (number five) of the NPSI (paresthesia/dysesthesia- Q11/Q12) have shown aggravation of those symptoms by 10% at the two-years follow-up. No surgery- or hardware-related complications were reported in the group. Transient adverse effects related to the stimulation were eliminated during the programming sessions. Conclusion: PAG/PVG DBS is an effective and safe method of treatment of medically refractory neuropathic facial pain. The effectiveness of the treatment tends to decrease at 2 years follow-up. The clinical symptoms which tend to respond the best is burning pain. Symptoms like paresthesia and dysesthesia might increase after DBS treatment, even without active stimulation.

Epigenetic Downregulation of Hsa-miR-193b-3p Increases Cyclin D1 Expression Level and Cell Proliferation in Human Meningiomas.

Meningiomas are common intracranial tumors in adults. Abnormal microRNA (miRNA) expression plays a role in their pathogenesis. Change in miRNA expression level can be caused by impaired epigenetic regulation of miRNA-encoding genes. We found the genomic region covering the MIR193B gene to be DNA hypermethylated in meningiomas based on analysis of genome-wide methylation (HumanMethylation450K Illumina arrays). Hypermethylation of MIR193B was also confirmed via bisulfite pyrosequencing. Both hsa-miR-193b-3p and hsa-miR-193b-5p are downregulated in meningiomas. Lower expression of hsa-miR-193b-3p and higher MIR193B methylation was observed in World Health Organization (WHO) grade (G) II/III tumors as compared to GI meningiomas. CCND1 mRNA was identified as a target of hsa-miR-193b-3p as further validated using luciferase reporter assay in IOMM-Lee meningioma cells. IOMM-Lee cells transfected with hsa-miR-193b-3p mimic showed a decreased cyclin D1 level and lower cell viability and proliferation, confirming the suppressive nature of this miRNA. Cyclin D1 protein expression (immunoreactivity) was higher in atypical than in benign meningiomas, accordingly to observations of lower hsa-miR-193b-3p levels in GII tumors. The commonly observed hypermethylation of MIR193B in meningiomas apparently contributes to the downregulation of hsa-miR-193b-3p. Since hsa-miR-193b-3p regulates proliferation of meningioma cells through negative regulation of cyclin D1 expression, it seems to be an important tumor suppressor in meningiomas.

DNA methylation, combined with RNA sequencing, provide novel insight into molecular classification of chordomas and their microenvironment.

Chordomas are rare tumors of notochord remnants, occurring mainly in the sacrum and skull base. Despite of their unusually slow growth, chordomas are highly invasive and the involvement of adjacent critical structures causes treatment challenges. Due to the low incidence, the molecular pathogenesis of this entity remains largely unknown. This study aimed to investigate DNA methylation abnormalities and their impact on gene expression profiles in skull base chordomas. 32 tumor and 4 normal nucleus pulposus samples were subjected to DNA methylation and gene expression profiling with methylation microarrays and RNA sequencing. Genome-wide DNA methylation analysis revealed two distinct clusters for chordoma (termed subtypes C and I) with different patterns of aberrant DNA methylation. C Chordomas were characterized by general hypomethylation with hypermethylation of CpG islands, while I chordomas were generally hypermethylated. These differences were reflected by distinct distribution of differentially methylated probes (DMPs). Differentially methylated regions (DMRs) were identified, indicating aberrant methylation in known tumor-related genes in booth chordoma subtypes and regions encoding small RNAs in subtype C chordomas. Correlation between methylation and expression was observed in a minority of genes. Upregulation of TBXT in chordomas appeared to be related to lower methylation of tumor-specific DMR in gene promoter. Gene expression-based clusters of tumor samples did not overlap with DNA methylation-based subtypes. Nevertheless, they differ in transcriptomic profile that shows immune infiltration in I chordomas and up-regulation of cell cycle in C chordomas. Immune enrichment in chordomas I was confirmed with 3 independent deconvolution methods and immunohistochemistry. Copy number analysis showed higher chromosomal instability in C chordomas. Nine out of eight had deletion of CDKN2A/B loci and downregulation of genes encoded in related chromosomal band. No significant difference in patients' survival was observed between tumor subtypes, however, shorter survival was observed in patients with higher number of copy number alterations.

