Thymic stromal lymphopoietin contributes to ozone-induced exacerbations of eosinophilic airway inflammation via granulocyte colony-stimulating factor in mice.

BACKGROUND: Ozone is one of the triggers of asthma, but its impact on the pathophysiology of asthma, such as via airway inflammation and airway hyperresponsiveness (AHR), is not fully understood. Thymic stromal lymphopoietin (TSLP) is increasingly seen as a crucial molecule associated with asthma severity, such as corticosteroid resistance. METHODS: Female BALB/c mice sensitized and challenged with house dust mite (HDM) were exposed to ozone at 2 ppm for 3 h. Airway inflammation was assessed by the presence of inflammatory cells in bronchoalveolar lavage fluid and concentrations of cytokines including TSLP in lung. Anti-TSLP antibody was administered to mice to block the signal. Survival and adhesion of bone marrow-derived eosinophils in response to granulocyte colony-stimulating factor (G-CSF) were evaluated. RESULTS: Ozone exposure increased eosinophilic airway inflammation and AHR in mice sensitized and challenged with HDM. In addition, TSLP, but not IL-33 and IL-25, was increased in lung by ozone exposure. To confirm whether TSLP signaling is associated with airway responses to ozone, an anti-TSLP antibody was administered, and it significantly attenuated eosinophilic airway inflammation, but not AHR. Interestingly, G-CSF, but not type 2 cytokines such as IL-4, IL-5, and IL-13, was regulated by TSLP signaling associated with eosinophilic airway inflammation, and G-CSF prolonged survival and activated eosinophil adhesion. CONCLUSIONS: The present data show that TSLP contributes to ozone-induced exacerbations of eosinophilic airway inflammation and provide greater understanding of ozone-induced severity mechanisms in the pathophysiology of asthma related to TSLP and G-CSF.

Sinus pericranii associated with syntelencephaly: a case report.

BACKGROUND: Sinus pericranii is a rare cranial venous malformation resulting in a subcutaneous mass due to abnormal communication between intracranial and subperiosteal/interperiosteal veins. To date, to the best of our knowledge, there are no reports of sinus pericranii associated with syntelencephaly, a subtype of lobar holoprosencephaly. We herein report a case of sinus pericranii associated with syntelencephaly. This report can provide us better understanding of the etiology of sinus pericranii, the potential risks, and the treatment options for these patients. CASE PRESENTATION: A 2-year-4-month old female patient who received the diagnosis of syntelencephaly as a neonate presented with a subcutaneous mass in the parietal region. The mass was soft, nonpulsatile, 3 × 2 cm in size, and showed enlargement in the lying position. Color cranial Doppler ultrasound, head magnetic resonance imaging (MRI), and cerebral angiography revealed a dilated vessel passing through the parietal bone and forming a communication between the superior sagittal sinus and scalp veins. Based on these findings, sinus pericranii was diagnosed. The head MRI also showed coronal craniosynostosis, a tight posterior fossa. At age 2 years and 7 months, the patient underwent a transection of the sinus pericranii and the mass resolved without any complications or recurrences for more than 2.5 years to date. CONCLUSION: Sinus pericranii is a rare cranial and venous malformation sometimes accompanied by brain malformations or craniosynostosis that may become more apparent as the brain and skull develop. Since this condition can be complicated by intracranial hemorrhage and sinus thrombosis, early detection is necessary to determine the treatment options. Physicians should be alert to the possibility of this condition if they observe a soft cranial mass that appears to decrease in size in the sitting position and bulge in the lying position.

Repeat endoscopic third ventriculostomy combined with choroid plexus cauterization as salvage surgery for failed endoscopic third ventriculostomy.

