Publications by authors named "Seow Wan Tew"

37 Publications

Revascularisation surgery for paediatric moyamoya disease: The Singapore experience.

J Clin Neurosci 2020 Dec 25;82(Pt B):207-213. Epub 2020 Nov 25.

Division of Neurosurgery, Department of Surgery, National University Hospital, 5 Lower Kent Ridge Rd, 119074, Singapore.

Moyamoya disease (MMD) is characterized by the spontaneous occlusion of the distal internal carotid arteries and resultant neo-angiogenesis of fragile collateral blood vessels. Direct and indirect revascularization surgeries have shown to effectively reduce stroke risks in paediatric MMD, whereby the latter is a more utilised technique in children. This study was undertaken to determine the outcomes of revascularization in Singapore's multi-ethnic, Southeast Asian paediatric population. This is an ethics-approved study conducted in Singapore's 2 tertiary children hospital units: KK Women's and Children's Hospital and National University Hospital. Sixteen patients with a diagnosis of ischaemic-type MMD are recruited between 01 January 2002 to 31 January 2019; and a total of 24 surgeries are undertaken (24 cerebral hemispheres). There are 2 cases of stroke within 30 days post-surgery. However, no stroke recurrence is observed beyond 30 days after surgery in all patients. Four patients reported recurrent transient ischaemic attack symptoms in the follow-up period ranging from 3 months to 12 years. Data analyses show a statistically significant improvement in modified Rankin's Scale (mMRS) in post-operative patients from baseline to discharge, and at 3 months after surgery. Our study also observes that predictors of recurrent ischaemic events include higher pre-operative MRS, Suzuki stage and perioperative infarction. To the authors' knowledge, this is the first study to date reporting the outcomes of revascularisation in a paediatric Southeast Asian cohort.
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http://dx.doi.org/10.1016/j.jocn.2020.11.008DOI Listing
December 2020

Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore.

BMC Neurol 2020 Nov 14;20(1):415. Epub 2020 Nov 14.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Background: Germinomas (IG) account for up to 50% of all intracranial germ cell tumours. These tumours are reputed to be more prevalent in Oriental populations in comparison to Western cohorts. Biological characteristics of IG in other ethnic groups are unknown. Singapore is a multi-ethnic country with diverse cultures. Owing to inter-racial heterogeneity, the authors hypothesize there are molecular differences between paediatric IG patients in our local population. The aims of this study are exploratory: firstly, to identify molecular characteristics in this tumour type and circulating CSF unique to different racial cohorts; and next, to corroborate our findings with published literature.

Methods: This is a single-institution, retrospective study of prospectively collected data. Inclusion criteria encompass all paediatric patients with histologically confirmed IG. Excess CSF and brain tumour tissues are collected for molecular analysis. Tumour tissues are subjected to a next generation sequencing (NGS) targeted panel for KIT and PDGRA. All CSF samples are profiled via a high-throughput miRNA multiplexed workflow. Results are then corroborated with existing literature and public databases.

Results: In our cohort of 14 patients, there are KIT exon variants in the tumour tissues and CSF miRNAs corroborative with published studies. Separately, there are also KIT exon variants and miRNAs not previously highlighted in IG. A subgroup analysis demonstrates differential CSF miRNAs between Chinese and Malay IG patients.

Conclusion: This is the first in-depth molecular study of a mixed ethnic population of paediatric IGs from a Southeast Asian cohort. Validation studies are required to assess the relevance of novel findings in our study.
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http://dx.doi.org/10.1186/s12883-020-01981-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666528PMC
November 2020

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

BMC Cancer 2020 Jun 15;20(1):554. Epub 2020 Jun 15.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Background: Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pathways within the tumour microenvironment for various cancers. In this study, the authors explore the involvement of cerebrospinal fluid (CSF) cytokines in Group 3 and 4 MB patients with disseminated disease.

Methods: This is an ethics approved, retrospective study of prospectively collected data based at a single institution. Patient clinicpathological data and corresponding bio-materials are collected after informed consent. All CSF samples are interrogated using a proteomic array. Resultant expression data of selected cytokines are correlated with each individual's clinical information. Statistical analysis is employed to determine the significance of the expression of CSF cytokines in Group 3 and 4 patients with metastatic MB versus non-metastatic MB.

