Effect of prehospital advanced airway management on out-of-hospital cardiac arrest due to asphyxia: A JAAM-OHCA registry-based observational study in Japan.

Aim: To investigate the relationship between prehospital advanced airway management (AAM) and neurological outcomes in patients with asphyxia-related out-of-hospital cardiac arrest (OHCA). Methods: We retrospectively analyzed data from the Japanese Association for Acute Medicine OHCA registry between June 2014 and December 2017. Patients with asphyxia-related cardiac arrest aged ≥18 years were included. The primary outcome was a 1-month favorable neurological outcome (cerebral performance category [CPC] 1-2). Results: Of the 34,754 patients in the 2014-2017 JAAM-OHCA Registry, 1956 were included in our analysis. Cerebral performance category 1-2 was observed in 31 patients (1.6%), while CPC 3-5 was observed in 1925 patients (98.4%). Although prehospital AAM was associated with unfavorable neurological outcomes (odds ratio [OR], 0.269; 95% confidence interval [CI], 0.114-0.633; p = 0.003) in the univariate analysis, the association was not significant in the multivariate analysis. Compared with the AAM group, the non-AAM group showed increased rates of cardiac arrest after emergency medical service contact (4.3 vs. 7.2%, p = 0.009) and Glasgow Coma Scale ≥4 at hospital admission (1.9% vs. 4.7%, p = 0.004). Among the 903 patients for whom the time to return of spontaneous circulation (ROSC) could be calculated, the time from witnessed cardiac arrest to ROSC was significantly shorter (median, 8.5 vs. 37.0 min; p < 0.001) for those with favorable neurological outcomes than for those without. Conclusion: Prehospital AAM is not associated with improved neurological outcomes among those with asphyxia-related OHCA. However, the time from cardiac arrest to the first ROSC was significantly shorter among those with favorable outcomes.

Anti-tumor effects of perampanel in malignant glioma cells.

Glioblastoma has a poor prognosis even after multimodal treatment, such as surgery, chemotherapy and radiation therapy. Patients with glioblastoma frequently develop epileptic seizures during the clinical course of the disease and often require antiepileptic drugs. Therefore, agents with both antiepileptic and antitumoral effects may be very useful for glioblastoma treatment. Perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist, is an antiepileptic drug that is widely used for intractable epilepsy. The present study aimed to assess the potential antitumoral effects of perampanel using malignant glioma cell lines. The cell proliferation inhibitory effect was evaluated using six malignant glioma cell lines (A-172, AM-38, T98G, U-138MG, U-251MG and YH-13). A dose-dependent inhibitory effect of perampanel on cell viability was demonstrated; however, the sensitivity of cells to perampanel varied and further antitumoral effects were demonstrated in combination with temozolomide (TMZ) in certain malignant glioma cells. Furthermore, cell cycle distribution and apoptosis induction analyses were performed in T98G and U-251MG cells using a fluorescence activated cell sorter (FACS) and the expression levels of apoptosis-related proteins were evaluated using western blotting. No significant change was demonstrated in the proportions of cells in the G0/G1, S and G2/M phases under 1.0 µM perampanel treatment, whereas induction of apoptosis was demonstrated using FACS at 10 µM perampanel and western blotting at 1.0 µM perampanel in both glioma cell lines. Overexpression of SERPINE1 may be related to poor prognosis in patients with gliomas. The combination of 1.0 µM perampanel and 5.0 µM tiplaxtinin, a SERPINE1 inhibitor, demonstrated further reduced cell viability in perampanel-resistant U-138MG cells, which have high expression levels of SERPINE1. These results indicated that the antitumor effect of perampanel may not be expected for malignant gliomas with higher expression levels of SERPINE1. The findings of the present study suggested that the antiepileptic drug perampanel may also have an antitumor effect through the induction of apoptosis, which is increased when combined with TMZ in certain malignant glioma cells. These findings also suggested that SERPINE1 expression may be involved in perampanel susceptibility. These results may lead to new therapeutic strategies for malignant glioma.

