Preoperatively difficult-to-diagnose medulla oblongata germinoma: A case report and literature review.

Background: Intracranial germinomas are rare tumors, accounting for 0.5-2% of primary intracranial neoplasms. While they typically occur in the pineal gland, suprasellar region, basal ganglia, and thalamus, germinomas arising in the medulla oblongata are exceptionally rare. Diagnosis of medulla oblongata germinoma is challenging, potentially leading to misdiagnosis and poor prognosis. Case Description: We present a case of a 29-year-old man complaining of left leg numbness. Radiological findings revealed a contrast-enhanced lesion in the medulla oblongata. The patient underwent tumor biopsy, and intraoperative pathological diagnosis (IOD) suspected the diagnosis of medulla oblongata germinoma. He underwent chemoradiotherapy after confirming the diagnosis of germinoma. Intracranial germinoma arising in the medulla oblongata differs from germinomas in other locations due to its higher incidence in individuals in their 20s and a slight female predominance. Conclusion: When encountering lesions in the medulla oblongata, germinoma should be considered as one of the differential diagnoses, and surgical strategies including IOD should be planned accordingly.

Infant-type hemispheric glioma occurring at the cervicomedullary region in a 5-month-old infant: A case report with a special emphasis on molecular classification.

Background: High-grade gliomas in infancy are uncommon and have different clinical and molecular characteristics from those in adults. Recently, advances in molecular diagnostics have made progress in determining treatment strategies; however, the robust treatment has not yet been elucidated. We, herein, present a case of infantile glioma occurring at the cervicomedullary region. Case Description: A 5-month-old infant developed left upper limb weakness and torticollis at 3 months of age. Magnetic resonance imaging revealed T2 hyperintensity from the medulla oblongata to the upper cervical cord. She underwent a biopsy for the lesion and pathological examination findings confirmed the presence of a high-grade astrocytoma with IDH wildtype-, H3K27M wildtype-, BRAF wildtype-, and ETV-NTRK3 fusion-positivity. Postoperatively, she underwent chemoradiotherapy, but she had marked tumor growth during the treatment. According to the new World Health Organization classification, the patient's tumor is an infantile "hemispheric" glioma. Conclusion: The characteristics and prognosis of NTRK-fused glioma are not fully understood, it is noteworthy that these tumors commonly occur in the brainstem. Further studies are needed to determine the prognosis of each tumor type and its sensitivity to treatment. This information will help in the reclassification of the tumors and identification of the precise treatment of this rare type of tumor.

Longitudinal health-related quality of life analysis in childhood cancer survivors after proton beam therapy.

PURPOSE: Whilst proton beam therapy (PBT) for children with cancer is expected to reduce their comorbidities, to date only a limited number of studies have been published. To analyze the long-term comorbidity and health-related quality of life (HRQoL) of childhood cancer survivors (CCSs) after PBT, we conducted a questionnaire-based study. METHODS: Questionnaires were sent to CCSs who underwent PBT at the University of Tsukuba Hospital during the period from 1984 to 2020. Scores from 41 CCSs who did not undergo PBT (noPBT-CCSs) and from the general population were used for comparison. RESULTS: In total, 110 individuals who underwent PBT participated in the study. Among them, 40 individuals were longitudinally analyzed. The range of change in the scores was significantly greater in the CCSs whose initial scores were low. Although the comorbidity levels were more severe, HRQoL tended to be better in the PBT-CCSs than in the noPBT-CCSs with central nervous system (CNS) or solid tumors, respectively. When compared with the general population, the psychosocial health summary scores and its components were not different in the noPBT-CNS-CCSs. On the other hand, the psychosocial health summary scores and/or at least one of the scores of emotional, social, and school functioning were significantly higher in the other CCSs groups. CONCLUSIONS: The HRQoL scores of CCSs with low initial scores can be greatly changed over time. Appropriate psychosocial support for this population is warranted. PBT may avoid reduction in HRQoL in terms of the psychosocial functioning of CCSs with CNS tumors.

