Long-term Outcomes of Protocol-Based Treatment for Newly Diagnosed Medulloblastoma.

PURPOSE: The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC. MATERIALS AND METHODS: Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment. RESULTS: In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6 to 100) and 95.8% (95% CI, 88.2 to 100), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95% CI, 51.4 to 83.4) and 72.3% (95% CI, 58.4 to 89.6), respectively. CONCLUSION: High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC.

Medical Applications of 3D Printing and Standardization Issues.

The three-dimensional (3D) printing itself is not a novel technology, it is more than 30 years old. Stereolithographic (SLA) technology has been used as the first and popular technology for medical application of 3D printing. Since 1991 Radiology and Plastic Surgery have published articles about SLA for rapid prototyping anatomical 3D models. Medical applications of 3D printing have been popularizing and stabilizing so far. Implantable medical devices such as metal or absorbable implants, surgical guide systems, prosthesis and orthosis, and 3D anatomical models for normal or diseased anatomy have been developing and expanding its markets so far. There are many obstacles, such as insurance, authorization as a medical device, and lack of standards technology for further expansion of medical applications. Many technical specifications and guidelines for authorization as medical device have been published by regulatory bodies from many countries. Even though international standards for 3D printing have been developing more and more, there have been few standards for medical application of 3D printing. In this harsh environment academia, company, research institute, regulatory bodies, and government have been doing good job for the development of 3D printing industry.

Effectiveness of C1 Laminectomy for Chiari Malformation Type 1: Posterior Fossa Volume Expansion and Syrinx-Volume Decrease Rate.

PURPOSE: This study aimed to analyze the effect of foramen magnum decompression with C1 laminectomy (C1L) for Chiari malformation type 1 (CM-1) in terms of improving clinical symptoms, expanding posterior fossa volume, and decreasing syrinx volume. MATERIALS AND METHODS: Between January 2007 and June 2019, 107 patients with CM-1 were included. The median patient age was 13±13 years (range: 9 months-60 years), female-to-male ratio was 1:1, and average length of tonsil herniation was 13±5 mm (range: 5-24 mm). Surgical techniques were divided into four groups based on duraplasty or C1L usage. Among the study subjects, 38 patients underwent duraplasty and had their syrinx volumes measured separately on serial magnetic resonance imaging. A three-dimensional visualization software was used to evaluate the syrinx-volume decrease rate. RESULTS: Bony decompression exhibited a mere 20% volume expansion of the lower-half posterior fossa. C1L offered a 3% additional volume expansion, which rose to 5% when duraplasty was added (p=0.029). There were no significant differences in complication rate when C1L was combined with duraplasty (p=0.526). Syrinx volumes were analyzed in 38 patients who had undergone duraplasty. Among them, 28 patients who had undergone duraplasty without C1L demonstrated a 5.9% monthly decrease in syrinx volume, which was 7.5% in the remaining 10 patients with C1L (p=0.040). CONCLUSION: C1L was effective in increasing posterior fossa volume expansion, both with and without duraplasty. A more rapid decrease in syrinx volume occurred when C1L was combined with duraplasty.

Inter-Slice Resolution Improvement Using Convolutional Neural Network with Orbital Bone Edge-Aware in Facial CT Images.

The 3D modeling of orbital bones in facial CT images is essential to provide a customized implant for reconstructions of orbit and related structures during surgery. However, 3D models of the orbital bone show an aliasing effect and disconnected thin bone in the inter-slice direction because the slice thickness is two to three times larger than the pixel spacing. To improve the inter-slice resolution of facial CT images, we propose a method based on a 2D convolutional neural network (CNN) that uses the spatial information on the sagittal and axial planes and the orbital bone edge-aware (OBE) loss. First, intermediate slices are generated on the sagittal plane. Second, the generated intermediate slices are transformed to an axial image, which is then compared with the original axial image. To generate intermediate slices with an accurate orbital bone structure, the OBE loss considering the orbital bone structure on the sagittal and axial planes is used. To improve the perceptual quality of the generated intermediate slices, the feature map difference loss is additionally used on the axial plane. In the experiment, the proposed method showed the best performance among bilinear and bicubic interpolations, 3D SRGAN, and a 2D CNN-based method. Experimental results confirmed that the proposed method can generate intermediate slices with clear edges of thin bones as well as cortical bones on both the sagittal and the axial plane.

