Hypotensive Effect of Electric Stimulation of Caudal Ventrolateral Medulla in Freely Moving Rats.

Background and Objectives: An altered sympathetic function is established in primary arterial hypertension (PAH) development. Therefore, PAH could be targeted by applying an electric current to the medulla where reflex centers for blood pressure control reside. This study aims to evaluate the electric caudal ventrolateral medulla (CVLM) stimulation effect on blood pressure and animal survivability in a freely moving rat model. Materials and Methods: A total of 20 Wistar rats aged 12-16 weeks were randomly assigned to either: the experimental group (n = 10; electrode tip implanted in CVLM region) or the control group (n = 10; tip implanted 4 mm above the CVLM in the cerebellum). After a period of recovery (4 days), an experimental phase ensued, divided into an "OFF stimulation" period (5-7 days post-surgery) and an "ON stimulation" period (8-14 days post-surgery). Results: Three animals (15%, one in the control, two in the experimental group) dropped out due to postoperative complications. Arterial pressure in the experimental group rats during the "OFF stimulation" period decreased by 8.23 mm Hg (p = 0.001) and heart rate by 26.93 beats/min (p = 0.008). Conclusions: From a physiological perspective, CVLM could be an effective deep brain stimulation (DBS) target for drug-resistant hypertension: able to influence the baroreflex arc directly, having no known direct integrative or neuroendocrine function. Targeting the baroreflex regulatory center, but not its sensory or effector parts, could lead to a more predictable effect and stability of the control system. Although targeting neural centers in the medullary region is considered dangerous and prone to complications, it could open a new vista for deep brain stimulation therapy. A possible change in electrode design would be required to apply CVLM DBS in clinical trials in the future.

Association Between the Cerebral Autoregulation Index (Pressure Reactivity), Patient's Clinical Outcome, and Quality of ABP(t) and ICP(t) Signals for CA Monitoring.

Background and Objectives: The aim of this study was to explore the association between the cerebral autoregulation (CA) index, the pressure reactivity index (PRx), the patient's clinical outcome, and the quality of arterial blood pressure (ABP(t)) and intracranial blood pressure (ICP(t)) signals by comparing two filtering methods to derive the PRx. Materials and Methods: Data from 60 traumatic brain injury (TBI) patients were collected. Moving averaging and FIR (Finite Impulse Response) filtering were performed on the ABP(t) and ICP(t) signals, and the PRx was estimated from both filtered datasets. Sensitivity, specificity, and receiver-operating characteristic (ROC) curves with the area under the curves (AUCs) were determined using patient outcomes as a reference. The outcome chosen for comparison among the two filtering methods were mortality and survival. Results: The FIR filtering approach, compared with clinical outcome, had a sensitivity of 70%, a specificity of 81%, and a level of significance p = 0.001 with an area under the curve (AUC) of 0.78. The moving average filtering method compared with the clinical outcome had a sensitivity of 58%, a specificity of 72%, and a level of significance p = 0.054, with an area under the curve (AUC) of 0.66. Conclusions: The FIR (optimal) filtering approach was found to be more sensitive for discriminating between two clinical outcomes, namely intact (survival) and impaired (death) cerebral autoregulation for TBI treatment decision making.

Non-invasive Cerebrovascular Autoregulation Assessment Using the Volumetric Reactivity Index: Prospective Study.

