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Spontaneous spinal epidural hematoma (SSEH) is a very rare clinical entity with potential diagnostic difficulties and which can result in severe neurological deficit. The etiology of this rare condition is largely not known, but with potential predisposition in patients on anticoagulation medication. This includes the novel anticoagulants with direct inhibition of the factor Xa mechanism (DOACs). These medications are supposed to have more predictable pharmacokinetics with fewer severe haemorrhagic adverse events in comparison with standard warfarin therapy. However, in the last few years, an increasing number of case reports have been published of haemorrhage into the central nervous system. We present a case of non-traumatic spinal epidural hematoma in the lumbar region in a patient on chronic apixaban therapy. To the best of our knowledge, it is the first described SSEH in the lumbar region associated with apixaban therapy.

Chemoresistance of cancer cells is a hallmark of treatment failure and the poor patient prognosis. The mechanism of resistance is often connected to the overexpression of specific kinases involved in DNA damage response cascade. Contrary, selected kinase inhibition can augment cancer cell sensitization to conventional therapy, enabling more efficient treatment. Among those kinases, ataxia-telangiectasia and Rad3-related kinase (ATR), the major responder to replication stress, stands out as one of the most attractive targets. Inspired by clinical candidates targeting ATR, we designed and prepared a small, focused library of 40 novel compounds building on 7-azaindoles, 2,7-diazaindoles, and 1H-pyrazoles as core structures. All the compounds alone or combined with cisplatin (CDDP) were screened against a panel of nine cancer cell lines and one healthy cell line. Three highlighted compounds (3, 22, and 29) were selected for broad oncology panel screening containing 104 kinases. Only compound 29, the 2,7-diazaindole representative, showed ATR inhibitory efficacy with the IC

A highly water soluble, nano-formulated curcumin was used for the treatment of the experimental model of spinal cord injury (SCI) in rats. Nanocurcumin and a vehicle nanocarrier as a control, were delivered both locally, immediately after the spinal cord injury, and intraperitoneally during the 4 consecutive weeks after SCI. The efficacy of the treatment was assessed using behavioral tests, which were performed during the experiment, weekly for 9 weeks. The behavioral tests (BBB, flat beam test, rotarod, motoRater) revealed a significant improvement in the nanocurcumin treated group, compared to the nanocarrier control. An immunohistochemical analysis of the spinal cord tissue was performed at the end of the experiment and this proved a significant preservation of the white matter tissue, a reduced area of glial scaring and a higher amount of newly sprouted axons in the nanocurcumin treated group. The expression of endogenous genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, Nfkβ) and interleukins (IL-1β, TNF-α, IL-6, IL-12, CCL-5, IL-11, IL-10, IL-13) was evaluated by qPCR and showed changes in the expression of the inflammatory cytokines in the first two weeks after SCI.

This study describes a pilot clinical validation of a new low-cost system for the continuous monitoring of the human body's cardiorespiratory activities within the magnetic resonance examination area. This study primarily focuses on monitoring cardiac activity and the related cardiac triggering. The patented system tested by the authors is based on seismocardiography (SCG). The study was conducted on 18 subjects on a Siemens Prisma 3T MR scanner. Standard anatomical and diffusion sequences were used to test cardiac activity monitoring. A wide range of commonly used diagnostic sequences were used to test imaging of the heart by means of cardiac triggering. System functionality was verified against a commercially available electrocardiography (ECG) system. Monitoring of cardiac activity (detection of the R-R interval in ECG and the AO-AO interval in SCG) was objectively evaluated by determining the overall probability of correct detection (ACC), sensitivity (SE), positive predictive value (PPV), and harmonic mean between SE and PPV, i.e. F1. Imaging quality control using Cardiac Triggering was performed by subjective evaluation of images by the physicians. The study conducted clearly confirmed the functionality of the system in terms of continuous cardiac activity monitoring. In all 18 subjects, a mean PPV > 99% was achieved; F1 > 99 %; SE > 99 %; ACC > 98 %; 1.96 sigma < 3.5 bpm. Also, Cardiac Triggering functionality was confirmed by the physicians on the basis of analyzing cardiac images using the T1/T2 balanced echo sequences and the T1 flash sequence measured natively. Web of Science 7 118629 118608

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th–April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017–2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