Salvage multiple burr hole surgery in patients with Moyamoya disease: efficacy evaluation using probabilistic independent component analysis of dynamic susceptibility contrast perfusion MRI.

PURPOSE: Multiple burr hole surgery is considered to be an option for achieving indirect revascularization in patients with ischemic Moyamoya disease (MMD). We aimed to investigate the efficacy of stand-alone multiple burr hole surgery for salvage revascularization in patients with MMD by assessing the hemodynamic changes via normalized time-to-peak (nTTP) analysis and independent component analysis (ICA) of preoperative and postoperative dynamic susceptibility contrast (DSC) perfusion MRI data. METHODS: The DSC perfusion MRI data of 25 hemispheres from 21 patients with MMD, who underwent multiple burr hole surgery for salvage revascularization due to persistent or recurrent symptoms after primary revascularization with modified encephaloduroarteriosynangiosis (mEDAS), were analyzed. The nTTP, which was measured using the region of interests covering the entire surgical hemisphere, was compared between the preoperative and postoperative images. ICA was used to compare the relative arterial and venous components of the surgical hemispheres between the respective preoperative and postoperative images. RESULTS: The median postoperative nTTP (1.80 s) was significantly shorter than the median preoperative nTTP (4.10 s) (P < 0.001). The postoperative relative arterial component of the surgical hemisphere (median: 0.04) was significantly higher than the preoperative relative arterial component (median: - 0.02, P < 0.001). In contrast, the postoperative relative venous component of the surgical hemisphere (median: - 0.05) was significantly lower than the preoperative value (median: 0.05, P < 0.001). CONCLUSION: The improvement in cerebral perfusion parameters observed on postoperative DSC perfusion MRI demonstrated that stand-alone multiple burr hole surgery could be a favorable salvage revascularization technique after mEDAS failure in patients with ischemic MMD.

The feasibility of performing multiple burr hole surgery in pediatric moyamoya patients as a response to failed mEDAS.

OBJECTIVE: To investigate the feasibility and clinical effectiveness of performing multiple burr hole surgery in pediatric moyamoya patients as a response to failed modified encephaloduroarteriosynangiosis (mEDAS). METHODS: From January 2014 to May 2018, multiple burr hole surgery (MBS) was conducted on 16 hemispheres in 12 patients as a secondary treatment following mEDAS. The male-to-female ratio was 1:2 and the average age at the time of mEDAS was 6 years old. The average patient age was 9 ± 3 years olds (range 7-17) at the time of MBS which occurred an average of 46 months after mEDAS. An average of 10 ± 1 holes (range 8-13) were made. Time-to-peak (TTP) magnetic resonance images (MRI) were taken along 20 axial cuts. Of these cuts, two consecutive cuts on the lateral ventricle were selected to calculate the average value of the region of interest (ROI). The value of the cerebellum was subtracted from the average value of two consecutive cuts. The ROI value was analyzed using a paired t test by SPSS 20 (SPSS Inc., Chicago, IL, USA). RESULTS: All 16 cases presented improvement of clinical symptoms as determined by ROI analysis of the TTP MRI images. The average ROI value was 5.03 ± 6.36 before MBS and - 15.54 ± 9.42 after MBS. The average change in the ROI value was - 20.58 ± 12.59. The ROI value decreased in all cases after MBS. Magnetic resonance angiography (MRA) also showed a positive effect on vascularization. CONCLUSION: In pediatric moyamoya patients, MBS is recommended as secondary option as a response to failed mEDAS. Its clinical effectiveness was shown by analyzing TTP images and assisted by MRA and digital subtraction angiography.

Determining the optimal timing of screening spinal cord ultrasonography to detect filum terminale lipoma in infants.