Results: A total of 10 patients are recruited for this study. Median age of the cohort is 6.6 years old. Based on Nanostring gene expression analysis, 5 patients have Group 3 as their molecular subtype and the remaining 5 are Group 4. There are 2 non-metastatic versus 3 metastatic patients within each molecular subtype. Proteomic CSF analysis of all patients for both subtypes show higher expression of CCL2 in the metastatic group versus the non-metastatic group. Within the Group 3 subtype, the MYC-amplified Group 3 MB patients with existing and delayed metastases express higher levels of CXCL1, IL6 and IL8 in their CSF specimens at initial presentation. Furthermore, a longitudinal study of metastatic Group 3 MB observes that selected cytokines are differentially expressed in MYC-amplified metastatic Group 3 MB, in comparison to the non-MYC amplified metastatic Group 3 MB patient.

Conclusion: This study demonstrates higher expression of selected CSF cytokines, in particular CCL2, in metastatic Group 3 and 4 MB patients. Although our results are preliminary, they establish a proof-of-concept basis for continued work in a larger cohort of patients affected by this devastating disease.
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http://dx.doi.org/10.1186/s12885-020-07048-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296667PMC
June 2020

Intraoperative visual evoked potential monitoring for optic pathway glioma in an infant: A case description.

Clin Neurophysiol 2020 Aug 19;131(8):1772-1774. Epub 2020 May 19.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore; Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; SingHealth Duke-NUS Neuroscience Academic Clinical Program, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2020.05.007DOI Listing
August 2020

Biventricular hydrocephalus secondary to aqueductal developmental venous anomaly.

J Clin Neurosci 2020 Jun 13;76:240-243. Epub 2020 Apr 13.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore; Department of Neurosurgery, National Neuroscience Institute, Singapore; SingHealth Duke-NUS Neuroscience Academic Clinical Program, Singapore.

Developmental venous anomaly (DVA) is the most common type of intracranial vascular malformation. These lesions are benign and are considered to be non-pathological variants of normal deep parenchymal veins. Although most of them are asymptomatic, a small subset of them located in aqueductal region have been reported to cause obstructive hydrocephalus. The authors present an interesting case of biventricular hydrocephalus secondary to a DVA located on the proximal aqueduct in an adolescent patient. This case is discussed with in corroboration with current literature and management recommendations.
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http://dx.doi.org/10.1016/j.jocn.2020.04.039DOI Listing
June 2020

Paediatric meningiomas in Singapore - Case series of a rare entity.

J Clin Neurosci 2020 Mar 14;73:62-66. Epub 2020 Feb 14.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore; Department of Neurosurgery, National Neuroscience Institute, Singapore; SingHealth Duke-NUS Neuroscience Academic Clinical Program, Singapore. Electronic address:

Paediatric meningiomas are extremely rare. These tumours constitute only 2 to 3% of all childhood brain tumours. Despite similarities in histological features between PMs and their adult counterparts, there are important distinctions between them. In this case series, the authors describe their experience in paediatric meningiomas in Singapore's 2 children's hospitals from 1998 to 2018. The primary aim of this retrospective study is to evaluate the clinical, radiological and pathological characteristics, and associated outcomes of paediatric patients diagnosed with meningioma managed in our local institutions. Following that, the study's findings are secondary aims are corroborated with published literature. A total of 10 patients (4 males and 6 females) were identified for this study within the period of 01 January 1998 to 31 December 2018. Their ages ranged from 1 year old to 18 years old (median age 10.5 years old). Two of the patients had NF1 and NF2 respectively. There were 9 intracranial and 1 intraspinal paediatric meningiomas. Seven patients achieved gross total resection and 3 patients had subtotal resection. Eight patients did not have tumour recurrence or increase in size of tumour remnant during the course of their follow-up. In congruency with the literature, up to 40% of our patients had higher grade meningiomas and 55.6% had large tumour volumes more than 30 cm. Owing to the paucity of knowledge for this unusual tumour, the authors emphasize the need for closer surveillance and in-depth genomic studies to identify novel therapies for this challenging condition.
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http://dx.doi.org/10.1016/j.jocn.2020.01.044DOI Listing
March 2020

The National Neuroscience Institute External Ventricular Drain Study: A Pragmatic Multisite Risk-Stratification Pathway to Reduce Ventriculostomy-Related Infection.