Remodeling of venous drainage after the treatment of dural sinus malformation with arteriovenous shunts in a neonate: a case report and literature review.

Dural sinus malformations (DSMs) are rare congenital vascular diseases characterized by a giant venous pouch with or without arteriovenous shunts. We present a neonatal case of DSM that was diagnosed prenatally and treated via endovascular intervention in the early postnatal period. The patient presented with a large DSM involving the torcular Herophilion prenatal magnetic resonance imaging (MRI). Enlargement of the head circumference and respiratory failure rapidly progressed after birth. On the 5th day after birth, the neonate underwent endovascular occlusion via the umbilical artery. The arteriovenous shunt was occluded, and the reflux from the enlarged venous pouch to the dural sinus was decreased. No additional procedure other than ventriculoperitoneal shunting was required. The neonate's development slowly caught up to normal parameters. Follow-up MRI demonstrated the successful development of the venous drainage system. DSMs are characterized by an abnormally dilated dural sinus, which can block the venous return and ultimately increase intracranial pressure and cerebral ischemia. Long-term follow-up indicates that an abnormally developed dural sinus can be reconstructed by appropriate and timely treatment.

Traumatic dissection of the anterior cerebral artery secondary to a rugby related impact: A case report with emphasis on the usefulness of T1-VISTA.

Background: Cerebrovascular injuries (CVIs) are not usually considered in the differential diagnosis of sport-related head injuries (SRHIs). We encountered a rugby player with traumatic dissection of the anterior cerebral artery (ACA) after impact on the forehead. Head magnetic resonance imaging (MRI) with T1-volume isotropic turbo spin-echo acquisition (VISTA) was used to diagnose the patient. Case Description: The patient was a 21-year-old man. During a rugby tackle, his forehead collided with the forehead of an opponent. He did not have a headache or disturbance of consciousness immediately after the SRHI. On the 2nd day of illness, he had transient weakness of the left lower limb several times. On the 3rd day of illness, he visited our hospital. MRI revealed occlusion of the right ACA and acute infarction of the right medial frontal lobe. T1-VISTA revealed intramural hematoma of the occluded artery. He was diagnosed with acute cerebral infarction due to dissection of the ACA and was followed up for vascular changes with T1-VISTA. The vessel had recanalized and the size of the intramural hematoma had decreased 1 and 3 months after the SRHI, respectively. Conclusion: Accurate detection of morphological changes in cerebral arteries is important for the diagnosis of intracranial vascular injuries. When paralysis or sensory deficits occur after SRHIs, it is difficult to differentiate between concussion from CVI. Athletes with red-flag symptoms after SRHIs should not merely be suspected to have concussion; they should be considered for imaging studies.

Gastrointestinal bleeding/ulcer among paediatric cancer patients after proton beam therapy.

BACKGROUND: The details of gastrointestinal bleeding/ulcer in paediatric cancer patients treated with proton beam therapy have not been reported previously. METHODS: Patients aged 15 years or younger at the time of proton beam therapy and whose gastrointestinal tract was included in the irradiated field participated. RESULTS: A total of 124 patients participated in the study; their median age at irradiation was 5.4 years. Concurrent chemotherapies were vincristine-cyclophosphamide (16 patients), irinotecan-based treatment (16 patients), vincristine-cyclophosphamide-ifosfamide-etoposide (14 patients), other chemotherapy (27 patients) and no chemotherapy (51 patients). Gastrointestinal bleeding/ulcer occurred in four patients (3.2%), with no death due to the bleeding/ulcer. The sites of the gastrointestinal bleeding/ulcer were the stomach (two patients) and the duodenum (two patients). The ages of the four patients at PBT were 5.3, 13.8, 14.2 and 14.8 years, which were significantly older than those of patients without GI bleeding/ulcer (p = 0.017). The maximum irradiated doses to the GI tract in the four patients were 43.2, 45, 50.4 and 50.4 gray equivalent, respectively. The concomitant chemotherapy was vincristine-cyclophosphamide-ifosfamide-etoposide 3 and vincristine-cyclophosphamide 1. Weeks from proton beam therapy to bleeding/ulcer were 15, 20, 22 and 264. DISCUSSION AND CONCLUSIONS: Patients who developed gastrointestinal bleeding/ulcer were treated concurrently with vincristine-cyclophosphamide-ifosfamide-etoposide or vincristine-cyclophosphamide, and their ages were older than those of patients without gastrointestinal bleeding/ulcer. Bleeding occurred in the upper gastrointestinal tract in all the cases, and most cases occurred early and during chemotherapy. Upper gastrointestinal irradiation in older children undergoing intensive chemotherapy may increase the risk of developing gastrointestinal complications.

Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission.

OBJECTIVE: To evaluate the pathomechanism of the recurrence of intracranial germinoma after complete response and to confirm the association of the initial magnetic resonance imaging and therapeutic factors with recurrence. METHODS: This study included patients who were followed up for ≥5 years and who were treated in our hospital from 1980 to 2021. Those with germinoma and germinoma with syncytiotrophoblastic giant cells were diagnosed pathologically. Data were categorizedbased on "gender," "single region," "intraventricular dissemination at the initial diagnosis," "hydrocephalus," "types of radiation therapy (RT)," and "chemotherapy." Fisher's exact probability test was used to assess differences between the no recurrence and recurrence groups. RESULTS: Among 43 patients, 34 had no recurrence, 5 had delayed recurrence (≥60 months), and 4 had early recurrence (<60 months). Follow-up periods were 143.5 (60-380), 198 (88-222), and 132.5 (75-291) months for the no recurrence, delayed recurrence, and early recurrence groups, respectively. Five patients with delayed recurrence showed 3 intracranial lesions and 2 spinal lesions. Four patients with early recurrence showed 3 intracranial lesions and 1 spinal lesion. Differences in delayed recurrences (focal RT vs. RT including whole-ventricle system; P = 0.0491) were significant in Fisher's exact test. CONCLUSIONS: RT including the whole-ventricle system reduces delayed craniospinal relapses including dissemination, local, and distant recurrences even ≥5 years after complete response in patients with primary central nervous system germinoma.

Endoscopic third ventriculostomy for noncommunicating hydrocephalus by vertebrobasilar dolichoectasia: A case report.

Background: Vertebrobasilar dolichoectasia (VBD) is a vasculopathy characterized by the elongation, widening, and tortuosity of a cerebral artery. Rarely, hydrocephalus results when the extended basilar artery impairs communication of the cerebral ventricle and cerebrospinal fluid dynamics. We experienced such a case when a patient underwent endoscopic third ventriculostomy (ETV) for noncommunicating hydrocephalus with VBD. Case Description: A 54-year-old man presented with cognitive dysfunction and was diagnosed with VBD by magnetic resonance imaging (MRI). Seven years later, he exhibited subacute impaired consciousness due to acute noncommunicating hydrocephalus, undergoing external ventricular drainage (EVD) that improved consciousness. After EVD removal, the noncommunicating hydrocephalus did not recur; however, 7 months later, subacute consciousness impairment due to noncommunicating hydrocephalus was again observed. MRI showed a significant dilation of both lateral ventricles and ballooning of the third ventricle while the right posterior cerebral artery shifted slightly posteriorly. The patient underwent ETV and clinical symptoms improved. One year after the treatment, MRI observed a patent ETV fenestration and no deleterious changes in clinical symptoms were observed. Conclusion: ETV can be an effective treatment for the noncommunicating hydrocephalus with VBD when performed with preoperative assessment of vascular anatomy and attention to vascular injury.

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.

Cancer-Predisposition Genetic Analysis in Children with Brain Tumors Treated at a Single Institution in Japan.