PURPOSE: The purpose of this study was to identify the optimal timing for screening spinal cord ultrasonography (US) to detect filum terminale lipoma in infants. METHODS: We retrospectively reviewed infants (<12 months old) who underwent repeated spinal cord US between April 2011 and January 2019. We excluded infants if they only had one US examination, or if they had lesions other than filum terminale lipoma. Infants with filum terminale lipoma on magnetic resonance imaging were included in the lipoma group and the others in the control group. A linear mixed model was used to assess differences in the growth pattern of filum terminale thickness by age and group. The cutoff thickness on US and its diagnostic performance were assessed according to age. RESULTS: Among 442 infants with 901 US examinations, 46 were included in the lipoma group and 58 in the control group. Sixty-seven infants had unmeasurable filum terminale thickness on initial US, including 55 neonates (82.1%) before 1 month of age. The lipoma group had significantly greater filum terminale thickness than the control group (P<0.001). Thickness increased with age in the lipoma group (P=0.027). The sensitivity of US was 87.5% and the area under the receiver operating characteristic curve was 0.949 (95% confidence interval, 0.849 to 0.991) with a cutoff value of 1.1 mm in 4- to 6-month-old infants. CONCLUSION: Screening spinal cord US could effectively diagnose filum terminale lipoma in 4- to 6-month-old infants with a cutoff thickness of 1.1 mm. Spinal cord US can be used to screen young infants with intraspinal abnormalities.

Optimization of Intracranial Germinoma Treatment: Radiotherapy Alone with Reduced Volume and Dose.

PURPOSE: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx). METHODS AND MATERIALS: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis. RESULTS: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively. CONCLUSIONS: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable.

Precise detection of low-level somatic mutation in resected epilepsy brain tissue.

Low-level somatic mutations have been shown to be the major genetic etiology of intractable epilepsy. The extents thereof, however, have yet to be systematically and accurately explored in a large cohort of resected epilepsy brain tissues. Moreover, clinically useful and precise analysis tools for detecting low-level somatic mutations from unmatched formalin-fixed paraffin-embedded (FFPE) brain samples, the most clinically relevant samples, are still lacking. In total, 446 tissues samples from 232 intractable epilepsy patients with various brain pathologies were analyzed using deep sequencing (average read depth, 1112x) of known epilepsy-related genes (up to 28 genes) followed by confirmatory site-specific amplicon sequencing. Pathogenic mutations were discovered in 31.9% (74 of 232) of the resected epilepsy brain tissues and were recurrently found in only eight major focal epilepsy genes, including AKT3, DEPDC5, MTOR, PIK3CA, TSC1, TSC2, SCL35A2, and BRAF. Somatic mutations, two-hit mutations, and germline mutations accounted for 22.0% (51), 0.9% (2), and 9.1% (21) of the patients with intractable epilepsy, respectively. The majority of pathogenic somatic mutations (62.3%, 33 of 53) had a low variant allelic frequency of less than 5%. The use of deep sequencing replicates in the eight major focal epilepsy genes robustly increased PPVs to 50-100% and sensitivities to 71-100%. In an independent FCDII cohort of only unmatched FFPE brain tissues, deep sequencing replicates in the eight major focal epilepsy genes identified pathogenic somatic mutations in 33.3% (5 of 15) of FCDII individuals (similar to the genetic detecting rate in the entire FCDII cohort) without any false-positive calls. Deep sequencing replicates of major focal epilepsy genes in unmatched FFPE brain tissues can be used to accurately and efficiently detect low-level somatic mutations, thereby improving overall patient care by enriching genetic counseling and informing treatment decisions.

Modified Cranioplasty Technique Using 3-Dimensional Printed Implants in Preventing Temporalis Muscle Hollowing.