World Neurosurg 2020 Mar 19;135:e126-e136. Epub 2019 Nov 19.

Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore. Electronic address:

Objective: Ventriculostomy-related infection (VRI) is associated with potential serious morbidity, extended hospitalization duration, increased health care costs, and mortality. We assessed the effectiveness of a pragmatic risk-stratification pathway for external ventricular drain (EVD) management, allowing for surgical decision making, in reducing the rate of VRIs.

Methods: Two studies were performed concurrently. A retrospective audit of EVD infection rates and outcomes in our unit across 3 hospitals was conducted from January to December 2014. The second prospective study compared the same variables during the implementation of the EVD pathway across the 3 sites from January 2015 to December 2016.

Results: The number of patients requiring EVDs increased from 2014 to 2016 (165 vs. 189 vs. 197 patients, respectively), with a significant increase in patients with intraventricular hemorrhage (P = 0.009). Despite increasing risk, overall EVD infections decreased during the implementation period, from 4.8% (8/165) in 2014 to 3.7% in 2015 (7/189) and 2.0% in 2016 (4/197, P = 0.33). In 2 sites (site 1, 2.0% vs. 2.1% vs. 1.9%, and site 2, 4.7% vs. 5.0% vs. 5.3%), transition to the EVD risk-stratification pathway maintained already low infection rates; in site 3, EVD infections decreased from 6.8% (5/73) to 3.9% (4/102) and 0% (0/86, P = 0.06).

Conclusions: The introduction of a pragmatic evidence-based risk-stratification pathway, in which different options for EVD management are incorporated, results in low EVD infection rates across a multisite institutional practice. Our results are comparable to published protocols involving the implementation of standard care bundles and/or antibacterial EVDs alone, in reducing VRIs.
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http://dx.doi.org/10.1016/j.wneu.2019.11.070DOI Listing
March 2020

Right middle cerebral artery infarct after minor head trauma in an infant: Case report and literature review.

Int J Pediatr Adolesc Med 2019 Sep 28;6(3):121-124. Epub 2019 May 28.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore.

Ishaemic stroke (IS) in the paediatric population is extremely rare. In this age group, the occurrence of IS often concurs with underlying congenital heart disease, haematological, metabolic or immunological conditions. In contrast, the association between IS and minor head injury in children has been sparse in current literature. The authors report a case of a healthy 9-month-old male who was found to have a right middle cerebral artery territory infarct after a minor head injury. An extensive medical workup was performed, and it was negative for any previously undiagnosed co-morbidities. Given the paucity of such cases, the condition and its management are discussed in corroboration with current literature.
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http://dx.doi.org/10.1016/j.ijpam.2019.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824157PMC
September 2019

Use of an Offsite Intraoperative MRI Operating Theater for Pediatric Brain Tumor Surgery: Experience from a Singapore Children's Hospital.

World Neurosurg 2020 Mar 23;135:e28-e35. Epub 2019 Oct 23.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore; Department of Neurosurgery, National Neuroscience Institute, Singapore; SingHealth Duke-NUS Neuroscience Academic Clinical Program, Singapore.

Background: Intraoperative magnetic resonance imaging (iMRI) has been recognized as a useful adjunct for brain tumor surgery in pediatric patients. There is minimal data on the use of an offsite intraoperative magnetic resonance imaging operating theater (iMRI OT), whereby vehicle transfer of patients is involved. The primary aim of this study is to validate the feasibility of perioperative patient transfer to use an offsite iMRI OT for patients with pediatric brain tumor. Secondary objectives include the assessment of tumor resection efficacy and perioperative outcomes in our patient cohort.

Methods: This is a retrospective, single-institution clinical study of prospectively collected data from Singapore's largest children hospital. Variables of interest include issues encountered during interhospital transfer, achievement of surgical aims, length of stay in hospital, and postoperative complications. Our findings were compared with results of related studies published in the literature.

Results: From January 1, 2009 to December 31, 2018, a total of 35 pediatric operative cases were performed in our offsite iMRI OT. Within this cohort, 24 of these were brain tumor surgery cases. For all the patients in this study, use of the iMRI OT influenced intraoperative decisions. Average ambulance transport time from parent hospital to the iMRI OT was 30.5 minutes, and from iMRI OT back to the parent hospital after surgery was 27.7 minutes. The average length of hospitalization stay was 7.9 days per patient. There were no ferromagnetic accidents during perioperative iMRI scanning and no airway/hemodynamic incidents in patients encountered during interhospital transfer.