Background/aim Resistance to glioblastoma (GB) therapy is attributed to the presence of glioblastoma stem cells (GSC). Here, we defined the behavior of GSC as it pertains to proliferation, migration, and angiogenesis. Materials and methods Human-derived GSC were isolated and cultured from GB patient tumors. Xenograft GSC were extracted from the xenograft tumors, and spheroids were created and compared with human GSC spheroids by flow cytometry, migration, proliferation, and angiogenesis assays. Oct3/4 and Sox2, GFAP, and Ku80 expression was assessed by immunoanalysis. Results The xenograft model showed the formation of two different tumors with distinct characteristics. Tumors formed at 2 weeks were less aggressive with well-defined margins, whereas tumors formed in 5 months were diffuse and aggressive. Expression of Oct3/4 and Sox2 was positive in both human and xenograft GSC. Positive Ku80 expression in xenograft GSC confirmed their human origin. Human and xenograft GSC migrated vigorously in collagen and Matrigel, respectively. Xenograft GSC displayed a higher rate of migration and invasion than human GSC. Conclusion Human GSC were more aggressive in growth and proliferation than xenograft GSC, while xenograft GSC had increased invasion and migration compared to human GSC. A simple in vitro spheroid system for GSC provides a superior platform for the development of precision medicine in the treatment of GB.

Despite the variety of experimental models of spinal cord injury (SCI) currently used, the model of the ventral compression cord injury, which is commonly seen in humans, is very limited. Ventral balloon compression injury reflects the common anatomical mechanism of a human lesion and has the advantage of grading the injury severity by controlling the inflated volume of the balloon. In this study, ventral compression of the SCI was performed by the anterior epidural placement of the balloon of a 2F Fogarty&rsquo, s catheter, via laminectomy, at the level of T10. The balloon was rapidly inflated with 10 or 15 &mu, L of saline and rested in situ for 5 min. The severity of the lesion was assessed by behavioral and immunohistochemical tests. Compression with the volume of 15 &mu, L resulted in severe motor and sensory deficits represented by the complete inability to move across a horizontal ladder, a final Basso, Beattie and Bresnahan (BBB) score of 7.4 and a decreased withdrawal time in the plantar test (11.6 s). Histology and immunohistochemistry revealed a significant loss of white and gray matter with a loss of motoneuron, and an increased size of astrogliosis. An inflation volume of 10 &mu, L resulted in a mild transient deficit. There are no other balloon compression models of ventral spinal cord injury. This study provided and validated a novel, easily replicable model of the ventral compression SCI, introduced by an inflated balloon of Fogarty&acute, s catheter. For a severe incomplete deficit, an inflated volume should be maintained at 15 &mu, L.

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a translesional spinal network after SCI. We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI. We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.

Purpose: Primary cell lines are a valuable tool for evaluation of tumor behavior or sensitivity to anticancer treatment and appropriate dissociation of cells could preserve genomic profile of the original tissue. The main aim of our study was to compare the influence of two methods of glioblastoma multiforme (GBM) cell derivation (mechanic&mdash, MD, enzymatic&mdash, ED) on basic biological properties of thus derived cells and correlate them to the ones obtained from stabilized GBM cell line A-172. Methods: Cell proliferation and migration (xCELLigence Real-Time Cell Analysis), expression of microRNAs and protein markers (RT-PCR and Western blotting), morphology (phase contrast and fluorescent microscopy), and accumulation of temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) inside the cells (LC-MS analysis) were carried out in five different samples of GBM (GBM1, GBM2, GBM32, GBM33, GBM34), with each of them processed by MD and ED types of isolations. The same analyses were done in the A-172 cell line too. Results: Primary GBM cells obtained by ED or MD approaches significantly differ in biological behavior and properties of these cells. Unlike in primary MD GBM cells, higher proliferation, as well as migration, was observed in primary ED GBM cells, which were also associated with the acquired mesenchymal phenotype and higher sensitivity to TMZ. Finally, the same analyses of stabilized GBM cell line A-172 revealed several important differences in measured parameters. Conclusions: GBM cells obtained by MD and ED dissociation show considerable heterogeneity, but based on our results, MD approach should be the preferred method of primary GBM cell isolation

The publication presents a comparative study of two fibre-optic sensors in the application of heart rate (HR) and respiratory rate (RR) monitoring of the human body. After consultation with clinical practitioners, two types of non-invasive measuring and analysis systems based on fibre Bragg grating (FBG) and fibre-optic interferometer (FOI) have been designed and assembled. These systems use probes (both patent pending) that have been encapsulated in the bio-compatible polydimethylsiloxane (PMDS). The main advantage of PDMS is that it is electrically non-conductive and, as well as optical fibres, has low permeability. The initial verification measurement of the system designed was performed on four subjects in a harsh magnetic resonance (MR) environment under the supervision of a senior radiology assistant. A follow-up comparative study was conducted, upon a consent of twenty volunteers, in a laboratory environment with a minimum motion load and discussed with a head doctor of the Radiodiagnostic Institute. The goal of the laboratory study was to perform measurements that would simulate as closely as possible the environment of harsh MR or the environment of long-term health care facilities, hospitals and clinics. Conventional HR and RR measurement systems based on ECG measurements and changes in the thoracic circumference were used as references. The data acquired was compared by the objective Bland-Altman (B-A) method and discussed with practitioners. The results obtained confirmed the functionality of the designed probes, both in the case of RR and HR measurements (for both types of B-A, more than 95% of the values lie within the +/- 1.96 SD range), while demonstrating higher accuracy of the interferometric probe (in case of the RR determination, 95.66% for the FOI probe and 95.53% for the FBG probe, in case of the HR determination, 96.22% for the FOI probe and 95.23% for the FBG probe). Web of Science 18 11 art. no. 3713