BACKGROUND: This prospective study of an innovative non-invasive ultrasonic cerebrovascular autoregulation (CA) monitoring method is based on real-time measurements of intracranial blood volume (IBV) reactions following changes in arterial blood pressure. In this study, we aimed to determine the clinical applicability of a non-invasive CA monitoring method by performing a prospective comparative clinical study of simultaneous invasive and non-invasive CA monitoring on intensive care patients. METHODS: CA was monitored in 61 patients with severe traumatic brain injuries invasively by calculating the pressure reactivity index (PRx) and non-invasively by calculating the volumetric reactivity index (VRx) simultaneously. The PRx was calculated as a moving correlation coefficient between intracranial pressure and arterial blood pressure slow waves. The VRx was calculated as a moving correlation coefficient between arterial blood pressure and non-invasively-measured IBV slow waves. RESULTS: A linear regression between VRx and PRx averaged per patients' monitoring session showed a significant correlation (r = 0.843, p < 0.001; 95% confidence interval 0.751 - 0.903). The standard deviation of the difference between VRx and PRx was 0.192; bias was - 0.065. CONCLUSIONS: This prospective clinical study of the non-invasive ultrasonic volumetric reactivity index VRx monitoring, based on ultrasonic time-of-flight measurements of IBV dynamics, showed significant coincidence of non-invasive VRx index with invasive PRx index. The ultrasonic time-of-flight method reflects blood volume changes inside the acoustic path, which crosses both hemispheres of the brain. This method does not reflect locally and invasively-recorded intracranial pressure slow waves, but the autoregulatory reactions of both hemispheres of the brain. Therefore, VRx can be used as a non-invasive cerebrovascular autoregulation index in the same way as PRx and can also provide information about the CA status encompassing all intracranial hemodynamics.

Association between vertebral artery hypoplasia and posterior circulation stroke.

BACKGROUND: The clinical significance of vertebral artery (VA) hypoplasia is under discussion. The aim of this retrospective study is to evaluate a hypothesis of a possible causal link between VA hypoplasia (VAH) and the incidence of posterior circulation stroke (PCS) or TIA depending on the degree of VAH and vascular risk factors. METHODS: A total of 367 symptomatic (PCS or TIA) and 742 asymptomatic subjects, were selected to participate in the study. The extracranial arteries were examined by ultrasound. VAH was defined as VA diameter in entire course <3 mm, although different degrees of VAH were examined. All the symptomatic patients underwent MRI or CT and MRA or CTA. The study assessed all the subjects in terms of their age, gender, co-risk factors (hypertension, hyperlipidemia, diabetes mellitus, peripheral arterial diseases, atrial fibrillation, myocardial infarction), as well as height of 180 healthy volunteers. RESULTS: VAH, regardless of the degree of severity, was more frequent in patients with non-cardioembolic PCS or TIA rather than in asymptomatic patients. The increasing degree of hypoplasia in patients under 65 years of age was a predictor of PCS/TIA, OR = 1.8, 95% CI: 1.3-2.5; p < 0.001. In subjects older than 65 years of age, this association failed. Only in patients aged under 50, VAH was significantly more frequent in the TIA group rather than in the PCS group (68.2% and 50%, respectively; p = 0.047). The optimal VA diameter cutoff point separating PCS/TIA and asymptomatic group was 2.7 mm. This value may vary in different populations, because VA diameter showed a significant dependence on sex as well as anthropometric parameters (height). With the increasing degree of VAH, the likelihood of the occurrence of the distal VA part stenosis/occlusion was growing (OR = 1.6, 95% CI: 1.2-2.1; p = 0.002). The distal VA stenosis/occlusion was likely to occur where the VA diameter was <2.2 mm. CONCLUSIONS: The impact of the VAH on PCS/TIA and its pathogenetic mechanism was significantly influenced by age. The cutoff point of VA diameter, affecting the occurrence of PCS in different populations may vary because VA diameter depends on gender and anthropometric parameters (especially height).

Optimal differentiation of high- and low-grade glioma and metastasis: a meta-analysis of perfusion, diffusion, and spectroscopy metrics.

