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Diffuse midline glioma (DMG) which occurs in midline structures and characterized by harboring K27M mutation in genes encoding the histone 3 protein is classified as World Health Organization (WHO) grade IV regardless of histological findings and has a poor prognosis. Nevertheless, because of its relatively rare incidence compared with other high-grade gliomas, a comprehensive description encompassing clinical features and genomic profiles of DMG is still lacking.In this study, we analyzed data of 24 patients who were diagnosed as DMG which was confirmed by surgical specimens in both pediatric and adult patients. We described the clinical outcomes of patients with DMG and their genomic profiles through a retrospective analysis of 24 patients with DMG.The clinical characteristics of the 24 patients with DMG were analyzed. Ten patients (41%) underwent tumor resection and 14 patients (59%) underwent tumor biopsy. The median overall survival was 10.4 months (95% confidence interval [CI], 8.4 to 12.5) and progression free survival was 3.9 months (95% CI, 2.6 to 5.2). Fifteen patients (62%) were accompanied by hydrocephalus. None of the patient, tumor, or treatment factors had any significant associated with survival. In both immunohistochemistry staining (n=24) and targeted next generation sequencing (n=15), TP53 mutation was the most common genetic mutation (25% and 46%, respectively) found in the patients except alterations in histone 3 protein.Although surgical treatment of patient with DMG does not affect the overall survival prognosis, it can help improve the patient's accompanying neurological symptoms in some limited cases. Hydrocephalus is often accompanied with DMG and treatment for hydrocephalus is often also required. Multidisciplinary therapeutic approach is needed.

BACKGROUND AND PURPOSE Managing hydrocephalus in patients with vestibular schwannoma (VS) is controversial. We evaluated the clinical factors associated with hydrocephalus. METHODS Between 2000 and 2019, 562 patients with VS were treated at our institute. We applied endoscopic third ventriculostomy (ETV), external ventricular drainage (EVD), and ventriculoperitoneal (VP) shunts to patients with hydrocephalus. The relationships of patient, tumor, and surgical variables with the hydrocephalus outcome were assessed. RESULTS Preoperative hydrocephalus (Evans ratio ≥0.3) was present in 128 patients. Six patients who received a preresectional VP shunt were excluded after analyzing the hydrocephalus outcome. Seven of the remaining 122 patients had severe hydrocephalus (Evans ratio ≥0.4). Primary tumor resection, VP shunting, ETV, and EVD were performed in 60, 6, 57, and 5 patients, respectively. The hydrocephalus treatment failure rate was highest in the EVD group. Persistent hydrocephalus was present in five (8%) and seven (12%) patients in the primary resection and ETV groups, respectively. Multivariate analysis revealed that severe hydrocephalus, the cystic tumor, and the extent of resection (subtotal resection or partial resection) were associated with hydrocephalus treatment failure. CONCLUSIONS Larger ventricles and a higher cystic portion are predictive of persistent hydrocephalus. We recommend attempting near-total tumor resection in patients with VS.

Background Indirect bypass surgery is used to improve the hemodynamic status of the pediatric moyamoya disease (MMD). Symptomatic cerebral infarction during the early postoperative period may be the most frustrating complication. Objective The purpose of this study is to investigate the factors associated with early post-operative symptomatic cerebral infarction. Methods Between January 2000 and February 2014, we performed 1241 indirect bypass surgeries for 659 pediatric MMD patients. Symptomatic infarction during the early postoperative period was diagnosed in 63 operations of 61 patients. Results The overall incidence of symptomatic cerebral infarction after indirect bypass surgery was 5.1 %. The median age of postoperative infarcted patients was 6 years (mean 6.4 years, range of 1 to 15 years). Performing of two craniotomies in single operation resulted in a higher rate of cerebral infarction. Moreover, young patients (under six years old) showed a relatively higher incidence than older patients. In a matched analysis, immediate postoperative hemoglobin levels of more than 13 g/dL was associated with decreased infarction risk (odd ratio=0.144, p=0.003). The mutation of the methylenetetrahydrofolate reductase (MTHFR) gene occurred in relatively high proportion of our infarction group. Conclusion Postoperative symptomatic infarctions can occur despite a unified surgical method and formulaic perioperative management protocol. Patient-centered factors, such as the young age, genetic background of MTHFR and particular medical conditions including hyperthyroidism, renovascular hypertension and hemolytic uremic syndrome, as well as management related factors including two craniotomies and low immediate postoperative hemoglobin level could be risk factors for early postoperative symptomatic cerebral infarction.

Head injuries are the most common type of birth injuries. Among them, most of the injuries is limited to the scalp. and the prognosis is good enough to be unnoticed in some cases. Intracranial injuries caused by excessive forces during delivery are rare. However, since some of them can be fatal, it is necessary to suspect it at an early stage and evaluate thoroughly if there are abnormal findings in the patient.