Human mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis. Endogenous gene expression (Gfap, Casp3, Irf5, Cd86, Mrc1, Cd163) was studied with quantitative Real-time polymerase chain reaction (qRT PCR). Significant recovery of functional outcome was observed in all of the treated groups except for the single application of the lowest number of cells. Histochemical analyses revealed a gradually increasing effect of grafted cells, resulting in a significant increase in the number of GAP43+ fibers, a higher amount of spared gray matter and reduced astrogliosis. mRNA expression of macrophage markers and apoptosis was downregulated after the repeated application of 1.5 million cells. We conclude that the effect of hWJ-MSCs on spinal cord regeneration is dose-dependent and potentiated by repeated application.

This article reports an unusual case of aggressive extraocular sebaceous carcinoma located on the scalp with subsequent usurpation of the bone and penetrating through the bone and meninges to the brain in a 56-year-old man affected by Muir-Torre syndrome. Microscopically, the sebaceous neoplasm was located in the middle to deep dermis without any connection to the epidermis and showed a multinodular growth with neoplastic nodules with a central comedo-type necrosis separated from each other by fibrovascular stroma. The nodules were composed of varying proportions of mature sebaceous cells and atypical basaloid cells with high degree of atypia, including high nuclear/cytoplasmic ratio, nuclear pleomorphism, macronucleoli, atypical mitoses, and necrosis. The neoplasm was totally removed. Histopathological examinations of the recurrent lesion showed identical morphological features and, in addition, signs of the tumors growing through the periosteum were noted. In the final excision specimen, both the dura mater and the brain tissue were infiltrated by the sebaceous carcinoma. The diagnosis of Muir-Torre syndrome was confirmed by molecular genetic investigation that revealed an identical germline mutation in MSH2 gene in several family members, some of whom had colorectal tumors.

Phonation into a straw is used in voice training and therapy. This study investigated its’ effects on the vocal tract adjustments. Magnetic resonance images were taken from one female phonating first on [a:], then into a plastic drinking straw and then again on [a:]. Acoustic samples were recorded from her and 10 other females. The samples were analyzed for fundamental frequency, sound pressure level (SPL), five lowest formant frequencies (F1–F5) and SPL of the speaker's formant cluster range (2.5–4.5 kHz). During and after phonation into a straw, the midsagittal area of the vocal tract increased and the velar closure improved. The ratio of the transversal area of the lower pharynx over that of the epilarynx increased both during (27%) and after the straw (20%). The overall SPL and the SPL of the speaker's formant cluster increased. The frequencies of F2, F4 and F5 decreased, while F3 increased. The distances between F4 and F3 and F5 and F4 decreased by 49%. For the 10 subjects, F3 increased, F4 decreased and the distance between F3 and F4 decreased significantly. The results suggest that exercising with a straw helps establishing a speaker's formant cluster, which increases loudness and thus improves vocal economy.

BACKGROUND AND PURPOSEThe basal ganglia and the cerebellum have both emerged as important structures involved in the processing of temporal information. METHODSWe examined the roles of the cerebellum and striatum in predictive motor timing during a target interception task in healthy individuals (HC group; n = 21) and in patients with early Parkinson's disease (early stage PD group; n = 20) using functional magnetic resonance imaging. RESULTSDespite having similar hit ratios, the PD failed more often than the HC to postpone their actions until the right moment and to adapt their behavior from one trial to the next. We found more activation in the right cerebellar lobule VI in HC than in early stage PD during successful trials. Successful trial-by-trial adjustments were associated with higher activity in the right putamen and lobule VI of the cerebellum in HC. CONCLUSIONSWe conclude that both the cerebellum and striatum are involved in predictive motor timing tasks. The cerebellar activity is associated exclusively with the postponement of action until the right moment, whereas both the cerebellum and striatum are needed for successful adaptation of motor actions from one trial to the next. We found a general hypoactivation'' of basal ganglia and cerebellum in early stage PD relative to HC, indicating that even in early stages of the PD there could be functional perturbations in the motor system beyond striatum.