Brain tumors affect one-third of all children with cancer. Approximately 10% of children with cancer carry variants in cancer-predisposition genes. However, germline analyses in large cohorts of Asian children have not been reported. Thirty-eight Japanese patients with pediatric brain tumors were included in this study (19 boys, 19 girls). DNA was extracted from the patients' peripheral blood, and cancer-associated genes were analyzed using targeted resequencing. Rare variants with allele frequencies <0.1% in the general population and variants suspected to be pathogenic were extracted and analyzed. Pathogenic variants were found in 7 patients (18%): 2 nonsense variants of CHEK2 and FANCI; 2 frameshift deletions in SMARCB1 and PTCH1; and 3 missense variants of TSC1, WRN, and MLH1. The median age at diagnosis was 9.1 years, and three of the 7 patients had a family history of cancer. One patient diagnosed with basal cell nevus syndrome, also called Gorlin syndrome, developed a second neoplasm, and another with an SMARCB1 variant and an atypical teratoid/rhabdoid tumor developed a thyroid adenomatous nodule. This is the first cancer-related germline analysis with detailed clinical information reported in Japanese children with brain tumors. The prevalence was almost equivalent to that in white children.

Global Surgery Indicators and Pediatric Hydrocephalus: A Multicenter Cross-Country Comparative Study Building the Case for Health System Strengthening.

Objective: The aim of this study is to compare specific three-institution, cross-country data that are relevant to the Global Surgery indicators and the functioning of health systems. Methods: We retrospectively reviewed the clinical and socioeconomic characteristics of pediatric patients who underwent cerebrospinal fluid (CSF) diversion surgery for hydrocephalus in three different centers: the University of Tsukuba Hospital in Ibaraki, Japan (HIC), the Jose R. Reyes Memorial Medical Center in Manila, Philippines [low-to-middle-income country (LMIC)], and the Federal Neurosurgical Center in Novosibirsk, Russia (UMIC). The outcomes of interest were the timing of CSF diversion surgery and mortality. Statistical tests included descriptive statistics, Cox proportional hazards model, and logistic regression. Nation-level data were also obtained to provide the relevant socioeconomic contexts in discussing the results. Results: In total, 159 children were included, where 13 are from Japan, 99 are from the Philippines, and 47 are from the Russian Federation. The median time to surgery at the specific neurosurgical centers was 6 days in the Philippines and 1 day in both Japan and Russia. For the cohort from the Philippines, non-poor patients were more likely to receive CSF diversion surgery at an earlier time (HR = 4.74, 95% CI 2.34-9.61, p <0.001). In the same center, those with infantile or posthemorrhagic hydrocephalus (HR = 3.72, 95% CI 1.70-8.15, p = 0.001) were more likely to receive CSF diversion earlier compared to those with congenital hydrocephalus, and those with postinfectious (HR = 0.39, 95% CI 0.22-0.70, p = 0.002) or myelomeningocele-associated hydrocephalus (HR = 0.46, 95% CI 0.22-0.95, p = 0.037) were less likely to undergo surgery at an earlier time. For Russia, older patients were more likely to receive or require early CSF diversion (HR = 1.07, 95% CI 1.01-1.14, p = 0.035). External ventricular drain (EVD) insertion was found to be associated with mortality (cOR 14.45, 95% CI 1.28-162.97, p = 0.031). Conclusion: In this study, Filipino children underwent late time-interval of CSF diversion surgery and had mortality differences compared to their Japanese and Russian counterparts. These disparities may reflect on the functioning of the health systems of respective countries.

Involvement of the optic pathway and outcome of visual function in patients with neurohypophyseal germ cell tumor.