Conclusions: In our local context, the use of interhospital transfers for access to iMRI OT is a safe and feasible option in ensuring good patient outcomes for a select group of patients with pediatric brain tumors.
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http://dx.doi.org/10.1016/j.wneu.2019.10.083DOI Listing
March 2020

The Seow Operative Score (SOS) as a decision-making adjunct for paediatric Chiari I malformation: a preliminary study.

Childs Nerv Syst 2019 10 7;35(10):1777-1783. Epub 2019 Jun 7.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Purpose: The natural history of Chiari I malformation (C1M) in the paediatric population is poorly understood. There are conflicting reports with regards to surgical indications, operative techniques and peri-operative prognostic indicators. In this paper, we report our institutional experience in the management of paediatric C1M.

Methods: The workflow process which includes preferred imaging modalities, surgical techniques and indications for intervention is discussed. In particular, we describe one of our current projects-an in-house designed Seow Operative Score (SOS) as a feasibility scoring system for neurosurgical intervention in our local cohort of paediatric C1M patients.

Results: In our series, we have 2 groups: 10 non-operated patients versus 19 operated patients. In the non-operated group, the majority of patients had a SOS of 0 to 1. One patient had a score of 2.5 and was kept under close surveillance. Follow-up imaging demonstrated resolution of the cerebellar herniation and intraspinal syrinx. In the operated group, 17 patients had a SOS of 3 or more. Two patients had a SOS of 2. For these 2, 1 developed progressive symptoms, and the other had an extensive cervico-thoracic syrinx. Decision was made for surgery after a period of surveillance.

Conclusions: In this paper, we report our institutional experience in managing paediatric C1M and, at the same time, highlight salient points of our practices. Meanwhile, we advocate collective global efforts and in-depth research for better disease understanding of this challenging condition.
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http://dx.doi.org/10.1007/s00381-019-04226-9DOI Listing
October 2019

Giant Aneurysm Arising from Anomalous Branch of the Middle Cerebral Artery in a Pediatric Patient: Case Report and Review of the Literature.

World Neurosurg 2019 Aug 10;128:165-168. Epub 2019 May 10.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore; Department of Neurosurgery, National Neuroscience Institute, Singapore; SingHealth Duke-NUS Neuroscience Academic Clinical Program, Singapore. Electronic address:

Background: Pediatric intracranial aneurysms are extremely rare. In this age group, cerebral vascular anomalies have been associated with the development of intracranial aneurysms.

Case Description: We present a case of a previously well 11-year-old boy who presented with seizures secondary to a giant, unruptured, and partially thrombosed right middle cerebral artery (MCA) aneurysm. Extensive workup for underlying infective and autoimmune etiology was negative. Of interest, this vascular lesion was found to originate from an anomalous M2 branch, which ran an aberrant parallel course within the Sylvian fissure to the main and distally bifurcating MCA. The patient underwent successful surgical clipping and excision of the giant aneurysm.

Conclusions: Because of the infrequency of the diagnosis, clinical presentation, and its unique neurovascular anatomy, the management of this case is discussed in corroboration with current literature. In addition, highlighting this unusual case in an individual adds to the growing body of literature for better disease understanding, especially in the pediatric population.
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http://dx.doi.org/10.1016/j.wneu.2019.05.012DOI Listing
August 2019

Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.

Eur J Med Genet 2020 Feb 13;63(2):103652. Epub 2019 Apr 13.

Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatrics Academic Clinical Programme, Duke-NUS Medical School, Singapore; Institute of Precision Medicine, SingHealth Duke-NUS Medical School, Singapore. Electronic address:

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.
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http://dx.doi.org/10.1016/j.ejmg.2019.04.009DOI Listing
February 2020

A germline variant of TP53 in paediatric diffuse leptomeningeal glioneuronal tumour.

Childs Nerv Syst 2019 06 2;35(6):1021-1027. Epub 2019 Apr 2.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Purpose: Diffuse leptomeningeal glioneuronal tumour (DLGNT) is an extremely rare tumour involving the neuroaxis. At present, its exact pathogenesis and associated factors remain incompletely characterised. Recent molecular investigations in a small cohort have offered some insights into this disease. However, the role of germline findings has not yet been fully explored in affected patients. The authors present a case of DLGNT, focusing on the clinical and molecular features with reference to current disease knowledge.