SUMMARY The aims of this retrospective computed tomography (CT) study were to determine the occurrence of severe root resorption involving the pulpal canal of adjacent permanent teeth associated with ectopically erupting canines, and to verify the existence of related factors. The sample consisted of 255 consecutive patients (159 females and 96 males, mean age 18.4 and 16.8 years, respectively). Three hundred and thirty-four ectopic maxillary canines and adjacent teeth were analysed using CT images. Statistical significance was evaluated with chi-square and Fisher’s exact tests. The results showed that severe root resorption of adjacent permanent teeth occurred in 17.7 per cent of ectopic canines and was equally common in females and males. Severe root resorption affected 12.6 per cent of the lateral incisors, 4.8 per cent of the first premolars, and 2.1 per cent of the central incisors. No relationship was found between the type or side of ectopic eruption, inclination of the longitudinal axis of the ectopic canine and the occurrence of severe root resorption. A significant relationship was found between a bucco-lingual position of the ectopic canine and root resorption (P < 0.05). Root resorption mainly occurred in the apical third (57.6 per cent) and apical and middle thirds (27.1 per cent). A significant relationship existed between the occurrence of root resorption and complete loss of space for the erupting canine (P < 0.05). No association was found between alignment of the upper permanent incisor and root resorption. A widened dental follicle occurred in 15 per cent of ectopic canines but did not cause root resorption of the adjacent permanent teeth. Since root resorption is asymptomatic, early detection by radiographic examination is essential for correct diagnosis and treatment.

PURPOSE: To assess whether structural and metabolic brain abnormalities are correlated in MTLE/HS syndrome. METHODS: Optimized voxel‐based morphometry (VBM) of gray matter concentration (GMC) and gray matter volume (GMV) and proton magnetic resonance spectroscopy measurements from both‐sided hippocampal and thalamic regions were performed in 20 MTLE/HS patients and 20 sex‐ and age‐matched healthy controls. The local GMC and GMV values were calculated in both the affected and unaffected hippocampi and ipsilateral and contralateral thalami in patients and healthy subjects, and these were compared. VBM variables and NAA, NAA/Cr and NAA/(Cr+Cho) values from the investigated brain regions were correlated. RESULTS: (1) Analysis revealed significantly more extensive GMV reduction than GMC reduction in patients' affected hippocampus. In addition, significant GMV reduction was observed in the ipsilateral thalamus in MTLE/HS patients. (2) Significant decreases in all VBM and MRS variables were revealed in the affected hippocampus. Whilst practically normal GMC values were revealed in patients' both‐sided thalamic regions, a significant decrease in local GMV and metabolic measurements were found in the patients' ipsilateral thalamus. (3) Pearson's correlations between structural and metabolic abnormalities were significant for the ipsilateral thalamus only. CONCLUSION: Structural and metabolic abnormalities as detected by optimized voxel‐based morphometry and (1)H MRS in hippocampal and thalamic regions are only partially correlated in MTLE/HS patients. It seems therefore reasonable that both methods reflect different aspects of brain pathology, which, at least to some degree, might be independently ongoing. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

The analysis of functional magnetic resonance imaging (fMRI) data involves multiple stages of data pre-processing before the activation can be statistically detected. Spatial smoothing is a very common pre-processing step in the analysis of functional brain imaging data. This study presents a broad perspective on the influence of spatial smoothing on fMRI group activation results. The data obtained from 20 volunteers during a visual oddball task were used for this study. Spatial smoothing using an isotropic gaussian filter kernel with full width at half maximum (FWHM) sizes 2 to 30 mm with a step of 2 mm was applied in two levels - smoothing of fMRI data and/or smoothing of single-subject contrast files prior to general linear model random-effects group analysis generating statistical parametric maps. Five regions of interest were defined, and several parameters (coordinates of nearest local maxima, t value, corrected threshold, effect size, residual values, etc.) were evaluated to examine the effects of spatial smoothing. The optimal filter size for group analysis is discussed according to various criteria. For our experiment, the optimal FWHM is about 8 mm. We can conclude that for robust experiments and an adequate number of subjects in the study, the optimal FWHM for single-subject inference is similar to that for group inference (about 8 mm, according to spatial resolution). For less robust experiments and fewer subjects in the study, a higher FWHM would be optimal for group inference than for single-subject inferences.