Pathway-level mutation analysis in primary high-grade serous ovarian cancer and matched brain metastases.

Brain metastases (BMs) in ovarian cancer (OC) are a rare event. BMs occur most frequently in high-grade serous (HGS) OC. The molecular features of BMs in HGSOC are poorly understood. We performed a whole-exome sequencing analysis of ten matched pairs of formalin-fixed paraffin-embedded samples from primary HGSOC and corresponding BMs. Enrichment significance (p value; false discovery rate) was computed using the Reactome, the Kyoto Encyclopedia of Genes and Genomes pathway collections, and the Gene Ontology Biological Processes. Germline DNA damage repair variants were found in seven cases (70%) and involved the BRCA1, BRCA2, ATM, RAD50, ERCC4, RPA1, MLHI, and ATR genes. Somatic mutations of TP53 were found in nine cases (90%) and were the only stable mutations between the primary tumor and BMs. Disturbed pathways in BMs versus primary HGSOC constituted a complex network and included the cell cycle, the degradation of the extracellular matrix, cell junction organization, nucleotide metabolism, lipid metabolism, the immune system, G-protein-coupled receptors, intracellular vesicular transport, and reaction to chemical stimuli (Golgi vesicle transport and olfactory signaling). Pathway analysis approaches allow for a more intuitive interpretation of the data as compared to considering single-gene aberrations and provide an opportunity to identify clinically informative alterations in HGSOC BM.

The Usefulness of Prognostic Tools in Breast Cancer Patients with Brain Metastases.

BACKGROUND: Determining the proper therapy is challenging in breast cancer (BC) patients with brain metastases (BM) due to the variability of an individual's prognosis and the variety of treatment options available. Several prognostic tools for BC patients with BM have been proposed. Our review summarizes the current knowledge on this topic. METHODS: We searched PubMed for prognostic tools concerning BC patients with BM, published from January 1997 (since the Radiation Therapy Oncology Group developed) to December 2021. Our criteria were limited to adults with newly diagnosed BM regardless of the presence or absence of any leptomeningeal metastases. RESULTS: 31 prognostic tools were selected: 13 analyzed mixed cohorts with some BC cases and 18 exclusively analyzed BC prognostic tools. The majority of prognostic tools in BC patients with BM included: the performance status, the age at BM diagnosis, the number of BM (rarely the volume), the primary tumor phenotype/genotype and the extracranial metastasis status as a result of systemic therapy. The prognostic tools differed in their specific cut-off values. CONCLUSION: Prognostic tools have variable precision in determining the survival of BC patients with BM. Advances in local and systemic treatment significantly affect survival, therefore, it is necessary to update the survival indices used depending on the type and period of treatment.

Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors.

Corticotroph pituitary adenomas commonly cause Cushing's disease (CD), but some of them are clinically silent. The reason why they do not cause endocrinological symptoms remains unclear. We used data from small RNA sequencing in adenomas causing CD (n = 28) and silent ones (n = 20) to explore the role of miRNA in hormone secretion and clinical status of the tumors. By comparing miRNA profiles, we identified 19 miRNAs differentially expressed in clinically functioning and silent corticotroph adenomas. The analysis of their putative target genes indicates a role of miRNAs in regulation of the corticosteroid receptors expression. Adenomas causing CD have higher expression of hsa-miR-124-3p and hsa-miR-135-5p and lower expression of their target genes NR3C1 and NR3C2. The role of hsa-miR-124-3p in the regulation of NR3C1 was further validated in vitro using AtT-20/D16v-F2 cells. The cells transfected with miR-124-3p mimics showed lower levels of glucocorticoid receptor expression than control cells while the interaction between miR-124-3p and NR3C1 3' UTR was confirmed using luciferase reporter assay. The results indicate a relatively small difference in miRNA expression between clinically functioning and silent corticotroph pituitary adenomas. High expression of hsa-miR-124-3p in adenomas causing CD plays a role in the regulation of glucocorticoid receptor level and probably in reducing the effect of negative feedback mediated by corticosteroids.

