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.

Feasibility and efficacy of endoscopic transorbital optic canal decompression for meningiomas causing compressive optic neuropathy.

OBJECTIVE: The endoscopic transorbital approach (ETOA) and transorbital anterior clinoidectomy have been suggested as novel procedures through which to reach the superolateral compartments of the orbit, allowing optic canal decompression. However, there is limited literature describing the technical details and surgical outcomes of these procedures. In this study, the authors aimed to analyze the feasibility and efficacy of endoscopic transorbital decompression of the optic canal through anterior clinoidectomy for compressive optic neuropathic lesions. METHODS: Between 2016 and 2022, the authors performed ETOA for compressive optic neuropathic lesions in 14 patients. All these patients underwent transorbital anterior clinoidectomy through the surgically defined "intraorbital clinoidal triangle," which is composed of the roof of the superior orbital fissure, the medial margin of the optic canal, the medial border of the superior orbital fissure, and the optic strut. Demographic data, tumor characteristics, pre- and postoperative imaging, pre- and postoperative visual examinations, and surgical outcomes were retrospectively reviewed. RESULTS: The mean age at the time of ETOA was 53.3 years (range 41-64 years), and the mean follow-up was 16.8 months (range 6.7-51.4 months). The inclusion criterion in this study was having a meningioma (14 patients). In the preoperative visual function examination, 7 patients with a meningioma showed progressive visual impairment. After endoscopic transorbital optic canal decompression, visual function improved in 5 patients, remained unchanged in 8 patients, and worsened in 1 patient. No new-onset neurological deficit was associated with ETOA and anterior clinoidectomy in any patients. CONCLUSIONS: Endoscopic transorbital decompression of the optic canal with extradural anterior clinoidectomy is a safe and feasible technique that avoids significant injury to the clinoidal internal carotid artery and surrounding neurovascular structures.

Endoscopic Transorbital Surgery for Trigeminal Schwannoma: Introduction of a Novel Approach: 2-Dimensional Operative Video.

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: The major indications of endoscopic transorbital approach include spheno-orbital meningiomas, cavernous sinus lesions, and Meckel cave lesion such as trigeminal schwannomas. It can avoid excessive brain retraction and allows for a fast recovery to the normal daily living activity. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: To access the cavernous sinus, the sagittal crest and meningo-orbital band should be identified and cut. ESSENTIAL STEPS OF THE PROCEDURE: 1. Skin incision along the superior eyelid is performed. 2. Careful dissection of the soft tissue under the orbicularis is required not to injure the orbital septum. 3. After the lateral orbital rim is exposed, the periosteum and periorbita are elevated from the lateral orbital wall. 4. Drilling of the zygomatic bone within the orbit exposes the temporalis muscle first followed by the exposure of the temporal dura. It is essential to obtain adequate working room when the base of the greater sphenoidal wing is drilled. The sagittal crest should be removed, and the meningo-orbital band should be cut to expose the lateral cavernous sinus wall. PITFALLS/AVOIDANCE OF COMPLICATIONS: For successful access through the orbit, endoscopic transorbital approach needs to minimize the retraction of the orbit. To achieve this goal, retraction of the orbit should be limited to a maximum of 10 minutes. VARIANTS AND INDICATIONS OF THEIR USE: This approach can be combined with lateral orbitotomy. It provides a wider working room and makes surgery easier to access the lateral temporal lobe.The patient consented to the procedure, and the participants and any identifiable individuals consented to publication of his/her image. Images at 1:29 reproduced from Corrivetti F, de Notaris M, Di Somma A, et al, "Sagittal crest": definition, stepwise dissection, and clinical implications from a transorbital perspective, Operative Neurosurgery , 22(5), p e206-e212, ©2022, by permission from the Congress of Neurological Surgeons. Video screen capture from The Neurosurgical Atlas at 1:06 used with permission from Aaron Cohen-Gadol; ©The Neurosurgical Atlas, all rights reserved.

Factors Affecting Cage Obliquity and the Relationship between Cage Obliquity and Radiological Outcomes in Oblique Lateral Interbody Fusion at the L4-L5 Level.