INTRODUCTION: To perform a meta-analysis of advanced magnetic resonance imaging (MRI) metrics, including relative cerebral blood volume (rCBV), normalized apparent diffusion coefficient (nADC), and spectroscopy ratios choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA), for the differentiation of high- and low-grade gliomas (HGG, LGG) and metastases (MTS). METHODS: For systematic review, 83 articles (dated 2000-2013) were selected from the NCBI database. Twenty-four, twenty-two, and eight articles were included respectively for spectroscopy, rCBV, and nADC meta-analysis. In the meta-analysis, we calculated overall means for rCBV, nADC, Cho/Cr (short TE-from 20 to 35 ms, medium-from 135 to 144 ms), and Cho/NAA for the HGG, LGG, and MTS groups. We used random effects model to obtain weighted averages and select thresholds. RESULTS: Overall means (with 95% CI) for rCBV, nADC, Cho/Cr (short and medium echo time, TE), and Cho/NAA were: for HGG 5.47 (4.78-6.15), 1.38 (1.16-1.60), 2.40 (1.67-3.13), 3.27 (2.78-3.77), and 4.71 (3.24-6.19); for LGG 2.00 (1.71-2.28), 1.61 (1.36-1.87), 1.46 (1.20-1.72), 1.71 (1.49-1.93), and 2.36 (1.50-3.23); for MTS 5.06 (3.85-6.27), 1.35 (1.06-1.64), 1.89 (1.72-2.06), 3.14 (1.57-4.72), (Cho/NAA was not available). LGG had significantly lower rCBV, Cho/Cr, and Cho/NAA values than HGG or MTS. No significant differences were found for nADC. CONCLUSIONS: Best differentiation between HGG and LGG is obtained from rCBV, Cho/Cr, and Cho/NAA metrics. MTS could not be reliably distinguished from HGG by the methods investigated.

Association between the outcome of traumatic brain injury patients and cerebrovascular autoregulation, cerebral perfusion pressure, age, and injury grades.

BACKGROUND AND OBJECTIVE: The aim of this study was to explore the association of cerebrovascular autoregulation (CA) and optimal cerebral perfusion pressure (CPP) managing conditions with the outcome of traumatic brain injury (TBI) patients including additional information about the patients' age and grade of diffuse axonal injury (DAI). MATERIALS AND METHODS: The CA monitoring of 28 TBI patients was performed by using ICM+ software (Cambridge, UK). The CA status estimating pressure reactivity indexes (PRx) and CPP data were processed in order to obtain information on the patient-specific treatment conditions by calculating the optimal CPP. RESULTS: There was a negative correlation between the Glasgow outcome scale (GOS) score and PRx (r=-0.448 at hospital discharge and r=-0.402 after 6 months). The estimated threshold value PRx of >0.24 was associated with mortality. The correlation coefficients between the GOS score and the difference CPP-optimal CPP were 0.549 at hospital discharge and 0.484 after 6 months. The threshold value of CPP declination from ΔCPPopt per -6mmHg was associated with mortality. Poorer outcome was predicted for elderly TBI patients (aged >47 years) and patients having a DAI grade of 3. CONCLUSIONS: The association of the GOS score with CPP, CA impairment conditions, age and diffuse axonal injury (DAI) grade showed that the outcomes of TBI patients were associated with patient-specific CPP management and better outcomes were obtained for younger patients, for patients having lower DAI grade and for patients whose CPP was kept within the range from the optimal CPP to the optimal CPP+10mmHg.

Simulated Injuries of the Sheep Ossicular Chain: Correlations With Their Radiological Images.

Hypothesis We hypothesized that a sheep temporal bone would be a suitable model to study correlations between simulated middle ear injuries and their radiological appearances. Simulated ossicular chain injuries correlate well with their radiological images, and post-processing techniques provide optimal visualization of the sheep ossicles. Background The subtle ossicular trauma may be difficult to assess due to the small size of the structures. The precise radiological and clinical correlations of the ossicular injuries are not well documented. Methods The most common traumatic ossicular chain injuries were systematically simulated in the sheep temporal bone model. The images of the temporal bones were obtained with a high-resolution computed tomography scanner. The values of the dislocations were measured from the obtained images as well as in the temporal bones using calipers. Two observers independently evaluated the fine structures of the auditory ossicles using oblique multiplanar reconstructions (MPRs) and maximum intensity projections (MIPs). All segments of the facial nerve were also visualized. Results Optimal visualization planes of the sheep's middle ear joints have been obtained. The coincidence of simulated ossicular injuries in the specimens and MIPs was 40%. All structures of the ossicular chain were clearly distinguished except for the stapes footplate. Evaluation of the traumatic changes of the incudostapedial joint was challenging. Conclusions The sheep temporal bone is a suitable model for studying the correlations between pathological alterations in the ossicular chain and their radiological appearances. The post-processing MIP technique provides a more accurate and easier diagnosis of traumatic ossicular chain injuries than MPRs alone.