Methods: A 4-year-old male presented with raised intracranial pressure symptoms secondary to extensive leptomeningeal disease of the brain and spine. Preliminary impression was that of an inflammatory lesion.

Results: A lumbar biopsy of the lesion confirmed DLGNT on routine diagnostic examination. Further molecular analysis of his tumour and blood demonstrated a previously unreported TP53 exon 5 (c.147V > I) germline variant. Based on the latest DLGNT molecular subtyping classification, his tumour falls into the group with better clinical outcome. However, his germline findings may add an extra layer of uncertainty to his overall prognosis.

Conclusion: Given that much remains unknown in many rare paediatric tumours at this stage, isolated findings found in an individual may be of significance. Supplementary genetic information, together with tumour molecular analysis, add to our current understanding of this uncommon disease. This case highlights the benefit of combined clinical and molecular efforts, including germline testing, especially for children affected by such challenging neoplasms.
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http://dx.doi.org/10.1007/s00381-019-04128-wDOI Listing
June 2019

Thoracic epidural haematoma after spinal manipulation treatment.

Childs Nerv Syst 2019 05 22;35(5):735-737. Epub 2019 Mar 22.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore, Singapore.

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http://dx.doi.org/10.1007/s00381-019-04122-2DOI Listing
May 2019

Primary paediatric epidural sarcomas: molecular exploration of three cases.

BMC Cancer 2019 Feb 28;19(1):182. Epub 2019 Feb 28.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore.

Background: Primary paediatric epidural sarcomas are extremely rare. Overall, there remains a paucity of knowledge in paediatric epidural sarcomas owing to the infrequent number of cases. The Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) is a next-generation sequencing assay that has been reported to be a useful technique to detect recurrent fusion in sarcomas. We report the molecular exploration of 3 primary paediatric epidural sarcomas-one in the cranium (mesenchymal chondrosarcoma) and 2 in the spine (mesenchymal chondrosarcoma and Ewing sarcoma respectively).

Case Presentation: This is a study approved by the hospital ethics board. Clinico-pathological information from 3 consenting patients with primary epidural sarcomas was collected. These selected tumours are interrogated via Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) for genomic aberrations. Results were validated with RT-PCR and Sanger sequencing. All findings are corroborated and discussed in concordance with current literature. Our findings show 2 variants of the HEY1-NCOA2 gene fusion: HEY1 (exon 4)-NCOA2 (exon 13) and HEY1 (exon 4)-NCOA2 (exon 14), in both mesenchymal chondrosarcoma patients. Next, the Ewing sarcoma tumour is found to have EWSR1 (exon 10)-FLI1 (exon 8) translocation based on NGS. This result is not detected via conventional fluorescence in situ testing.

Conclusions: This is a molecularly-centered study based on 3 unique primary paediatric epidural sarcomas. Our findings to add to the growing body of literature for these exceptionally rare and malignant neoplasms. The authors advocate global collaborative efforts and in-depth studies for targeted therapy to benefit affected children.
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http://dx.doi.org/10.1186/s12885-019-5368-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394101PMC
February 2019

Synchronous Chiari III Malformation and Polydactyly.

World Neurosurg 2018 Oct 27;118:301-303. Epub 2018 Jul 27.

National Neuroscience Institute, Department of Neurosurgery, National Neuroscience Institute, Singapore. Electronic address:

Background: Chiari III malformation is an extremely rare congenital anomaly. At present, its primary and associated pathognomonic factors remain poorly understood. The authors report a case of a male neonate born with an occipital encephalocoele with herniation of posterior fossa contents associated with bilateral postaxial polydactyly.

Case Description: The patient is a dichorionic, diamniotic twin conceived via assisted reproductive methods; his twin sister has no congenital anomaly. Neurosurgical management included successful repair of the encephalocoele and subsequent cerebrospinal fluid diversion via a ventriculoperitoneal shunt.

Conclusions: Owing to the uniqueness of this patient's presentation, the concurrent diagnoses of Chiari III malformation and polydactyly are discussed in concordance with updated literature.
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http://dx.doi.org/10.1016/j.wneu.2018.07.155DOI Listing
October 2018

Management of brain abscesses: where are we now?