OBJECTIVE: This retrospective study investigated the factors that affect cage obliquity angle despite orthogonal maneuvers performed during oblique lateral interbody fusion (OLIF) and assessed the relationship between cage obliquity angle and radiological outcomes post-surgery. METHODS: Twenty-nine males who underwent L4-L5 OLIF for lumbar degenerative disease between 2019 and 2021 with a followup duration greater than 12 months were analyzed. Radiological parameters were measured including psoas muscle volume, total psoas area index (total psoas muscle area [cm2]/height squared [m2]), distance from the iliac artery to the origin of the psoas muscle (DIAPM), angle between the origin of the psoas muscle and the center of the vertebral disc (APCVD), iliac crest height, disc height, lumbar flexibility (lumbar flexion angle minus extension angle), cage location ratio, cage-induced segmental lumbar lordosis (LL) (postoperative index level segmental LL minus used cage angle), foraminal height changes, fusion grade. RESULTS: DIAPM, APCVD, iliac crest height, postoperative index level segmental LL, and cage-induced segmental LL were significantly correlated with OLIF cage obliquity angle. However, other radiological parameters did not correlate with cage obliquity. Based on multiple regression analysis, the predictive equation for the OLIF cage obliquity angle was 13.062-0.318×DIAPM+0.325×A PCVD+0.174×iliac crest height. The greater the cage obliquity, the smaller the segmental LL compared to the cage angle used. CONCLUSION: At the L4-L5 level, OLIF cage obliquity was affected by DIAPM, APCVD, and iliac crest height, and as the cage obliquity angle increases, LL agnle achievable by the used cage could not be obtained.

Progression of Ossification of Posterior Longitudinal Ligament After Anterior Cervical Discectomy and Fusion in Military Patients Exposed to Minor Trauma.

Objective: Ossification of the posterior longitudinal ligament (OPLL) can progress even after cervical spine surgery and may cause neurological injury as a result of minor trauma. The purpose of this study was to investigate the preventive factors associated with OPLL progression after anterior cervical discectomy and fusion (ACDF), a procedure commonly performed in clinical practice. Methods: We retrospectively investigated 295 male soldiers who underwent ACDF surgery between 2012 and 2017. Patients who were followed up for >12 months using dynamic radiography and computed tomography (CT) were included in the study. Radiological parameters investigated included OPLL progression, C2-C7 angles on dynamic radiography, segmental angles, C2-C7 cervical sagittal vertical axis (C2-C7 SVA), and the T1 slope. These parameters were measured preoperatively and 1 year postoperatively. Results: A total of 49 patients were enrolled, and 10 patients were confirmed to have OPLL progression. Comparison between the OPLL progression and non-progression groups showed no statistically significant differences in pre- and postoperative cervical range of motion. However, statistically significant differences were observed in the postoperative neutral C2-C7 angle (progression -3.9°±6.4° vs. non-progression -13.4°±7.9°, p=0.001) and the SVA change (progression 5.8±7.9 mm vs. non-progression -3.7±6.3 mm, p=0.00). The cutoff values were -8.01° for the postoperative neutral C2-C7 angle and 1.4 mm for SVA changes. Conclusion: Increased SVA (>1.4 mm) and a small postoperative neutral C2-C7 angle (>-8.01°) 1 year after ACDF were associated with OPLL progression. It is important to be mindful of these factors during follow-up after ACDF, because additional surgical treatment may be necessary for OPLL progression due to neurological injury caused by minor trauma.

Leptomeningeal Spread at the Diagnosis of Glioblastoma Multiforme: A Case Report and Literature Review.