Impaired cerebral autoregulation detected in early prevasospasm period is associated with unfavorable outcome after spontaneous subarachnoid hemorrhage: an observational prospective pilot study.

BACKGROUND: Subarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes. METHODS: The pilot observational study included 29 SAH patients whose CA status was estimated 2-3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2-3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device. RESULTS: Statistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039). CONCLUSIONS: A relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 - Retrospectively registered, https://www. CLINICALTRIALS: gov/study/NCT06028906 .

Plasma of COVID-19 Patients Does Not Alter Electrical Resistance of Human Endothelial Blood-Brain Barrier In Vitro.

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study, we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon γ-induced protein 10 kDa, hepatocyte growth factor, and interleukin-18 in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not affect BBB paracellular pathway directly and suggest that pathological remodeling (if any) of BBB during COVID-19 may occur through indirect or yet unknown mechanisms.

Cerebrospinal fluid volume as an early radiological factor for clinical course prediction after aneurysmal subarachnoid hemorrhage. A pilot study.

BACKGROUND: The pathological mechanisms following aneurysmal subarachnoid hemorrhage (SAH) are poorly understood. Limited clinical evidence exists on the association between cerebrospinal fluid (CSF) volume and the risk of delayed cerebral ischemia (DCI) or cerebral vasospasm (CV). In this study, we raised the hypothesis that the amount of CSF or its ratio to hemorrhage blood volume, as determined from non-contrast Computed Tomography (NCCT) images taken on admission, could be a significant predictor for CV and DCI. METHODS: The pilot study included a retrospective analysis of NCCT scans of 49 SAH patients taken shortly after an aneurysm rupture (33 males, 16 females, mean age 56.4 ± 15 years). The SynthStrip and Slicer3D software tools were used to extract radiological factors - CSF, brain, and hemorrhage volumes from the NCCT images. The "pure" CSF volume (VCSF) was estimated in the range of [-15, 15] Hounsfield units (HU). RESULTS: VCSF was negatively associated with the risk of CV occurrence (p = 0.0049) and DCI (p = 0.0069), but was not associated with patients' outcomes. The hemorrhage volume (VSAH) was positively associated with an unfavorable outcome (p = 0.0032) but was not associated with CV/DCI. The ratio VSAH/VCSF was positively associated with, both, DCI (p = 0.031) and unfavorable outcome (p = 0.002). The CSF volume normalized by the brain volume showed the highest characteristics for DCI prediction (AUC = 0.791, sensitivity = 0.80, specificity = 0.812) and CV prediction (AUC = 0.769, sensitivity = 0.812, specificity = 0.70). CONCLUSION: It was demonstrated that "pure" CSF volume retrieved from the initial NCCT images of SAH patients (including CV, Non-CV, DCI, Non-DCI groups) is a more significant predictor of DCI and CV compared to other routinely used radiological biomarkers. VCSF could be used to predict clinical course as well as to personalize the management of SAH patients. Larger multicenter clinical trials should be performed to test the added value of the proposed methodology.

Remotely Programmable Deep Brain Stimulator Combined with an Invasive Blood Pressure Monitoring System for a Non-Tethered Rat Model in Hypertension Research.

The control circuits of blood pressure have a strong neural regulatory element important in the pathogenesis of essential drug-resistant hypertension. Targeting lower medullary neural control mechanisms of blood pressure by electrical stimulation could be beneficial, and therefore, a novel device is needed. This paper presents a remotely programmable deep brain stimulator with an invasive continuous blood pressure monitoring system in a non-tethered rat model. The device is designed for lower medullary deep brain stimulation research with minimal interference to a daily animal routine. Electrodes were implanted in the caudal ventrolateral medulla. Animal survivability, catheter patency rates, and device data drift were evaluated. Eight out of ten rats survived the surgery and testing period with no or mild temporary neurological compromise. The study revealed that carotid catheters filled with heparinized glycerol ensure better catheter patency rates and blood pressure transduction. There was no significant drift in the device's pressure sensitivity during the experiment. To our knowledge, this is the first experimental study to show considerable animal survival after lower medullary implantation. Combining the ability to measure and monitor invasive blood pressure with a closed-loop brain pulse generator in a single device could be of potential value in future hemodynamic animal research.

