Efficacy and safety of intraventricular fibrinolytic therapy for post-intraventricular hemorrhagic hydrocephalus in extreme low birth weight infants: a preliminary clinical study.

PURPOSE: To evaluate the efficacy and safety of our unique therapy for treating post-intraventricular hemorrhagic hydrocephalus (PIVHH) in low birth weight infants (LBWls) through an early stage fibrinolytic therapeutic strategy involving urokinase (UK) injection into the lateral ventricle, called the "Ventricular Lavage (VL) therapy." METHODS: Overall, 43 consecutive infants with PIVHH were included. Most were extremely LBWIs (n = 39). Other cases included very LBWIs (n = 2) and full-term infants (n = 2). VL therapy involved continuous external ventricular drainage (EVD) management using a very fine catheter and intermittent slow injection of 6000 IU of UK every 3-6 h to actively dissolve hematomas. RESULTS: Early EVD management (within 3 weeks of IVH onset) was performed in 25 infants, with combination VL therapy in 21 infants. Five initiated late EVD management (≥ 3 weeks after IVH onset); the remaining 13 were treated conservatively for several weeks, delaying surgical intervention. Eighteen of 21 (86%) infants who received VL therapy did not require permanent shunt surgery. There were no serious complications, including the absence of secondary hemorrhage and infection. Two-thirds of the infants treated in the late stages required permanent shunt, and various shunt-related complications frequently occurred. A good outcome occurred in 13/17 infants in the early treatment group, despite most subjects having an IVH grade IV, and in 6/15 in the late treatment group. CONCLUSIONS: Permanent shunt surgery needs were dramatically reduced following early VL therapy, and functional outcomes were favorable. VL therapy might be a promising strategy that could lead to the development of new treatments for PIVHH.

Greenstick fracture-hinge decompressive craniotomy in infants: illustrative case and literature review of techniques for decompressive craniotomy without bone removal.

PURPOSE: We present the potential usefulness of a greenstick fracture-hinge decompressive craniotomy, a variant of a hinge-craniotomy, as an alternative technique for use with a decompressive craniectomy (DC) in infants. A literature review of hinge-craniotomy procedures and technical variants is also provided, with a focus on complications associated with a DC peculiar to infants and children. METHODS: Illustrative case presentation along with literature review. RESULT: Significant rates of complications associated with a DC and subsequent cranioplasty have been reported, such as bone flap resorption, hydrocephalus, cerebrospinal fluid collection, and infection, especially in infants. A hinge-craniotomy is an older technique reported to have potential usefulness with some modifications, though concerns have been raised about adequate decompression and definitive indications. CONCLUSION: A DC procedure performed in children, especially infants, includes a significantly high risk of various complications; thus, a hinge-craniotomy technique is worthwhile for consideration to avoid such complications. Additional studies are required to clarify whether this technique may contribute to reduce complications related to a DC in infants and children.

Systematic exploitation of thermotropic bicontinuous cubic phase families from 1,2-bis(aryloyl)hydrazine-based molecules.

Rational design of molecules that exhibit a thermotropic bicontinuous cubic (Cub) phase has been earnestly desired. In this work, we describe the suitable selection of a molecular motif that has enabled the systematic exploitation of eight new series of Cub-phase molecules with symmetric molecular cores, N-n (1), PB-n (2), S-n (3), and PEB-n (4), and unsymmetric cores, B-N-n (5), B-PB-n (6), B-S-n (7), and B-PEB-n (8). These eight series all originate from achiral chain-core-chain type rod-like molecules that exhibit two types of Cub phases, an achiral Ia3d phase, and a chiral phase. All the Ia3d phases formed were found to be isomorphous structures, with their cell dimensions being proportional to the core size, and the same was true for the latter chiral phase. We demonstrated that the formation is mainly governed by the segregation between core and alkyl moieties of the molecules, and thus, by the weight fraction of the core portion fcore. This work also demonstrates that the central dicarbonylhydrazine linkage bearing intermolecular hydrogen bonding ability exhibits a pinning effect that prevents slippage of π-stacks of molecules, which is critical for the formation of the two Cub phases that are composed of chiral networks with twisted molecular arrangements. In each series, the emergence of spontaneous chirality formation that occurred in the chiral phase was limited to between 0.36 and 0.50 in the range of fcore. An interesting insight was that the introduced unsymmetry of the molecular core strongly influenced the phase behavior, which lowered the temperature range of Cub phases to around that of the smallest core series B-n, while the high temperature limit (Tc) was roughly proportional to the core size, as determined by the strength of intermolecular π-π interactions.

A mitochondrial thioredoxin-sensitive mechanism regulates TGF-ß-mediated gene expression associated with epithelial-mesenchymal transition.