Purpose To investigate the fundamental connectivity architecture of neural structures involved in the goal-directed processing of target events. Methods Twenty healthy volunteers underwent event-related functional magnetic resonance imaging (fMRI) while performing a standard oddball task. In the task, two types of visual stimuli – rare (target) and frequent – were randomly presented, and subjects were instructed to mentally count the target stimuli. Dynamic causal modeling (DCM), in combination with Bayes factors was used to compare competing neurophysiological models with different intrinsic connectivity structures and input regions within the network of brain regions underlying target stimulus processing. Results Conventional analysis of fMRI data revealed significantly greater activation in response to the target stimuli (in comparison to the frequent stimuli) in several brain regions, including the intraparietal sulci and supramarginal gyri, the anterior and posterior cingulate gyri, the inferior and middle frontal gyri, the superior temporal sulcus, the precuneus/cuneus, and the subcortical grey matter (caudate and thalamus). The most extensive cortical activations were found in the right intraparietal sulcus (IPS), the anterior cingulate cortex (ACC), and the right lateral prefrontal cortex (PFC). These three regions were entered into the DCM. A comparison on a group level revealed that the dynamic causal models in which the ACC and alternatively the IPS served as input regions were superior to a model in which the PFC was assumed to receive external inputs. No significant difference was observed between the fully connected models with ACC and IPS as input regions. Subsequent analysis of the intrinsic connectivity within two investigated models (IPS and ACC) disclosed significant parallel forward connections from the IPS to the frontal areas and from the ACC to the PFC and the IPS. Conclusion Our findings indicate that during target stimulus processing there is a bidirectional frontoparietal information flow, very likely reflecting parallel activation of two distinct but partially overlapping attentional or attentional/event-encoding neural systems. Additionally, a simple hierarchy within the right frontal lobe is suggested with the ACC exerting influence over the PFC.

Physeal cartilage is known to have poor self-repair capacity after injury. Evaluation of the ability of cultured mesenchymal stem cells to repair damaged physis is the topic of current research. In 10 immature New Zealand white rabbits autogenous mesenchymal stem cells were transplanted into a iatrogenic physeal defect in a lateral portion of the distal growth plate of the right femur. The same defect without stem cells transplantation in the left femoral distal physis served as a control. In our study, we used our own technique of implantation of MSCs with a newly modified gel scaffold (New Composite Hyaluronate/Collagen Type I/Fibrin Scaffold). The rabbits were euthanized 4 months after transplantation. Bone length discrepancy and valgus deformity were measured from femoral radiographs. Healing of the defect was investigated histologically. The ability of mesenchymal stem cells to survive and promote cartilage healing in the physeal defect was assessed by immunofluorescence. Average difference in femur length measured from surgery to euthanasia (4 months) was 0.61 ± 0.19 cm after preventive transplantation of MSCs in the right femur, but only 0.11 ± 0.07 cm in the left femur. Average angular (valgus) deformity of the right femur with MSCs preventively transplanted to iatrogenically damaged distal femoral physis was 1.2 ± 0.72 °. Valgus deformity in the left femur was 5.4 ± 2.5 °. Prophylactic transplantation of autogenous mesenchymal stem cells to iatrogenically damaged distal growth plate of the rabbit femur prevented a bone bridge formation and resulted in healing of the physeal defect with hyaline cartilage. Immunofluorescence examination showed that the chondrocytes newly formed in growth zone are the result of implanted MSCs differentiation. Femur growth in traumatized physis was maintained even after transplantation of autogenous MSCs. As compared with the opposite femur (with physeal defect but without transplanted MSCs), the bone showed no significant shortening or valgus deformity (p = 0.018).

Introduction Changes of brain morphology are now considered as a part of the pathology of schizophrenia. Voxel-based morphometry may be used to study regional changes of the grey matter in the whole brain. It is advantageous to study first-episode patients to prevent the influence of many possible biasing factors when trying to identify primary pathological processes underlying the manifestation of the illness. Objective To investigate regional grey matter changes in the first-episode schizophrenia patients. Methods Optimized voxel-based morphometry was used to detect changes in grey matter volume in 22 patients with first-episode schizophrenia compared with 18 healthy volunteers of comparable age, gender and handedness. Results The first-episode schizophrenia group had significantly reduced grey matter volume in the prefrontal cortex (inferior and middle prefrontal gyrus, cingulate gyrus). We identified no differences in the temporal cortex. Conclusion Our data support the theoretical assumption that prefrontal dysfunction underlines the primary pathology and clinical manifestation of schizophrenia. We are inclined to explain the differences in the pattern of morphological changes reported in other first-episode studies – especially the lack of changes in the temporal cortex – by heterogeneity of schizophrenia, potential progression and antipsychotic medication effect.

Gal P., A. Neaas, L. Planka, H. Kecova, L. Kfien, P. Krupa, J. Hluailova, D. Usvald: Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits. Acta Vet. Brno 2007, 76: 265-275. Mesenchymal stem cells (MSCs) from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation) and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation). The results were compared with the data for the control defects (without stem cell implantation) in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm) compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm). Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °). On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °). For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study demonstrated that allogenic mesenchymal stem cells in a new composite hyaluronate/collagen type I/fibrin scaffold repaired iatrogenic defects in the distal femoral physes in rabbits without the use of immunosuppressive therapy. The use of allogenic mesenchymal stem cells for the repair of physeal defects may be an alternative to autologous MSCs transplantation. An allogenic approach would enable mesenchymal stem cells to be isolated from any donor, providing a readily available source of cells for cartilage tissue repair.

