Endoscopic transorbital approach in children: surgical technique and early results.

OBJECTIVE: In this study, the authors aimed to describe the endoscopic transorbital approach (ETOA) in children. METHODS: Six pediatric patients (2 girls and 4 boys) underwent the ETOA for paramedian skull base lesions at a single institution between September 2016 and February 2023. RESULTS: The median age at the time of surgery was 7.5 (range 4-18) years. The median follow-up period was 33 (range 9-60) months. In this series, the ETOA level of difficulty included stage 1 (n = 2, 33.3%), stage 3 (n = 3, 50%), and stage 5 (n = 1, 16.7%). The ETOA was performed for tumor resection in 4 cases; the final pathology consisted of fibrous dysplasia, pilocytic astrocytoma, metastatic neuroblastoma, and choroid plexus papilloma. The procedure was also performed for repair of a petrous apex meningocele and for lateral orbital wall decompression of traumatic lateral rectus muscle entrapment. One patient experienced a transient cranial nerve III palsy after the procedure. There were no operative deaths in this series. CONCLUSIONS: In select cases, the ETOA can be considered a minimally invasive alternative for conventional skull base approaches in the armamentarium of pediatric skull base surgery. Further investigation and the accumulation of experience are warranted in the future to enhance the efficacy and applicability of the ETOA in pediatric patients.

Risk Stratification of Childhood Medulloblastoma Using Integrated Diagnosis: Discrepancies with Clinical Risk Stratification.

BACKGROUND: Recent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB. METHODS: The nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues. RESULTS: A total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 out of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system. CONCLUSION: The new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.

Gamma Knife Radiosurgery for Incidental, Symptomatic Unruptured, and Ruptured Brain Arteriovenous Malformations.

BACKGROUND: This study was performed to investigate clinical characteristics and outcome after gamma knife radiosurgery (GKS) in patients with incidental, symptomatic unruptured, or ruptured arteriovenous malformations (AVMs). METHODS: A total of 491 patients with brain AVMs treated with GKS from June 2002 to September 2017 were retrospectively reviewed. All patients were classified into the incidental (n = 105), symptomatic unruptured (n = 216), or ruptured AVM (n = 170) groups. RESULTS: The mean age at diagnosis of incidental, symptomatic unruptured, and ruptured AVMs was 40.3, 36.7, and 27.6 years, respectively. The mean nidus volume was 3.9, 5.7, and 2.4 cm3, respectively. Deep venous drainage was identified in 34, 54, and 76% patients, respectively. There were no significant differences in obliteration rates after GKS between the 3 groups (64.8, 61.1, and 65.9%, respectively) after a mean follow-up period of 60.5 months; however, patients with incidental AVM had a significantly lower post-GKS hemorrhage rate than patients with symptomatic unruptured or ruptured AVMs (annual hemorrhage rate of 1.07, 2.87, and 2.69%; p = 0.028 and p = 0.049, respectively). CONCLUSIONS: There is a significant difference in clinical and anatomical characteristics between incidental, symptomatic unruptured, and ruptured AVMs. The obliteration rate after GKS is not significantly different between the 3 groups. Meanwhile, an older age at diagnosis and lower hemorrhage rate after GKS in incidental AVMs suggest that they have a more indolent natural course with a lower life-long risk of hemorrhage.

Comparison between retrosigmoid and translabyrinthine approaches for large vestibular schwannoma: focus on cerebellar injury and morbidities.