BACKGROUND: Patients with neurohypophyseal germ cell tumors (GCTs) typically present with visual problems. Hence, this study aimed to assess optic pathway involvement based on clinical and radiological findings and to validate the outcome of visual function. METHODS: A total of 16 patients with newly diagnosed neurohypophyseal GCTs who were treated at the University of Tsukuba Hospital between 2000 and 2020 were included in this study. RESULTS: The median interval from symptom onset to diagnosis was 173.5 days (range, 33-1588 days). Patients with visual disturbance at diagnosis had a longer time to diagnosis compared with those without. Ophthalmologic abnormalities were frequently observed, with an incidence rate of 69%. Fifty percent of patients exhibited optic pathway involvement detected via magnetic resonance imaging (MRI). Visual impairment was more severe in the patients with optic pathway involvement (p = 0.002). Post-treatment visual impairment was improved but was still significantly severe in patients with optic pathway involvement than in those without involvement (p = 0.010). Visual field deficit more likely remained with an improvement rate of 50%, whereas the improvement rate of visual acuity was 78%. Further, none developed late-onset visual deterioration during the follow-up period. CONCLUSIONS: Visual disturbance and optic pathway involvement are common in neurohypophyseal GCTs. Visual impairment particularly in patients with optic pathway involvement on MRI is more likely to remain at follow-up, although the outcome of visual function is acceptable in most cases.

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.

Association of Kabuki syndrome and tethered cord syndrome: a report of three cases and literature review.

Kabuki syndrome (KS) is a congenital disorder characterized by distinctive facial features, skeletal and dermatoglyphic abnormalities, mild-to-moderate intellectual disability, and postnatal growth deficiency. Recently, mutations in the KMT2D and KDM6A genes have been identified as the causative factors in most KS cases. In this study, we present three cases of KS associated with tethered cord syndrome. All cases had a sacral dimple, which is a skin stigmata, and radiological abnormalities, including fatty or thickened filum terminale. Untethering surgery was performed and clinical improvement was achieved. Although in the association between KS and closed neural tube defect (NTD) has rarely been discussed, we emphasize that sacral dimples in KS and tethered cord syndrome are not uncommon. The KS patients with sacral dimple must be carefully investigated by radiological examination and urological study if there is abnormality. Further understanding of the genetic mechanism underlying KS might provide a novel insight on the correlation between the genetics and development of closed NTDs.

Usefulness of postoperative ventriculography and intracranial pressure monitoring following endoscopic third ventriculostomy.

PURPOSE: The authors sought to determine whether the insertion of an external ventricular drain (EVD) at the time of surgery to monitor intracranial pressure (ICP) and ventriculography done within the first day following an endoscopic third ventriculostomy (ETV) is of benefit in postoperative patient management. METHODS: Following IRB approval, ETV procedures done by the senior author between January 1, 2007, and December 31, 2016, were reviewed. Included in a consecutive fashion were all patients who underwent an ETV with placement of an external ventricular drain (EVD) that was preceded preoperatively by an MRI or CT study and followed by a contrast CT ventriculogram within the first postoperative day. RESULTS: Identified were 72 patients who met the above criteria; however, technical ventriculography failure occurred in 4 (6%) and were eliminated from the analysis. Of the remaining 68 patients, contrasted CSF was seen in the basal cisterns/subarachnoid spaces (SAS) in 66 (97%) indicating a patent ETV and absent in 2 (3%) indicating a non-patent ETV. Of the 66 patients with a patent ETV, 34 (52%) patients were discharged on postoperative days 1 (8), 2 (13), and 3 (13) as their ICPs were not elevated and their clinical symptoms normal. EVDs placed at the time of the ETV recorded raised ICP > 20 cm H2O in 17/68 (25%) patients for 1 or more days, all of whom had a patent ETV. Because of persistently elevated ICP requiring CSF drainage for control, 4 of these patients were shunted on postoperative days 5, 6, 6, and 10 and 3 with prolonged elevated ICP for 5, 6, and 11 days postoperatively were not shunted as their ICP and symptoms progressively normalized. The remaining 17/68 (25%) patients did not have a postoperative ICP > 20 cm H2O; 14 were discharged after resolution of symptoms and other clinical factors, 1 was shunted on postoperative day 3 due to persistent symptoms and a consistently large volume of CSF drainage, and 2 had a non-patent ETV with 1 undergoing shunt placement and the other discharged because of the absence of symptoms. The sensitivity of ventriculography was only 13%; however, the specificity was 98% and the accuracy 88%. CONCLUSION: After reviewing this series, the continued use of a postoperative EVD appears appropriate as the risk is low and it provides ventricular access to control ICP, thereby, improving patients' safety and reducing the need for CSF shunting on an urgent/emergent basis should the ETV prove to be unsuccessful. From our limited series, the usefulness of a 1-day postoperative ETV ventriculogram is less clear and would need confirmation with additional studies.