Objective: To characterize the clinical, EEG, and brain imaging findings in an adult case series of patients with de novo refractory status epilepticus (SE) occurring after a febrile illness. Methods: A retrospective study (2010–2013) was undertaken with the following inclusion criteria: (1) previously healthy adults with refractory SE; (2) seizure onset 0–21 days after a febrile illness; (3) lacking evidence of infectious agents in CSF; (4) no history of seizures (febrile or afebrile) or previous or concomitant neurologic disorder. Results: Among 155 refractory SE cases observed in the study period, 6 patients (17–35 years old) fulfilled the inclusion criteria. Confusion and stupor were the most common symptoms at disease onset, followed after a few days by acute repeated seizures that were uncountable in all but one. Seizures consisted of focal motor/myoclonic phenomena with subsequent generalization. Antiepileptic drugs failed in every patient to control seizures, with all participants requiring intensive care unit admission. Barbiturate coma with burst-suppression pattern was applied in 4 out of 6 patients for 5–14 days. One participant died in the acute phase. In each patient, we observed a reversible bilateral claustrum MRI hyperintensity on T2-weighted sequences, without restricted diffusion, time-related with SE. All patients had negative multiple neural antibodies testing. Four out of 5 surviving patients developed chronic epilepsy. Conclusions: This is a hypothesis-generating study of a preliminary nature supporting the role of the claustrum in postfebrile de novo SE; future prospective studies are needed to delineate the specificity of this condition, its pathogenesis, and the etiology.

Summary Purpose To investigate possible neuronal dysfunction of the thalamus in patients suffering from typical absence epilepsy, using magnetic resonance spectroscopy (MRS). Special attention was paid to levels of N -acetylaspartate (NAA) and creatine (Cr), and to the NAA/Cr ratio. Methods MRS was performed over the right and left thalamus in nine patients suffering from typical absence epilepsy, and in nine sex- and age-matched healthy controls. All patients and controls were examined using a standard MRS-CSI (chemical shift imaging) technique. Results Statistical analysis of the obtained data demonstrated a significantly lower thalamic NAA/Cr ratio in patients with typical absence epilepsy when compared to the healthy controls. Our MRS data showed symmetrical distribution of NAA/Cr ratio in the right and left thalamus within both the patient group and the group of healthy controls. No significant correlation between the patients' thalamic NAA/Cr values and the duration of the epilepsy or seizure frequency was revealed. Conclusions The present MRS data clearly indicate neuronal dysfunction in the thalami of patients with typical absence epilepsy. In agreement with other recent MRS findings in different idiopathic generalized epilepsy syndromes, our results confirm the role of the thalamus as an important structure in the pathogenesis of typical absence epilepsy.

The spatial locations of brain activation related to self-paced repetitive movements, i.e., writing simple dots, were studied using event-related fMRI. Ten healthy right-handed subjects were scanned while performing the protocol with self-paced repetitive movement. In a protocol with self-paced dot writing, we observed significant activation in regions known to participate in motor control: Contralateral to the movement in the primary sensorimotor and supramarginal cortices, the supplementary motor area (SMA) and the underlying cingulate, and, to a lesser extent, the sensorimotor region ipsilateral to the writing hand. When the fMRI was compared with the map of the brain areas electrically active with self-paced movements (intracerebral recordings; Rektor et al., 1994 , 1998 , 2001, b , c , 2003 ), there was an evident overlap of most results. Nevertheless, the electrophysiological studies were more sensitive in uncovering small active areas, i.e., in the premotor and prefrontal cortices. The Bereitschafspotential (BP) with Movement Accompanying Potential (MAP) and hemodynamic changes overlap in regions where the BP were displayed consistently. In some other regions, the BP recordings were inconsistent, i.e., in the prefrontal cortex, where about half of the contacts displayed BP generators while the other half did not. In these regions the hemodynamic changes were not significant. The spatial limitations of the intracerebral electrodes is a result of the fact that the electrodes are submerged in the cerebral tissue and record in their immediate vicinity. The fMRI that indirectly measures activity of larger populations of neurons has better spatial resolution. Electrophysiological techniques with intracranial recordings may reveal even subtle generators of electrical activity.

To investigate the inter- and intrahemispheric reorganization of the language cortex in left temporal lobe epilepsy (TLE) with left-sided hippocampal sclerosis. A functional magnetic resonance imaging was performed on 13 right-handed patients suffering from medically intractable left TLE, and in 13 sex- and age-matched healthy controls. The activation paradigm used was a silent word generation task. A language laterality index (LI) was calculated from the number of activated voxels in the right and left anterior two-thirds of the hemispheres. Significant differences between the patients and the controls were observed in the activation of the left-sided inferior frontal gyrus. Less consistent findings in this region, as well as the relative protection of Broca's area from the activation, were revealed in the patients. In addition, different patterns of activation were proven in the cerebellum and other cortical as well as subcortical brain structures within both hemispheres. Significant differences were also found in the values of the language LIs between the investigated groups: these values suggested a more bihemispheric language representation in the patients. As anticipated, lateralization of the language functions in the epileptics significantly decreased in connection with an earlier age of initial insult. Our results support the hypothesis of a significant intra- and interhemispheric functional reorganization of language-related neuronal networks in left TLE.