Objective In complex lumbosacral lipomatous malformation or retethering, “crotch” dissection, an incision on the dura or lipoma at the site lateral to the lipoma-cord fusion line saving underlying roots, is often not easy. Attempts of this dissection in complex and obscured conditions may cause damage to the spinal cord or nerve roots. A method for caudal extension of untethering while positive areas on electrical stimulation were encountered during the crotch dissection of lumbosacral lipomatous malformation is described. Methods After thinning out the negative-response area just caudal to the positive-response area, a small perforation is made at the negative-response area skipping the positive-response area with probing the dissection direction through the subarachnoid space by an inside-out fashion. Subsequently, the procedure is continued caudally from the perforation site. Results Safe caudal extension of untethering is possible using this method. Illustrative operative photographs are shown. Conclusions By using this method, safe untethering can be achieved avoiding root injuries in complicated lipomas such as chaotic or retethering cases.

OBJECTIVEEndothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model.METHODSA CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies.RESULTSThe normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups.CONCLUSIONSThese results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.

As per the 2016 World Health Organization (WHO) guidelines on the classification of central nervous system tumors, solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) constitute a single disease entity, known as SFT/HPC. This study provides a clinical analysis of these tumors and describes the treatment outcomes of SFT/HPCs. This retrospective study included 76 patients with histopathologically proven SFT/HPC. Reclassification according to the 2016 WHO guideline was done for patients who were diagnosed with SFT or HPC based on the 2007 WHO classification. Recurrence-free survival (RFS) and overall survival (OS) were evaluated for all patients and subgroups. The median follow-up period was 77.9 months. The median RFS and OS were 126.5 and 136.8 months, respectively. The 1-, 5-, 10-, and 15-year RFS rates were 93%, 72%, 40%, and 40%, respectively. The 1-, 5-, 10- and 15-year OS rates were 97%, 89%, 54%, and 35%, respectively. In multivariable analyses, stereotactic radiosurgery (SRS; p = 0.009, hazard ratio [HR] 6.986), female sex (p = 0.023, HR 1.76), and age over 45 (p = 0.037, HR 2.74) were associated with shorter RFS. Patients who underwent SRS as initial treatment had a shorter OS than that of patients who underwent primary resection (p

Objective To evaluate the clinical significance of intraoperative bulbocavernosus reflex (BCR) during untethering surgery in predicting post-operative voiding function. Methods We conducted a retrospective review of pediatric patients who underwent untethering surgery with available intraoperative baseline BCR. BCR response during surgery was classified into loss or maintenance. Post-operative voiding function was determined as worsened or maintained based on history, postvoid residual urine measurement, and urodynamic study (UDS). Data regarding demographics, diagnosis, pre-operative voiding difficulty, re-untethering, syrinx, and abnormalities in electromyography were collected for analysis. Results We included 106 patients, with a mean age of 3.3 years, and 49 patients were male. BCR was lost in 15 patients during surgery and voiding function worsened in 14 patients after surgery. Lumbosacral lipoma was the most common diagnosis, and 16 patients were diagnosed with lipomyelomeningocele (LMMC). The sensitivity and specificity of intraoperative BCR for post-operative worsening of voiding function were 35.7%, and 88.5% at 6 months, respectively. The diagnosis of LMMC was statistically significant in a logistic regression analysis. The specificity of BCR at 6 months in patients with diagnosis other than LMMC was 93.4%, and intraoperative BCR was significant in a logistic regression analysis. Conclusions Intraoperative BCR during untethering could predict bladder function 6 months post-operatively with high specificity (88.5%), particularly in cases other than LMMC (93.4%), indicating that voiding function deterioration will not occur if intraoperative BCR is preserved. Significance Intraoperative BCR during untethering surgery is a useful tool to predict post-operative voiding outcome.

Lesional mesial temporal lobe epilepsy (mTLE) concerns a lesion other than mesial hippocampal sclerosis present in the mesial temporal lobe and causing seizures. The lesions are usually composed of focal cortical dysplasia (FCD) or are tumorous. These are good candidates for surgical treatment. Sometimes, it is difficult to distinguish between tumors and FCD and to determine the extent of required removal. 11C-methionine positron emission tomography (PET) is helpful in differentiating lesions before surgery in lesional mTLE. In 11C-methionine PET imaging, tumors show a hot uptake, whereas FCD does not. In case of tumorous conditions, the removal of only specific lesions may be considered because the seizure outcome is dependent on complete excision of the tumor. There are several ways to safely access mesial temporal structures. The transsylvian-transcisternal approach is a good way to access the mesial structures while preserving the lateral and basal temporal structures. Actual lesions associated with epileptogenesis in FCD may be larger than they appear on magnetic resonance imaging. For this reason, evaluations to locate sufficient epileptogenic foci, including invasive studies, should be completed for FCD, and epilepsy surgery should be performed according to these results. Regardless, the ultimate goal of all epilepsy surgeries is to maximize seizure control while maintaining neurological function. Therefore, a tailored approach based on the properties of the lesion is needed.