Cognitive Functions of Pediatric Brain Tumor Survivors Treated With Proton Beam Therapy: A Case Series.

Pediatric brain tumor survivors who received proton beam therapy at the University of Tsukuba Hospital from 2004 to 2011 were retrospectively evaluated for cognitive function. Five patients were included. The median age of diagnosis was 5.4 years (range: 1.5 to 12.5 y) and the median follow-up time was 5.8 years (range: 3.1 to 8.1 y). IQ scores at follow-up were decreased in 2 of 5 patients; 1 underwent whole-brain irradiation and the other was examined just after surgical removal of recurrent tumors. Local proton beam therapy may preserve cognitive function in survivors of pediatric brain tumors.

Familial cerebral cavernous malformation presenting with epilepsy caused by mutation in the CCM2 gene: A case report.

RATIONALE: Cerebral cavernous malformation (CCM) of the familial type is caused by abnormalities in the CCM1, CCM2, and CCM3 genes. These 3 proteins forming a complex associate with the maintenance of vascular endothelial cell-cell junctions. Dysfunction of these proteins results in the development of hemangiomas and abnormal intercellular junctions. PATIENT CONCERNS: We report a 68-year-old man with familial cerebral cavernous malformation with initial presentation as convulsions at an advanced age. Brain magnetic resonance imaging revealed multiple cavernous hemangiomas in the right occipital lobe. The convulsions were considered to be induced by hemorrhage from cavernous hemangioma in the right occipital lobe. DIAGNOSES: Genetic screening of the CCM1, CCM2, and CCM3 genes revealed a novel mutation in the CCM2 gene (exon4 c: 359 T>A, p: V120D). No abnormalities were found in CCM1 or CCM3. Therefore, we diagnosed the patient with familial CCM caused by a CCM2 mutation. INTERVENTIONS: This patient was treated with the administration of levetiracetam at a dosage of 1000 mg/day. OUTCOMES: No seizures have been observed since the antiepileptic drug was administered. We performed brain magnetic resonance imaging (MRI) regularly to follow-up on appearance of new cerebral hemorrhages and cavernous hemangiomas. LESSONS: This report reviews cases of familial cerebral cavernous malformations caused by abnormalities in the CCM2 gene. This mutation site mediates interactions with CCM1 and CCM3. The mutation occurs in the phosphotyrosine binding (PTB) site, which is considered functionally important to CCM2.

An Aggressive Extension of Dumbbell-Type Pediatric Skull Base Meningioma: A Case Report with Review of the Literature.

BACKGROUND: Pediatric meningiomas account for less than 2% of pediatric brain tumors. Pediatric clear cell meningiomas (CCMs) occurring in the posterior fossa are particularly rare. Therapeutic strategies differ among the previous pediatric CCM case reports. Therefore, to clarify the clinical features of pediatric CCMs, we report a rare case of dumbbell-type pediatric CCM and a corresponding literature review. CASE DESCRIPTION: A 7-year-old boy with complaints of headache, left facial palsy, dysarthria, and left-sided ataxic gait was emergently admitted to our hospital. His consciousness level was slight stupor, with Glasgow Coma Scale score 3-5-6, and he showed left ptosis, dysarthria, and ataxias of the left trunk and extremities. Magnetic resonance imaging (MRI) scan showed acute obstructive hydrocephalus because of the tumor's compression of the brainstem. The dumbbell-shaped tumor extended from the lateral wall of the cavernous sinus, through the left Meckel's cave, to the cerebellopontine angle. Physical examination and perioperative MRI scan showed no evidence regarding neurofibromatosis type I or II. The tumor was removed in a 2-staged operation. Postoperative proton therapy was done to treat some residual tumors. One year after postoperative proton therapy, there is no recurrence, and apart from left corneal and facial hypesthesia, he is healthy. CONCLUSIONS: We reported a rare case of pediatric skull base-type CCM with huge extension originating from the anteromedial wall of Meckel's cave firmly adhered to the cavernous sinus wall to the posterior fossa that was successfully treated with surgery and postoperative proton therapy. CCM has a high recurrence rate; therefore, careful prolonged follow-up is needed.