This study aimed to compare the surgical outcomes and morbidities of retrosigmoid and translabyrinthine approaches for large vestibular schwannoma (VS), with a focus on cerebellar injury and morbidities. Eighty-six consecutive patients with large VS, with a maximal extrameatal diameter > 3.0 cm, were reviewed between August 2010 and September 2018. The surgical outcomes, operating time, volume change of perioperative cerebellar edema, and inpatient rehabilitation related to cerebellar morbidities were compared between the two approaches. In total, 53 and 33 patients underwent the retrosigmoid and translabyrinthine approaches, respectively. The median follow-up time was 34.5 months. Surgical outcomes, including the extent of resection, tumor recurrence, and facial nerve preservation, showed no significant differences between the two groups. Patients who underwent the retrosigmoid approach showed a marginal trend for postoperative lower cranial nerve (LCN) dysfunction (P = 0.068). Although the approaching procedure time was longer in the translabyrinthine group, the tumor resection time was significantly longer in the retrosigmoid group (P = 0.001). The median change in the volume of the perioperative cerebellar edema was significantly larger in the retrosigmoid group (P < 0.001) and significantly related to the retrosigmoid approach, solid VS, and tumor resection time. Most cerebellar and LCN deficits were transient; however, the patients in the retrosigmoid group underwent inpatient rehabilitation more than those in the translabyrinthine group (P = 0.018). Both surgical approaches show equivalent surgical outcomes. Notably, the translabyrinthine approach for large VS has advantages in that it reduces cerebellar injury and related morbidities.

Optimal Volume of the Residual Tumor to Predict Long-term Tumor Control Using Stereotactic Radiosurgery after Facial Nerve-preserving Surgery for Vestibular Schwannomas.

BACKGROUND: Intended subtotal resection (STR) followed by adjuvant gamma knife radiosurgery (GKRS) has emerged as an effective treatment option for facial nerve (FN) preservation in vestibular schwannomas (VSs). This study aimed to identify the optimal cut-off volume of residual VS to predict favorable outcomes in terms of both tumor control and FN preservation. METHODS: This retrospective study assessed the patients who underwent adjuvant GKRS for residual VS after microsurgery. A total of 68 patients who had been followed up for ≥ 24 months after GKRS were included. Tumor progression was defined as an increase in tumor volume (TV) of ≥ 20%. House-Brackmann grades I and II were considered to indicate good FN function. RESULTS: The median residual TV was 2.5 cm³ (range: 0.3-27.4). The median follow-up period after the first adjuvant GKRS was 64 months (range: 25.7-152.4). Eight (12%) patients showed tumor progression. In multivariate analyses, residual TV was associated with tumor progression (P = 0.003; hazard ratio [HR], 1.229; 95% confidence interval [CI], 1.075-1.405). A residual TV of 6.4 cm³ was identified as the cut-off volume for showing the greatest difference in progression-free survival (PFS). The 5-year PFS rates in the group with residual TVs of < 6.4 cm³ (54 patients) and that with residual TVs of ≥ 6.4 cm³ (14 patients) were 93.3% and 69.3%, respectively (P = 0.014). A good FN outcome was achieved in 57 (84%) patients. Residual TV was not associated with good FN function during the immediate postoperative period (P = 0.695; odds ratio [OR], 1.024; 95% CI, 0.908-1.156) or at the last follow-up (P = 0.755; OR, 0.980; 95% CI, 0.866-1.110). CONCLUSION: In this study, residual TV was associated with tumor progression in VS after adjuvant GKRS following STR. As preservation of FN function is not correlated with the extent of resection, optimal volume reduction is imperative to achieve long-term tumor control. Our findings will help surgeons predict the prognosis of residual VS after FN-preserving surgery.

Tandem High-dose Chemotherapy without Craniospinal Irradiation in Treatment of Non-metastatic Malignant Brain Tumors in Very Young Children.

BACKGROUND: Infants and very young children with malignant brain tumors have a poorer survival and a higher risk for neurologic deficits. The present study evaluated the feasibility and effectiveness of multimodal treatment including tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in minimizing use of radiotherapy (RT) in very young children with non-metastatic malignant brain tumors. METHODS: Twenty consecutive patients younger than 3 years were enrolled between 2004 and 2017. Tandem HDCT/auto-SCT was performed after six cycles of induction chemotherapy. Local RT was administered only to patients with post-operative gross residual tumor at older than 3 years. Since September 2015, early post-operative local RT for patients with atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor was administered. RESULTS: All 20 enrolled patients underwent the first HDCT/auto-SCT, and 18 proceeded to the second. Two patients died from toxicity during the second HDCT/auto-SCT, and four patients experienced relapse/progression (one localized and three metastatic), three of whom remained alive after salvage treatment including RT. A total of 17 patients remained alive at a median 7.8 (range, 2.5-5.7) years from diagnosis. Nine survivors received no RT, six survivors received local RT alone, and two survivors who experienced metastatic relapse after tandem HDCT/auto-SCT received both local and craniospinal RT. The 5-year overall, event-free, and craniospinal RT-free survival rates were 85.0% ± 8.0%, 70.0% ± 10.2%, and 75.0% ± 9.7%, respectively. Neuroendocrine and neurocognitive functions evaluated 5 years after tandem HDCT/auto-SCT were acceptable. CONCLUSION: Our results suggest that non-metastatic malignant brain tumors in very young children could be treated with multimodal therapy including tandem HDCT/auto-SCT while minimizing RT, particularly craniospinal RT.