PURPOSE: Although the endoscopic third ventriculostomy (ETV) is an effective treatment for hydrocephalus, failures do on occasion occur. In such cases, a repeat ETV or shunt insertion is usually performed. However, there is, as of yet, no clear consensus on the best measure to take in the event of a failed ETV. We herein examined the outcomes of a repeat ETV combined with choroid plexus cauterization for ETV failure. METHODS: All patients who underwent an ETV at the Department of Neurosurgery at Tokyo Metropolitan Children's Medical Center between April 2013 and March 2019 were retrospectively analyzed. RESULTS: In total, 36 patients received an ETV. Six patients experienced ETV failure; three of these underwent a repeat ETV combined with choroid plexus cauterization. Three of the six patients who experienced early ETV failure received a ventriculoperitoneal shunt. During the median follow-up period of 42 months (range: 32-73 months), all repeat ETVs were successful. CONCLUSION: A repeat ETV combined with choroid plexus cauterization can be an effective salvage therapy in the event of ETV failure.

Flow diverter stents for pediatric traumatic carotid cavernous fistula: a case report and literature review.

A 10-year-old, male patient with a head injury caused by a fall presented with chemosis, exophthalmos, right orbital bruit, and intracranial venous reflux, based on which posttraumatic carotid cavernous fistula (CCF) was diagnosed. Coil embolization was semi-urgently performed for the dangerous venous drainage. After the treatment, right abducens nerve palsy newly appeared. To treat the neurological symptoms and preserve the parent artery, curative endovascular treatment using a pipeline embolization device (PED) with coil embolization was performed after starting dual antiplatelet therapy (DAPT). The CCF and abducens nerve palsy finally resolved, and the internal carotid artery (ICA) was remodeled. Use of the PED with adjunctive coil embolization was effective and safe in the present case of pediatric traumatic direct CCF.

Nonsurgical treatment of cerebral ischemia associated with ACTA2 cerebral arteriopathy: a case report and literature review.

Mutations in ACTA2 gene can lead to multisystemic smooth muscle dysfunction, including cerebrovascular disease. Treatment strategies for this rare entity remain controversial, and patients are at increasing risk of neurological sequelae. We herein present the case of an 11-year-old boy previously diagnosed with an ACTA2 gene mutation who developed repetitive transient ischemic attacks and treated with bosentan, an oral endothelin receptor antagonist. Magnetic resonance imaging revealed bilateral, periventricular white matter T2 hyperintensities, and magnetic resonance angiography identified several abnormalities including fusiform dilatation in the proximal segments of internal cerebral arteries, together with followed by terminal segmental stenosis. The distal branches showed a markedly straightened course with no increase in lenticulostriate collaterals. Magnetic resonance imaging also revealed an increase in the number and size of large periventricular white matter lesions located in the left frontal lobe with the progression of ischemic symptoms. Instead of revascularization surgery, the administration of bosentan was started due to the high risk of perioperative ischemic sequelae. After bosentan initiation, the patient's repetitive episodes of cerebral ischemia ceased, and there has been no increase in the number of white matter lesions for 7 years. Bosentan might be beneficial for treating cerebral ischemia associated with ACTA2 cerebral arteriopathy by maintaining the dilatation of stenotic vessels and adequate systemic blood flow and should be considered before performing revascularization surgery.

[Ommaya Reservoir and the External Ventricular Drainage].

Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of hydrocephalus pathologies, treatment options are limited. It is difficult for pediatric neurosurgeons to select and perform appropriate surgical procedures for neonates and infants. Treatment options for hydrocephalus are broadly divided into permanent and temporary. Permanent treatments include cerebrospinal fluid shunt and endoscopic third ventriculostomy; temporary treatment entails cerebrospinal fluid drainage using lumbar puncture and intermittent cerebrospinal fluid drainage with an Ommaya reservoir, ventricular drainage, and ventriculosubgaleal shunt. This article describes in detail Ommaya reservoir placement and ventricular drainage as representative procedures for temporarily treating hydrocephalus.

Fronto-orbital advancement in a patient with Marshall-Smith syndrome: a case report and review of the literature.