Approximately two-thirds of glioblastoma (GBM) patients progress to leptomeningeal spread (LMS) within two years. While 90% of LMS cases are diagnosed during the progression and/or recurrence of GBM (defined as secondary LMS), LMS presentation at the time of GBM diagnosis (defined as primary LMS) is very rare. 18F-fluorodeoxy glucose positron emission tomography computed tomography (18F-FDG PET/CT) study helps to diagnose the multifocal spread of the malignant primary brain tumor. Our patient was a 31-year-old man with a tumorous lesion located in the right temporal lobe, a wide area of the leptomeninges, and spinal cord (thoracic 5/6, and lumbar 1 level) involvement as a concurrent manifestation. After the removal of the right temporal tumor, the clinical status progressed rapidly, showing signs of increased intracranial pressure and hydrocephalus caused by LMS. He underwent a ventriculoperitoneal shunt a week after craniotomy. During management, progression of cord compression, paraplegia, bone marrow suppression related to radiochemotherapy, intercurrent infections, and persistent ascites due to peritoneal metastasis of the LMS through the shunt system was observed. The patient finally succumbed to the disease nine months after the diagnosis of simultaneous GBM and LMS. The overall survival of primary LMS with GBM in our case was nine months, which is shorter than that of secondary LMS with GBM. The survival period after the diagnosis of LMS did not seem to be significantly different between primary and secondary LMS. To determine the prognostic effect and difference between primary and secondary LMS, further cooperative studies with large-volume data analysis are warranted.

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.

Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors.

PURPOSE: This study aimed to compare the early hematological dynamics and acute toxicities between proton beam craniospinal irradiation (PrCSI) and photon beam craniospinal irradiation (PhCSI) for pediatric brain tumors. MATERIALS AND METHODS: We retrospectively reviewed patients with pediatric brain tumors who received craniospinal irradiation (CSI). The average change in hemoglobin levels (ΔHbavg), absolute lymphocyte counts (ΔALCavg), and platelet counts (ΔPLTavg) from baseline values was evaluated and compared between the PrCSI and PhCSI groups at 1 and 2 weeks after the initiation of CSI, 1 week before and at the end of radiotherapy, and 3-4 weeks after the completion of radiotherapy using t test and mixed-model analysis. RESULTS: The PrCSI and PhCSI groups consisted of 36 and 30 patients, respectively. There were no significant differences in ΔHbavg between the two groups at any timepoint. However, ΔALCavg and ΔPLTavg were significantly lower in the PhCSI group than in PrCSI group at every timepoint, demonstrating that PrCSI resulted in a significantly lower rate of decline and better recovery of absolute lymphocyte and platelet counts. The rate of grade 3 acute anemia was significantly lower in the PrCSI group than in in the PhCSI group. CONCLUSION: PrCSI showed a lower rate of decline and better recovery of absolute lymphocyte and platelet counts than PhCSI in the CSI for pediatric brain tumors. Grade 3 acute anemia was significantly less frequent in the PrCSI group than in the PhCSI group. Further large-scale studies are warranted to confirm these results.

Outcome of endoscopic transcortical intraventricular biopsy of isolated thickened pituitary stalk lesions in children.

OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of endoscopic transcortical intraventricular biopsy in pediatric patients with isolated thickened pituitary stalk lesions. METHODS: From 1994 to 2018, 16 pediatric patients (8 males and 8 females) underwent endoscopic transcortical intraventricular biopsy at a single institution to establish an accurate pathological diagnosis for appropriate treatment strategies. RESULTS: Preoperatively, the median diameter of the pituitary stalks was 5.31 ± 1.67 mm (range 3.86-9.17 mm). Overall, the diagnostic yield at endoscopic intraventricular biopsy was 93.8%. Histopathological diagnosis included germinoma (n = 10, 62.5%), Langerhans cell histiocytosis (n = 4, 25%), pilocytic astrocytoma (n = 1, 6.3%), and pituicytoma (n = 1, 6.3%). Two patients developed new diabetes insipidus after the procedure, and 3 patients had new postoperative hypothyroidism. There were no postoperative neurological deficits in this series. CONCLUSIONS: Neuroendoscopic biopsy via the transcortical intraventricular corridor was shown to be safe and to aid in a reliable histopathological diagnosis in the management of isolated pituitary stalk lesions in pediatric patients. It can be considered a minimally invasive alternative to open biopsy via transcranial or endonasal corridors.

Mechanical and Durability Properties of Latex-Modified Hybrid Fiber-Reinforced Roller-Compacted Rapid-Set Cement Concrete for Pavement Repair.