Objective Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy in children. Epilepsy surgery has been a valuable treatment option to achieve seizure freedom in these intractable epilepsy patients. We aimed to present long-term surgical outcome, in relation to pathological severity, and to assess predictive factors of epilepsy surgery in pediatric isolated FCD. Methods We retrospectively analyzed the data of 58 children and adolescents, with FCD International League Against Epilepsy (ILAE) task force classification types I and II, who underwent resective epilepsy surgery and were followed for at least 2 years after surgery. Results The mean age at epilepsy onset was 4.3 years (0–14.2 years), and mean age at epilepsy surgery was 9.4 years (0.4–17.5 years). The mean duration of postoperative follow-up was 5.1 ± 2.6 years (2–12.4 years). Of 58 patients, 62% of patients achieved Engel class I at 2 years postoperatively, 58% at 5 years postoperatively, and 53% at the last follow up. Forty eight percent of our cohort successfully discontinued antiepileptic medication. Of 30 patients with seizure recurrence, 83% of seizures recurred within 2 years after surgery. We observed that FCD type IIb was significantly associated with a better surgical outcome. At fifth postoperative year, 88% of FCD IIb patients were seizure free compared with 21% of type I and 57% of type IIa patients ( P = 0.043). By multivariate analysis, lesion on MRI ( P = 0.02) and complete resection ( P Significance Epilepsy surgery is highly effective; more than half of medically intractable epilepsy patients achieved seizure freedom after surgery. In addition, we found significant difference in surgical outcomes according to the ILAE task force classification. Lesion on MRI and complete resection were the most important predictive factors for favorable seizure outcome in isolated FCD patients.

Hydrocephalus-related symptoms are mostly improved after successful endoscopic third ventriculostomy (ETV). However, visual symptoms can be different. This study was focused on visual symptoms. We analyzed the magnetic resonance images (MRI) of the orbit and visual outcomes. From August 2006 to November 2016, 50 patients with hydrocephalus underwent ETV. The male-to-female ratio was 33:17, and the median age was 61 years (range, 5–74 years). There were 18 pediatric and 32 adult patients. Abnormal orbital MRI findings included prominent subarachnoid space around the optic nerves and vertical tortuosity of the optic nerves. We retrospectively analyzed clinical symptoms, causes of hydrocephalus, ETV success score (ETVSS), ETV success rate, ETV complications, orbital MRI findings, and visual impairment score (VIS). The median duration of follow-up was 59 months (range, 3–113 months). The most common symptoms were headache, vomiting, and gait disturbance. Visual symptoms were found in 6 patients (12%). The most common causes of hydrocephalus were posterior fossa tumor in 13 patients, pineal tumor in 12, aqueductal stenosis in 8, thalamic malignant glioma in 7, and tectal glioma in 4. ETVSS was 70 in 3 patients, 80 in 34 patients, and 90 in 13 patients. ETV success rate was 80%. ETVSS 70 showed the trend in short-term survival compared to ETVSS 90 and 80. ETV complications included epidural hematoma requiring operation in one patient, transient hemiparesis in two patients, and infection in two patients. Preoperative abnormal orbital MRI findings were found in 18 patients and postoperative findings in 7 patients. Four of six patients with visual symptoms had abnormal MR findings. Three patients did not show VIS improvement, including two with severe visual symptoms. Patients with severe visual impairment were found to have bad outcomes. The visual symptoms related with increased intracranial pressure should be carefully monitored and controlled to improve outcomes.

Benign extracerebral fluid collection (bECFC) can be complicated by subdural hematoma (SDH) or subdural fluid collection (SDFC). The etiology, natural history, and management strategy for SDH/SDFC in bECFC are not fully understood. We retrospectively reviewed the cases of bECFC patients complicated with SDH/SDFC and tried (1) to confirm the fact that bECFC children are vulnerable to SDH/SDFC, (2) to investigate the clinical significance of 'trauma history' witnessed by a caregiver, and (3) to determine optimal management for them. Among 213 bECFC patients identified from January 2000 to August 2015, 20 patients (male:female = 14:6; median age, 6.5 months; range 1–16 months) complicated by SDH/SDFC documented with brain imaging were evaluated for their clinical manifestations, radiologic features, and management outcomes. The median follow-up period was 9.5 months. They were divided into two groups (traumatic group versus non-traumatic group) according to whether objective radiologic evidence of head injury was present or not, and the two groups were analyzed for any clinical differences between them. We also evaluated the clinical significance of witnessed traumatic events by caregivers as an additional independent variable in the analysis. The incidence of SDH/SDFC in bECFC patients was 9.4% (20/213) in our data. In a comparative analysis, the traumatic group is more likely to have 'acute' stage SDH, whereas the non-traumatic group is more likely to have 'chronic' stage SDH. The trauma history witnessed by caregivers did not show clinical significance in the data analysis when included as an independent variable. The prognosis of SDH/SDFC in bECFC patients was favorable without surgery in most of patients regardless of whether the patient has evidence of head trauma or not. Benign ECFC is vulnerable to SDH/SDFC development. For the bECFC patients complicated by SDH/SDFC, the trauma history witnessed by a caregiver did not show any clinical significance. A 'wait and watch' strategy is sufficient for the management of SDH/SDFC in bECFC patients.