Gamma Knife Radiosurgery for ARUBA-Eligible Patients with Unruptured Brain Arteriovenous Malformations.

BACKGROUND: A randomized trial of unruptured brain arteriovenous malformations (ARUBA) reported superior outcomes in conservative management compared to interventional treatment. There were numerous limitations to the study. This study aimed to investigate the efficacy of gamma knife radiosurgery (GKS) for patients with brain arteriovenous malformations (AVMs) by comparing its outcomes to those of the ARUBA study. METHODS: We retrospectively reviewed ARUBA-eligible patients treated with GKS from June 2002 to September 2017 and compared against those in the ARUBA study. AVM obliteration and hemorrhage rates, and clinical outcomes following GKS were also evaluated. RESULTS: The ARUBA-eligible cohort comprised 264 patients. The Spetzler-Martin grade was Grade I to II in 52.7% and III to IV in 47.3% of the patients. The mean AVM nidus volume, marginal dose, and follow-up period were 4.8 cm³, 20.8 Gy, and 55.5 months, respectively. AVM obliteration was achieved in 62.1%. The annual hemorrhage rate after GKS was 3.4%. A stroke or death occurred in 14.0%. The overall stroke or death rate of the ARUBA-eligible cohort was significantly lower than that of the interventional arm of the ARUBA study (P < 0.001) and did not significantly differ from that of the medical arm in the ARUBA study (P = 0.601). CONCLUSION: GKS was shown to achieve a favorable outcome with low procedure-related morbidity in majority of the ARUBA-eligible patients. The outcome after GKS in our patients was not inferior to that of medical care alone in the ARUBA study. It is suggested that GKS is rather superior to medical care considering the short follow-up duration of the ARUBA study.

Multimodal treatment including tandem high-dose chemotherapy and autologous stem cell transplantation in children with anaplastic ependymomas.

In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto-SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto-SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto-SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto-SCT, and 13 subsequently underwent the second HDCT/auto-SCT. One patient died from hepatic VOD during the second HDCT/auto-SCT; other toxicities occurring during tandem HDCT/auto-SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5-year overall and event-free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto-SCT could be a feasible option for improving survival in children with anaplastic ependymomas.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents.

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT.

Clinical Features of Superficially Located Brain Arteriovenous Malformations with Transdural Arterial Communication.

BACKGROUND: Contrary to deeply located brain arteriovenous malformations (AVMs), superficially located AVMs are more likely to have transdural arterial communications (TACs). However, the clinical and radiologic characteristics of patients presenting with AVMs and TACs are poorly understood. The purpose of this study is to determine whether clinicoradiological features of cerebral AVMs differ according to TAC. METHODS: Between 2002 and 2012, 438 consecutive patients with a brain AVM were treated in our hospital. Among them were 124 patients with superficially located brain AVMs who met the inclusion and exclusion criteria of our study. We retrospectively reviewed the clinicoradiological features of their TACs to explore the variation in characteristics. RESULTS: Thirty-two of the 124 patients with a superficially located AVM (25.8%) had TAC. Radiologic findings of brain AVM images with TAC showed that TAC occurred significantly more frequently among larger AVMs (with vs. without TAC, 11.2 vs. 4.0 ml) and among diffuse AVMs (56.3 vs. 28.3%, p = 0.004). Clinical findings indicate that TAC was associated with chronic headache (43.8 vs. 12.0%, p < 0.001) and older age (43.1 vs. 36.6 years, p = 0.037). CONCLUSIONS: Brain AVM with TAC seems to be accompanied by distinctive clinical features, such as chronic headache and older age. Larger size and diffuseness of the AVM were also associated with TAC. Findings from this study and the prognostic significance of TAC should be further explored in a large prospective study.

Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic Factors.

BACKGROUND/AIMS: To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. METHODS: We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. RESULTS: The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. CONCLUSION: Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.

Coexistence of intracranial Langerhans cell histiocytosis and Erdheim-Chester disease in a pediatric patient: a case report.

INTRODUCTION: The co-occurrence of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) is extremely rare and almost all cases were reported in adults. CASE REPORT: We describe a case of intracranial LCH and ECD that was confirmed by histopathological and molecular studies. A three-year-old boy presented with headache and right exophthalmos and brain magnetic resonance images (MRI) revealed multiple intracranial tumors. Whole body MRI showed osteolytic lesions typical of LCH in flat bones and osteosclerotic changes typical of ECD in long bones. DISCUSSION: Histologically, the biopsy samples from the posterior fossa and occipital skull mass revealed areas of both LCH and ECD. Immunohistochemically, the LCH contained CD1a-positive Langerhans cells and the ECD had CD1a-negative, CD68-positive foamy histiocytes. BRAF (V600E) mutations were detected in both the LCH and ECD areas. The coexistence of LCH and ECD in the same biopsy and the BRAF (V600E) mutation status in both histologic types support the recent re-classification of the histiocytic disorder into LCH, ECD, and "mixed histiocytosis", which reflects tumorigenesis for all three from a common progenitor cell.

Clinical outcome of neurofibromatosis type 2-related vestibular schwannoma: treatment strategies and challenges.

To discuss the appropriate treatment strategy for NF2-related vestibular schwannoma (VS) according to our experiences, we analyzed long-term clinical and radiological data focusing on NF2-related VS patients. Seventeen NF2-related VS patients were included. Based on their first management modality for VS, we classified these patients into the following four groups: microsurgery (MS), fractionated gamma knife radiosurgery (f-GKS), single session gamma knife radiosurgery (s-GKS), and conservative management (CM). Each patient was assessed for each separate ear. Changes of tumor volume and hearing status for 32 ears in 17 patients according to their first treatment modality were evaluated. The mean follow-up duration and tumor volume of the MS (4 ears, 4 patients), f-GKS (12 ears, 10 patients), s-GKS (8 ears, 7 patients), and CM (8 ears, 7 patients) groups were 3.9 years and 1.6 mL; 5.1 years and 11.1 mL; 8.4 years and 5.6 mL; and 6.1 years and 1.6 mL, respectively. Relatively lower local control rates were observed in the MS and the CM group (0 and 12.5 %, respectively). On the other hand, better local control rates for follow-up periods of 5.1 and 8.4 years were achieved in the f-GKS and the s-GKS groups (75 and 50 %, respectively). However, hearing preservation in all treatment modalities could not be achieved effectively. Long-term preservation of hearing in at least one serviceable ear as well as tumor control should be considered for each patient. Therefore, a proper treatment option should be selected at the appropriate time according to clinical characteristics of individual patients.

Highly unstable cervical spine injury in an infant: a case report.

UNLABELLED: Although the rate of surgical intervention for pediatric cervical spine injuries has risen, none of these instrumentation techniques has been reported in children less than 1 year of age. Additional consideration with placement of wires or cables is not safe because of the presence of cartilaginous bone and poor bone strength. The authors report a technique of internal fixation without fusion using nonabsorbable synthetic suture in an infant with unstable cervical injury. METHODS: A 5-month-old girl was transported to emergency department and computed tomography showed severe distraction injury at the C6-7 level with total disruption of the facet joints bilaterally. To improve her general condition, she was placed in a customized occipito-cervical brace until surgical stabilization could be performed. After 1 month, surgical fixation was performed. After removing all soft tissues at the appropriate level, a hole was made in the center of the superior articular process of C6. A nonabsorbable suture (2-0 Ethibond; Ethicon, Somerville, NJ, USA) was passed from the superior articular process to the facet joint. The suture was passed into the spinous process of the lower level, and it was progressively tightened and radiographs were taken until anatomic reduction was achieved. RESULTS: After surgery, solid fusion was achieved. She was able to sit up in a stroller after 6 months. CONCLUSION: As surgical treatment of pediatric cervical spine injuries is unsuitable for infants, the Ethibond sutures are strong enough to hold and stabilize the spine. This suturing technique can be used as an alternative treatment for cervical injury in infants.