Salvage Treatment for Progressive Brain Metastases in Breast Cancer.

Survival of patients with breast cancer has increased in recent years due to the improvement of systemic treatment options. Nevertheless, the occurrence of brain metastases is associated with a poor prognosis. Moreover, most drugs do not penetrate the central nervous system because of the blood-brain barrier. Thus, confirmed intracranial progression after local therapy is especially challenging. The available methods of salvage treatment include surgery, stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), whole-brain radiotherapy, and systemic therapies. This narrative review discusses possible strategies of salvage treatment for progressive brain metastases in breast cancer. It covers possibilities of repeated local treatment using the same method as applied previously, other methods of local therapy, and options of salvage systemic treatment. Repeated local therapy may provide a significant benefit in intracranial progression-free survival and overall survival. However, it could lead to significant toxicity. Thus, the choice of optimal methods should be carefully discussed within the multidisciplinary tumor board.

A New Implantable Closed-Loop Clinical Neural Interface: First Application in Parkinson's Disease.

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson's disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBSR System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson's disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place.

Influence of Bilateral Subthalamic Nucleus Deep Brain Stimulation on the Lipid Profile in Patients With Parkinson's Disease.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a valuable alternative to pharmacotherapy alone in an advanced Parkinson's disease (PD). Given the growing number of patients with STN-DBS, its impact on the comorbidities should be considered. Aim: The aim of this study was to evaluate the influence of bilateral STN-DBS on the lipid profile in patients with PD. Methods: Three groups of parkinsonian patients were included: 20 treated pharmacologically-PHT group, 20 newly qualified for STN-DBS-DBS group, and 14 postoperative patients (median 30 months after surgery)-POP group. Plasma concentrations of the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and body weight were measured thrice in 9 ± 2 month intervals. Results: A significant increase in the LDL-C concentration is observed early after surgery in the DBS group (11.4 mg/dl, P < 0.01) followed by adverse changes in the HDL-C (-7.7 mg/dl, P = 0.01) and TG (14.1 mg/dl, P = 0.05) plasma levels. In the POP group, the average level of TC at the first visit was significantly higher (P < 0.01) than in the other groups and the TG level was higher than in the PHT group during the follow-up (P < 0.01). A strong positive correlation with body weight alteration after surgery was observed only for long-term changes in the TG levels. Conclusions: Our data indicate that STN-DBS may negatively affect the cardiometabolic profile of patients. Similarly to body weight gain, an increase in the LDL-C concentration occurred early after surgery while adverse changes in the HDL-C and TG plasma levels were more gradual.

Radiation therapy in patients with implanted deep brain stimulation.

BACKGROUND: As deep brain stimulation (DBS) and radiation therapy (RT) have become established treatments for movement disorders and malignancies respectively, patients being treated with both simultaneously are becoming more frequent. OBJECTIVES: Literature regarding the safety of RT in patients with implanted DBS is scarce, and there are no clear guidelines on how to manage them. METHODS: We present a follow-up of two Parkinson's Disease (PD) patients with DBS undergoing RT in the context of previous literature. RESULTS: No adverse events nor malfunctioning of the DBS system were observed. This was in line with previous reports. CONCLUSIONS: Since there are no clear safety guidelines for RT in DBS patients, it is important to document experience in this field. A combined approach involving multidisciplinary discussions between neurosurgeons, radiotherapists, clinical oncologists and neurologists is recommended.

The potential neuromodulatory impact of subthalamic nucleus deep brain stimulation on Parkinson's disease progression.