OBJECTIVEDue to their distinct location, suprasellar arachnoid cysts are known to cause a wide variety of problems, such as hydrocephalus, endocrine symptoms, and visual abnormalities. The long-term outcome of these cysts has not been elucidated. To find out the long-term outcome of suprasellar arachnoid cysts, a retrospective review of the patients was performed. The neurological and endocrine symptoms were thoroughly reviewed.METHODSForty-five patients with suprasellar arachnoid cysts, with an average follow-up duration of 9.7 years, were enrolled in the study. A comprehensive review was performed of the results of follow-up regarding not only neurological symptoms but also endocrine status. The outcomes of 8 patients who did not undergo operations and were asymptomatic or had symptoms unrelated to the cyst were included in the series.RESULTSSurgery was most effective for the symptoms related to hydrocephalus (improvement in 32 of 32), but endocrine symptoms persisted after surgery (4 of 4) and required further medical management. More surprisingly, a fairly large number of patients (14 of 40; 1 was excluded because no pre- or postoperative endocrine evaluation was available) who had not shown endocrine symptoms at the time of the initial diagnosis and treatment later developed endocrine abnormalities such as precocious puberty and growth hormone deficiency. The patients with endocrine symptoms detected during the follow-up included those in both the operated (n = 12 of 32) and nonoperated (n = 2 of 8) groups who had been stable during follow-up since the initial diagnosis.CONCLUSIONSThis study implies that patients with suprasellar arachnoid cysts can develop late endocrine problems during follow-up, even if other symptoms related to the cyst have been successfully treated. Hence, patients with these cysts need long-term follow-up for not only neurological symptoms but also endocrine abnormalities.

OBJECTIVESince the entity limited dorsal myeloschisis (LDM) was proposed, numerous confusing clinical cases have been renamed according to the embryopathogenesis. However, clinical application of this label appears to require some clarification with regard to pathology. There have been cases in which all criteria for the diagnosis of LDM were met except for the presence of a neural component in the stalk, an entity the authors call “probable” LDM. The present study was performed to meticulously review these cases and suggest that a modified surgical strategy using limited laminectomy is sufficient to achieve the surgical goal of untethering.METHODSThe authors retrospectively reviewed the imaging findings, operative notes, and pathology reports of spinal dysraphism patients with subcutaneous stalk lesions who had presented to their institution between 2010 and 2014.RESULTSAmong 33 patients with LDM, 13 had the typical nonsaccular lesions with simple subcutaneous stalks connecting the skin opening to the spinal cord. Four cases had “true” LDM meeting all criteria for diagnosis, including pathological confirmation of CNS tissue by immunohistochemical staining with glial fibrillary acidic protein. There were also 9 cases in which all clinical, imaging, and surgical findings were compatible with LDM, but the “neural” component in the resected stalk was not confirmed. For all the cases, limited exposure of the stalk was done and satisfactory untethering was achieved.CONCLUSIONSOne can speculate based on the initial error of embryogenesis that if the entire stalk were traced to the point of insertion on the cord, the neural component would be proven. However, this would require an extended level of laminectomy/laminotomy, which may be unnecessary, at least with regard to the completeness of untethering. Therefore, the authors propose that for some selected cases of LDM, a minimal extent of laminectomy may suffice for untethering, although it may be insufficient for diagnosing a true LDM.

A variety of complications in endoscopic third ventriculostomy have been reported, including neurovascular injury, hemodynamic alterations, endocrinologic abnormalities, electrolyte imbalances, cerebrospinal fluid leakage, fever and infection. Even though most complications are transient, the overall rate of permanent morbidity is 2.38% and the overall mortality rate is 0.28%. To avoid these serious complications, we should keep in mind potential complications and how to prevent them. Proper decisions with regard to surgical indication, choice of endoscopic entry and trajectory, careful endoscopic procedures with anatomic orientation, bleeding control and tight closure are emphasized for the prevention of complications.

Pediatric spinal vascular diseases are extremely rare. We aimed to evaluate their clinical characteristics and treatment outcomes in our institute. A total of 10 patient files were retrospectively reviewed, including 3 cases of intramedullary arteriovenous malformations (AVMs), 6 cases of perimedullary arteriovenous fistulas (AVFs), and 1 case of epidural AVF. Clinical features, radiological findings, treatment results, and clinical outcomes were evaluated. The median durations of the radiologic and clinical follow-ups were 17.7 and 107.9 months, respectively. The male to female ratio was 1:1, with a median age at diagnosis of 9 years. All AVMs were juvenile type, all perimedullary AVFs were high flow types (three type IVb and three type IVc), and one epidural AVF was associated with intradural venous drainage. Most cases (90 %) were located in the cervical spine and conus medullaris. Acute neurological deterioration was identified in five patients; however, bleeding was identified in only one patient. Two cases were surgically treated, seven cases underwent embolization, and one case underwent radiosurgery. Three cases were completely obliterated, and their clinical states were improved (n = 2; 66.7 %) and stationary (n = 1; 33.3 %). Meanwhile, seven cases were incompletely obliterated, and their clinical states were improved (n = 2; 28.6 %), stationary (n = 3; 42.8 %), and aggravated (n = 2; 28.6 %). Pediatric spinal AVMs and AVFs were mostly complex and high flow types, and complete obliteration could not be satisfactorily achieved. Incompletely treated lesions should be closely followed up because they may worsen.