This study evaluated the mechanical properties and durability performance of latex-modified hybrid fiber-reinforced roller-compacted rapid-set cement concrete (LMHFRCRSC) for emergency repair of concrete pavement. Experimental parameters included the blend ratio of the hybrid fiber, which comprised natural jute fiber (0-0.2 vol.%) and structural synthetic fiber (0-2 vol.%). The mechanical performance of LMHFRCRSC of various blend ratios was evaluated in terms of compressive, flexural, and splitting tensile strength. Durability assessment included chlorine ion penetration and abrasion resistance measurements. Compressive and flexural strength values of 21 and 3.5 MPa, respectively, were the set targets after 4 h of curing; a compressive strength of 35 MPa, a flexural strength of 4.5 MPa, a splitting tensile strength of 4.2 MPa, and chloride ion penetration of 2000 C or less were required after 28 days of curing. Our test results confirmed that all mix proportions satisfied the target values, regardless of the blend ratio of the hybrid fiber. Specifically, the mechanical performance of the concrete improved as the blend ratio of the structural synthetic fiber increased. With regard to durability, a greater amount of jute fiber, a hydrophilic fiber, enhanced the concrete's durability. Additionally, incorporating jute fiber of 0.6 kg/m3 provided excellent chlorine ion penetration resistance. The optimal blend ratio for the hybrid fiber was natural jute fiber at 0.6 kg/m3 and structural synthetic fiber at 13.65 kg/m3 (mix: J0.6 + P13.65); with this mix proportion, a chloride ion penetration amount of 1000 C or less and maximum mechanical performance were achieved.

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.

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.

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years.

PURPOSE: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years. MATERIALS AND METHODS: A search of medical records from seven centers was performed between January 2005 and December 2016. RESULTS: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01). CONCLUSION: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.

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.

Clinical, Hormonal, and Neuroradiological Characteristics and Therapeutic Outcomes of Prolactinomas in Children and Adolescents at a Single Center.

Background/Purpose: A prolactinoma is the most common pituitary adenoma, but it is relatively rare in childhood and adolescence. There is only limited research about the clinical spectrum, treatment, and outcomes of prolactinomas in childhood and adolescence. In this single-center cohort study, we assessed the clinical, hormonal, and neuroradiological characteristics and therapeutic outcomes of children and adolescents with prolactinomas. Methods: This retrospective cohort study included 25 patients with prolactinomas diagnosed before 19 years of age, who presented at Samsung Medical Center during a 15-year period (March 2005 to August 2019). Results: The median age at diagnosis was 16.9 (range 10.1-18.5) years, and 80% of the patients were female. The common clinical manifestations at diagnosis were galactorrhea (10/20, 50%) and amenorrhea (9/20, 45%) among females and visual field defects (3/5, 60%) and headaches (2/5, 40%) among males. In our cohort, macroadenomas accounted for 56% of cases, and the rate of overall responsiveness to dopamine agonists (DAs) was 56% (10/18). Male gender, the prolactin (PRL) level at diagnosis, and the presence of panhypopituitarism were positively correlated with maximum tumor diameter (r = 0.443, P = 0.026; r = 0.710, P < 0.001; and r = 0.623, P = 0.001, respectively). After the trans-sphenoidal approach (TSA), 53% (8/15) of patients showed normalization of the PRL level. Three patients, who underwent gamma knife surgery (GKS) owing to either resistance or intolerance to DAs or recurrence after the TSA, achieved a normal PRL level accompanied with marked tumor reduction and symptom remission. Conclusions: A macroprolactinoma is more prevalent than a microprolactinoma in children and adolescents than in adults. Male gender, increased PRL levels, and the presence of panhypopituitarism at diagnosis are closely related to macroprolactinomas in children and adolescents.

Promising survival rate but high incidence of treatment-related mortality after reduced-dose craniospinal radiotherapy and tandem high-dose chemotherapy in patients with high-risk medulloblastoma.