INTRODUCTION: STN-DBS has been claimed to change progressionsymptomsin animal models of PD, but information is lacking about the possible neuromodulatory role of STN-DBS in humans. The aim of this prospective controlled study was to evaluate the long-term impact of STN-DBS on motor disabilities and cognitive impairment in PD patients in comparison to Best-Medical-Therapy (BMT) and Long-term-Post-Operative (POP) groups. MATERIAL AND METHODS: Patients were divided into 3 groups: the BMT-group consisted of 20 patients treated only with pharmacotherapy, the DBS-group consisted of 20 PD patients who underwent bilateral STN-DBS (examined pre- and postoperatively) and the POP-group consisted of 14 long-term postoperative patients in median 30 month-time after DBS. UPDRS III scale was measured during 3 visits in 9 ± 2 months periods (V1, V2, V3) in total-OFF phase. Cognitive assessment was performed during each visit in total-ON phase. RESULTS: The comparable UPDRS III OFF gain was observed in both BMT-group and POP-group evaluations (p < 0.05). UPDRS III OFF results in DBS-group revealed significant UPDRS III OFF increase in ΔV2-V1 assessment (p < 0.05) with no significant UPDRS III OFF alteration in ΔV3-V2 DBS-group evaluation (p > 0.05). Cognitive assessment revealed significant alterations between DBS-group and BMT-group in working memory, executive functions and learning abilities (p < 0.05). CONCLUSIONS: The impact of STN-DBS on UPDRS III OFF score and cognitive alterations suggest its neuromodulatory role, mainly during the first 9-18 months after surgery.

Evaluating reflexive saccades and UDPRS as markers of Deep Brain Stimulation and Best Medical Treatment improvements in Parkinson's disease patients: a prospective controlled study.

INTRODUCTION: To date, there has been no clear evidence regarding the evaluation of saccades as a monitoring tool of motor impairment in Parkinson's disease (PD) Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) patients. The aim of this study was to evaluate the long-term impact of STN-DBS and pharmacological treatment on reflexive saccades' (RS) parameters and UPDRS alterations. MATERIAL AND METHODS: The DBS group consisted of 20 PD patients who underwent bilateral STN-DBS. The Postoperative (POP) group consisted of 14 post-DBS patients. The Best Medical Therapy (BMT) group consisted of 20 patients on pharmacotherapy only. RS parameters and the UPDRS scale were measured during three visits in four phases of treatment (i.e. BMT-ON/OFF, DBS-ON/OFF). RESULTS: The significant UPDRS III and UPDRS. Total improvements were observed in all three study groups (p < 0.05), but RS latency improvement was stated only in the DBS group in the DBS-ON phase (p < 0.05). A significant correlation between RS latency increase and UPDRS III score worsening was found in all study groups, with the most evident effect in the UPDRS III ON phase (p < 0.05). CONCLUSION: RS parameters correlated with UPDRS III outcomes during the postoperative period in DBS-STN patients. Therefore, saccadic evaluation may be a good biomarker of the patient's response to surgical and/or pharmacological treatment.

Diamond Nanoparticles Downregulate Expression of CycD and CycE in Glioma Cells.

Our previous studies have shown that diamond nanoparticles (NDs) exhibited antiangiogenic and proapoptotic properties in vitro in glioblastoma multiforme (GBM) cells and in tumors in vivo. Moreover, NDs inhibited adhesion, leading to the suppression of migration and invasion of GBM. In the present study, we hypothesized that the NDs might also inhibit proliferation and cell cycle in glioma cells. Experiments were performed in vitro with the U87 and U118 lines of GBM cells, and for comparison, the Hs5 line of stromal cells (normal cells) after 24 h and 72 h of treatment. The analyses included cell morphology, cell death, viability, and cell cycle analysis, double timing assay, and gene expression (Rb, E2F1, CycA, CycB, CycD, CycE, PTEN, Ki-67). After 72 h of ND treatment, the expression level of Rb, CycD, and CycE in the U118 cells, and E2F1, CycD, and CycE in the U87 cells were significantly lower in comparison to those in the control group. We observed that decreased expression of cyclins inhibited the G1/S phase transition, arresting the cell cycle in the G0/G1 phase in glioma cells. The NDs did not affect the cell cycle as well as PTEN and Ki-67 expression in normal cells (Hs5), although it can be assumed that the NDs reduced proliferation and altered the cell cycle in fast dividing cells.

Subthalamic and pallidal oscillatory activity in patients with Neurodegeneration with Brain Iron Accumulation type I (NBIA-I).