Anatomical Variations of Superior Sagittal Sinus and Tributary Bridging Veins: A Cadaveric Study.

Background and objective Injuries to the parasagittal cerebrovenous structures may lead to devastating complications. Being aware of the inherent anatomical heterogeneity in the region might lower the rate of undesirable outcomes. In this study, our goal was to characterize the superior sagittal sinus (SSS) positioning in relation to the midline and depict tributary bridging veins (BVs) distribution over the lateral surface of the cerebral hemispheres. Methods We performed anatomical dissections of the brain in 10 cadaveric specimens (five females and five males; median age: 52 years, range: 44-74 years). Measurements (in mm) of the SSS width and deviation of its lateral margin from the midline were obtained along the entire length of the structure at six craniometric points [at mid-distance between Nasion and Bregma (½ N-B); at Bregma (B); in the middle of the Bregma-Lambda segment (½ B-L); at Lambda (L); halfway between Lambda and Inion (½ L-I); and at Inion (I)]. The count, diameter, and lateral insertion points of the draining BVs were also documented in three segments [Nasion-Bregma (N-B), Bregma-Lambda (B-L), and Lambda-Inion (L-I)]. Results The width of the SSS increased progressively along the direction of the blood flow (p<0.01). There was an SSS lateral deviation bias to the right, but the comparison failed to reach the significance level (p=0.12). The maximal lateralization of the SSS in the pre-Lambdal interval was 13.1 mm on the right side and 11.7 mm on the left side. These values increased up to 19.8 mm and 15.1 mm in the torcular area on the right and left sides, respectively. A total of 191 BVs were identified (a mean of 19.1 ± 2.5 per individual). The L-I segment showed a lower number of BVs as compared to its N-B and B-L counterparts (mean: 0.9 ± 0.6 vs. 8 ± 1.8 and 10.2 ± 2, respectively, p<0.01). Along the entire span of the SSS, the average diameter of the BVs was larger on the right side (mean: 1.4 ± 0.9 mm vs. 1.1 ± 0.8 mm on the left, p<0.01). The average lateralization of BVs dural entry points was lower on the left side in the B-L segment (mean: 5.6 ± 6.4 mm vs. 8.8 ± 6.7 mm on the right, p<0.01). There was a statistically significant trend of decreasing BVs lateralization with each consecutive SSS segment (mean: 10.9 ± 7.4 mm in the N-B segment, 7.3 ± 6.7 mm in B-L, and 1.6 ± 1.2 mm in L-I, p<0.01). The maximal lateral deviation of BVs insertion points was 33.6 mm in N-B, 30 mm in B-L, and 4.1 mm in L-I portions of the SSS. Conclusions In most cases, the SSS deviated laterally from the midline, up to 13 mm in the pre-Lambdal segment and up to 20 mm in the torcular area. Right-sided BVs were of larger average diameters. The lateral insertion points of BVs decreased along the rostrocaudal span of the SSS.

Plexiform neurofibroma of the cauda equina with follow-up of 10 years: A case report.

BACKGROUND: Plexiform neurofibromas are extremely rarely found in the region of cauda equina and can pose a significant challenge in the diagnostic and management sense. To our knowledge, only 7 cases of cauda equina neurofibromatosis (CENF) have been reported up-to-date. CASE SUMMARY: We describe a case of a 55-year-old man with a 10 years history of progressive lower extremities weakness and bladder dysfunction. Before presenting, patient was misdiagnosed with idiopathic polyneuropathy. Lumbar spine MRI revealed a tortuous tumorous masses in the cauda equina region, extending through the Th12-L4 vertebrae. The patient underwent Th12-L3 Laminectomy with duraplasty. During the operation, the most enlarged electroneurographically silent nerve root was resected, anticipating inadequate decompression if nerve root was spared. The patient's neurological condition improved post-operatively, but urinary retention became the major complaint. We provide a follow-up period of 10 years. During this time, the patient's condition progressively worsened despite extensive decompression. The consequent MRI scans showed progressive enlargement of cauda equina roots and increasing lumbar stenosis, predominantly affecting L3-L4 segment. During the follow-up 8 years after the operation, the patient complained of worsening lower extremities sensorimotor function and neurogenic claudication. Subsequent MRI revealed lumbar spine stenosis at the level of L3-L4, requiring further decompression. The patient underwent a second surgery involving L4-L5 Laminectomy with duraplasty and L2-L5 transpedicular fixation. The post-operative period was uneventful. Latest follow-up 18 mo after the second surgery revealed substantial improvement in patient's well-being. CONCLUSION: CENF should be kept in mind during the differential diagnostic work-up for polyneuropathies. Management with an extensive decompression, duraplasty and primary spinal fixation represents a rational approach to achieve a sustained symptomatic improvement and superior overall outcome.

