A case of papilledema in Camurati-Engelmann disease treated effectively with prednisolone.

Camurati-Engelmann disease (CED) causes bone pain, muscle weakness, and cranial nerve symptoms due to abnormal thickening of the long bones of the limbs and the cortex of the skull. The pathophysiology of CED is a gain-of-function variant of transforming growth factor beta 1 (TGFB1). The ophthalmological symptoms of CED are usually caused by increased intracranial pressure and optic canal stenosis. Here, we report the case of a patient in whom prednisolone was effective against papilledema caused by CED. In this case, when papilledema was observed in both fundi, the patient showed increased bone pain, fever, and elevated CRP and ALP levels. Brain magnetic resonance imaging (MRI) revealed a high short tau inversion recovery (STIR) signal in both optic nerves, suggesting edematous changes. Prednisolone ameliorated bone pain, fever, and papilledema, resulting in a slight improvement of the visual function of the right eye. Our results suggest that prednisolone may be effective in treating ophthalmologic symptoms in addition to bone pain in patients with CED.

A case of germinoma located in the fornix inducing transsynaptic atrophy of the Papez circuit.

Germinoma is a rare CNS germ cell tumor preferentially affecting children and young adults. Intracranial germinomas arise typically in the neurohypophysis and pineal region and occasionally in the basal ganglia and thalamus. Germinomas in the basal ganglia and thalamus are characterized by the ipsilateral cerebral and brainstem hemiatrophy with slowly progressive neurological deficits, which is due to tumor infiltration into the thalamocortical and corticospinal tract and induction of anterograde and retrograde Wallerian degeneration. We report an 11-year-old boy with a mass located in the fornix incidentally discovered on the first work-up of his minor head injury. Imaging findings revealed the ipsilateral atrophy of the mammillary body and the fornix. Stereotactic brain biopsy was performed and the final diagnosis was germinoma. The ipsilateral atrophy of the mammillary body and the fornix implied the transsynaptic degeneration via the Papez circuit. We discuss the unique nature of germinomas and underlying pathological mechanisms.

[Multidirectional Cranial Distraction Osteogenesis for Craniosynostosis].

In this article we explain in detail the Multidirectional Cranial Distraction Osteogenesis(MCDO)procedure for treating craniosynostosis, in which the multiple cranial bone flaps are pulled up in different directions by the external distractor with the helmet-type frame. MCDO has several advantages over conventional procedures such as unilateral cranial distraction osteogenesis(UCDO). First, the design of the osteotomy in MCDO is flexible depending on the deformities. Each bone flap can be moved to the desired direction in MCDO, while being moved only in one direction along the axis of the distractor in UCDO. This enables remodeling of the deformed cranium to the desired shape. Second, compared with UCDO, the distance between each bone flap after distraction is narrower in MCDO, allowing earlier bone formation and fusion, and thus a shorter consolidation period. Third, the expansion efficacy of MCDO is greater than that of UCDO. The maximum defects of MCDO were the large amount of osteotomy and the resulting heavy bleeding. Therefore, we have recently attempted to improve the design and procedure of osteotomy. The MCDO method allows all phenotypes of skull deformity to be reshaped by distraction osteogenesis.

[Precision Medicine for Ependymoma].

Herein we discuss precision medicine for ependymoma. We reviewed the new molecular classifications of ependymoma, studies on the molecular mechanisms involved in carcinogenesis and proliferation, and the various studies exploring new therapeutic strategies. Of the nine molecular classifications of ependymoma, supratentorial ependymomas with ZFTA fusion, posterior fossa PFA group, and spinal ependymomas with MYCN amplification are treatment-resistant, and candidates for precision medicine. Precision medicine is considered to select a treatment method based on molecular biological information, but its application is thought to be difficult for ependymomas with few somatic mutations. Recent studies have shown that epigenetic mechanisms are involved in the development and growth of PFA ependymomas without recurrent somatic mutations. It has been found that ZFTA forms fusion genes with various genes other than the typical ZFTA-RELA fusion, and a common therapeutic target has been suggested for the genes downstream of it. Unfortunately, these findings have not yet been clinically applied to precision medicine for ependymoma, but newer discoveries are gradually accumulating. Further development of research is warranted.

A case of a rosette-forming glioneuronal tumor with clinicopathological features of a dysembryoplastic neuroepithelial tumor and fibroblast growth factor receptor 1 internal tandem duplication.