OBJECTIVE: The present report aimed to document the clinical features of a case of Marshall-Smith syndrome (MSS), an extremely rare embryonic developmental disorder with associated craniosynostosis. PATIENT AND METHOD: We presented herein a case of a 2-year-old female patient with MSS who underwent fronto-orbital advancement for multisuture craniosynostosis. RESULTS: The patient's proptosis improved after surgery, and no further surgical intervention was required for corneal exposure. A second FOA followed by revision tarsorrhaphy further improved eye closure. CONCLUSION: Surgical procedures to correct dysplastic features and limit neurological impairment are a worthwhile supportive treatment for improving the quality of life and general condition of patients with MSS.

Developmental changes in the occipital cranial sutures of children less than 2 years of age.

PURPOSE: The occipital bone is located on the boundary between the membranous and cartilage bones and contains a wide variety of accessory sutures. In this study, we describe the age distribution of pediatric patients who are less than 2 years of age with occipital cranial sutures using a three-dimensional computed tomography (3D-CT). METHODS: A total of 167 consecutive patients who are less than 2 years of age and underwent computed tomography for head trauma were included in this study. RESULTS: Based on the results of this study, various types of sutures were observed among the pediatric participants. In particular, superior median fissures, mendosal sutures, other interparietal segment's accessory sutures, and interparietal sutures were noted in 21%, 35%, 9%, and 6% of the participants, respectively. Additionally, Wormian bones within the lambdoid suture were noted in 32% of the patients. The median age of children with superior median fissure and mendosal suture was 0 month. Meanwhile, superior median fissure was not observed among children older than 5 months of age. In this population, 13 patients (8%) were found to have skull fracture. CONCLUSIONS: Knowledge of the normal cranial anatomy and developmental patterns of cranial sutures is crucial in the evaluation of questionable fractures in the occipital region. A combination of 3D-CT and axial bone window imaging is useful in differentiating normal structures from pathological changes in the cranium.

Clinical Features of Bilambdoid and Sagittal Synostosis (BLSS): A Retrospective Multicenter Study in Japan.

ABSTRACT: Bilambdoid and sagittal synostosis (BLSS), a rare form of multisutural craniosynostosis, is sometimes known as the Mercedes-Benz syndrome due to the appearance of the fused sagittal and bilateral lambdoid sutures. Although previous studies have described some of its clinical features, the pathology of this disease is not yet fully understood. Moreover, it has been pointed out that BLSS is more common among individuals of Hispanic ethnicity, but its incidence in Asia remains unclear. In the present study, BLSS cases in Japan were analyzed to determine the characteristics of the condition in Japan. Three hospitals in Tokyo participated in the present study. Patients with BLSS who underwent cranial remodeling were included. Data on patient demographics, clinical symptoms, status of the cranial sutures, morphological subclassification, surgical procedures, developmental status, and genetic mutations were analyzed. In total, 22 patients met the enrollment criteria and were included, indicating a higher incidence of BLSS in Japan than in other nations reported in previous studies. In terms of morphological subclassification, there were 15 brachycephalic, 4 dolichocephalic, and 3 normocephalic. For the initial cranial procedure, 7 patients underwent a single-stage cranioplasty, 13 underwent a posterior distraction, and 2 underwent lateral expansion. Patients with a normocephalic cranial morphology tended to undergo surgery at an older age than patients with the other two types. Appropriate timing for surgery is important for healthy development; hence, surgeons should remember that BLSS can lead to "balanced dysmorphism" that may have led to a delay in diagnosis due to its normal-looking morphology.

