Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients.

BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

A rare case of non-traumatic spinal epidural hematoma in lumbar region associated with apixaban therapy.

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.

Microsurgical versus endoscopic surgery for non-functioning pituitary adenomas: a retrospective study.

AIM: To compare microsurgical technique (mTSS) and endoscopic technique (eTSS) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: We retrospectively evaluated the charts of 50 patients who underwent either mTSS or eTSS for NFPA in the Department of Neurosurgery, University Hospital Hradec Kralove from 2013 to 2019. We enrolled all patients who were not treated by postoperative adjuvant radiotherapy and who underwent at least two regular postoperative magnetic resonance imaging (MRI) tests. We compared the groups in terms of the extent of resection, surgery duration, blood loss, complication rate, overall clinical effect on the endocrinological and ophthalmological deficit, and postoperative growth pattern of the residual tumor mass. RESULTS: The mTSS group had significantly shorter surgical time (75 min vs 127 min, P<0.001) and lower perioperative blood loss (156 mL vs 256 mL, P=0.027). The groups did not significantly differ in the extent of resection, overall clinical or hormonal effect, and the complication rate. The extent of resection did not correlate with tumor consistency, while the tumor growth rate did not correlate with age or Ki-67 expression. CONCLUSIONS: There was no major difference between the approaches in surgery radicality or safeness. However, eTSS remains the method of choice due to its potentially higher postoperative preservation of hormonal functions.

The Evaluation of Glioblastoma Cell Dissociation and Its Influence on Its Behavior.

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-MD; enzymatic-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.

Magnetic Resonance Imaging Compatible Non-Invasive Fibre-Optic Sensors Based on the Bragg Gratings and Interferometers in the Application of Monitoring Heart and Respiration Rate of the Human Body: A Comparative Study.

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).

The Effect of Human Mesenchymal Stem Cells Derived from Wharton's Jelly in Spinal Cord Injury Treatment Is Dose-Dependent and Can Be Facilitated by Repeated Application.

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.

Aggressive Extraocular Sebaceous Carcinoma of the Scalp Involving the Brain in a Patient With Muir-Torre Syndrome.

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.

NANOTECHNOLOGY - NEW TRENDS IN THE TREATMENT OF BRAIN TUMOURS.

High grade gliomas are some of the deadliest human tumours. Conventional treatments such as surgery, radiotherapy and chemotherapy have only a limited effect. Nowadays, resection is the common treatment of choice and although new approaches, such as perioperative magnetic resonance imaging or fluorescent microscopy have been developed, the survival rate of diagnosed patients is still very low. The inefficacy of conventional methods has led to the development of new strategies and the significant progress of nanotechnology in recent years. These platforms can be used either as novel imaging tools or to improve anticancer drug delivery into tumours while minimizing its distribution and toxicity in healthy tissues. Amongst the new nanotechnology platforms used for delivery into the brain tissue are: polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of small molecular weight drugs as well as macromolecules - proteins, peptides and genes. The unique properties of these nanoparticles, such as surface charge, particle size, composition and ability to modify their surface with tissue recognition ligands and antibodies, improve their biodistribution and pharmacokinetics. All of the above mentioned characteristics make of nanoplatforms a very suitable tool for its use in targeted, personalized medicine, where they could possibly carry large doses of therapeutic agents specifically into malignant cells while avoiding healthy cells. This review poses new possibilities in the large field of nanotechnology with special interest in the treatment of high grade brain tumours.

Prognostic Factors for Survival in Glioblastoma: A Retrospective Analysis Focused on the Role of Hemoglobin.

Background: Although several prognostic factors for survival have been identified in glioblastoma, there are numerous other potential markers (such as hemoglobin) whose role has not yet been confirmed. The aim of this study was to evaluate a wide range of potential prognostic factors, including HIF-1α and hemoglobin levels, for survival in glioblastoma. A secondary aim was to determine whether hemoglobin levels were associated with HIF-1α expression. Methods: A retrospective study of 136 patients treated for glioblastoma at our institution between 2012 and 2021 was performed. Cox univariate and multivariate analyses were carried out. Kaplan-Meier survival curves were generated. In addition, bivariate non-parametric correlation analyses were performed for key variables. Results: Median survival was 11.9 months (range: 0-119.4). According to the univariate analysis, 13 variables were significantly associated with survival: age, performance status, extent of surgery, tumor depth, tumor size, epilepsy, postoperative chemoradiotherapy, IDH mutations, CD44, HIF-1α, HIF-1ß, vimentin, and PDFGR. According to the multivariate regression analysis, only four variables remained significantly associated with survival: age, extent of surgery, epilepsy, and HIF-1α expression. No significant association was observed between hemoglobin levels (low <120 g/L in females or <140 g/L in males vs. high ≥120 or ≥140 g/L) and survival or HIF-1α/HIF-1ß expression. Conclusions: In this retrospective study of patients with glioblastoma, four variables-age, extent of surgery, HIF-1α expression, and epilepsy-were significant prognostic factors for survival. Hemoglobin levels were not significantly associated with survival or HIF-1α expression. Although hypoxia is a well-recognized component of the glioblastoma microenvironment, more research is needed to understand the pathogenesis of onset tumor hypoxia and treatment implication.