Childs Nerv Syst 2018 10 3;34(10):1871-1880. Epub 2018 Jul 3.

Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore.

Introduction: Brain abscesses affect all age groups and are not peculiar to a particular country, race, or geographical location. It is a disease that, in the past, carried a high morbidity and mortality. With improvements in medical technology and expertise, outcomes have improved tremendously. The causative organisms vary vastly and have evolved with time. Treatment of brain abscesses is primarily with antimicrobial therapy but surgery plays a vital role in achieving better outcomes.

Content: In this article, we review the literature to find out how the epidemiology of this disease has changed through the years and re-visit the basic pathological process of abscess evolution and highlight the new research in the biochemical pathways that initiate and regulate this process. We also highlight how magnetic resonance imaging and its various modalities have improved diagnostic accuracy. Finally, we discuss the pros and cons of traditional open surgery versus newer minimally invasive methods.
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http://dx.doi.org/10.1007/s00381-018-3886-7DOI Listing
October 2018

Intra-operative cerebrospinal fluid sampling versus post-operative lumbar puncture for detection of leptomeningeal disease in malignant paediatric brain tumours.

PLoS One 2018 3;13(5):e0196696. Epub 2018 May 3.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore, Singapore.

Introduction: Leptomeningeal disease is a feared sequelae of malignant paediatric brain tumours. Current methods for its detection is the combined use of cranio-spinal MRI, and CSF cytology from a post-operative lumbar puncture. In this study, the authors hypothesize that CSF taken at the start of surgery, either from an external ventricular drain or neuroendoscope will have equal sensitivity for positive tumour cells, in comparison to lumbar puncture. Secondary hypotheses include positive correlation between CSF cytology and MRI findings of LMD. From a clinical perspective, the key aim of the study was for affected paediatric patients to avoid an additional procedure of a lumbar puncture, often performed under anaesthesia after neurosurgical intervention.

Methods: This is single-institution, retrospective study of paediatric patients diagnosed with malignant brain tumours. Its main aim was to compare cytological data from CSF collected at the time of surgery versus data from an interval lumbar puncture. In addition, MRI imaging of the same cohort of patients was examined for leptomeningeal disease and corroborated against CSF tumour cytology findings.

Results: Thirty patients are recruited for this study. Data analysis demonstrates a statistically significant association between our intra-operative CSF and LP sampling. Furthermore, our results also show for significant correlation between evidence of leptomeningeal disease on MRI findings versus intra-operative CSF positivity for tumour cells.

Conclusion: Although this is a retrospective study with a limited population, our data concurs with potential to avoid an additional procedure for the paediatric patient diagnosed with a malignant brain tumour.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933788PMC
August 2018

Cystic Cavernoma of Fourth Ventricle in Pediatric Patient.

World Neurosurg 2018 Mar 26;111:255-257. Epub 2017 Dec 26.

National Neuroscience Institute, Jalan Tan Tock Seng, Singapore, Singapore. Electronic address:

Background: Cystic cerebral cavernomas belong to a rare subset of cavernous malformations in the brain. At present, there is limited information with regard to the demographics and etiology of this condition.

Case Description: The authors present a case of a previously well 13-year-old male who presented with symptoms secondary to a cystic lesion of the fourth ventricle compressing on his brainstem. He underwent stereotactic aspiration of the cystic lesion and insertion of an Ommaya reservoir in the same setting. Postoperatively, his symptoms improved. The cyst fluid did not yield any positive cytology or culture results. A repeat MRI brain did not demonstrate evidence of any underlying lesion. However, the patient was readmitted for hemorrhage into the region of his previous fourth ventricular lesion. Surgical evacuation of the haematoma was performed and intraoperative tissue was sent for pathological interrogation. The final histology reported a cavernoma.

Conclusions: This is an unusual presentation of an intracranial vascular anomaly in a pediatric patient. Key features of the case include the diagnostic dilemma and management challenges faced from a neurosurgical perspective.
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http://dx.doi.org/10.1016/j.wneu.2017.12.106DOI Listing
March 2018

DTI fusion with conventional MR imaging in intra-operative MRI suite for paediatric brainstem glioma biopsy.