Feasibility of the optimal cerebral perfusion pressure value identification without a delay that is too long.

Optimal cerebral perfusion pressure (CPPopt)-targeted treatment of traumatic brain injury (TBI) patients requires 2-8 h multi-modal monitoring data accumulation to identify CPPopt value for individual patient. Minimizing the time required for monitoring data accumulation is needed to improve the efficacy of CPPopt-targeted therapy. A retrospective analysis of multimodal physiological monitoring data from 87 severe TBI patients was performed by separately representing cerebrovascular autoregulation (CA) indices in relation to CPP, arterial blood pressure (ABP), and intracranial pressure (ICP) to improve the existing CPPopt identification algorithms. Machine learning (ML)-based algorithms were developed for automatic identification of informative data segments that were used for reliable CPPopt, ABPopt, ICPopt and the lower/upper limits of CA (LLCA/ULCA) identification. The reference datasets of the informative data segments and, artifact-distorted segments, and the datasets of different clinical situations were used for training the ML-based algorithms, allowing us to choose the appropriate individualized CPP-, ABP- or ICP-guided management for 79% of the full monitoring time for the studied population. The developed ML-based algorithms allow us to recognize informative physiological ABP/ICP variations within 24 min intervals with an accuracy up to 79% (compared to the initial accuracy of 74%) and use these segments for timely optimal value identification or CA limits determination in CPP, ABP or ICP data. Prospective clinical studies are needed to prove the efficiency of the developed algorithms.

The Effectiveness of Dichloroacetate on Human Glioblastoma Xenograft Growth Depends on Na+ and Mg2+ Cations.

The study's aim was to investigate the effectiveness of sodium dichloroacetate (NaDCA) or magnesium dichloroacetate (MgDCA) on adult U87 MG and pediatric PBT24 cell lines glioblastoma (GB) xenografts in a chicken chorioallantoic membrane (CAM) model. The study groups were: treated with 10 mM, 5 mM of NaDCA, and 5 mM, 2.5 mM of MgDCA, and controls. The U87 MG and PBT24 xenografts growth, frequency of tumor invasion into CAM, CAM thickening, and the number of blood vessels in CAM differed depending on the dichloroacetate salt treatment. NaDCA impact on U87 MG and PBT24 tumor on proliferating cell nunclear antigen (PCNA) and enhancer of zeste homolog 2 (EZH2) expression in the tumor was different, depending on the NaDCA dose. The 5 mM MgDCA impact was more potent and had similar effects on U87 MG and PBT24 tumors, and its impact was also reflected in changes in PCNA and EZH2 expression in tumor cells. The U87 MG and PBT24 tumor response variations to treatment with different NaDCA concentration on tumor growth or a contrast between NaDCA and MgDCA effectiveness may reflect some differences in U87 MG and PBT24 cell biology.

Optimal Cerebral Perfusion Pressure: Targeted Treatment for Severe Traumatic Brain Injury.