Endoscopic neurosurgery minimises the trauma to the brain tissue, while maintains the ability to work under direct vision. The principles of stereotactic neurosurgery and neuronavigation with full use of computer technique are associated with neuroendoscopy at the author's department. The surgery is described as a dynamic process consisting of data acquisition, transmission, presurgical planning and storage. The group of patients consists of 290 endoscopic surgeries, mainly for hydrocephalus. The preferred data source is MRI scan in an extent depending on the case treated. Hospital PACS is used for data transmission to the surgical workstation. Trajectory can be easily planned by the special software Praezis Plus and virtual endoscopy images can be integrated to the planning procedure in the most difficult cases. Intraoperative image updating utilises the C-arm GE. In no cases, the surgery had to be converted into the open microsurgery due to uncontrollable bleeding. Moreover, there were no complications caused by the processing. The procedure is being further optimised and tailored to the demands of the different surgical procedures.

Symptoms signs of benign and malignant tumors were observed during paleopathological analysis of skeletal remains from the city of Brno in the Czech Republic. Approximately 1,200 skeletons were examined from two Modern era archaeology sites: the Mala Nova ulice (Little New Street) cemetery and the cemetery of the Nemocnice Milosrdných bratri (Merciful Brothers' Hospital). Osteomas, usually located on the flat bones of the cranial vault, were the most frequent skeletal pathology. Symptoms signs of malignant tumors were observed in three cases. In one case lytic foci caused by the metastases of a malignant tumor in the soft tissue was observed. Traces of myeloma multiplex were found in two individuals. Living conditions in that period, and possible carcinogenic environmental influences were assessed for the general population of Brno. This report contributes to a better understanding of the historical development of cancers and the clarification of possible causes for their modern increase of incidence.

Purpose: Cervical myelopathy is a problem from both neurosurgical and orthopaedic view. The cause may be osteochondrotic changes or multiple-level stenosis of the cervical spinal canal together with spinal cord changes, clinically correlating with the disturbance of the long spinal tracts function, with an equivalent derived from imaging methods being the deficiency of spinal cord blood vessels and T2 WI changes visible on MRI. The aim of this paper was to verify the cause of cervical spondylotic myelopathy in various spinal segments and surgery, which is targeted towards the offending lesion. Methods: 3-D reconstruction of the spinal canal derived from both CT and MRI images enables presurgical planning in virtual reality in advance before the surgical procedure and it is possible to individualise the choice of the implanted material for the reconstruction of the spinal canal. The surgical procedure itself is usually performed in two steps and is directed towards the reconstitution of the spinal canal according to the virtual reality conditions. Results: Seven patients were operated on for multi-level cervical stenosis extending from C2 to C7. The real image is presented as a result of postsurgical neuroradiological investigations and is compared with the presurgical virtual reality. Conclusions: The results of surgeries presented in 2-D reconstruction do not enable the exact spatial imaging of the spinal canal and may therefore be the cause of surgical failures. CT and MRI 3-D reconstruction makes possible presurgical planning in the conditions of 3-D space, skeletal decompression and what remains to be considered is the plasty of dura mater, and how it can be documented. The results of electrophysiological investigations in cervical myelopathy patients do not enable targeted surgery in patients with long stenoses, on the opposite side the 3-D reconstruction of both skeletal and spinal cord structures eliminates this disadvantage, as the surgical solution demonstrates.

Cilem sděleni je kasuistika 91lete pacientky přijate k elektivni koronarografii pro typicke namahove bolesti na hrudi a dusnost, trvajici již několik let, výrazněji zhorsene v poslednim měsici, podle funkcni klasifikace NYHA III.Koronarografie odhalila fistulu odstupujici z proximalniho segmentu ramus interventricularis anterior (RIA), drenujici do proximalni casti arteria pulmonalis. Fistula byla uzavřena perkutanni implantaci tři platinových spiral s optimalnim ucinkem, výkon proběhl bez komplikaci. Pacientka na kontrole rok po výkonu udava naproste vymizeni potiži.