Proton therapy for newly diagnosed pediatric diffuse intrinsic pontine glioma.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a type of brain malignancy with a very poor prognosis. Although various radiation and chemotherapy protocols have been attempted, only conventional radiotherapy has yielded improvements in survival. In this study, we aimed to compare proton therapy versus conventional photon radiotherapy in terms of the outcomes of pediatric patients with DIPG. METHODS: This retrospective review included 12 pediatric patients with newly diagnosed DIPG who received a total proton therapy dose of 54 Gy (relative biological effectiveness) in 30 fractions at the University of Tsukuba Hospital between 2011 and 2017 (proton group). We additionally reviewed the medical records of 10 patients with DIPG who previously underwent conventional photon radiotherapy at our institute (historical cohort). RESULTS: The median progression-free survival (PFS) duration was 5 months (range 1-11 months), and the 6-, 12-, and 18-month PFS rates were 50%, 33%, and 25%, respectively. The median overall survival (OS) duration was 9 months (range 4-48 months), and the 6-, 12-, 18-, and 24-month OS rates were 66.8%, 50%, 41%, and 20%, respectively. There were no significant differences in survival between the proton and historical groups (PFS, p = 0.169 and OS, p = 0.16). CONCLUSIONS: Proton therapy was well tolerated by the majority of patients. No severe adverse events, including radiation necrosis, were recorded. Proton therapy did not yield superior survival outcomes vs. conventional photon radiotherapy in patients with DIPG at our institution. Further research is needed to identify the factors associated with better survival in this population.

Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers.

Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are KRAS, HRAS, and NRAS. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, MRAS (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down-slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low-set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the MRAS gene represents a causative gene for RASopathy.

Surgical Treatment of Growing Skull Fracture: Technical Aspects of Cranial Bone Reconstruction.

BACKGROUND: Growing skull fracture (GSF) is a rare, posttraumatic complication observed mainly in young infants. In GSF, the skull fracture associated with an underlying dural tear gradually expands due to herniation of the intracranial tissue into the fracture site. Many reports have discussed GSF from various points of view. However, only a few studies have focused on the details of cranial reconstruction. The present study aims to redress this omission by shedding some light on bone work in GSF surgery. METHODS: Patients registered in the institutional database who underwent surgical repair of GSF were retrospectively reviewed. RESULTS: Four patients underwent surgical repair for GSF. The site of injury was parietal in 3 patients and occipital in 1 patient . Age at the time of injury ranged from 3 months to 1 year 5 months (mean: 7 months). The duration from injury to surgery ranged from 5 to 7 months (mean: 5 months). In all patients, dural reconstruction was performed with autologous periosteum and cranial reconstruction was performed with an autologous calvarial bone graft. Regardless of the age distribution, split bone grafting was possible for all patients. CONCLUSION: To diagnose GSF promptly and thereby reduce the risk of neurologic sequelae, careful observation of the course, and education of the patients' parents are desirable. Although most children with GSF are under 3 years old, the age before the formation of the diploic layer, split bone grafts should be considered for the treatment of GSF to reduce the risk of residual cranial bone defects.

Hyper-vascular giant cavernous malformation in a child: a case report and review.

INTRODUCTION: Giant cavernous malformation (GCM) in children is a rare vascular anomaly, and its natural history is unclear. Despite their giant size, intraparenchymal GCMs are low-flow vascular malformations. Herein, we report a case of hyper-vascular intraparenchymal GCM with an AV shunt in a child. CASE: A 3-year-old boy had had an enlarged head since infancy. Magnetic resonance (MR) images on admission showed a strikingly enhanced mass lesion, 6 cm in size. A 4-vessel CAG demonstrated a hyper-vascular mass with an AV shunt. After transarterial embolization, the patient underwent total excision of the mass. The tumor bled easily, during surgery the patient lost 400 cm3 in blood. Histopathological examination confirmed the diagnosis of cavernous hemangioma. CONCLUSION: The differential diagnosis of intraparenchymal, strikingly-enhanced tumors with an AV shunt include hyper-vascular GCMs. Consideration of potential for bleeding during the operation is also important.

Reversible diffusion weighted imaging hyperintensities during the acute phase of ischemic stroke in pediatric moyamoya disease: a case report.