Indication, timing, and method for surgical treatment of lumbosacral lipoma are controversial. Radical resection of the lumbosacral lipoma and complete reconstruction of the placode are supported in that better long-term outcome can be achieved without increasing complication rate compared with traditional surgical techniques. We analyzed the early surgical outcomes of lumbosacral lipoma treated with the untethering and radical excision of fat. Retrospective analysis of surgically treated 81 fresh lumbosacral lipoma cases with dorsal, transitional, and chaotic types and true lipomyelomeningocele (LMMC) was performed. Caudal and filar types were excluded. Complete untethering was accomplished in 98%. Radical excision of the lipoma was attempted in all cases and achieved in 83%. Postoperative neurological complication was observed in 8 cases (10%). Group of lipoma types (dorsal + transitional vs. chaotic + true LMMC) and availability of radical lipoma excision turn out to be factors related to neurological outcomes in univariate analysis (p

It is well known that the preoperative enlarged sac in occult spinal dysraphism, in which the spinal cord is attached to its dome, can be associated with neurological deficits by aggravation of spinal cord traction. We experienced a similar phenomenon during the early stage of untethering surgery for “lipomyelomeningocele in a strict sense (LMMC).” We report a case of a 3-month-old girl with LMMC, which showed decreased motor evoked potentials (MEPs) in the lower extremities during the early stage of untethering surgery. The sac was released from the original nest by incision with separation of the overlying skin and dissection from the muscle fascia. The sac became rounder, and the spinal cord attached to the dome of the sac was further stretched. After aspiration of cerebrospinal fluid from the sac, the MEPs recovered. Postoperatively, the patient had no neurological deficits. Although this phenomenon rarely occurs, release of the herniated sac of LMMC from the original nest during the early stage of untethering surgery may result in neurological changes. Application of intraoperative neurophysiological monitoring helps to detect electrophysiological deterioration and can prevent neurological deficits.

BACKGROUND AND PURPOSE This study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD). METHODS We retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery. RESULTS We attempted AED withdrawal in 40 patients. The median time of starting the AED reduction was 10.8 months after surgery. Of these 40 patients, 14 patients (35%) experienced seizure recurrence during AED reduction or after AED withdrawal. Half of the 14 patients who experienced recurrence regained seizure freedom after AED reintroduction and optimization. Compared with their preoperative status, the AED dose or number was decreased in 57.1% of patients, and remained unchanged in 14.3% after surgery. A multivariate analysis found that incomplete resection (p=0.004) and epileptic discharges on the postoperative EEG (p=0.025) were important predictors of seizure recurrence after AED withdrawal. Over the mean follow-up duration of 4.5 years after surgery, 34 patients (48.6% of the entire cohort) were seizure-free with and without AEDs. CONCLUSIONS Children with incomplete resection and epileptic discharges on postoperative EEG are at a high risk of seizure recurrence after drug withdrawal. Complete resection of FCD may lead to a favorable surgical outcome and successful AED withdrawal after surgery.

Background Limited dorsal myeloschisis (LDM) is postulated to be a result of incomplete dysjunction in primary neurulation. However, clinical experience of LDM located below the first-second sacral (S1-S2) vertebral level, which is formed from secondary neurulation (S2-coccyx), suggested that LDM may not be entirely explained as an error of primary neurulation. Objective To elucidate the location and characteristics of LDM to investigate the possible relation of its pathoembryogenesis to secondary neurulation. Methods Twenty-eight patients were surgically treated for LDM from 2010 to 2015. Since the level where the LDM stalk penetrates the interspinous ligament is most clearly defined on the preoperative MRI and operative field, this level was assessed to find out whether the lesions can occur in the region of secondary neurulation. Results Eleven patients (39%) with typical morphology of the stalk had interspinous defect levels lower than S1-S2. These patients were not different from 17 patients with classic LDMs at a level above or at S1-S2. This result shows that other than the low level of the interspinous level, 11 patients had lesions that could be defined as LDMs. Conclusion By elucidating the location of LDM lesions (in particular, the interspinous level), we propose that LDM may be caused by errors of secondary neurulation. The hypothesis seems more plausible due to the supportive fact that the process of separation between the cutaneous and neural ectoderm is present during secondary neurulation. Hence, incomplete disjunction of the two ectoderms during secondary neurulation may result in LDM, similar to the pathomechanism proposed during primary neurulation.

