Relationship between the Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Brain Tumors.

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play critical roles in regulating processes associated with malignant behavior. These endopeptidases selectively degrade components of the extracellular matrix (ECM), growth factors, and their receptors, contributing to cancer cell invasiveness and migratory characteristics by disrupting the basal membrane. However, the expression profile and role of various matrix metalloproteinases remain unclear, and only a few studies have focused on differences between diagnoses of brain tumors. Using quantitative real-time PCR analysis, we identified the expression pattern of ECM modulators (n = 10) in biopsies from glioblastoma (GBM; n = 20), astrocytoma (AST; n = 9), and meningioma (MNG; n = 19) patients. We found eight deregulated genes in the glioblastoma group compared to the benign meningioma group, with only MMP9 (FC = 2.55; p = 0.09) and TIMP4 (7.28; p < 0.0001) upregulated in an aggressive form. The most substantial positive change in fold regulation for all tumors was detected in matrix metalloproteinase 2 (MNG = 30.9, AST = 4.28, and GBM = 4.12). Notably, we observed an influence of TIMP1, demonstrating a positive correlation with MMP8, MMP9, and MMP10 in tumor samples. Subsequently, we examined the protein levels of the investigated MMPs (n = 7) and TIMPs (n = 3) via immunodetection. We confirmed elevated levels of MMPs and TIMPs in GBM patients compared to meningiomas and astrocytomas. Even when correlating glioblastomas versus astrocytomas, we showed a significantly increased level of MMP1, MMP3, MMP13, and TIMP1. The identified metalloproteases may play a key role in the process of gliomagenesis and may represent potential targets for personalized therapy. However, as we have not confirmed the relationship between mRNA expression and protein levels in individual samples, it is therefore natural that the regulation of metalloproteases will be subject to several factors.

Incidence and severity of dysphagia after anterior cervical discectomy and fusion with zero-profile spacer: prospective study with 3-years follow-up.

INTRODUCTION: Dysphagia after anterior cervical discectomy and fusion (ACDF) is a regular complication. The aim of this study was to identify risk factors for incidence and severity of dysphagia after ACDF with zero-profile spacer. METHODS: Incidence and severity of dysphagia was evaluated preoperatively and for time of three years after ACDF (regular outpatient check-ups) ‒ prospective study with 3-years follow-up. Severity of dysphagia was assessed subjectively using Bazaz‒Yoo dysphagia score. Influence of selected factors on the incidence and severity of postoperative dysphagia was evaluated. Following statistical methods were used: Fisher's exact test, unpaired Student's t-test, one-way ANOVA and Spearman's correlation coefficient. Level of significance was defined as p ˂ 0.05. Correlations between paired parameters were evaluated according to Spearman's correlation. RESULTS: Our study included 133 patients who underwent one-, two- or three-level ACDF with zero-profile spacer in years 2013‒2018. Myelopathy and GERD had significant impact on incidence and severity of pre-existing dysphagia. Risk factors for incidence of dysphagia after ACDF were number of treated segments, myelopathy, pre-existing dysphagia and surgery of C4/5 segment. Age of patients, duration of surgery and pre-existing dysphagia correlated positively very weakly to weakly with severity of dysphagia after ACDF. Number of treated segments, myelopathy, GERD and surgery of the C4/5 segment were risk factors for greater severity of postoperative dysphagia. CONCLUSION: Risk factors for incidence and severity of pre-existing dysphagia were myelopathy and GERD. Risk factors for dysphagia incidence after ACDF were number of treated segments, pre-existing dysphagia, myelopathy and surgery of C4/5 segment (Tab. 6, Fig. 1, Ref. 30).

Safety and efficacy of simple training protocol in patients after mild traumatic brain injury.