Transforming growth factor (TGF)-ß is a pro-oncogenic cytokine that induces the epithelial-mesenchymal transition (EMT), a crucial event in tumor progression. During TGF-ß-mediated EMT in NMuMG mouse mammary epithelial cells, we observed sustained increases in reactive oxygen species (ROS) levels in the cytoplasm and mitochondria with a concomitant decrease in mitochondrial membrane potential and intracellular glutathione levels. In pseudo ρ0 cells, whose respiratory chain function was impaired, the increase in intracellular ROS levels was abrogated, suggesting an important role of mitochondrial activity as a trigger for TGF-ß-stimulated ROS generation. In line with this, TGF-ß-mediated expression of the EMT marker fibronectin was inhibited not only by chemicals that interfere with ROS signaling but also by exogenously expressed mitochondrial thioredoxin (TXN2) independent of Smad signaling. Of note, TGF-ß-mediated induction of HMGA2, a central mediator of EMT and metastatic progression, was similarly impaired by TXN2 expression, revealing a novel mechanism involving a thiol oxidation reaction in mitochondria, which regulates TGF-ß-mediated gene expression associated with EMT.

Cytotoxic human peripheral blood-derived γδT cells kill glioblastoma cell lines: implications for cell-based immunotherapy for patients with glioblastoma.

Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate the feasibility of γδT cell-based immunotherapy for patients with GBM, we focused on the killing of GBM cell lines by γδT cells and the molecular mechanisms involved in these cell-cell interactions. Peripheral blood mononuclear cells were expanded in ZOL and interleukin (IL)-2 for 14 days, and γδT cells were enriched in the expanded cells by the immunomagnetic depletion of αßT cells. Gliomas are resistant to NK cells but susceptible to lymphokine-activated killer cells and some cytotoxic T lymphocytes. When the γδT cell-mediated killing of three GBM cell lines (U87MG, U138MG and A172 cells) and an NK-sensitive leukemia cell line (K562 cells) were tested, 32% U87MG, 15% U138MG, 1% A172, and 50% K562 cells were killed at an effector:target ratio of 5:1. The γδT cell-mediated killing of all three GBM cell lines was significantly enhanced by ZOL and this ZOL-enhanced killing was blocked by an anti-T cell receptor (TcR) antibody. These results indicated that TcR γδ is crucial for the recognition of ZOL-treated GBM cells by γδT cells. Since the low level killing of GBM cells by the γδT cells was enhanced by ZOL, γδT cell-targeting therapy in combination with ZOL treatment could be effective for patients with GBM.

Communicating Syringomyelia.

BACKGROUND: Communicating syringomyelia can develop in association with hydrocephalus, with communication between syringomyelia and the fourth ventricle a representative neuroimaging finding. CASE DESCRIPTION: A 51-year-old woman presented with slowly progressive bladder dysfunction and scoliosis. She had a nonfunctioning cerebrospinal fluid shunt that had been placed after birth for neonatal hydrocephalus. Tetraventricular enlargement and a holocord syrinx were noted in neuroimaging findings, while phase contrast magnetic resonance imaging and ventriculography revealed communication between the syrinx and fourth ventricle via a dilated central canal. Placement of a de novo ventriculoperitoneal shunt led to collapse of the syringomyelia, though apparent improvement of clinical symptoms was not obtained. CONCLUSIONS: Communicating syringomyelia can develop as a late complication in patients with shunted hydrocephalus. In the majority of reported cases, shunt revision has been shown to be effective, though some cases require posterior fossa decompression and exploration.

Linac-based fractionated stereotactic radiotherapy with a micro-multileaf collimator for large brain metastasis unsuitable for surgical resection.

The aim of this study was to assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018 we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor with ≥30 mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n = 17, 81%), ovary (n = 2, 9.5%), rectum (n = 1, 4.8%) and esophagus (n = 1, 4.8%). The median pretreatment Karnofsky performance status was 50 (range: 50-80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1-86 months). The range of tumor volume was 8.7-26.5 cm3 (median: 17.1 cm3). All patients were basically treated with 35Gy in 5 fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.

Linac-Based Fractionated Stereotactic Radiotherapy with a Micro-Multileaf Collimator for Brainstem Metastasis.

BACKGROUND: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. RESULTS: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. CONCLUSIONS: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.

Gradually Progressive Symptoms of Normal Pressure Hydrocephalus Caused by an Arachnoid Cyst in the Fourth Ventricle: a Case Report.