Anti­tumor effects of anti­epileptic drugs in malignant glioma cells.

Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A­172, AM­38, T98G, U­138MG, U­251MG and YH­13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U­251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U­251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial­mesenchymal transition following perampanel treatment was analyzed using reverse transcription­quantitative PCR in the T98G and U­251MG cell lines. The expression of Rac1 and RhoA, which constitute the cytoskeleton that enhances cell motility, were reduced in both cell lines. Furthermore, the expression of the mesenchymal marker N­cadherin, which promotes cell migration and infiltration, was decreased, but the expression of the epithelial marker E­cadherin, which strengthens cell­cell adhesion and reduces cell motility, was increased. Furthermore, the expression of matrix metalloproteinase­2, a proteolytic enzyme, was reduced. These effects may reduce cell motility and increase adhesion between cells, suggesting that perampanel treatment suppressed cell migration. In conclusion, the present study suggests that perampanel may be more beneficial in terms of antitumor efficacy than other antiepileptic drugs for the treatment of malignant glioma.

Pneumomediastinum as patient self-inflicted lung injury in patients with acute respiratory distress syndrome due to COVID-19: a case series.

Background: In patients with coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 infection, pneumomediastinum has been increasingly reported in cases of noninvasive oxygen therapy, including high-flow nasal cannula, and invasive mechanical ventilation. However, its pathogenesis is still not understood. Case Presentation: We report two cases of pneumomediastinum in acute respiratory distress syndrome (ARDS) caused by COVID-19. In both cases, control of spontaneous breathing with neuromuscular blocking agents resulted in resolution of pneumoperitoneum. Conclusion: The improvement of pneumomediastinum with control of spontaneous breathing suggested patient self-inflicted lung injury as a possible mechanism in this case series. In ARDS cases with pneumomediastinum, in addition to controlling plateau pressure with conventional lung protective ventilation, spontaneous breathing should be controlled if the patient's inspiratory effort is suspected to be strong.

Pathophysiologic Mechanisms of Hypothermia-Induced Pancreatic Injury in a Rat Model of Body Surface Cooling.

OBJECTIVE: The mechanisms underlying hypothermia-induced pancreatic injury are unclear. Thus, we investigated the pathophysiology of hypothermia-induced pancreatic injury. METHODS: We created a normal circulatory model with body surface cooling in rats. We divided the rats into control (36°C-38°C), mild hypothermia (33°C-35°C), moderate hypothermia (30°C-32°C), and severe hypothermia (27°C-29°C) (n = 5 per group) groups. Then, we induced circulatory failure with a cooling model using high-dose inhalation anesthesia and divided the rats into control (36°C-38°C) and severe hypothermia (27°C-29°C) (n = 5 per group) groups. Serum samples were collected before the introduction of hypothermia. Serum and pancreatic tissue were collected after maintaining the target body temperature for 1 hour. RESULTS: Hematoxylin and eosin staining of the pancreas revealed vacuoles and edema in the hypothermia group. Serum amylase (P = 0.056), lactic acid (P < 0.05), interleukin 1ß (P < 0.05), interleukin 6 (P < 0.05), and tumor necrosis factor α (P = 0.13) levels were suppressed by hypothermia. The circulatory failure model exhibited pancreatic injury. CONCLUSIONS: Hypothermia induced bilateral effects on the pancreas. Morphologically, hypothermia induced pancreatic injury based on characteristic pathology typified by vacuoles. Serologically, hypothermia induced protective effects on the pancreas by suppressing amylase and inflammatory cytokine levels.

Antitumor effects of ribavirin in combination with TMZ and IFN-ß in malignant glioma cells.