Childs Nerv Syst 2018 01 24;34(1):19-21. Epub 2017 Oct 24.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

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http://dx.doi.org/10.1007/s00381-017-3627-3DOI Listing
January 2018

Response to Re: The Australasian contribution to the development of neurosurgery in Singapore.

ANZ J Surg 2017 07;87(7-8):640

Division of Neurosurgery, Department of Surgery, National University Hospital Singapore, Singapore.

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http://dx.doi.org/10.1111/ans.14094DOI Listing
July 2017

Concurrent paediatric medulloblastoma and Chiari I malformation with syringomyelia.

Childs Nerv Syst 2017 Jun 21;33(6):881-883. Epub 2017 Apr 21.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

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http://dx.doi.org/10.1007/s00381-017-3413-2DOI Listing
June 2017

Medulloblastoma with tri-vergent melanocytic, myogenic and cartiligious elements.

J Clin Neurosci 2017 07 23;41:100-103. Epub 2017 Mar 23.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore; Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; SingHealth Duke-NUS Neuroscience Academic Clinical Program, Singapore. Electronic address:

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http://dx.doi.org/10.1016/j.jocn.2017.03.030DOI Listing
July 2017

Anomalous intracranial germinoma with unilateral cerebral peduncle swelling.

Childs Nerv Syst 2017 Apr 10;33(4):563-565. Epub 2017 Mar 10.

Neurosurgical Service, KK Women's and Children's Hospital (Singapore), 100 Bukit Timah Road, Singapore, 229899, Singapore.

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http://dx.doi.org/10.1007/s00381-017-3355-8DOI Listing
April 2017

Post-operative diffusion weighted imaging as a predictor of posterior fossa syndrome permanence in paediatric medulloblastoma.

Childs Nerv Syst 2017 Mar 11;33(3):457-465. Epub 2017 Feb 11.

Neurosurgical Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Purpose: Posterior fossa syndrome (PFS) is a serious complication faced by neurosurgeons and their patients, especially in paediatric medulloblastoma patients. The uncertain aetiology of PFS, myriad of cited risk factors and therapeutic challenges make this phenomenon an elusive entity. The primary objective of this study was to identify associative factors related to the development of PFS in medulloblastoma patient post-tumour resection.

Methods: This is a retrospective study based at a single institution. Patient data and all related information were collected from the hospital records, in accordance to a list of possible risk factors associated with PFS. These included pre-operative tumour volume, hydrocephalus, age, gender, extent of resection, metastasis, ventriculoperitoneal shunt insertion, post-operative meningitis and radiological changes in MRI. Additional variables included molecular and histological subtypes of each patient's medulloblastoma tumour. Statistical analysis was employed to determine evidence of each variable's significance in PFS permanence.

Results: A total of 19 patients with appropriately complete data was identified. Initial univariate analysis did not show any statistical significance. However, multivariate analysis for MRI-specific changes reported bilateral DWI restricted diffusion changes involving both right and left sides of the surgical cavity was of statistical significance for PFS permanence.

Conclusion: The authors performed a clinical study that evaluated possible risk factors for permanent PFS in paediatric medulloblastoma patients. Analysis of collated results found that post-operative DWI restriction in bilateral regions within the surgical cavity demonstrated statistical significance as a predictor of PFS permanence-a novel finding in the current literature.
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http://dx.doi.org/10.1007/s00381-017-3356-7DOI Listing
March 2017

The Australasian contribution to the development of neurosurgery in Singapore.

ANZ J Surg 2016 Dec;86(12):961-962

Division of Neurosurgery, Department of Surgery, National University Hospital Singapore, Singapore.

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http://dx.doi.org/10.1111/ans.13743DOI Listing
December 2016

Late pediatric ventriculoperitoneal shunt failures: a Singapore tertiary institution's experience.

Neurosurg Focus 2016 Nov;41(5):E7

Neurosurgical Service, KKH Women's and Children's Hospital.