Unilateral intracranial arteriopathy in pediatric stroke: course, outcome, and prediction of reversible arteriopathy.

BACKGROUND AND PURPOSE: The nonprogressive, often reversible, unilateral arteriopathy known as transient (focal) cerebral arteriopathy has become a leading cause of childhood arterial ischemic stroke. However, it is not a well-recognized arteriopathy in East Asian countries where moyamoya disease is prevalent. METHODS: We retrospectively reviewed 74 children and adolescents (<18 years) with arterial ischemic stroke and intracranial arteriopathy to identify 29 patients with unilateral large-artery arteriopathy mainly in the anterior circulation. Among them, 25 patients who fulfilled the following inclusion criteria were analyzed to determine the angiographic course and outcome: (1) repeated vascular imaging at least twice and (2) absence of thrombotic disorders or cardiac diseases. RESULTS: The course of unilateral arteriopathy was classified as reversible in 17 patients (68%), progressive in 5 (20%), and stable in 3 (12%). Nine of the 17 patients with reversible arteriopathy exhibited initial worsening of the arteriopathy mostly within 1 month, but the worsened arteriopathy began to improve within 3 months and continued to improve even after a few years. Two of these 9 patients experienced stroke progression at 6 days. Of the variables analyzed, infarction involving the basal ganglia (15 of 17) and arterial beading on angiography performed within 2 weeks (10 of 12) were associated with reversible arteriopathy. Involvement of the ipsilateral posterior cerebral artery was rare (1 of 17). CONCLUSIONS: The possibility of reversible arteriopathy should be suspected in children and adolescents presenting with arterial ischemic stroke and unilateral arteriopathy.

Toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation using carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens for malignant brain tumors in children and young adults.

The number of studies examining the use of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) to treat high-risk or recurrent brain tumors is increasing. However, studies addressing the toxicity associated with tandem HDCT/auto-SCT, particularly during the second HDCT/auto-SCT, are very limited. For this reason, we retrospectively evaluated the toxicity of tandem HDCT/auto-SCT with carboplatin-thiotepa-etoposide (CTE) and cyclophosphamide-melphalan (CM) regimens when used to treat high-risk or recurrent brain tumors. A total of 109 patients who received a first HDCT/auto-SCT and 100 who proceeded to a second HDCT/auto-SCT between May 2005 and December 2013 were included. Hematologic recovery was rapid during both the first and second HDCT/auto-SCT. In the first HDCT/auto-SCT, mucositis-related gastrointestinal toxicity was frequent, and two (1.8 %) patients died from toxicity [one hepatic veno-occlusive disease (VOD) and one sepsis]. In the second HDCT/auto-SCT, mucositis-related toxicity was milder than in the first round. However, hepatic VOD frequency was high (20.0 %), and six (6.0 %) patients died from toxicity (four hepatic VODs, one asphyxia, and one sepsis). Multivariate analysis indicated that age younger than 8 years was the only significant predictor for hepatic VOD. All six patients who died from toxicity during the second HDCT/auto-SCT were younger than 9 years of age. This study demonstrates that tandem HDCT/auto-SCT using CTE/CM regimens was generally feasible. However, dose reduction during the second HDCT/auto-SCT in young children might be needed to decrease the death rate from toxicity.

Intensive chemotherapy followed by reduced-dose radiotherapy for biopsy-proven CNS germinoma with elevated beta-human chorionic gonadotropin.