OBJECTIVES: Neurodegeneration with Brain Iron Accumulation type I (NBIA-I) is a rare hereditary neurodegenerative disorder with pallidal degeneration leading to disabling generalized dystonia and parkinsonism. Pallidal or subthalamic deep brain stimulation can partially alleviate motor symptoms. Disease-specific patterns of abnormally enhanced oscillatory neuronal activity recorded from the basal ganglia have been described in patients with movement disorders undergoing deep brain stimulation (DBS). Here we studied oscillatory activity recorded from the internal globus pallidus (GPi) and the subthalamic nucleus (STN) to characterize neuronal activity patterns in NBIA-I. METHODS: We recorded local field potentials (LFP) from DBS electrodes in 6 juvenile patients with NBIA-I who underwent functional neurosurgery. Four patients were implanted in the STN and two patients in the GPi. Recordings were performed during wakeful rest. An FFT-based approach was used to analyze the power spectrum in the target area. RESULTS: In all patients we found distinct peaks in the low frequency (7-12 Hz) and in 5 out 6 also in the beta frequency range (15-30 Hz) with the largest beta peak in the patient that presented with the most prominent bradykinesia. No distinct peaks occurred in the gamma frequency range (35-100 Hz). The oscillatory pattern did not differ between STN and GPi. CONCLUSIONS: Here we show for the first time the oscillatory activity pattern in the STN and the GPi in juvenile patients with dystonia plus syndrome due to NBIA-I. The low frequency peak we found is in line with previous studies in patients with isolated idiopathic dystonia. In our cohort, the pallidal beta band activity may be related to more severe motor slowing in dystonia plus syndrome such as NBIA-I. SIGNIFICANCE: Our results further support the link between hyperkinetic motor symptoms such as dystonia and enhanced basal ganglia low frequency activity irrespective of the underlying etiology of dystonia.

The Neuromodulatory Impact of Subthalamic Nucleus Deep Brain Stimulation on Gait and Postural Instability in Parkinson's Disease Patients: A Prospective Case Controlled Study.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) has been an established method in improvement of motor disabilities in Parkinson's disease (PD) patients. It has been also claimed to have an impact on balance and gait disorders in PD patients, but the previous results are conflicting. Objective: The aim of this prospective controlled study was to evaluate the impact of STN-DBS on balance disorders in PD patients in comparison with Best-Medical-Therapy (BMT) and Long-term-Post-Operative (POP) group. Methods: DBS-group consisted of 20 PD patients (8F, 12M) who underwent bilateral STN DBS. POP-group consisted of 14 post-DBS patients (6F, 8M) in median 30 months-time after surgery. Control group (BMT-group) consisted of 20 patients (11F, 9M) who did not undergo surgical intervention. UPDRS III scale and balance tests (Up And Go Test, Dual Task- Timed Up And Go Test, Tandem Walk Test) and posturography parameters were measured during 3 visits in 9 ± 2months periods (V1, V2, V3) 4 phases of treatment (BMT-ON/OFF, DBS-ON/OFF). Results: We have observed the slowdown of gait and postural instability progression in first 9 post-operative months followed by co-existent enhancement of balance disorders in next 9-months evaluation (p < 0.05) in balance tests (Up and Go, TWT) and in posturography examination parameters (p < 0.05). The effect was not observed neither in BMT-group nor POP-group (p > 0.05): these groups revealed constant progression of static and dynamic instability (p > 0.05). Conclusions: STN-DBS can have modulatory effect on static and dynamic instability in PD patients: it can temporarily improve balance disorders. mainly during first 9 post-operative months, but with possible following deterioration of the symptoms in next post-operative months.

Cytokines in the pathogenesis of hemophilic arthropathy.

Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia. Clinical and subclinical joint bleeding episodes gradually lead to irreversible changes manifesting themselves as pain, progressing ankylosis, marked limitation of the range of motion, muscle atrophy and osteoporosis commonly concomitant with joint deformity resulting from chronic proliferative synovitis and both cartilage and bone degeneration leading to the final functional impairment of the joint. In spite of numerous studies, the pathophysiology of HA has not been fully elucidated, especially as regards immunopathological mechanisms which are associated with the subclinical and early stage of the disease and to be more precise, with chronic joint inflammation. It needs to be emphasized that the pathophysiological processes occurring in a joint with HA are most probably highly mediated by interactions within the cytokine network and other inflammatory mediators present in the tissues of affected joint. Among numerous compounds participating in the induction of an inflammatory process in the pathogenesis of HA, cytokines seem to play a leading role. The most important group controlling the disease seems to be well known inflammatory cytokines, including IL-1ß, TNFα and IL-6. The second group with antagonistic effect is formed by anti-inflammatory cytokines such as IL-4 and IL-10. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of HA with respect to cellular and intracellular signaling pathways is still under investigation. This review, summarizes and discusses the current knowledge about cytokine network in the pathogenesis of HA, indicating possible molecular and cellular mechanisms that may provide potential new therapeutic directions.

Impact of STN-DBS on mood, drive, anhedonia and risk of psychiatric side-effects in the population of PD patients.

BACKGROUND: DBS is a surgical method of choice for various movement disorders, especially for Parkinson's disease (PD). Many publications showing improvement in motor symptoms and quality of life have been presented while there is little comprehensive research evaluation of the impact of DBS on mental state and psychiatric side-effects. OBJECT: The purpose of this study was to assess the impact of DBS on mood, drive, anhedonia and psychotic symptoms in the group of PD patients. METHODS: 60 patients with PD were treated with STN-DBS. Mental state and psychiatric side effects were assessed with the use of MADRS, HADRS, BDI, BPRS, YMS, SHAPS, CGI and PGI rating scales. Evaluation was performed five times in the period from the day before surgery to six months after implantation of the DBS. RESULTS: This study showed an improvement of mood, which has followed within a month after the start of stimulation and manifested in MADRS, HADRS, BDI scores reduction. The trend towards improvement was maintained over the following 6months. No manic episodes appeared, 2 cases of mild hypomania were observed. Psychotic symptoms occurred in 1 patient. Anhedonia reduction observed during the first 30days after initiating the stimulation persisted in the assessment six months after implantation of the DBS. CONCLUSIONS: The survey results confirm the effect of stimulation on mood, drive, ability to feel pleasure. Psychiatric side effects such as phase change were rare and mild, while psychotic symptoms that occurred in one patient ware manageable through medication. Further intensive research in this topic are required.

Mutational Analysis of Recurrent Meningioma Progressing From Atypical to Rhabdoid Subtype.

BACKGROUND: Rhabdoid meningioma is rare aggressive meningioma histological subtype that develops predominantly through progression from less malignant tumors. Owing to its low incidence, this tumor's biological background is unknown. The aim of this study was to profile somatic mutations in 4 meningioma samples from the same patient, derived previously from 4 subsequent tumor resections. CASE DESCRIPTION: A 58-year-old woman presented with recurrent meningioma progressing from atypical to rhabdoid subtype. Four tumor samples that represent a primary tumor (atypical GII) and 3 recurrent tumors that were subsequently removed (anaplastic GIII, rhabdoid GIII, and anaplastic/rhabdoid GIII) from this patient were subjected to mutational analysis of coding sequences of 952 tumor-related genes. Three mutations were identified in all tumor samples exhibiting a high allelic frequency: ARID1A frameshift deletion, NF2 in-frame deletion, and missense variant of SRSF2. The predicted inactivating effect of ARID1A deletion was confirmed by immunohistochemical staining of tumor sections in which a high proportion of cells lacked protein expression. Additional low-allelic-fraction mutations were observed in all tumor samples, likely representing "passenger," low-effect mutations that reflect a clonal selection of tumor cells through malignant progression of the meningioma. CONCLUSION: The mutation of ARID1A that encodes the subunit of the SWI/SNF complex represents the most likely driver of the tumor's malignant potential. It also may be involved in the acquisition of the rhabdoid phenotype, given that mutations in chromatin remodeling proteins are the hallmark of atypical teratoid/rhabdoid tumors.