BACKGROUND: Arachnoid cysts in the fourth ventricle are extremely rare, with only 13 cases having been described in the literature. Especially, only 1 case of a patient older than 70 years has been reported. Arachnoid cysts in the fourth ventricle may cause obstructive hydrocephalus. Here, we report the case of a 72-year-old man who presented with an arachnoid cyst in the fourth ventricle that caused gradually progressive symptoms of normal pressure hydrocephalus. METHODS: A 72-year-old man complaining of persistent dizziness and gait difficulty was admitted to our hospital due to a gradual worsening of his symptoms and apparent cognitive impairment. Computed tomography scan of the head showed symmetrically dilated third, fourth, and lateral ventricles. RESULT: Though we performed a ventriculoperitoneal shunt operation, his trunk ataxia persisted. We finally diagnosed an arachnoid cyst in the fourth ventricle by direct ventricular infusion of enhanced material. We performed direct surgical fenestration of the cyst and achieved a good outcome. CONCLUSION: Arachnoid cysts of the fourth ventricle are exceedingly rare, but it is important to recognize them because they cause normal pressure hydrocephalus symptoms and cerebellar or brainstem deficit. We propose detailed neurologic and radiologic examinations of patients with normal pressure hydrocephalus symptoms to avoid unnecessary shunt.

Effectiveness of intraoperative indocyanine green videoangiography in direct surgical treatment of pediatric intracranial pial arteriovenous fistula.

Intracranial pial arteriovenous fistulas (AVFs) are rare cerebrovascular lesions. The authors report a rare case of pediatric pial AVF treated by direct disconnection with the aid of indocyanine green (ICG) videoangiography. A 3-year-old girl presented with developmental problems. Magnetic resonance imaging revealed brain atrophy and an anomalous left temporal vascular mass. Angiography showed a high-flow pial AVF in the early arterial phase fed by the M1 portion of the left middle cerebral artery and draining into the superficial sylvian vein and the vein of Trolard with a large varix. Given that her fistula was located in a superficial region that was easily accessible by craniotomy, the authors successfully disconnected her pial AVF by direct surgery aided by ICG videoangiography, which clearly confirmed the shunting point. In this report, the authors discuss the existing literature and compare the relative merits of endovascular versus surgical options for the treatment of pial AVF.

Intracranial meningioma as initial clinical manifestation of occult lung carcinoma: case report.

Intracranial meningioma with intratumor metastasis have been occasionally reported. However, to our knowledge, there are almost no reports of malignant tumors initially discovered due to metastasis to meningioma. A 74-year-old woman presented with amnesia. Magnetic resonance imaging showed a well-defined mass arising from falcotentorial junction and homogeneous enhancement. Histopathologic findings showed that the mass was a meningothelial meningioma, with the majority of the tumor cells propagating in sheets, however, a single area in the tumor tissue showed the different histology. Immunohistologically, cytokeratin 7 (CK7), thyroid transcription factor-1 (TTF-1), and Napsin were positive, which led to lung adenocarcinoma metastasis. Furthermore, E-cadherin staining showed a 70% positive rate in lung adenocarcinoma and 30% in meningothelial meningioma. We report our experiences regarding a case of lung cancer that metastasized to intracranial meningioma and its clinical presentation and pathology.

Comparison between two separate injections and a single injection of double-dose contrast medium for contrast-enhanced MR imaging of metastatic brain tumors.

PURPOSE: As stereotactic radiotherapy (SRT) becomes widespread, precise information including number, location, and margin of lesions is required when magnetic resonance (MR) imaging of brain metastasis is performed. We compare methods using 2 separate injections and a single injection for the administration of a double dose of contrast medium for contrastenhanced MR imaging. MATERIALS AND METHODS: We divided 40 patients with brain metastasis into 2 groups of 20 patients. Group A received 2 separate injections (0.2 + 0.2 mL/kg) of contrast medium (gadoteridol); Group B received a single injection of the same total dose (0.4 mL/kg). Group A underwent spin echo (SE) T1-weighted imaging (T1WI) and magnetization prepared rapid acquisition with gradient echo sequence (MPRAGE) after each injection, and Group B underwent the same MR studies at the same timing as Group A. We evaluated the number, signal-to-noise ratio (SNR), diameter, margin delineation, and volume of lesions and compared them between early and delayed studies by the 2 methods. RESULTS: The number of detected lesions was largest in delayed studies of MPRAGE in both groups. The SNR of the lesions was statistically lower in early studies of Group A than other studies. Delayed studies of Group B showed statistically better margin delineation than other studies on both SE-T1WI and MPRAGE studies. Diameter and enhanced volume were statistically significantly larger on delayed phase than early phase in both groups. CONCLUSION: Use of a single injection of double-dose contrast medium and longer delay time may improve margin delineation of lesions for the study of brain metastasis. Enhanced volume was larger on delayed phase, and it may influence selection of therapeutic strategy.