AIMS: Mild Traumatic Brain Injury (mTBI) is the most common type of craniocerebral injury. Proper management appears to be a key factor in preventing post-concussion syndrome. The aim of this prospective study was to evaluate the effect and safety of selected training protocol in patients after mTBI. METHODS: This was a prospective study that included 25 patients with mTBI and 25 matched healthy controls. Assessments were performed in two sessions and included a post-concussion symptoms questionnaire, battery of neurocognitive tests, and magnetic resonance with tractography. Participants were divided into two groups: a passive subgroup with no specific recommendations and an active subgroup with simple physical and cognitive training. RESULTS: The training program with slightly higher initial physical and cognitive loads was well tolerated and was harmless according to the noninferiority test. The tractography showed overall temporal posttraumatic changes in the brain. The predictive model was able to distinguish between patients and controls in the first (AUC=0.807) and second (AUC=0.652) sessions. In general, tractography had an overall predictive dominance of measures. CONCLUSION: The results from our study objectively point to the safety of our chosen training protocol, simultaneously with the signs of slight benefits in specific cognitive domains. The study also showed the capability of machine learning and predictive models in mTBI patient recognition.

Non-acute subdural hematoma: estimation of recurrence using CT-volumetric measurements.

OBJECTIVES: To identify risk factors for unilateral non-acute subdural hematomas NASH recurrence, as well as to perform volumetric quantitative analysis of hematoma, postoperative pneumocephalus and extent of hematoma evacuation. BACKGROUND: Recurrence of NASH increases morbidity and mortality and has negative socio-economic consequences. Its accurate prediction could improve patient specific care. METHODS: Records of 102 patients after unilateral NASH evacuation during the period from 2014 to 2020 with a 4-month follow-up were evaluated. Impacts of preoperative clinical signs and factors on the incidence of NASH recurrence were evaluated, namely those of age, gender, timing of surgery, hematoma side, surgical technique (number of burr holes, trepanation versus craniotomy), duration of drainage, antithrombotic agents, morphological type of hematoma, preoperative hematoma volume (PHV), post-evacuation hematoma cavity volume (PHCV), pneumocephalus volume (PCV) and extent of hematoma evacuation (EHE) on the incidence of NASH recurrence were evaluated. RESULTS: An overall recurrence rate of 13.7 % was observed. Preoperative hematoma volume, postoperative hematoma cavity volume and postoperative pneumocephalus volume had a significant impact on incidence of recurrence. CONCLUSIONS: Pre- and postoperative volumetric evaluations, of patients with NASH, particularly the measurements of preoperative hematoma volume and postoperative volume of hematoma cavity and pneumocephalus have a potential to improve the prediction of clinically significant recurrence (Tab. 6, Fig. 3, Ref. 51). Text in PDF www.elis.sk Keywords: subdural hematoma, recurrence, pneumocephalus, risk factors.

Proton magnetic resonance spectroscopy changes in the brainstem in patients after mild traumatic brain injury with loss of consciousness.

INTRODUCTION: Loss of consciousness (LOC) is used as a diagnostic feature of mild traumatic brain injury (MTBI). However, only 10% of concussions result in LOC. There are only a limited number of in-vivo studies dealing with unconsciousness and structural and functional integrity of the brainstem in patients with MTBI. The aim of our pilot study was to assess the sensitivity of proton magnetic resonance spectroscopy (1H-MRS) to detect metabolic changes in the brainstem in patients after MTBI with unconscioussness. METHODS: Twenty-four patients (12 with LOC, and 12 without LOC) within 3 days of MTBI and 19 healthy controls were examined. All subjects underwent single-voxel 1H-MRS examination of the upper brainstem. Spectra were evaluated using LCModel software. Ratios of total N-acetylaspartate (tNAA), total choline-containing compounds (tCho) and glutamate plus glutamine (Glx) to total creatine (tCre) were used for calculations. RESULTS: We found a significant decrease in tNAA/tCre and tCho/tCre ratios in the patient group with LOC when compared with the control group of healthy volunteers (P=0.002 and P=0.041, respectively), and a significant decrease in the tNAA/tCre ratio in the LOC group when compared with patients without LOC (P=0.04). Other metabolite ratios in the brainstem did not show any significant group differences. CONCLUSION: Our findings indicate that decrease of tNAA/tCre ratio in the upper brainstem using single-voxel 1H-MRS may provide a potential biomarker for MTBI associated with LOC.

Random Forest-Based Prediction of Outcome and Mortality in Patients with Traumatic Brain Injury Undergoing Primary Decompressive Craniectomy.