The prognosis of gioblastoma, the standard chemotherapy agent for which is temozolomide (TMZ), remains poor despite recent advances in multimodal treatments. Therefore, it is necessary to identify and develop novel therapeutics for this malignant disease. Ribavirin, an anti-viral agent which is one of the standard agents for treatment of chronic hepatitis C in combination with interferon (IFN), was recently revealed to have an antitumor potential towards various tumor cells, including malignant glioma cells. The aim of the present study was to examine the antitumor effect of ribavirin in combination with TMZ and IFN-ß on glioma cells and to evaluate the possibility that such combinations might represent a novel candidate for glioblastoma therapy. The combination of ribavirin with TMZ and IFN-ß displayed a significant cell growth inhibitory effect with a ribavirin dose-dependency, including a relatively low concentration of ribavirin, on not only TMZ-sensitive but also TMZ-resistant malignant glioma cells. The antitumor efficacy of such a combination further indicated a synergistic interaction when assessed by the Chou-Talalay method. Furthermore, flow cytometry analysis suggested that apoptosis induction was one of the possible biological processes underlying the synergistic antitumor effect of these triple combination treatments. Therefore, such combinations may be potentially important in the clinical setting for glioblastoma treatment, although further detailed studies, e.g. on the adverse effects, are required.

IFN­ß sensitizes TRAIL­induced apoptosis by upregulation of death receptor 5 in malignant glioma cells.

Tumor necrosis factor­related apoptosis­inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, induces apoptosis in cancer cells by binding to its receptors, death receptor 4 (DR4) and DR5, without affecting normal cells, and is therefore considered to be a promising antitumor agent for use in cancer treatment. However, several studies have indicated that most glioma cell lines display resistance to TRAIL­induced apoptosis. To overcome such resistance and to improve the efficacy of TRAIL­based therapies, identification of ideal agents for combinational treatment is important for achieving rational clinical treatment in glioblastoma patients. The main aim of this study was to investigate whether interferon­ß (IFN­ß) (with its pleiotropic antitumor activities) could sensitize malignant glioma cells to TRAIL­induced apoptosis using glioma cell lines. TRAIL exhibited a dose­dependent antitumor effect in all of the 7 types of malignant glioma cell lines, although the intensity of the effect varied among the cell lines. In addition, combined treatment with TRAIL (low clinical dose: 1 ng/ml) and IFN­ß (clinically relevant concentration: 10 IU/ml) in A­172, AM­38, T98G, U­138MG and U­251MG demonstrated a more marked antitumor effect than TRAIL alone. Furthermore, the antitumor effect of the combined treatment with TRAIL and IFN­ß may be enhanced via an extrinsic apoptotic system, and upregulation of DR5 was revealed to play an important role in this process in U­138MG cells. These findings provide an experimental basis to suggest that combined treatment with TRAIL and IFN­ß may offer a new therapeutic strategy for malignant gliomas.

The prognostic value of agonal respiration in refractory cardiac arrest: a case series of non-shockable cardiac arrest successfully resuscitated through extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Agonal respiration following out-of-hospital cardiac arrest is associated with favorable neurological outcomes. Resuscitation using extracorporeal membrane oxygenation could contribute to achieving favorable neurological outcomes in patients with refractory cardiac arrest. CASE PRESENTATION: We report two cases of refractory cardiac arrest with non-shockable rhythms and agonal respiration; both patients were successfully resuscitated through extracorporeal cardiopulmonary resuscitation (ECPR). Both patients were breathing spontaneously upon arrival. One patient was asystolic and the other experienced pulseless electrical activity followed by ventricular fibrillation. Agonal respiration was observed in both and ECPR was implemented, leading to a favorable neurological outcome at discharge. CONCLUSION: The presence of agonal respiration has the potential to confer a favorable neurological outcome in patients with refractory cardiac arrest if maintained, even when the initial cardiac rhythm is not shockable. In these cases, resuscitation should not be abandoned, and ECPR should be considered.

Efficacy of ribavirin against malignant glioma cell lines: Follow-up study.