BACKGROUND: In this study, we report the follow-up results of reduced dose of craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) in patients with high-risk medulloblastoma (MB). METHODS: Newly diagnosed high-risk MB patients (metastatic disease, postoperative residual tumor >1.5 cm2 , or large cell/anaplastic histology) over 3 years of age were enrolled in this study. Two cycles of pre-RT chemotherapy, radiotherapy (RT) including reduced-dose CSRT (23.4 or 30.6 Gy), four cycles of post-RT chemotherapy, and tandem HDCT were administered. NanoString and DNA sequencing were performed using archival tissues. RESULTS: In all, 40 patients were enrolled, and molecular subgrouping was possible in 21 patients (2 wingless, 3 sonic hedgehog, 8 Group 3, and 8 group 4). All patients including two patients who experienced progression during the induction chemotherapy underwent HDCT. Relapse/progression occurred only in four patients (5-year cumulative incidence [CI] 10.4 ± 0.3%). However, six patients died from treatment-related mortality (TRM) (four acute TRMs and two late TRMs) resulting in 18.5 ± 0.5% of 5-year CI. Taken together, the 5-year event-free survival and overall survival were 71.1 ± 8.0% and 73.2 ± 7.9%, respectively. Late effects were evaluated in 25 patients and high-tone hearing loss, endocrine dysfunction, dyslipidemia, and growth retardation were common. CONCLUSIONS: The strategy using tandem HDCT following reduced-dose CSRT showed promising results in terms of low relapse/progression rate; however, the high TRM rate indicates that modification of HDCT regimen and careful selection of patients who can benefit from HDCT will be needed in the future study.

Induction Chemotherapy Reduces Radiation Therapy Dose and Volume in the Treatment of Intracranial Germinoma: Results of the SMC-G13 Trial.

PURPOSE: We performed a prospective single-arm trial (NCT02782754) to explore the feasibility of reducing radiation therapy (RT) dose when induction chemotherapy is combined in the treatment of intracranial germinoma with beta-human chorionic gonadotropin levels <200 mIU/mL. METHODS AND MATERIALS: All patients aged 3 to 35 years from November 2012 to June 2018 were eligible for this study. Four cycles of induction chemotherapy were given before RT. Carboplatin/etoposide and cyclophosphamide/etoposide regimens were used in alternation every 3 weeks. A dose of 18 Gy of craniospinal RT for metastatic tumors, whole brain RT for basal ganglia tumors, or otherwise whole ventricular RT followed by 12.6 Gy of boost RT to the primary tumor bed was administered after induction chemotherapy. The primary endpoint of this study was progression-free survival. RESULTS: A total of 41 consecutive patients were enrolled (location: suprasellar in 12, pineal in 12, both suprasellar and pineal in 11, and basal ganglia in 6 patients). Eleven patients had leptomeningeal seeding. Toxicity during chemotherapy was mild, except for bone marrow suppression. Tumor status after induction chemotherapy was complete response in 33 patients and partial response in 8. All but 2 patients completed the scheduled treatment. All patients but 1 remained event free during a median follow-up of 3.4 (range, 0.3-7.0) years from diagnosis. The 1 patient experienced relapse and died of tumor bleeding. Late effects were not significant except for neuroendocrine dysfunction already present at diagnosis. Vertical growth and cognitive function were not significantly disturbed by treatment. CONCLUSIONS: This study showed the feasibility of reducing RT dose/volume with induction chemotherapy in pathologically pure germinoma with elevated beta-human chorionic gonadotropin levels up to 200 mIU/mL.

Moyamoya Disease and Spectrums of RNF213 Vasculopathy.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. A polymorphism (R4810K) in the Ring Finger Protein 213 (RNF213) gene, at chromosome 17q25.3, is the strongest genetic susceptibility factor for MMD in East Asian populations. MMD was regarded prevalent in childhood and in East Asian populations. However, the so-called MMD could represent only the tip of the iceberg. MMD is increasingly reported in adult patients and in Western populations. Moreover, the RNF213 variant was recently reported to be associated with non-MMD disorders, such as intracranial atherosclerosis and systemic vasculopathy (e.g., peripheral pulmonary artery stenosis and renal artery stenosis). In this review, we summarize the spectrums of RNF213 vasculopathy in terms of clinical and genetic phenotypes. Continuous efforts are required for pathophysiology-based diagnoses and treatment, which will benefit from collaboration between clinicians and researchers, and between stroke and vascular physicians.

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.