Diagnostic Utility of Immunohistochemical Detection of MEOX2, SOX11, INSM1 and EGFR in Gliomas.

Histological identification of dispersed glioma cells in small biopsies can be challenging, especially in tumours lacking the IDH1 R132H mutation or alterations in TP53. We postulated that immunohistochemical detection of proteins expressed preferentially in gliomas (EGFR, MEOX2, CD34) or during embryonal development (SOX11, INSM1) can be used to distinguish reactive gliosis from glioma. Tissue microarrays of 46 reactive glioses, 81 glioblastomas, 34 IDH1-mutant diffuse gliomas, and 23 gliomas of other types were analysed. Glial neoplasms were significantly more often (p < 0.001, χ2) positive for EGFR (34.1% vs. 0%), MEOX2 (49.3% vs. 2.3%), SOX11 (70.5% vs. 20.4%), and INSM1 (65.4% vs. 2.3%). In 94.3% (66/70) of the glioblastomas, the expression of at least two markers was observed, while no reactive gliosis showed coexpression of any of the proteins. Compared to IDH1-mutant tumours, glioblastomas showed significantly higher expression of EGFR, MEOX2, and CD34 and significantly lower positivity for SOX11. Non-diffuse gliomas were only rarely positive for any of the five markers tested. Our results indicate that immunohistochemical detection of EGFR, MEOX2, SOX11, and INSM1 can be useful for detection of glioblastoma cells in limited histological samples, especially when used in combination.

Flow Preserving Endovascular Treatment of Traumatic Pseudoaneurysms of the Distal Anterior Cerebral Artery-Case Reports and Review of Literature.

Traumatic intracranial pseudoaneurysms (tIPAs) are a very rare pathology caused by blunt or penetrating head trauma. Diagnostic and therapeutic challenges of tIPAs are due to their unpredictable onset during the initial injury, or in a delayed manner, their unclear traumatic mechanism. Moreover, the presence of subarachnoid, subdural, or intraventricular hematoma may often cause them to be overlooked, which can potentially be followed by lethal rebleeding. Treatment of these lesions is controversial and on a case-by-case basis with regard to endovascular therapy or open surgery. We report two cases of three tIPAs of the distal anterior cerebral artery (dACA) with immediate and delayed onset after the trauma. Endovascular therapy resulted in complete obliteration of lesions with flow preservation in the parent artery using the flow diverter-assisted coiling strategy. The aim of this manuscript is to discuss the mechanism, angioanatomical characteristics, and current treatment options for these exceptional lesions.

The Translesional Spinal Network and Its Reorganization after Spinal Cord Injury.

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.

7-Azaindole, 2,7-diazaindole, and 1H-pyrazole as core structures for novel anticancer agents with potential chemosensitizing properties.

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 IC50 around 10 µM. In contrast, the compound 22, 7-azaindole congener with the most pronounced cytotoxicity profile exceeding CDDP alone or in combination with CDDP, expressed the multi-kinase activity. Highlighted representatives, including compound 29, were also effective alone against primary glioblastoma. Overall, we showed that 7-azaindole, and 2,7-diazaindole scaffolds could be considered novel pharmacophores delivering anticancer activity.

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017-2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017-2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

Root resorption associated with ectopically erupting maxillary permanent canines: a computed tomography study.

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.

Understanding the Biological Basis of Glioblastoma Patient-derived Spheroids.

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.

Trends and outcomes for non-elective neurosurgical procedures in Central Europe during the COVID-19 pandemic.

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.

Moyamoya disease associated with fibromuscular dysplasia of intrapulmonary bronchial arteries-a case report.

A case is reported of a 40-year-old woman clinically diagnosed as moyamoya disease with associated fibromuscular dysplasia of intrapulmonary bronchial arteries incidentally revealed during autoptic examination. Moyamoya disease represents an idiopathic noninflammatory and nonatherosclerotic arterio-occlusive process of intracranial arteries. Prolonged brain ischemia leads to formation of tiny and fragile collaterals. Clinically, patients with moyamoya angiopathy commonly present with severe neurological symptoms caused by brain infarction or hemorrhage. Histologically, the steno-occlusive process is based on fibrocellular thickening of intima and intimal smooth muscle cell proliferation. In the literature, extracranial arterial involvement, i.e. fibromuscular dysplasia of renal or pulmonary arteries, has been described in several cases of moyamoya disease. Our aim is to show a unique case of moyamoya disease associated with fibromuscular dysplasia affecting an uncommon site.

New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats.

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's catheter, via laminectomy, at the level of T10. The balloon was rapidly inflated with 10 or 15 µL 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 µL 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 µL 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´s catheter. For a severe incomplete deficit, an inflated volume should be maintained at 15 µL.

Outcome of patients with negative CT angiography results for arterial occlusion treated with intravenous thrombolysis.

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.