BACKGROUND: Various prognostic models are used to predict mortality and functional outcome in patients after traumatic brain injury with a trend to incorporate machine learning protocols. None of these models is focused exactly on the subgroup of patients indicated for decompressive craniectomy. Evidence regarding efficiency of this surgery is still incomplete, especially in patients undergoing primary decompressive craniectomy with evacuation of traumatic mass lesions. METHODS: In a prospective study with a 6-month follow-up period, we assessed postoperative outcome and mortality of 40 patients who underwent primary decompressive craniectomy for traumatic brain injuries during 2018-2019. The results were analyzed in relation to a wide spectrum of preoperatively available demographic, clinical, radiographic, and laboratory data. Random forest algorithms were trained for prediction of both mortality and unfavorable outcome, with their accuracy quantified by area under the receiver operating curves (AUCs) for out-of-bag samples. RESULTS: At the end of the follow-up period, we observed mortality of 57.5%. Favorable outcome (Glasgow Outcome Scale [GOS] score 4-5) was achieved by 30% of our patients. Random forest-based prediction models constructed for 6-month mortality and outcome reached a moderate predictive ability, with AUC = 0.811 and AUC = 0.873, respectively. Random forest models trained on handpicked variables showed slightly decreased AUC = 0.787 for 6-month mortality and AUC = 0.846 for 6-month outcome and increased out-of-bag error rates. CONCLUSIONS: Random forest algorithms show promising results in prediction of postoperative outcome and mortality in patients undergoing primary decompressive craniectomy. The best performance was achieved by Classification Random forest for 6-month outcome.

Incidence and risk factors of early postoperative complications in patients after decompressive craniectomy: a 5-year experience.

PURPOSE: Decompressive craniectomy is an effective measure to reduce a pathologically elevated intracranial pressure. Patients' survival and life quality following this surgery have been a subject of several studies and significantly differ according to the primary diagnosis. Since this operation is often associated with a wide spectrum of possibly serious complications, we aimed to describe their incidence and possible associated risk factors. METHODS: We evaluated 118 patients who underwent decompressive craniectomy at our clinic during years 2013-2017. The indications included traumatic brain injuries, ischaemic or haemorrhagic strokes and postoperative complications of planned neurosurgical procedures. Subsequently, we assessed the incidence of early postoperative complications (occurring during the first 3 postoperative weeks). The results were statistically analysed with relation to a wide selection of possible risk factors. RESULTS: At least one early surgical postoperative complication occurred in 87 (73.73%) patients, the most frequent being a development of an extraaxial fluid collection in 41 (34.75%) patients. We were able to identify risk factors linked with extraaxial fluid collections, subcutaneous and extradural haematomas, postoperative seizures and meningitis. An overall need for reoperation was 13.56%. Neither the duration of the surgery nor the qualification of the operating surgeon had any effect on the complications' occurrence. CONCLUSIONS: Decompressive craniectomy is associated with numerous early postoperative complications with a various degree of severity. Most cases of complications can, however, be managed in a conservative way. The risk factors linked with postoperative complications should be taken into account during the indication process in each individual patient.

Change in sagittal profile after implantation of anchored interbody cage in the surgical procedure for degenerative cervical spine disease.

BACKGROUND: The aim of this study was to verify the relationship between changes in the segmental sagittal profile (SSP) and changes in the global sagittal profile (GSP) after anterior cervical discectomy with anchored cage implantation (ACDF). STUDY DESIGN: Prospective study with 2-year follow-up. METHODS: This study includes 104 patients after 1-level or 2-level ACDF operated between the May 2013 and March 2016. SSP was evaluated by Cobb angle measurement of operated motion segment (CobbS) and GSP was evaluated by Cobb angle measurement in C2-C7 segments (CobbG). Both SSP and GSP were measured pre- and postoperatively within a 24 months follow-up period. The influence of factors such as age, gender, number of treated segments and osteoporosis was evaluated using t-tests. The correlation between SSP and GSP changes was assessed by Pearson's correlation coefficient. RESULTS: In the early postoperative period after 1-level ACDF, there was a significantly greater increase in CobbS compared to that of the 2-level ACDF (P=0.0149). Male patients experienced a significant decrease of CobbG during the first 6 months after surgery as well as patients with osteoporosis within 12 months after ACDF. After ACDF the SSP change weakly correlated with the GSP change. CONCLUSION: SSP change after 1- or 2-level ACDF correlates mostly weakly with GSP change. Male gender and osteoporosis were identified as risk factors for global lordotisation following ACDF.