Rosette-forming glioneuronal tumors (RGNTs) are benign WHO grade 1 tumors that occur in the ventricular system, particularly the fourth ventricle. RGNTs and dysembryoplastic neuroepithelial tumors (DNTs) are both categorized as neuronal and mixed neuronal-glial tumors and may be difficult to distinguish. Coexistence of the two tumor types has been reported. Here, we report a pediatric case of RGNT with DNT-like features showing intraventricular dissemination. The tumor occurred in the medial temporal lobe and presented with specific pathological glioneuronal elements including floating neurons, which are typical in DNTs, but was diagnosed as RGNT because of the presence of neurocytic rosettes. Genetic analysis detected fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain, which was previously reported to be specific for DNT. RGNTs with FGFR1-ITD may show atypical clinical presentation and pathological features.

Multi-directional Cranial Distraction Osteogenesis for Treating Sagittal Synostosis with Frontometaphyseal Dysplasia: A Case Report.

Frontometaphyseal dysplasia (FMD), also known as Gorlin-Cohen syndrome, is a rare genetic syndrome. This syndrome affects the skeletal system and connective tissue, and causes a wide spectrum of manifestations of the skull, tubular bones, cardiovascular system, urinary system, and/or gastrointestinal system. Craniofacial findings of FMD are characterized by protruding supraorbital ridge, broad nasal bridge, hypertelorism, down-slanting palpebral fissures, and/or micrognathia. We describe a case of a 2-year-old girl diagnosed with sagittal synostosis accompanied with FMD. She presents anterior sagittal synostosis cranial form, compressed cerebrospinal fluid space (which suggested increased intracranial pressure), and the supraorbital hyperostosis. She underwent multi-directional cranial distraction osteogenesis in the calvaria and shaving of the supraorbital ridges. Despite concerns about bone fragility associated with FMD, the surgery was accomplished as usual. The patient had no intra- and postoperative complications. After 6 months of follow-up, the cranial shape has improved and the cerebrospinal fluid space has widened, but the supraorbital ridge has protruded again. Re-protrusion of the supraorbital ridge appears to be due to age-appropriate vigorous osteogenesis. The multi-directional cranial distraction osteogenesis procedure has been useful for treating sagittal synostosis even concomitant with FMD.

Limited effects from professional identity formation-oriented intervention on self-regulated learning in a preclinical setting: a randomized-controlled study in Japan.

BACKGROUND: Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning. We designed a professional identity formation-oriented reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical year curriculum. METHODS: A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire. RESULTS: Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. CONCLUSIONS: Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.

Comprehensive Metabolomic Analysis of IDH1R132H Clinical Glioma Samples Reveals Suppression of ß-oxidation Due to Carnitine Deficiency.

Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II-IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in ß-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.

Multidirectional cranial distraction osteogenesis technique for treating bicoronal synostosis.

Fronto-orbital advancement by distraction osteogenesis is a useful means of surgically correcting bicoronal synostosis. However, the scope for morphological revision is limited. To address this issue, we developed a multidirectional cranial distraction osteogenesis (MCDO) technique that we quantitatively assessed in patients with bicoronal synostosis. In this case series, five patients with bicoronal synostosis were treated with MCDO at a mean age of 13.4 months (range 9-22 months). Distraction started 5 days after surgery and the activation period was 11.2 days (range 10-14 days). The distraction devices were removed 47.2 days (range 33-67 days) after completing distraction. Improved cranial shape was confirmed by CT data. Mean preoperative CI, APL, and ICV readings of 102.1%, 13.5 cm, and 1179.4 ml, respectively, had reached 94.0%, 14.9 cm, and 1323.9 ml, respectively, upon device removal. These values were well preserved at 1 year (90.4%, 15.8 cm, and 1461.3 ml, respectively). In conclusion, MCDO successfully enables both cranial expansion and correction of a flat forehead, constituting a valid treatment alternative for patients with bicoronal synostosis.

Filar cysts in rare cases may progress in size, particularly when associated with filar lipoma.