Fronto-temporal (FT) dysfunction is a characteristic feature of schizophrenia. We tried to find features of brain morphology that are connected with the solving of Verbal Fluency Task (VFT). We hypothesized that verbal fluency results correlate positively with gray and white matter volume in fronto-temporal areas. 25 first-episode schizophrenia men were tested using VFT. Brain morphology–regional gray and white matter volume was analyzed using optimized voxel-based morphometry. Correlations between VFT score and brain morphology were performed using General linear mode — regression analysis. There was a significant positive correlation of regional gray matter and VFT score in the posterior part of superior temporal gyrus, on the borders with middle temporal gyrus and inferior parietal lobule. As for the regional white matter volume there was one significant cluster in the depth of the inferior frontal gyrus, pars triangularis. The ability to generate context appropriate words is not only the result of abnormal FT co-operation or ability to “hire” prefrontal activity when necessary, but also stems from the condition of relevant neuronal networks.

Summary Objective The present study aimed to investigate the vocal tract and glottal function during and after phonation into a tube and a stirring straw. Methods A male classically trained singer was assessed. Computerized tomography (CT) was performed when the subject produced [a:] at comfortable speaking pitch, phonated into the resonance tube and when repeating [a:] after the exercise. Similar procedure was performed with a narrow straw after 15 minutes silence. Anatomic distances and area measures were obtained from CT midsagittal and transversal images. Acoustic, perceptual, electroglottographic (EGG), and subglottic pressure measures were also obtained. Results During and after phonation into the tube or straw, the velum closed the nasal passage better, the larynx position lowered, and hypopharynx area widened. Moreover, the ratio between the inlet of the lower pharynx and the outlet of the epilaryngeal tube became larger during and after tube/straw phonation. Acoustic results revealed a stronger spectral prominence in the singer/speaker's formant cluster region after exercising. Listening test demonstrated better voice quality after straw/tube than before. Contact quotient derived from EGG decreased during both tube and straw and remained lower after exercising. Subglottic pressure increased during straw and remained somewhat higher after it. Conclusion CT and acoustic results indicated that vocal exercises with increased vocal tract impedance lead to increased vocal efficiency and economy. One of the major changes was the more prominent singer's/speaker's formant cluster. Vocal tract and glottal modifications were more prominent during and after straw exercising compared with tube phonation.

The basal ganglia and the cerebellum have both emerged as important structures involved in the processing of temporal information.We examined the roles of the cerebellum and striatum in predictive motor timing during a target interception task in healthy individuals (HC group; n = 21) and in patients with early Parkinson's disease (early stage PD group; n = 20) using functional magnetic resonance imaging.Despite having similar hit ratios, the PD failed more often than the HC to postpone their actions until the right moment and to adapt their behavior from one trial to the next. We found more activation in the right cerebellar lobule VI in HC than in early stage PD during successful trials. Successful trial-by-trial adjustments were associated with higher activity in the right putamen and lobule VI of the cerebellum in HC.We conclude that both the cerebellum and striatum are involved in predictive motor timing tasks. The cerebellar activity is associated exclusively with the postponement of action until the right moment, whereas both the cerebellum and striatum are needed for successful adaptation of motor actions from one trial to the next. We found a general ''hypoactivation'' of basal ganglia and cerebellum in early stage PD relative to HC, indicating that even in early stages of the PD there could be functional perturbations in the motor system beyond striatum.

Background and Purpose— Stroke patients without evidence of arterial occlusion may not be suitable candidates for thrombolytic therapy. In our study, we investigated the outcomes of patients with negative CT angiography results for arterial occlusion. Methods— The study included patients treated within 3 hours after symptom onset with intravenous thrombolysis for significant neurological deficit between August 2003 and June 2007. All of the patients were documented with negative CT angiography results for arterial occlusion by independent reviews. Outcome measurements included modified Rankin score at 3 months, incidence of intracranial hemorrhage, and infarction volume on control CT. The predictors of unfavorable outcome (modified Rankin score, 2–6) were identified by multivariate logistic regression. Results— Altogether, 173 patients received intravenous thrombolysis; of those, 138 underwent CT angiography. The CT angiography results were negative for arterial occlusion in 39 (28%) of the patients: mean age, 71±10 years; 16 (41%) female; median baseline NIHSS, 11. At 3 months, modified Rankin score of 0 to 1 was achieved in 18 (46%) of the patients; 6 (15%) died; and 3 (8%) had symptomatic parenchymal hemorrhage. The median infarct volume was 1.5 cm 3 . The independent predictors of unfavorable clinical outcome were higher age (OR, 1.1; 95% CI, 1.01–1.27), and baseline NIHSS >12 (OR, 18.8; 95% CI, 1.4 to 261). One patient had encephalitis diagnosed. Conclusions— Negative baseline CT angiography is not uncommon. The risk of intracerebral hemorrhage after thrombolytic therapy for patients without evidence of arterial occlusion is similar to the risk carried in an unselected patient population. Given the prognosis, thrombolytic therapy seems justified; however, etiology other than stroke should be considered.