Time to diagnosis and clinical characteristics in pediatric brain tumor patients.

PURPOSE: We aimed to identify factors that affect the time to diagnosis in pediatric brain tumors and investigate the effect of time to diagnosis on clinical outcome. METHODS: A retrospective study of children with brain tumors aged less than 18 years diagnosed at the University of Tsukuba Hospital over a period of 7 years was conducted. RESULTS: Eighty-five consecutive patients, with a mean age of 9.1 years, were included in the study. The median interval from symptom onset to diagnosis was 45 days (range 0-1673); median interval from symptom onset to first presentation was 31.0 days; and median interval from first presentation to diagnosis was 13.5 days. Germinoma had the longest interval from symptom onset to first presentation, and from first presentation to diagnosis. Patients presenting with endocrine disorder had a significantly longer interval from symptom onset to first presentation (p = 0.019); those with visual disturbance (p = 0.016) or endocrine disorder (p = 0.030) had significantly longer intervals from first presentation to diagnosis. CONCLUSION: Pediatric brain tumor patients with germinoma and presenting symptoms of endocrine disorder or visual disturbance have a longer time to diagnosis. Although improved prognosis is not clearly related to a shorter time to diagnosis, we believe that early diagnosis can lead to improved treatment and better quality of life. A detailed medical history and neuroimaging studies at the earliest time possible are important for early diagnosis.

Novel neuroprotection using antioxidant nanoparticles in a mouse model of head trauma.

INTRODUCTION: Free radicals and reactive oxygen species are related to deteriorating pathological conditions after head trauma because of their secondary effects. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) scavenges free radicals; however, this molecule is also toxic. Here, we have evaluated the neuroprotective effect of antioxidant nanoparticles, which consisted of a novel core-shell type nanoparticle containing 4-amino-TEMPO, that is, redox-active nitroxide radical-containing nanoparticles (RNPs). METHODS: Institute of Cancer Research mice were subjected to a head-impact procedure, randomly divided into four groups and intravenously (3 mg/kg) administered phosphate-buffered saline, TEMPO, micelle (a self-assembling block copolymer micelle without a TEMPO moiety), or RNP through the tail vein immediately thereafter and intraperitoneally at days 1, 3, and 5 after traumatic brain injury (TBI). The RNP distribution was detected by rhodamine labeling. Cognitive behavior was assessed using the neurological severity score and a rotarod test at days 1, 3, and 7 following TBI, and contusion volume was measured at day 7 after TBI. Free radical-scavenging capacity was analyzed by electron paramagnetic resonance on day 1 after TBI, and immunostaining was used to observe mobilization of microglia (Iba-1) and rescued neuronal cells (NeuN). RESULTS: Redox-active nitroxide radical-containing nanoparticle was detected in the microvessels around the injured area in the brain. Cognitive behavior assessment was significantly better, and contusion volume was significantly smaller in the RNP group compared with the other groups. Superoxide anion scavenging capacity was significantly higher in the RNP group, and neuronal loss was significantly suppressed around the injured area at day 7 after TBI. Furthermore, in the RNP group, neurodegenerative microglia production was suppressed at days 3 and 7 after TBI, whereas neuroprotective microglia production was higher at day 7 after TBI. CONCLUSION: The RNP administration after TBI improved cognitive behavior and reduced contusion volume by improving reactive oxygen species scavenging capacity. Therefore, RNP may have a neuroprotective effect after TBI. LEVEL OF EVIDENCE: Therapeutic test.