BACKGROUND The existence of tethering tracts in spinal dysraphism, other than congenital dermal sinus (CDS), has been recognized and has been summated into an integrated concept of limited dorsal myeloschisis (LDM). OBJECTIVE To elucidate the underlying embryology of LDM in relation to CDS by focusing on the pathological features of special cases of tethering tracts. METHODS Out of 389 spinal dysraphism patients who were operated on from 2010 to 2016, 5 patients who had tethering tracts composed of both CDS and LDM (or "probable LDM" if only fibrous tissue was found) were identified. Their clinical presentation, radiological images, operative findings, and pathology were thoroughly reviewed. RESULTS Three nonsaccular-type patients harbored stalks in which the squamous epithelial lined sinus (CDS) was found in the distal portion, and fibroneural (LDM) or fibrous (probable LDM) tissue in the proximal part. Two patients had saccular lesions, and a stalk was found inside the sac, connecting a small pit on the skin to the spinal cord. The tracts were pathologically identical to a CDS. CONCLUSION This study reports the coexistence of CDS and LDM (or probable LDM) components. These unique cases support the hypothesis that the CDS and LDM are among a spectrum of an anomaly that is caused by failure of complete dysjunction between cutaneous and neural ectoderms. Neurosurgeons should be aware of the possibility of coexisting "CDS" components in cases suggestive of LDM. In such cases, not only untethering but also meticulous removal of the squamous epithelium is critical.

Human adipose tissue-derived mesenchymal stem cells expressing the secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (hAT-MSC.sTRAIL) have demonstrated therapeutic activity against various tumors in preclinical studies. However, the limited expression of TRAIL death receptors remains a challenge. We evaluated the therapeutic efficacy of panobinostat in enhancing the sensitivity of hAT-MSC.sTRAIL-mediated apoptosis in malignant glioma. Panobinostat effectively inhibited all malignant glioma cells (IC50, 0.03–0.23 μM), enhancing the expression of DRs, but not in hAT-MSCs. Combined treatment with hAT-MSC.sTRAIL and panobinostat significantly suppressed cell viability and enhanced apoptosis. In a diffuse intrinsic pontine glioma (DIPG) mouse model, the combined treatment induced decreases in tumor volume and prolonged survival. Our study demonstrates that panobinostat enhances the expression of TRAIL DRs and potentiates the anti-cancer effects of hAT-MSC.sTRAIL.

Acetazolamide-challenged brain single-photon emission computed tomography (SPECT) is used for the evaluation of cerebral perfusion in cerebrovascular diseases including moyamoya disease (MMD). Not a few patients experience adverse side effects during the acetazolamide-challenged brain SPECT, but most of the symptoms are mild and transient. To our knowledge, this is the first case report of severe brain infarction leading to death during the examination of an acetazolamide-challenged brain SPECT in a patient with MMD. An 11-year-old girl who had been diagnosed of MMD demonstrated sudden tonic movement during an acetazolamide-challenged brain SPECT as the preoperative examination for the second surgery. She had not experienced any adverse effect during the previous SPECT study and her first indirect bypass surgery on both left side and bifrontal area was uneventful. After she had seizures twice, she became unconscious and her pupils were dilated and fixed. Acute infarction involving bilateral occipital lobes, thalami, brainstem, and cerebellum was observed on brain magnetic resonance images which led to brain death. We report a mortality case of patient with MMD after the administration of acetazolamide during the examination of brain SPECT that was accompanied by an extensive acute infarction involving the bilateral occipital lobes and thalami, brainstem, and cerebellum. Physicians should be aware of this rare but serious complication.

Background Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU.AT/RT-6) and established AT/RT cell lines (BT-12 and BT-16) were used to assess therapeutic effects of combining DSF with radiation treatment (RT). Survival fraction by clonogenic assay, protein expression, immunofluorescence, and autophagy analysis were evaluated in vitro. Antitumor effects of combining DSF with RT were verified by bioluminescence imaging, tumor volume, and survival analysis in vivo. Results The results demonstrated that DSF at low concentration enhanced the radiosensitivity of AT/RT cells with reduction of survival fraction to 1.21‒1.58. DSF increased DNA double-strand break (γ-H2AX, p-DNA-PKcs, and p-ATM), apoptosis (cleaved caspase-3), autophagy (LC3B), and cell cycle arrest (p21) in irradiated AT/RT cells, while it decreased anti-apoptosis (nuclear factor-kappaB, Survivin, and B-cell lymphoma 2 [Bcl2]). In vivo, DSF and RT combined treatment significantly reduced tumor volumes and prolonged the survival of AT/RT mouse models compared with single treatments. The combined treatment also increased γ-H2AX, cleaved caspase-3, and LC3B expression and decreased ALDH1, Survivin, and Bcl2 expression in vivo. Conclusions DSF and RT combination therapy has additive therapeutic effects on AT/RT by potentiating programmed cell death, including apoptosis and autophagy of AT/RT cells. We suggest that DSF can be applied as a radiosensitizer in AT/RT treatment.