BACKGROUND: Temporalis muscle (TM) hollowing is a complication of cranioplasty which diminishes the aesthetical outcome of the surgery and results in suboptimal functional outcome. We present and compare a modified split-temporalis muscle elevated margin cranioplasty using 3-dimensional printed titanium implant with conventional 3-dimensional printed titanium implant cranioplasty to determine an effective treatment method. METHODS: A modified 3-dimensional printed cranial implant was designed where the anteroinferior border of the implant was extended and elevated between the frontozygomatic suture and root of zygomatic process. Furthermore, the implant was placed in between superficial and deep layers of the temporalis muscle. Aesthetical evaluation was carried out at the outpatient clinic, and a quantitative analysis showing the percentage difference in length of the operated and nonoperated sides was performed. RESULTS: For both conventional and augmented groups, there were 0% major or minor complications. Out of 10 conventional cranioplasty patients, there were 3 cases of mild and 1 case of severe TM hollowing, whereas for 10 augmented cranioplasty patients, there was only 1 patient with mild TM hollowing. When a quantitative analysis was carried out, the overall percentage difference in length at the coronal view for conventional and augmented cranioplasty was -2.17% and 0.07%, respectively. CONCLUSIONS: The augmented cranioplasty leads to superior aesthetical outcome, and the quantitative analysis also supports the efficacy of augmented cranioplasty. The surgery is technically simpler than the conventional method, therefore lowering the risk of surgical complications. Therefore, we hope that the modified cranioplasty method will be considered as an effected cranioplasty method for preventing TM hollowing.

Epilepsy Surgery for Children With Low-Grade Epilepsy-Associated Tumors: Factors Associated With Seizure Recurrence and Cognitive Function.

OBJECTIVE: Low-grade epilepsy-associated tumors (LEATs) are associated with childhood seizures that are typically drug-resistant, necessitating surgical interventions. In this study, we aimed to investigate the efficacy of surgical intervention in children with LEATs and to identify factors associated with seizure and cognitive outcomes. METHODS: We reviewed 58 children less than 18 years of age who underwent epilepsy surgery due to histopathologically confirmed LEATs and had a minimum postoperative follow-up duration of 24 months. RESULTS: Of the 58 patients who were followed for a median duration of 5.6 (IQR 3.2 to 10.0) years, 51 (87.9%) were seizure-free after surgery. In univariate analysis, shorter epilepsy duration, fewer antiepileptic drugs at time of surgery, gross total resection, and unilobar tumor involvement were associated with seizure freedom. In multivariate analysis, gross total resection was independently associated with seizure freedom. The preoperative and postoperative full-scale intelligence quotient (FSIQ) scores were 78.9 ± 27.1 and 80.9 ± 28.7, respectively. In univariate analysis, younger age at seizure onset, longer epilepsy duration, more antiepileptic drugs at time of surgery, multilobar tumor involvement, and presence of generalized epileptic discharges were associated with lower preoperative FSIQ. In multivariate analysis, longer epilepsy duration was independently associated with lower preoperative FSIQ scores. Postoperative FSIQ scores were significantly influenced by preoperative FSIQ scores. CONCLUSIONS: Epilepsy surgery for LEATs in children resulted in excellent seizure outcome. Gross total resection was the only independent factor associated with favorable seizure outcome. Preoperative and postoperative cognitive abilities were significantly influenced by epilepsy duration, so early surgical intervention should be considered.

Effects of Tranexamic Acid Based on its Population Pharmacokinetics in Pediatric Patients Undergoing Distraction Osteogenesis for Craniosynostosis: Rotational Thromboelastometry (ROTEMTM) Analysis.

Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEMTM) was conducted to monitor changes in coagulation perioperatively. Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.

Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas.

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing revealed that a subset of recurrent tumors initially diagnosed as locally recurrent medulloblastomas are secondary glioblastomas after radiotherapy, showing high similarity to the non-G-CIMP proneural subtype of glioblastoma. Further analysis, including whole exome sequencing, revealed missense mutations or complex gene fusion events in PDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicating PDGFRA as a putative driver in the development of secondary glioblastomas after treatment exposure. This result provides insight into the possible application of PDGFRA-targeted therapy in these second malignancies. Furthermore, genomic alterations of TP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role of TP53 alteration in the process. On the other hand, analysis of recurrent medulloblastomas revealed that the most prevalent alterations are the loss of 17p region including TP53 and gain of 7q region containing EZH2 which already exist in primary tumors. The 7q gain events are frequently accompanied by high expression levels of EZH2 in both primary and recurrent medulloblastomas, which provides a clue to a new therapeutic target to prevent recurrence. Considering the fact that it is often challenging to differentiate between recurrent medulloblastomas and secondary glioblastomas after radiotherapy, our findings have major clinical implications both for correct diagnosis and for potential therapeutic interventions in these devastating diseases.