Ribavirin, a nucleic acid analog, has been employed as an antiviral agent against RNA and DNA viruses and has become the standard agent used for chronic hepatitis C in combination with interferon-α2a. Furthermore, the potential antitumor efficacy of ribavirin has attracted increasing interest. Recently, we demonstrated a dose-dependent antitumor effect of ribavirin for seven types of malignant glioma cell lines. However, the mechanism underlying the antitumor effect of ribavirin has not yet been fully elucidated. Therefore, the main aim of the present study was to provide further relevant data using two types of malignant glioma cell lines (U-87MG and U-138MG) with different expression of MGMT. Dotted accumulations of γH2AX were found in the nuclei and increased levels of ATM and phosphorylated ATM protein expression were also observed following ribavirin treatment (10 µM of ribavirin, clinical relevant concentration) in both the malignant glioma cells, indicating double-strand breaks as one possible mechanism underlying the antitumor effect of ribavirin. In addition, based on assessements using FACS, ribavirin treatment tended to increase the G0/G1 phase, with a time­lapse, indicating the induction of G0/G1-phase arrest. Furthermore, an increased phosphorylated p53 and p21 protein expression was confirmed in both glioma cells. Additionally, analysis by FACS indicated that apoptosis was induced following ribavirin treatment and caspase cascade, downstream of the p53 pathway, which indicated the activation of both exogenous and endogenous apoptosis in both malignant glioma cell lines. These findings may provide an experimental basis for the clinical treatment of glioblastomas with ribavirin.

Evaluating quality indicators of tertiary care hospitals for trauma care in Japan.

OBJECTIVE: This study examined the associations between trauma mortality and quality of care indicators currently used in Japan. DESIGN: This is a retrospective two-level discrete-time survival analysis. Quality indicators were derived from the 2012-2013 annual hospital survey conducted by the Ministry of Health, Labour and Welfare. Trauma mortality data were derived from the Japan Trauma Data Bank for the period of April 2012 to March 2013. SETTING: Tertiary care centers designated as emergency and critical care centers (ECCCs) in Japan. PARTICIPANTS: The analysis included 12 378 patients aged ≥15 years with blunt trauma and an Injury Severity Score ≥9, registered to the data bank from 91 ECCCs. INTERVENTION: Quality of care indicators examined in the annual hospital survey. MAIN OUTCOME MEASURES: Deaths within 30 days. RESULTS: Of the 12 378 patients, 660 (5%) died within 30 days. Higher indicator score was significantly associated with lower mortality risk (hazard ratio [HR] for the second, third and fourth quartiles vs. lowest quartile 0.61, 0.55 and 0.52, respectively). Factors significantly associated with lower mortality risk were, higher patient volume (HR for the highest vs. lowest quartile, 0.74), director's qualification as specialist (HR 0.57) or consultant (HR 0.58), review of patient arrival process (HR 0.68), triage functions (HR 0.69), availability of psychiatrists (HR 0.75) and operating room being ready 24-h (HR 0.81). CONCLUSIONS: The study identified certain indicators associated with trauma patient mortality. Further refinement of indicators is required to specifically identify what needs changing.

Comparison of registry and government evaluation data to ascertain severe trauma cases in Japan.

Aims: Accurate evaluation of health care quality requires high-quality data, and case ascertainment (confirming eligible cases and deaths) is a foundation for accurate data collection. This study examined the accuracy of case ascertainment from two Japanese data sources. Methods: Using hospital-level data, we investigated the concordance in ascertaining trauma cases between a nationwide trauma registry (the Japan Trauma Data Bank) and annual government evaluations of tertiary hospitals between April 2012 and March 2013. We compared the median values for trauma case volumes, numbers of deaths, and case fatality rates from both data sources, and also evaluated the variability in discrepancies for the intrahospital differences of these outcomes. Results: The analyses included 136 hospitals. In the registry and annual evaluation data, the median case volumes were 120.5 cases and 180.5 cases, respectively; the median numbers of deaths were 11 and 12, respectively; and the median case fatality rates were 8.1% and 6.4%, respectively. There was broad variability in the intrahospital differences in these outcomes. Conclusions: The observed discordance between the two data sources implies that these data sources may have inaccuracies in case ascertainment. Measures are needed to evaluate and improve the accuracy of data from these sources.

Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus.

We examined the effects of silymarin, which was extracted from Silybum marianum, on delayed neuronal cell death in the rat hippocampus. Rats were divided into four groups: sham-operated rats (sham group), rats which underwent ischemic surgery (control group), rats which were treated with silymarin before and after ischemic surgery (pre group), and rats which were treated with silymarin after ischemic surgery only (post group). We performed the ischemic surgery by occluding the bilateral carotid arteries for 20min and sacrificed the rats one week after the surgery. Silymarin was administered orally at 200mg/kg body weight. Smaller numbers of delayed cell deaths were noted in the rat CA1 region of the pre- and post-groups, and no significant difference was observed between these groups. There were few apoptotic cell deaths in all groups. Compared to the control group, significantly fewer cell deaths by autophagy were found in the pre- and post-group. We concluded that silymarin exerts a preservation effect on delayed neuronal cell death in the rat hippocampus and this effect has nothing to do with the timing of administering of silymarin.

Antitumorigenic effect of interferon-ß by inhibition of undifferentiated glioblastoma cells.

Glioma stem-like cells (GSCs) are undifferentiated cells that are considered to be an origin of glioblastomas. Furthermore, they may contribute to treatment resistance and recurrence in glioblastomas. GSCs differentiate into differentiated glioma cells (non-glioma stem-like cells: non­GSCs), and interconversion might occur between GSCs and non-GSCs. We investigated whether interferon-beta (IFN-ß) could exert any efficacy towards GSCs or such interconversion processes. The neural stem cell marker CD133 and pluripotency marker Nanog in GSCs were analyzed to evaluate their differentiation levels. GSCs were considered to undergo differentiation into non-GSCs upon serum exposure, since the expression of CD133 and Nanog in the GSCs was negatively affected. Furthermore, the cells regained their undifferentiated features upon removal of the serum. However, we verified that IFN-ß reduced cell proliferation and tumor sphere formation in GSCs, and induced suppression of the restoration of such undifferentiated features. In addition, we also confirmed that IFN-ß suppressed the acquisition process of undifferentiated features in human malignant glioma cell lines. Our data thus suggest that IFN-ß could be an effective agent not only through its cell growth inhibitory effect on GSCs but also as a means of targeting the interconversion between GSCs and non-GSCs, indicating the possibility of IFN-ß being used to prevent treatment resistance and recurrence in glioblastomas, via the inhibition of undifferentiated features.

Characterization of glioma stem-like cells from human glioblastomas.

Glioma stem-like cells (GSCs) could have potential for tumorigenesis, treatment resistance, and tumor recurrence (GSC hypothesis). However, the mechanisms underlying such potential has remained elusive and few ultrastructural features of the cells have been reported in detail. We therefore undertook observations of the antigenic characteristics and ultrastructural features of GSCs isolated from human glioblastomas. Tumor spheres formed by variable numbers of cells, exhibiting a variable appearance in both their size and shape, were frequently seen in GSCs expressing the stem cell surface markers CD133 and CD15. Increased cell nucleus atypia, mitochondria, rough endoplasmic reticulum, coated vesicles, and microvilli, were noted in the GSCs. Furthermore, cells at division phases and different phases of the apoptotic process were occasionally observed. These findings could imply that GSCs have certain relations with human neural stem cells (NSCs) but are primitively different from undifferentiated NSCs. The data may provide support for the GSC hypothesis, and also facilitate the establishment of future glioblastoma treatments targeting GSCs.

Primary Sellar Neuroblastoma in an Elderly Patient: Case Report.