Chronic calcified subdural hematoma - case report of a rare diagnosis.

INTRODUCTION: Chronic calcified/ossified subdural hematoma is a rare diagnosis. The incidence of chronic calcified subdural hematoma is 0.3-2.7% of all chronic subdural hematomas. Surgical treatment is indicated in most cases, but there is still some controversy. MATERIALS AND METHODS: We present a case report of 81-year-old woman with calcified chronic subdural hematoma. Patient underwent an osteoplastic left craniotomy, evacuation of chronic subdural mass with careful dissection andsuccessful removal of inner and outer membrane. Postoperative CT scan showed removal of subdural hematoma, decrease of left shift of median line and good brain re-expansion. Postoperative period was without any serious complications. RESULTS: Subdural hematoma was successfully removed, resulting in a good recovery with complete resolution of patients symptoms. From our experience, we highly recommend surgical treatment in cases of chronic symptomatic calcified subdural hematomas.

Metabolomic profiling of blood plasma in patients with primary brain tumours: Basal plasma metabolites correlated with tumour grade and plasma biomarker analysis predicts feasibility of the successful statistical discrimination from healthy subjects - a preliminary study.

The brain tumours represent a complex tissue that has its own characteristic metabolic features and is interfaced with the whole organism. We investigated changes in basal blood plasma metabolites in the presence of primary brain tumour, their correlation with tumour grade, as well as the feasibility of statistical discrimination based on plasma metabolites. Together 60 plasma samples from patients with clinically defined glioblastoma, meningioma, oligodendrioglioma, astrocytoma, and non-specific glial tumour and plasma samples from 28 healthy volunteers without any cancer history were measured by NMR spectroscopy. In blood plasma of primary brain tumour patients, we found significantly increased levels of glycolytic metabolites glucose and pyruvate, and significantly decreased level of glutamine and also metabolites participating in tricarboxylic acid (TCA) cycle, citrate and succinate, when compared with controls. Further, plasma metabolites levels: tyrosine, phenylalanine, glucose, creatine and creatinine correlated significantly with tumour grade. In general, observed changes are parallel to the biochemistry expected for tumourous tissue and metabolic changes in plasma seem to follow the similar rules in all primary brain tumours, with very subtle variations among tumour types. Only two plasma metabolites tyrosine and phenylalanine were increased exclusively in blood plasma of patients with glioblastoma. Based on metabolite levels, an excellent discrimination between plasma from patient's tumours and controls was attainable. The metabolites creatine, pyruvate, glucose, formate, creatinine and citrate were of the highest discriminatory power.

Apoptosis-related gene expression in tumor tissue samples obtained from patients diagnosed with glioblastoma multiforme.

Tumors of the brain are very diverse in their biological behavior and are therefore considered a major issue in modern medicine. The heterogeneity of gliomas, their clinical presentation and their responses to treatment makes this type of tumor a challenging area of research. Glioblastoma multiforme (GBM) is the most common, and biologically the most aggressive, primary brain tumor in adults. The standard treatment for patients with newly diagnosed GBM consists of surgical resection, radiotherapy and chemotherapy. However, resistance to chemotherapy is a major obstacle to successful treatment. The aim of this study was to examine the changes occurring in the expression levels of apoptosis-associated genes in tumor tissue biopsy samples from 7 patients diagnosed with GBM and compare our results with a human astrocyte cell line (used as a reference) cultured under basic conditions. For molecular analysis, we used a commercial pre-designed microfluidic array to quantify the expression of 93 apoptosis-associated human genes. Significant changes in the expression levels of genes were observed in the tumor tissue samples obtained from patients with GBM. We determined significant changes in gene expression (n=32) in all apoptotic signaling pathways (BCl-2, TNF, Caspases, NF-κB, IAP and CARD), while the most pronounced deregulation (>5-fold) were observed in 46.9% events. The results of this study underline the importance of apoptosis in heterogenous tumor tissue. The identification of the apoptotic gene panel in tissue biopsies from patients with GBM may help improve the effectiveness of treatments for GBM in clinical practice and may broaden our understanding of brain tumor cell metabolism. Recognizing the changes in the expression of pro-apoptotic and anti-apoptotic genes may aid in the development of novel treatment strategies founded on a molecular basis.