BACKGROUND: Moyamoya disease is one of the primary causes of pediatric ischemic stroke, especially in East Asia. Areas of high signal intensity on diffusion weighted imaging (DWI) with decreased apparent diffusion coefficient (ADC) values usually point to irreversible ischemic damage. Reversibility of these DWI hyperintensities during the acute phase of ischemic stroke in pediatric moyamoya disease has not previously been reported. CASE REPORT: A 3-year-old girl was admitted to our emergency department due to sudden onset speech impairment and right hemiplegia. Computed tomography (CT) revealed a multilobal low-density area in the left cerebral hemisphere. The area was hyperintense on DWI with decreased ADC values. Magnetic resonance (MR) angiography revealed stenosis of the bilateral internal carotid artery bifurcations and their branches. Acute cerebral infarction due to moyamoya disease was diagnosed. MR images taken 4 days later showed resolution of most of the DWI hyperintensity areas. The initial decline in the ADC of the reversible DWI hyperintensities was less severe compared to the irreversible lesion. Within several days after onset, the patient became ambulatory although the follow-up MR fluid attenuated inversion recovery (FLAIR) images taken 2 weeks after onset revealed thinning of the corresponding cortical gyri. CONCLUSION: These findings indicate that a wide area of DWI hyperintensity during the acute phase of ischemic stroke can be reversed by appropriate treatment in pediatric moyamoya disease. To the best of our knowledge, this is the first report of reversible DWI hyperintensities over a wide cortical area during the acute phase of ischemic stroke in pediatric moyamoya disease.

Pediatric intraventricular arachnoid cysts in the body of lateral ventricle: surgical outcome and its embryologic background.

PURPOSE: The aim of this study is for the surgical treatment and outcome of the endoscopic fenestration of the arachnoid cyst located in the ventricular body to trigone in the pediatric population. Special concern was paid for the developmental origin of the intraventricular cysts estimated from the postoperative follow-up neuroimagings. PATIENTS AND METHODS: Between July 2002 and June 2015, we performed endoscopic and partly CT/MRI navigated fenestrations of intraventricular arachnoid cysts located at the body to trigone of the lateral ventricle in ten pediatric patients aged 2 months to 5 years. Based on the long axis of the cyst, we have opted for two surgical approaches: anterior approach via burr hole at Kocher's point and posterior approach via burr hole at the posterior occipital region. Fenestration was performed based on the intraoperative findings, either ventriculocystostomy, ventriculocystoventriculostomy, or ventriculocystocisternostomy. RESULTS: Intraventricular arachnoid cysts located in the body-trigone region showed a favorable outcome after endoscopic fenestration. All of the cysts shrank postoperatively. Follow-up neuroimagings taken between 6 and 126 months after surgery strongly suggested its relationship with the midline cisterns. Of our ten cases, eight were suggestive for originating from the velum interpositum cistern while two seemed to root from the quadrigeminal cistern. CONCLUSION: In the present study, we found that endoscopic fenestration of intraventricular arachnoid cysts in the body to trigone is a safe procedure with a satisfactory outcome. In our limited experience, there are two anatomic backgrounds; velum interpositum cistern and quadrigeminal cistern. Differentiation can be possible by neuroimagings, especially those obtained after surgery.

Risk factors for the occurrence of spina bifida (a case-control study) and the prevalence rate of spina bifida in Japan.

BACKGROUND: The Japanese government recommended in 2000 that women planning pregnancy should take 400 µg of folic acid daily to decrease the risk of having an infant with spina bifida. We aimed to identify risk factors for the occurrence of spina bifida and to evaluate how the prevalence rate has altered over the past 3 decades. METHODS: Subjects comprised 360 women who gave birth to spina bifida-affected offspring and 2333 women who gave birth to offspring without spina bifida between 2001 and 2012. A self-administered questionnaire was used to collect data, which were analyzed by multiple logistic regression models. The prevalence rate of spina bifida was obtained through data provided by international and domestic organizations. RESULTS: Four variables were significantly associated with the increased risk of having newborns afflicted with spina bifida: not taking folic acid supplements (odds ratios [OR], 2.50; 95% confidence interval [CI], 1.72-3.64), presence of spina bifida patients within third-degree relatives (OR, 4.26; 95% CI, 1.12-16.19), taking anti-epileptic drugs without folic acid (OR, 20·20; 95% CI, 2.06-198.17), and low birth weight in the newborns ≤ 2500 g (OR, 4.21; 95% CI, 3.18-5.59). The prevalence rate of spina bifida has remained 5 to 6 per 10,000 total births and has not shown any decreasing trend over the past 11 years. CONCLUSION: Four risk factors were identified among Japanese women. Because recommendations and information have not decreased the occurrence of spina bifida, the Japanese government should implement mandatory food fortification.