OBJECTIVEMoyamoya disease (MMD) is a unique cerebrovascular disorder characterized by the progressive occlusion of the bilateral internal carotid arteries. Endothelial colony-forming cells (ECFCs), previously termed “endothelial progenitor cells,” play an important role in the pathogenesis of MMD. In this study, the authors performed morphological and functional studies of the mitochondria of ECFCs from patients with MMD to present new insights into the pathogenesis of the disease.METHODSThe morphology of ECFCs from 5 MMD patients and 5 healthy controls was examined under both a transmission electron microscope and a confocal laser scanning microscope. The oxygen consumption rates (OCRs), mitochondrial membrane potentials (MMPs), intracellular Ca2+ concentrations, mitochondrial enzyme activities, and reactive oxygen species (ROS) levels were measured. Functional activity of the ECFCs was evaluated using a capillary tube formation assay.RESULTSThe ECFCs from the MMD patients displayed a disrupted mitochondrial morphology, including a shorter and more circular shape. The ECFC mitochondria from the MMD patients exhibited functional abnormalities, which were assessed as a decreased OCR and an increased intracellular Ca2+ concentration. Moreover, the ECFCs from MMD patients showed increased ROS levels. Interestingly, treatment with an ROS scavenger not only reversed the mitochondrial abnormalities but also restored the angiogenic activity of the ECFCs from the MMD patients.CONCLUSIONSThe mitochondria of ECFCs from MMD patients, as compared with those from healthy patients, exhibited morphological and functional abnormalities. This finding suggests that the mitochondrial abnormalities may have a role in the pathogenesis of MMD.

The posterior fossa dural opening requires the ligation of the occipital sinus to gain successful exposure. However, there could be a prominent occipital sinus which is functioning as the main drainage route and is harboring the risk of unpredictable massive hemorrhage during the dural opening. We introduce a safe method of posterior fossa dural incision to minimize hemorrhage from the occipital sinus using four curved hemostat clamps. For the dural incision at the midline part of the posterior cranial fossa, we used four curved hemostat clamps to occlude the prominent occipital sinus: one pair of clamps at the proximal part and the other pair at the distal part to occlude the occipital sinus. Dural incision was made between the two pairs of the curved hemostat clamps. By clamping of the sinus, it allows observation of possible brain swelling after occlusion of the occipital sinus as well as minimizes hemorrhage during incision of the midline dura of the posterior fossa. This method allows observation of brain swelling after occipital sinus occlusion and is an easy and safe incision of the midline dura minimizing hemorrhage in selected cases with a prominent occipital sinus.

Impaired swallowing in children who underwent posterior fossa brain tumor (PFBT) resection disrupts development and quality of life, yet its downstream consequences remain unclear. This study explored the risk factors and functional prognosis of postoperative swallowing impairment in pediatric patients (

Human adipose-derived mesenchymal stem cells expressing secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (hAT-MSC.sTRAIL) have demonstrated therapeutic activity against various tumors. However, sTRAIL resistance remains a challenge in developing anticancer strategies. To solve this problem, many studies have tried to combine drugs to produce synergism or sensitize resistant cancer cells. Histone deacetylase inhibitors (HDACi) have been known to induce expression of TRAIL death receptors 4 and 5 (DR4/DR5). Herein, we evaluated the use of combined therapy of hAT-MSC.sTRAIL with HDAC inhibitor, panobinostat, in enhancing sensitivity to hAT-MSC.sTRAIL mediated apoptosis against the brainstem glioma. A sTRAIL was introduced into the characterized hAT-MSCs using electroporation. To confirm appropriate treatment concentration of panobinostat to the glioblastoma cells, dose titration was tested using cell viability assay. The therapeutic effect of single or combination treatment against glioblastoma was evaluated using primary cultured glioblastoma cells and cell lines. Orthotopic xenograft brainstem glioma mouse model was established using engineered firefly luciferase expressing tumor cells for bioluminescence in vivo imaging. Panobinostat induced anti-proliferative effects in dose and time-dependent manner (IC50 range, 0.05-0.2 μM) and effectively enhanced the expression of TRAIL DR4 and DR5, but not decoy receptors. Combined hAT-MSC.sTRAIL and panobinostat significantly decreased the tumor cell growth compared to each alone. Intriguingly, the combination treatment not only induced apoptosis but also autophagy. Using a preclinical brainstem mouse model, we confirmed that the combination of hAT-MSC.sTRAIL and panobinostat was safe and induced regression of tumor volume. Furthermore, the combination therapy prolonged the survival of brainstem glioma-bearing mice. Our results suggested that combination therapy of panobinostat enhanced the anti-cancer effect of hAT-MSC.sTRAIL and represent potential therapeutic approach to the brainstem glioma. Citation Format: Seung Ah Choi, Chanhee Lee, Pil Ae Kwak, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Seung-Ki Kim. Synergistic effects of combined treatment with hAT-MSC.sTRAIL and panobinostat in brainstem glioma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3195.