A 71-year-old male presented with an isolated well-enhanced sellar lesion accompanied by hypopituitarism, diagnosed preoperatively as a pituitary adenoma, meningioma, or metastatic brain tumor. However, histological examinations yielded a diagnosis of neuroblastoma. Primary sellar neuroblastoma in the elderly is very rare. We therefore describe this case of primary sellar neuroblastoma, mimicking common pituitary tumor, and review the literature. There have so far been only nine reported cases of primary sellar neuroblastoma in the English literature. All reports like the present case, demonstrated similar neuroimaging of a "dumbbell-shaped extension in the sellar region." Moreover, the tumors may exhibit characteristic features, such as rapid tumor growth, hypopituitarism, or oculomotor nerve palsy, and these findings may represent helpful signs for the diagnosis of primary sellar neuroblastoma.

Efficacy of ribavirin against malignant glioma cell lines.

Ribavirin (1-ß-D-ribofuranosy-1,2,4-triazole-3-carboxamide) has been widely administered as an antiviral agent against RNA and DNA viruses. Ribavirin, in combination with interferon, has predominantly been applied in the treatment of the hepatitis C virus infection and its potential antitumor efficacy has recently become a point of interest. The aim of the present study was to evaluate the effect of ribavirin on the growth of malignant glioma cells, to identify novel predictive genes in malignant glioma cells (by analyzing gene expression profiles) and to assess the influence of ribavirin on the cell cycle of malignant glioma cells. The present study evaluated the antitumor efficacy of ribavirin against various malignant glioma cell lines (A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG and YH-13). After culturing the cells in ribavirin-containing culture medium (final concentration, 0-1,000 µM) for 72 h, the viable proliferated cells were harvested and counted. The half maximal inhibitory concentration of ribavirin, with regard to the growth of the malignant glioma cell lines, was determined from the concentration of ribavirin required for 50% growth inhibition in comparison to the untreated control cells. Furthermore, the current study identified the genes in which the gene expression levels correlated with the ribavirin sensitivity of the malignant glioma cells lines, using a high-density oligonucleotide array. Finally, cell cycle analysis was performed on the U-87MG cell line. It was identified that ribavirin inhibited the growth of all of the malignant glioma cell lines in a dose-dependent manner, although the ribavirin sensitivity varied between each cell line. Of the extracted genes, PDGFRA demonstrated the strongest positive correlation between gene expression level and ribavirin sensitivity. Cell cycle analysis of the U-87MG cell line demonstrated that ribavirin treatment induces G0/G1 arrest and thus may be an effective agent for inhibiting malignant glioma cell growth. Therefore, the results of the current study indicate that ribavirin may have potential as a therapeutic agent in the treatment of malignant gliomas.

Outcome and surgical management for geriatric traumatic brain injury: analysis of 888 cases registered in the Japan Neurotrauma Data Bank.

OBJECTIVE: As the aged population is rapidly growing globally, geriatric traumatic brain injury (TBI) becomes an increasing problem. There are higher mortality and poorer functional outcome in the geriatric TBI population (≥65 years) compared with younger groups despite neurosurgical interventions. Therefore, current treatment priorities and cost-effectiveness should be critically examined. We evaluated the benefit of surgical management in the elderly (≥65 years) after TBI. METHODS: A total of 3194 patients with confirmed TBI were enrolled from 1998 to 2011, in the Japan Neurotrauma Data Bank. Retrospective analysis was conducted from the Japan Neurotrauma Data Bank on 888 (28%) patients (≥65 years) who did and did not undergo surgery. In particular, the effect of low Glasgow coma scale (GCS) (3-5) was compared with outcome with and without surgery. RESULTS: Of all the patients 65 years of age and over, 478 (54%) were given surgical management (craniectomy, craniotomy, or burr-hole evacuation). This group of patients had significantly more favorable outcome at 6 months (18% vs. 7%) and less mortality (62% vs. 81%). However, within this surgical group, patients with initial GCS scores of 3-5 had significantly more unfavorable outcome (96% vs. 79%) and more mortality (87% vs. 57%) compared with those with GCS scores of 6-15. CONCLUSIONS: We confirmed that age is a major determinant of outcome after TBI. In addition, we found that neurosurgical management is associated with the improvement of the prognosis and a decrease in the rate of mortality in geriatric TBI. However, surgical management was not shown to be an effective treatment in elderly patients with GCS scores of 3-5.