In this study, 10 patients with biopsy-proven germinoma with a beta-human chorionic gonadotropin (ß-HCG) level >50 mIU/ml received intensive chemotherapy followed by reduced-dose radiotherapy (RT) to reduce late effects from RT. CSF ß-HCG levels were >200 mIU/ml in five patients. After endoscopic or stereotactic biopsy, four cycles of induction chemotherapy were administered prior to RT. A CEB regimen (carboplatin + etoposide + bleomycin) and a CyEB regimen (cyclophosphamide + etoposide + bleomycin) were alternated. No residual tumor remained after induction chemotherapy in six patients, only cystic lesions were present at the primary tumor site in three, and a small solid residual tumor was observed in the remaining patient; however, all these patients had normal ß-HCG levels. If complete response was achieved before initiation of RT, 19.5 Gy craniospinal RT (CSRT) + 10.8 Gy local RT was administered to the tumor bed. If residual lesion was suspected, the dose of RT was selected according to the presence/absence of tumor dissemination at diagnosis (19.5 Gy CSRT + 19.8 Gy local RT for localized tumors and 24.0 Gy CSRT + 16.2 Gy local RT for disseminated tumors). Eight patients, including four patients with a ß-HCG level >200 mIU/ml, received 19.5 Gy CSRT. All patients remain disease free at a median follow-up of 58 (range 35-94) months from diagnosis. Our data suggest that pathologically pure germinoma with a significantly elevated ß-HCG level might be cured with reduced-dose RT if intensive chemotherapy is provided.

Neovascularization precedes occlusion in moyamoya disease: angiographic findings in 172 pediatric patients.

BACKGROUND: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. METHODS: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. RESULTS: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. CONCLUSION: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.

Neuroendoscopic biopsy of pediatric brain tumors with small ventricle.

PURPOSE: Intraventricular endoscopic procedures to resect or biopsy peri- or intraventricular tumors may have not been used in patients with small ventricles due to the presumed difficulties with ventricular cannulation and the perceived risk of morbidity. The purpose of this study is to review the feasibility and safety of neuroendoscopic procedures in the biopsy of pediatric brain tumors with a small ventricle. METHODS: Between January 2006 and January 2013, 72 children were identified with brain tumors confirmed by transventricular endoscopic biopsy. Patients were divided into non-hydrocephalus and hydrocephalus groups, and the ratio of the two groups was 20:52. RESULTS: In 20 pediatric brain tumors with small ventricle, the targeted lesion was successfully approached under the guidance of neuronavigation. Navigational tracking was especially helpful in entering small ventricles and in approaching the third ventricle through the narrow foramen of Monro. The histopathologic diagnosis was established in all 20 patients: nine germinomas, three mixed germ cell tumors, two pilomyxoid astrocytomas, and two pilocytic astrocytomas. The tumor biopsy sites were the suprasellar area (n = 10), pineal area (n = 4), lateral ventricular wall (n = 4), and mammillary body (n = 1). There were no major morbidities related to the endoscopic procedure. CONCLUSION: Neuroendoscopic biopsy or resection of peri- or intraventricular tumors in pediatric patients without hydrocephalus is feasible. Navigation-guided neuroendoscopic procedures improved the accuracy of the neuroendoscopic approach and minimized brain trauma. The absence of ventriculomegaly in patients with brain tumor may not serve as a contraindication to neuroendoscopic tumor biopsy.

Central cord syndrome in a 7-year-old boy secondary to standing high jump.

Acute traumatic central cord syndrome is commonly associated with major trauma such as falling and motor vehicle crash, but minor or nontraumatic causes are very rare in children. As a consequence, most physicians frequently overlook children presenting with complaints of arm weakness when history of any definite major trauma does not exist, especially in the emergency department. We present the case of a 7-year-old boy who was experiencing weakness in both arms after a standing high jump with tilting his head back in school. He had no history of any definite trauma and no evidence of bone abnormalities on plain radiography and computed tomography of the cervical spine. Magnetic resonance imaging of the cervical spine revealed observable swelling with increased signal intensity at C1 to 4 levels. This case showed a spinal cord injury caused by standing high jump with neck extension alone. Therefore, the physicians have to consider the possibility of spinal cord injury even without any history of major trauma.