PURPOSE: Filar cysts (FCs) are detected incidentally on ultrasonography (US) of the neonatal spine. Their clinical significance has not been widely discussed in the literature because FCs are usually asymptomatic. This study aimed to investigate the clinical features of FCs and distinguish FCs that warrant attention. METHODS: We retrospectively analyzed 396 patients with lumbosacral skin stigmata. Patients who were younger than 1 month old at reference underwent US initially, and those older than 1 month of age underwent magnetic resonance imaging (MRI) at the age of 5-12 months. Patients with an FC in the US underwent subsequent MRI at the age of 5-12 months. Patients with an FC were followed clinically for at least 3 years. RESULTS: FCs were identified in 56 (14.1%) patients. Of the 195 children who underwent US initially, FCs were detected in 49 (25.1%) children. FCs were detected in seven children who underwent MRI initially. Of the 50 children with FCs who underwent MRI at the age of 5-12 months, FCs in 20 patients (40%) showed natural regression and FCs in 30 patients (60%) remained. Two of these 30 patients showed progression in size of the FC, and in both cases, the FCs were associated with a filar lipoma; however, the resected cysts were not neoplastic and did not have obvious clinical significance. CONCLUSIONS: Our study characterizes clinical features of filar cysts. Two-thirds of FCs remained in late infancy. The best sequence of MRI to follow-up FCs is heavily T2-weighted images.

Development of Multidirectional Cranial Distraction Osteogenesis for the Treatment of Craniosynostosis.

BACKGROUND: Previously, the authors developed a new method of distraction osteogenesis for the treatment of craniosynostosis, multidirectional cranial distraction osteogenesis (MCDO). The purpose of this study is to review the authors' experience of MCDO for remodeling of the anterior cranium in the patients of craniosynostosis. METHODS: Forty-five patients with craniosynostosis underwent MCDO for anterior cranial remodeling from 2003 to 2017. The ages of the patients ranged from 8 to 72 months (mean: 23.9 months, median: 13 months). The involved sutures included the bicoronal suture in 14 patients, unicoronal suture in 4 patients, sagittal suture in 14 patients, metopic suture in 2 patient, and multiple sutures in 10 patients. RESULTS: An improvement of in cranial shape was achieved in 40 patients. In 1 patient, intraoperative massive bleeding forced us finishing the procedure before completing the planned osteotomy. Transient cerebrospinal fluid leakage occurred in 3 patients during the activation phase but recovered with conservative therapy. The mean blood transfusion was 25.5 mL/kg. The phase of activation ranged from 7 to 17 days (mean, 10.6 days) and the consolidation period ranged from 16 to 67 days (mean, 32.4 days). Loosening of traction pins occurred in 7 patients, resulting in undercorrection in 2 patients, and loosening of anchor pins occurred in 19 patients, resulting in acceleration of removal of the devices in 7 patients. CONCLUSIONS: Multidirectional cranial distraction osteogenesis was effective and has several advantages over the conventional procedures. Therefore, the authors conclude that MCDO will be a useful alternative for all phenotypes of craniosynostosis.

Training of Intra-Axial Brain Tumor Resection Using a Self-Made Simple Device with Agar and Gelatin.

INTRODUCTION: Self-made devices composed of agar and gelatin gel were used for resident training in intra-axial brain tumor resection. The mixture gel of agar and gelatin is retractable and can be suctioned. Hardness of the gel depends on the concentration of the solution. Therefore, by changing the concentration, it is easy to make gels of various hardness. METHODS: In this study, a mass of gel that looked like a tumor was placed into another gel that looked like the brain. A part of the "brain" was regarded as the eloquent area. Three types of "tumor" were prepared: hard, moderately hard, and soft tumors. Residents tried to remove the tumor entirely with minimal brain invasion. The training was repeated with 3 types of gel. After resection, the weight of the residual tumor, resected normal brain, and resected eloquent area were measured, and the time taken for removal was recorded. RESULTS: These data were compared between residents and neurosurgeons. We also analyzed how these data improved with repeated practice. In most cases, residual tumor, resected normal brain, resected eloquent area, and time taken for removal were less in neurosurgeons than in residents. Repeated training made residents more skillful. The responses of the trainees were almost all favorable. CONCLUSIONS: Our devices with "tumors" of various hardness appear to be suitable for resident training in each surgical skill. For the next step of this study, we will attempt to fabricate more practical 3-dimensional gel models for presurgical simulation.

Multidirectional Cranial Distraction Osteogenesis with Simplified Modifications for Treating Sagittal Synostosis.