[Intrathecal baclofen treatment for spasticity in childhood . initial report of long-term follow up in Japan].

OBJECTIVE: Initial outcome of intrathecal baclofen (ITB) treatment in Japan is being reported on. METHODS: Chronological change of the Ashworth scale and complications after surgery were analyzed. Data were obtained from 71 children with severe spasticity who had received ITB screening tests by the end of March 2012. RESULTS: Pump implantations for ITB treatment were performed in 43 children out of 62 whose spasticity reduced after baclofen injection at the screening tests. Postoperative evaluations of ITB treatment were carried out within one year and, in some cases, more than 2 years after surgery. Complications related to baclofen were reported on 19 occasions in 12 children within one year of ITB pump implantation, and on 9 occasions in 4 children of the 21 who were followed for more than 2 years. Main complications were hypertonia of muscle, liver dysfunction, and low blood pressure. The frequency of complications was lower than that reported previously. There was no apparent evidence to indicate that complications developed more in children than in adults in this study. The postoperative values of Ashworth scale in the upper and lower extremities were reduced markedly when compared with preoperative levels, and the improvements were statistically significant (P < 0.05). CONCLUSIONS: This is the first report of outcome of ITB for severely disabled children with spasticity in Japan. It was confirmed that ITB for children with severe spasticity is a safe and effective treatment.

Physiological mechanism of increase in deoxy-hemoglobin concentration during neuronal activation in patients with cerebral ischemia: a simulation study with the balloon model.

Patients with cerebral ischemia or brain tumor have been reported to exhibit an increase of deoxygenated hemoglobin (deoxy-Hb) together with an increase of oxygenated hemoglobin (oxy-Hb). However, the physiological mechanisms underlying this hemodynamic response pattern are unclear. In this study, we performed a simulation using the balloon model (Buxton et al., Magn Reson Med 39:855-864, 1998). We hypothesized that the oxygen extraction rate during the rest period (E 0) in the patients is larger than in normal subjects, because the cerebral blood flow and the speed at which the blood passes through the brain tissues are lower in the patients. The simulation result showed an increase of deoxy-Hb as well as oxy-Hb, especially when E 0 is extremely high. Thus, the results of our simulation suggest that the increase of deoxy-Hb during activation in patients with ischemia or brain tumor is caused by an increased oxygen extraction rate at rest, compared with that of healthy adults.

Granular cell tumor of the neurohypophysis with optic tract edema.

Granular cell tumor of the neurohypophysis is a rare disease entity. To our knowledge, this is the first report concerning a granular cell tumor of the neurohypophysis associated with optic tract edema. A 55-year-old man underwent brain magnetic resonance imaging (MRI) for a medical check-up, and a suprasellar tumor was detected. Brain computed tomography (CT) demonstrated a well delineated, homogenous, slightly hyperdense suprasellar tumor. MRI detected a lobular tumor that was isointense on T1-weighted images, hypointense on T2-weighted images, and showed homogeneous enhancement after administration of a gadopentetate dimeglumine. T2-weighted images and fluid-attenuated inversion recovery (FLAIR) images demonstrated a hyperintense region in the optic tract. Subtotal tumor resection was performed, and histological examination confirmed the diagnosis of granular cell tumor. Postoperative MRI showed that the tumor volume was reduced and optic tract edema diminished compared with the preoperative findings. We also review the literature focusing on radiographic findings, and compare the effectiveness of MRI and CT for diagnosing granular cell tumor of the neurohypophysis.