Neuropsychological impacts of indirect revascularization for pediatric moyamoya disease.

PURPOSE: Moyamoya disease (MMD) commonly leads to neurocognitive impairment. This study was carried out to show that temporal encephaloduroarteriosynangiosis (EDAS) has a positive neuropsychological impact on pediatric MMD patients. METHODS: Fifty-five participants diagnosed with MMD from 2008 to 2014 were included in this retrospective study. The mean age at the preoperative evaluation was 9.5 years and the mean age at postoperative evaluation was 10.4. The average interval of initial and follow-up test was 10 months. K-WISC-III, Rey-Kim memory test, Children's Color Trails test (CCTT), Wisconsin Card Sorting Test (WCST), and Advanced Test of Attention (ATA) were used to evaluate patient's neurocognitive profile. RESULTS: In this study, preoperative and postoperative neuropsychological fields were compared. Prior operation, pediatric MMD patients showed 54.2% deficit of inattention but only around 2.5% deficit in verbal memory recall function. There was a significant increase of performance IQ and PO score component of PIQ improved almost 10 scores after surgery. For memorial function, there was an improvement of approximately 10 scores in MQ after the surgery. This study also showed parietal activation following surgical treatment which enhanced the ability to interpret visual materials, to register and to retrieve visual information. Interestingly, despite the parietal cover surgery, there was a significant improvement of performance on WCST and CCTT measuring the prefrontal executive function. Concerning failure to maintain set, no significant postoperative improvements were made. However, simple and selective visual attention on ATA was significantly improved postoperatively. CONCLUSIONS: The results from neuropsychological field comparison testifies the effectiveness of temporal EDAS in pediatric MMD patients. The surgery not only enhances the blood flow in operative regions, but it also improves the broad cerebral function including frontoparietal domains. Such alteration leads to overall advancement in cognitive function which are impaired due to MMD.

Effect of Unshaven Hair with Absorbable Sutures and Early Postoperative Shampoo on Cranial Surgery Site Infection.

BACKGROUND: Cranial surgical site infection is a significant cause of morbidity and mortality in hospitals. Preoperative hair shaving for cranial neurosurgical procedures is performed traditionally in an attempt to protect patients against complications from infections at cranial surgical sites. However, preoperative shaving of surgical incision sites using traditional surgical blades without properly washing the head after surgery can cause infections at surgical sites. Therefore, a rapid protocol in which the scalp remains unshaven and absorbable sutures are used for scalp closure with early postoperative shampooing is examined in this study. METHODS: A retrospective comparative study was conducted from January 2008 to December 2012. A total of 2,641 patients who underwent unshaven cranial surgery with absorbable sutures for scalp closure were enrolled in this study. Data of 1,882 patients who underwent surgery with the traditional protocol from January 2005 to December 2007 were also analyzed for comparison. RESULTS: Of 2,641 patients who underwent cranial surgery with the rapid protocol, all but 2 (0.07%) patients experienced satisfactory wound healing. Of 1,882 patients who underwent cranial surgery with the traditional protocol, 3 patients (0.15%) had infections. Each infection occurred at the superficial incisional surgical site. CONCLUSION: Unshaven cranial surgery using absorbable sutures for scalp closure with early postoperative shampooing is safe and effective in the cranial neurosurgery setting. This protocol has a positive psychological effect. It can help patients accept neurosurgical procedures and improve their self-image after the operation.

Direct versus indirect revascularization in the treatment of moyamoya disease.