Most frequent molecular and immunohistochemical markers present in selected types of brain tumors.

Tumors of brain tissue and meninges create a heterogeneous group with various biological behavior, therapy management and differing prognosis. Some of these do not require treatment, some can be cured by surgery and some are rapidly fatal despite treatment. Despite huge progress in tumor research, innovations in diagnostic tools and therapy, prognosis remains, in case of malignant tumor types, very serious. There has been an increased understanding of molecular abnormalities occurring in primary brain tumors. Genome-wide analyses of tumors have improved the knowledge in tumor biology. The aim of the research is to explain the oncogenesis features thus leading to the use of new therapeutic modalities in order to prolong survival rate of patients and at the same time providing satisfactory life quality. This article offers a short review of the basic genetic alterations present with some histological types of brain tumors.

Changes in heart rate variability in a premature infant with hydrocephalus.

Objective To define changes of heart rate variability in premature infant with hydrocephalus before and after drainage procedure. Study Design The authors report a case of a premature infant with hydrocephalus with analysis of heart rate variability before and after drainage procedure. Three subsequent recordings of the electrocardiography and heart rate variability were done: the first at the age of 22 days before insertion of ventriculoperitoneal shunt, the second at the age of 36 days with functional shunt, the third at the age of 71 days (before discharge). Results Before drainage operation, there was reduced heart rate variability in time and spectral domains, and sympathetic activity was dominant. After surgery, an increase in heart rate variability parameters was found, particularly with spectral analysis. The ratio of low-frequency/high-frequency band and relative power of the low-frequency band decreased, reflecting enhanced parasympathetic activity. Conclusion Results of the heart rate variability analysis in a preterm infant with hydrocephalus before and after drainage procedure showed marked improvement in chronotropic cardiac regulation. Evaluation of heart rate variability in premature infants with hydrocephalus with increased intracranial pressure can be an additional method for monitoring of cardiac dysregulation and improvement of the cardiovascular control after successful drainage procedure.

Measurement of the blood flow velocity in the pericallosal artery of children with hydrocephalus by transcranial Doppler ultrasonography--preliminary results.

AIM: The goal of this study was to evaluate selected parameters of the Doppler curve of the pericallosal artery at children with hydrocephalus. METHODS: 12 patients with hydrocephalus were divided into two groups. Group 1 comprised children needing cerebrospinal fluid drainage, and group 2 comprised children without any indication for drainage or with an already inserted well-functioning drainage system. Dilatation of the cerebral ventricles was determined by transcranial ultrasonography. Following parameters of a blood flow of the pericallosal branch of the anterior cerebral artery: peak systolic blood flow velocity (PSFV), end-diastolic blood flow velocity (EDFV) and resistive index (RI) were observed by transcranial Doppler ultrasonography. Parameters of The Doppler curve were measured without pressure (baseline parameters) and during compression of the anterior fontanelle (pressure provocation test). RESULTS: Group 1: baseline parameters: PSFV 68.9 +/- 13.52 cm/s, EDFV 18.26 +/- 10.39 cm/s, RI 0.76 +/- 0.12; parameters during pressure provocation test: PSFV 66.92 +/- 19.75 cm/s, EDFV 10.88 +/- 11.18 cm/s, RI 0.86 +/- 0.14. Group 2: baseline parameters: PSFV 59.95 +/- 19.38 cm/s, EDFV 20.65 +/- 8 cm/s, RI 0.65 +/- 0.04; parameters during the pressure provocation test: PSFV 57.14 +/- 18.91 cm/s, EDFV 17.7 +/- 8.3 cm/s, RI 0.68 +/- 0.05. CONCLUSION: The results show increased baseline and postcompressive values of RI of pericallosal artery in infants with hydrocephalus before drainage procedure and normal values of RI at children without the need for cerebrospinal fluid drainage or with a well-functioning drainage system.