BACKGROUND: Multidirectional cranial distraction osteogenesis (MCDO) is a procedure of ours developed earlier for treating craniosynostosis. However, the numerous bone flaps led to prolonged operative time and occasional bone detachment from dura. We have since simplified the osteotomy design. In treating sagittal synostosis, required bone flaps have been reduced to 11 (from ~20). METHODS: In a 2-year period (2014-2015), 5 boys with sagittal synostosis underwent MCDO using our simplified and fixed-form osteotomy. Mean age at surgery was 9.4 months (range, 8-11 months). Pre- and postoperative cranial morphology was assessed by cephalic index and by mid-sagittal vector analysis. RESULTS: Improved cranial shape was confirmed by 3-dimensional CT scans and by mid-sagittal vector index. Mean preoperative cephalic index (68.7) progressively increased to means of 78.5 immediately after distraction device removal, 75.2 at postoperative month 6, and 75.1 at 1 year postoperatively. There were no major complications, although transient cerebrospinal fluid leakage and loosening of anchor pins occurred in 1 patient. CONCLUSIONS: Simplified MCDO has a number of advantages over conventional distraction procedures such as discretionary reshaping/expansion of cranium and predictable osteogenesis and is a valid treatment option for patients with sagittal synostosis.

Embolization for Refractory Subacute Subdural Hematoma in a Child with Severe Hemophilia Type A.

Hemophilia is an X-linked hemorrhagic disease due to coagulation factor VIII or IX deficiency with approximately 5-10% incidence of central nervous system bleeding. We present an intriguing case of a refractory subacute subdural hematoma (SDH) controlled with endovascular embolization in a hemophilic patient. A 5-year-old severe hemophilic A boy presented with a life threatening left parietal subcortical hemorrhage, for which he underwent craniotomy and evacuation of the hematoma. Recurrent hemorrhage necessitated a repeat craniotomy. This was followed by three episodes of SDH development at the craniotomy site that were treated surgically, and finally controlled with embolization in the subacute period. This case presents a novel option for treating a refractory SDH in patients with coagulation disorders.

Use of Multidirectional Cranial Distraction Osteogenesis for Cranial Expansion in Syndromic Craniosynostosis.

Patients with syndromic craniosynostosis often require a large amount of cranial expansion to avoid intracranial hypertension, but the surgical procedure remains controversial. A patient of severe syndromic craniosynostosis with multiple bony defects and anomalous venous drainage at the occipital region was treated by multidirectional cranial distraction osteogenesis (MCDO) at the age of 8 months. Distraction started 5 days after surgery and ceased on postoperative day 16. The distraction devices were removed 27 days after completing distraction. After device removal, the increase of intracranial volume was 155 ml and the cephalic index was improved from 115.5 to 100.5. The resultant cranial shape was well maintained with minimal relapse at postoperative 9 months. In cases of syndromic craniosynostosis with multiple bony defects and/or anomalous venous drainage at the occipital region, expansion of the anterior cranium by MCDO is a viable alternative to conventional methods.

Distraction Osteogenesis Update: Introduction of Multidirectional Cranial Distraction Osteogenesis.

In this review, we discuss in detail our current procedure for treating craniosynostosis using multidirectional cranial distraction osteogenesis (MCDO). The MCDO method allows all phenotypes of skull deformity to be reshaped by distraction osteogenesis, except in patients who are 5 months of age or younger and patients with posterior cranial vault problems. We report the results of clinical data of 36 children with craniosynostosis who underwent MCDO between 2005 and 2014 in our institute. This method has the following benefits, such as a high flexibility of reshaping, shorter treatment period and less invasive secondary intervention. We also discuss the other distraction osteogenesis techniques that are used to treat craniosynostosis and compare them with MCDO. The preferred procedure for correction of craniosynostosis may depend on the patient's age, the extent of deformity, and the extent of correction achievable by surgery. We can arrange the combinations of various methods according to the advantage and disadvantage of each technique.

An Infant With Medulloepithelioma Successfully Treated by High-dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation Without Radiotherapy.

Medulloepithelioma of the central nervous system (CNS) is a rare primitive neuroectodermal tumor characterized by highly malignant behavior occurring in early childhood. Few cases have been reported and optimal management remains unknown. Here, we report a case of CNS medulloepithelioma successfully treated with high-dose chemotherapy (HDCTX) followed by autologous stem cell transplantation (auto-SCT) without radiotherapy. At the last follow-up, 3.0 years after onset, the patient was alive with no sign of relapse and normal development. To the best of our knowledge, this is the first reported case of long-term survival of CNS medulloepithelioma treated by HDCTX/auto-PBSCT without radiotherapy.