OBJECTIVE The introduction of ventriculoperitoneal shunts changed the way hydrocephalus was treated. Whereas much is known about the causes of shunt failure in the first few years, there is a paucity of data in the literature regarding the cause of late shunt failures. The authors conducted a study to find out the different causes of late shunt failures in their institution. METHODS A 10-year retrospective study of all the patients who were treated in the authors' hospital between 2006 and 2015 was conducted. Late shunt failures included those in patients who had to undergo shunt revision more than 5 years after their initial shunt insertion. The patient's notes and scans were reviewed to obtain the age and sex of the patient, the time it took for the shunt to fail, the reason for failure, and the patient's follow-up. RESULTS Forty-six patients in the authors' institution experienced 48 late shunt failures in the last 10 years. Their ages ranged from 7 to 26 years (12.23 ± 4.459 years [mean ± SD]). The time it took for the shunts to fail was between 6 and 24 years (mean 10.25 ± 3.77 years). Reasons for failure resulting in shunt revision include shunt fracture in 24 patients (50%), shunt blockage in 14 patients (29.2%), tract fibrosis in 6 patients (12.5%), shunt dislodgement in 2 patients (4.2%), and shunt erosion in 2 patients (4.2%). Postoperative follow-up for the patients ranged from 6 to 138 months (mean 45.15 ± 33.26 months). CONCLUSIONS Late shunt failure is caused by the effects of aging on the shunt, and the complications are different from early shunt failure. A large proportion are complications associated with shunt calcification. The authors advocate a long follow-up for pediatric patients with shunts in situ to monitor them for various causes of late shunt failure.
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http://dx.doi.org/10.3171/2016.8.FOCUS16277DOI Listing
November 2016

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

Authors:
Eric M Thompson Thomas Hielscher Eric Bouffet Marc Remke Betty Luu Sridharan Gururangan Roger E McLendon Darell D Bigner Eric S Lipp Sebastien Perreault Yoon-Jae Cho Gerald Grant Seung-Ki Kim Ji Yeoun Lee Amulya A Nageswara Rao Caterina Giannini Kay Ka Wai Li Ho-Keung Ng Yu Yao Toshihiro Kumabe Teiji Tominaga Wieslawa A Grajkowska Marta Perek-Polnik David C Y Low Wan Tew Seow Kenneth T E Chang Jaume Mora Ian F Pollack Ronald L Hamilton Sarah Leary Andrew S Moore Wendy J Ingram Andrew R Hallahan Anne Jouvet Michelle Fèvre-Montange Alexandre Vasiljevic Cecile Faure-Conter Tomoko Shofuda Naoki Kagawa Naoya Hashimoto Nada Jabado Alexander G Weil Tenzin Gayden Takafumi Wataya Tarek Shalaby Michael Grotzer Karel Zitterbart Jaroslav Sterba Leos Kren Tibor Hortobágyi Almos Klekner Bognár László Tímea Pócza Peter Hauser Ulrich Schüller Shin Jung Woo-Youl Jang Pim J French Johan M Kros Marie-Lise C van Veelen Luca Massimi Jeffrey R Leonard Joshua B Rubin Rajeev Vibhakar Lola B Chambless Michael K Cooper Reid C Thompson Claudia C Faria Alice Carvalho Sofia Nunes José Pimentel Xing Fan Karin M Muraszko Enrique López-Aguilar David Lyden Livia Garzia David J H Shih Noriyuki Kijima Christian Schneider Jennifer Adamski Paul A Northcott Marcel Kool David T W Jones Jennifer A Chan Ana Nikolic Maria Luisa Garre Erwin G Van Meir Satoru Osuka Jeffrey J Olson Arman Jahangiri Brandyn A Castro Nalin Gupta William A Weiss Iska Moxon-Emre Donald J Mabbott Alvaro Lassaletta Cynthia E Hawkins Uri Tabori James Drake Abhaya Kulkarni Peter Dirks James T Rutka Andrey Korshunov Stefan M Pfister Roger J Packer Vijay Ramaswamy Michael D Taylor

Lancet Oncol 2016 04 12;17(4):484-495. Epub 2016 Mar 12.

Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.

Methods: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm(2) tumour remaining), or sub-total resection (≥1·5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.

Findings: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084).

Interpretation: The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.

Funding: Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.
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http://dx.doi.org/10.1016/S1470-2045(15)00581-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907853PMC
April 2016

A Tribute to Tham Cheok Fai, "Founding Father" of Singapore Neurosurgery.

Ann Acad Med Singap 2015 Aug;44(8):307-11

Division of Neurosurgery, Department of Surgery, National University Hospital Singapore, Singapore.

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August 2015