Neoadjuvant Therapy with Everolimus for Subependymal Giant Cell Astrocytoma: A Case Report.

Direct surgical resection remains to be the standard treatment for tuberous sclerosis complex (TSC) with subependymal giant cell astrocytoma (SEGA). Medical therapy with everolimus (mammalian target of rapamycin inhibitor or mTOR) serves as a second-line treatment for patients with SEGA who are determined to be ineligible for surgical resection. Some recent studies have reported that neoadjuvant therapy for SEGA may be a useful, novel treatment. In this study, we herein present a case of SEGA and demonstrate the efficacy of preoperative everolimus therapy. We have also examined the utility and safety of neoadjuvant therapy for SEGA and investigated four previously reported cases of preoperative administration of mTOR inhibitors. In these cases, everolimus was administered preoperatively to shrink the tumor although the duration of treatment varied. Afterward, gross total tumor removal was conducted in all the cases. No postoperative complications were reported during the follow-up period. These findings indicate that neoadjuvant therapy with an mTOR inhibitor can be a potential treatment for SEGA. The findings of this present study also suggested that a short administration period of about 2 months may be sufficient to achieve preoperative tumor reduction.

Symptomatic enophthalmos due to sphenoid wing dysplasia appearing over 12 years in a patient with neurofibromatosis type 1: a case report and literature review.

Sphenoid wing dysplasia (SWD) is a common orbital complication of neurofibromatosis type 1 (NF1). However, enophthalmos associated with SWD is extremely rare, and details of its natural history are unclear. We present the case of a 14-year-old boy with an early childhood diagnosis of NF1 presenting with left blepharophimosis and enophthalmos for several months. Imaging demonstrated enlargement of the left lateral SWD, progression of the posteromedial deviation of the orbital contents, and sphenoid/ethmoid sinus deformation due to left temporal lobe compression over 12 years. Two characteristic changes were revealed on imaging: enlargement of the middle cranial fossa and deformation of the sphenoid/ethmoid sinuses. The orbital contents were compressed by the intracranial pressure of the temporal lobe and were displaced posteromedially into the space created by the deformed sphenoid/ethmoid sinuses. Because orbital symptoms can gradually become apparent over years with the progression of SWD and skeletal growth, long-term follow-up of orbital symptoms is recommended in patients with NF1.

Sterilizing Ability of High-Voltage Pulsed Discharge Plasma with Cavitation for Microorganisms Including Radio-Resistant Bacterium in Water.

There are various purification methods have been developed and applied to industrial wastewater with contaminated microorganisms. We previously reported that high-voltage pulsed discharge plasma with cavitation effectively kills Escherichia coli cells. We attempted to expand the application of this disinfection method by using microorganisms such as Bacillus subtilis, Deinococcus radiodurans, and Schizosaccharomyces pombe. These microbial cells were treated with the discharge plasma, and the cell viability, DNA damage, and morphological changes were analyzed to evaluate the bactericidal effect. Interestingly, D. radiodurans, a radio-resistant bacterium showed relatively high sensitivity to the discharge plasma. On the other hand, B. subtilis and S. pombe showed the resistance, showing both sporogenesis. The amount of DNA damage in the treated cells corresponded to the cell viability, but most of the treated cells did not show any morphological changes.