Identification of individual therapy targets is critical for traumatic brain injury (TBI) patients. Clinical outcomes depend on cerebrovascular autoregulation (CA) impairment. Here, we compare the effectiveness of optimal cerebral perfusion pressure (CPPopt)-targeted therapy in younger (<45 years of age) and elderly (≥45 years of age) TBI patients. Single-center multi-modal invasive arterial blood pressure(t), intracranial pressure (ICP)(t), cerebral perfusion pressure CPP(t), and CPPopt(t) monitoring (n = 81) was performed. ICM+ software was used for continuous CPPopt(t) status assessment by identification of pressure reactivity index (PRx). The most significant prognostic factors were age, Glasgow Coma Scale, serum glucose, and duration of longest CA ompairment event (LCAI) when PRx(t) >0.5 within 24 h after admission. The modeled accuracies for favorable and unfavorable outcome prediction were 86.5% and 90.9%, respectively. Age above 45 years and averaged ICP during all monitoring time above 21.3 mm Hg was associated with unfavorable outcome of an individual patient. Averaged CPP values close to CPPopt were associated with a better outcome in younger patients. Averaged ΔCPPopt <-5.0 mm Hg, averaged PRx >0.36, and LCAI >100 min were significantly associated with mortality for the younger patients. The critical values of averaged PRx >0.26 and LCAI >61 min were significantly associated with mortality for the elderly group. Autoregulation-guided treatment was important for individual TBI management, especially in younger patients. Further randomized multi-center studies are needed to prove final benefit.

Papillary Glioneuronal Tumour: A Case Report.

Only a few cases of papillary glioneuronal tumour (PGNT) with predominantly focal symptomatology are described in the literature. We report on the clinical, radiological, and histopathological features of PGNT. The intraoperative pathology revealed no tumour in the walls of the cyst, thus surgical resection of the nodule was performed leaving the cyst wall intact. There was no recurrence of tumour at the three-year follow-up, although a long-term follow-up is necessary.

Basal cell carcinoma of the scalp with destruction and invasion into the calvarium and dura mater: Report of 7 cases and review of literature.

Basal cell carcinoma (BCC) is the most common skin malignancy in humans. Giant BCC is a rarer entity that is characterised by aggressive biological behaviour. Intracranial invasion by a BCC on the scalp is extremely rare. The gold standard treatment of BCCs is represented by surgical excision with a wide variety of reconstructive techniques. In this paper, we describe the largest series to date of recurrent BCCs with intracranial extension involving the dura mater. We report recurrent giant BCC of the scalp with dura mater invasion in 7 patients. All patients in this series previously had more than 2 operations. Gadolinium-enhanced MRI revealed neoplastic invasion of the meninges and brain tissues. All patients had a multi-disciplinary team approach with the surgical margins ranging between 1 and 2 cm depending on the location and the size of the tumour. 5 of the patients underwent reconstruction of the skin defect by antero-lateral thigh flap, 1 patient underwent reconstruction with pedicled myocutaneous (trapezius) flap, and 1 with a pedicled myocutaneous latissimus dorsi flap. There was a mean follow-up of 5.3 years. 2 patients died due to cardio-pulmonary complications in the neuro-intensive care unit. A multi-disciplinary team approach and early aggressive tumour resection followed by sophisticated reconstructive and aesthetic procedures appears to be a reliable and realistic treatment modality for invasive BCC.

Importance of effusion of blood under the dura mater in forensic medicine: A STROBE - compliant retrospective study.

Subdural hemorrhage is commonly associated with mechanical brain injury and has a correspondingly high mortality rate. Subdural hematomas may immediately provoke symptoms or may be initially asymptomatic, with further symptoms evolving rapidly and fatally.The data regarding forensic autopsy of victims were obtained from The State Forensic Medicine Service of Lithuania between the years 2013 and 2016. A retrospective study was performed including 110 patients, whose cause of death was subdural hemorrhage. 95% confidence intervals were calculated.It was calculated, that in cases of sudden death, after subdural hemorrhage was diagnosed, a higher concentration of ethyl alcohol in blood (mean 2.22 ±â€Š1.3%) demanded a smaller amount of blood under the dura matter (mean 81.6 ±â€Š60.5 g) in order for the patient to die. It was also noted that hospitalized patients with subdural hemorrhage had a smaller concentration of blood ethyl alcohol (mean 1.33 ±â€Š1%) and a larger amount of blood under the dura (mean 135.6 ±â€Š82.9 g).Due to the toxic effect of ethyl alcohol, even a small amount (81.6 ±â€Š60.5 g) of blood under the dura matter can determine a sudden death.