Disulfiram (DSF) has been studied as an anticancer drug and radiosensitizer. In our previous study, the therapeutic potential of DSF against atypical teratoid/rhabdoid tumor (AT/RT), one of the most aggressive forms of childhood cancer, had been confirmed using in vitro and in vivo studies. To develop more effective and safer therapy in AT/RT, we evaluated the sensitizing potential of DSF on radiation therapy (RT). The effect of DSF in low concentration alone and in combination with RT was investigated in vitro and vivo. Clonogenic assay, western blot analysis, autophagy assay and γ-H2AX foci staining were performed using several primary cultured AT/RT cells and cell lines. Also, in vivo study was performed using AT/RT orthotopic xenograft mouse model. Combination therapy with DSF and RT potently reduced clonogenicity and down-regulated protein expression of survivin and BCL2. The combination treatment strongly promoted the autophagic cell death and produced abundant γ-H2AX foci in all AT/RT cells. Moreover, the combination treatment significantly reduced the tumor growth and prolonged the survival rate compared to single treatment in AT/RT mouse model. Taken together, our results demonstrated that the combination therapy with DSF and RT has a synergistic therapeutic effect on AT/RT, suggesting a potential clinical application for AT/RT patients. Citation Format: Yeoung Eun Lee, Seung Ah Choi, Pil Ae Kwak, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Youn Joo Moon, Anshika Jangra, Kyeung Min Joo, Seung-Ki Kim. Combined disulfiram and radiation therapy against atypical teratoid/rhabdoid tumor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3056.

There are limited data analyzing radiological and clinical factors for the functional outcomes of surgery for spinal metastasis. Also, there are few studies to investigate the relationship between the functional outcome and the patients' survival. Thus, analysis of both functional outcomes and the survival with their relationship in a possibly homogenous group of patients is worth being reported.To assess treatment outcomes of single-stage posterior decompression and stabilization (PDS) with or without corpectomy for thoracic vertebral metastases and to analyze factors affecting both the functional outcome and the patients' survival after the surgical intervention.Retrospective observational study.A consecutive series of 105 patients, who underwent the previously stated surgery for metastatic spinal cord compression (MSCC) of thoracic spine, were included and retrospectively analyzed.The postoperative functional outcomes were evaluated using visual analog scale and Frankel grade at postoperative 2 weeks, and all patients were followed for survival analysis.An institutional database was searched to identify all patients who underwent single-stage PDS for thoracic metastatic spinal tumors between March 2002 and June 2010. Demographic data as well as preoperative and postoperative medical conditions were collected from medical records. Radiological findings were confirmed on electronic archive. Survival data were obtained either on medical records or with a reference to governmental cancer registry system.Postoperative pain improvement was more evident in patients receiving anterior column reconstruction and four or more levels of fixation (p=.02 and0.01, respectively). Twenty-one patients (20%) showed improvement of the Frankel grade, and 10 of 21 Frankel C patients became ambulatory. The preoperative Karnofsky Performance Scale (≥70) and ambulatory status were significant predictors for the postoperative ambulatory function. After surgery, the median overall survival of the patients was 6.0 months. In the univariate analysis, the patient's age (younger than 60 years), type of primary cancer (ie, moderate and slow growth), no visceral metastases, less than three levels of spinal metastases, and postoperative adjuvant therapy were positively significant for the patients' survival (p.05). In the multivariate analysis, limited (less than three levels) spinal metastases and postoperative adjuvant therapy were proven to significantly prolong the patient's survival (hazard ratios of 0.53 and 0.48, respectively, p.05). Although the functional outcomes did not directly influence the patients' survival, the patients with better functional outcome showed increased chance of receiving postoperative adjuvant therapy (p.01).Single-stage PDS with or without corpectomy effectively improved the functional status of patients with MSCC of the thoracic spine and also afforded the patients to have more chances of postoperative adjuvant therapy, which was significant for patients' survival. Therefore, we suggest that the role of surgery in the management of MSCC could be not only a symptomatic palliation but also a strategy to prolong patients' survival.

Various operative techniques are available for the treatment of craniosynostosis. The patient's age at presentation is one of the most important factors in the determination of the surgical modality. Minimally invasive suturectomy and postoperative helmet therapy may be performed for relatively young infants, whose age is younger than 6 months. It relies upon the potential for rapid brain growth in this age group. Its minimal invasiveness is also advantageous. In this article, we review the advantages and limitations of minimally invasive suturectomy followed by helmet therapy for the treatment of craniosynostosis.

Paragonimiasis is caused by ingesting crustaceans, which are the intermediate hosts of Paragonimus. The involvement of the brain was a common presentation in Korea decades ago, but it becomes much less frequent in domestic medical practices. We observed a rare case of cerebral paragonimiasis manifesting with intracerebral hemorrhage. A 10-yr-old girl presented with sudden-onset dysarthria, right facial palsy and clumsiness of the right hand. Brain imaging showed acute intracerebral hemorrhage in the left frontal area. An occult vascular malformation or small arteriovenous malformation compressed by the hematoma was initially suspected. The lesion progressed for over 2 months until a delayed surgery was undertaken. Pathologic examination was consistent with cerebral paragonimiasis. After chemotherapy with praziquantel, the patient was monitored without neurological deficits or seizure attacks for 6 months. This case alerts practicing clinicians to the domestic transmission of a forgotten parasitic disease due to environmental changes.