OBJECTIVE For patients with moyamoya disease (MMD), surgical intervention is usually required because of progressive occlusion of the internal carotid artery. The indirect bypass method has been widely accepted as the treatment of choice in pediatric patients. However, in adult patients with MMD, the most effective treatment method remains a matter of debate. Here, the authors compared the clinical outcomes from MMD patients treated with either extracranial-intracranial arterial bypass (EIAB; 43 hemispheres) or modified encephaloduroarteriosynangiosis (mEDAS; 75 hemispheres) to investigate whether mEDAS is an effective surgical method for treating adults with symptomatic MMD. METHODS A comparative analysis was performed in patients treated using either mEDAS or EIAB. Collateral grading, collateral vein counting, and symptom analysis were used to assess the outcome of surgery. RESULTS Seventy-seven percent (58/75) of mEDAS cases and 83.7% (36/43) of EIAB cases in the analysis experienced improvement in their symptoms after surgery. Furthermore, patients in 98.7% (74/75) of mEDAS cases and those in 95.3% (41/43) of EIAB cases exhibited improved collateral grades. Increases in regions of perfusion were seen after both procedures. CONCLUSIONS Modified EDAS and EIAB both result in positive outcomes for symptomatic adults with MMD. However, when considering the benefit of both surgeries, the authors propose mEDAS, a simpler and less strenuous surgery with a lower risk of complications, as a sufficient and safe treatment option for symptomatic adults with MMD.

The Unnecessity of Positron Emission Tomography Computed Tomography in the Etiologic Evaluation of Neurodevelopmental Delay in Craniosynostosis Patients.

BACKGROUND: In evaluation of craniosynostosis patients in terms of neurodevelopmental delay, positron emission tomography computed tomography (PET-CT) scan can be used to assess brain abnormalities through glucose metabolism. We aimed to determine the unnecessity of PET-CT in this study. METHODS: Thirty-eight patients diagnosed with craniosynostosis who underwent distraction osteogenesis from October, 2010 to November, 2013 were reviewed. Magnetic resonance imaging (MRI) and PET-CT scan were carried out for evaluation of the brain structure and function, whereas X-ray and CT scan were taken for evaluation of the skull. RESULTS: Nine patients reported abnormal MRI findings which were not significant, and five patients showed local problem on brain on PET-CT scan. No correlation was found among them. CONCLUSION: PET-CT evaluation of possible abnormal brain findings do not affect surgical planning or require additional therapy. Preoperative PET-CT scan is not the essential study to get any etiologic information of the disease consequences or to establish the treatment plan.

PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory.

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner.

Exploring for the optimal structural design for the 3D-printing technology for cranial reconstruction: a biomechanical and histological study comparison of solid vs. porous structure.

PURPOSE: Cranioplasty for recovering skull defects carries the risk for a number of complications. Various materials are used, including autologous bone graft, metallic materials, and non-metallic materials, each of which has advantages and disadvantages. If the use of autologous bone is not feasible, those artificial materials also have constraints in the case of complex anatomy and/or irregular defects. MATERIAL AND METHODS: This study used metal 3D-printing technology to overcome these existing drawbacks and analyze the clinical and mechanical performance requirements. To find an optimal structure that satisfied the structural and mechanical stability requirements, we evaluated biomechanical stability using finite element analysis (FEA) and mechanical testing. To ensure clinical applicability, the model was subjected to histological evaluation. Each specimen was implanted in the femur of a rabbit and was evaluated using histological measurements and push-out test. RESULTS AND CONCLUSION: We believe that our data will provide the basis for future applications of a variety of unit structures and further clinical trials and research, as well as the direction for the study of other patient-specific implants.

Endoscopic Treatment of Hypothalamic Hamartomas.

Hypothalamic hamartoma (HH) is a benign indolent lesion despite the presentation of refractory epilepsy. Behavioral disturbances and endocrine problems are additional critical symptoms that arise along with HHs. Due to its nature of generating epileptiform discharge and spreading to cortical region, various management strategies have been proposed and combined. Surgical approaches with open craniotomy or endoscopy, stereotactic approaches with radiosurgery and gamma knife surgery or radiofrequency thermos-coagulation, and laser ablation have been introduced. Topographical dimension and the surgeon's preference are key factors for treatment modalities. Endoscopic disconnection has been one of the most favorable options performed in treating HHs. Here we discuss presurgical evaluation, patient selection, surgical procedures, and complications.