Somatic mitochondrial DNA mutations in different grades of glioma.

Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.

History of Neurosurgery in Malaysia: The Past, Present and Future.

The history of neurosurgery in Malaysia traces back to 1962 and is filled with stories of vibrant and humble neurosurgeons who have dedicated their life to patients and professions. The early development of neurological and neurosurgical services begins from the establishment of the neurosurgery unit at Hospital Kuala Lumpur (HKL), followed by the foundation of the Tunku Abdul Rahman Neuroscience Institute (IKTAR). Due to the exponentially increased demand for the care of neurosurgical patients, many universities and government hospitals have opened their neurosurgical units. In 2001, the formal residency training programme (USM Masters in Neurosurgery) started and since then has produced qualified neurosurgeons that empowered and shaped the present generation. The formation of the Neurosurgical Association of Malaysia (NAM) is another turning point towards bidirectional collaboration with the World Federation of Neurosurgical Societies (WFNS). Many opportunities were created for educational activities and the expansion of subspecialties in neurosurgery. This article describes the impact of the past neurosurgeons and the endeavors that they had gone through; the present neurosurgeons who pioneered the current neurosurgical services in Malaysia, and the future neurosurgeons that will continue the legacy and bring neurosurgery further ahead in this country.

Safety and Use of MLC601/MLC901 (NeuroAiDTM) in Primary Intracerebral Hemorrhage: A Cohort Study from the NeuroAiD Safe Treatment Registry.

BACKGROUND: MLC601/MLC901 (NeuroAiD™) is a combination of natural products shown to be safe and to aid neurological recovery after brain injuries, especially ischemic stroke. Few studies have investigated NeuroAiD in primary intracerebral hemorrhage (ICH). The NeuroAiD Safe Treatment (NeST) Registry explores NeuroAiD use in the real-world setting. This cohort study aimed to assess its use and safety in ICH. METHODS: The online NeST Registry of subjects with ICH given NeuroAiD prospectively collected clinical data at baseline and monthly visits (V) 1 to 3. Outcome measures included compliance, side effects, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Short Orientation-Memory-Concentration Test (SOMCT). RESULTS: Sixty-six subjects were included. NeuroAiD was well-tolerated with fair compliance over three months. Two non-serious side effects were reported. Mean scores significantly improved on all outcome scales. The proportion of subjects with favorable outcomes significantly improved from baseline to V3: NIHSS 0-4, from 12% to 59% (p < 0.0001); GCS 13-15, from 64% to 88% (p = 0.007); mRS 0-1, from 9% to 37% (p = 0.004); and SOMCT score 0-8, from 44% to 68% (p = 0.029). CONCLUSIONS: NeuroAiD in the real-world setting was safe and showed potential for a sustained positive effect on neurological recovery after ICH.

An Unusual Case of the Successful Treatment of Carbapenem-resistant Ventriculitis with Intravenous Colistin.

Ventriculitis is a well-documented complication of ventriculostomy, which is difficult to treat and is associated with high rates of mortality. There is a growing trend of resistance among many organisms, such as Acinetobacter baumannii, in particular, to most antibiotics with the exception of colistin. It is thought that colistin has poor blood-brain barrier penetration; therefore, in cases of ventriculitis, it is preferentially administered via the intrathecal or intraventricular route. These routes, in turn, risk introducing infections, which may perpetuate the problem. We report a case of multidrug-resistant Acinetobacter baumannii ventriculitis, which was treated successfully with intravenous colistin monotherapy.

Rare and Unique Case of Midline Anterior Arch of Atlas Non-formation Mimicking Jefferson Type 1 Fracture.

Cervical spine injuries are rare occurrences in children, especially the congenital anomalies of the atlas vertebra. Any injury involving the craniovertebral junction such as Jefferson fracture, is a valid cause for alarm due to the complex nature of the craniovertebral junction and the morbidity associated with it. We report the case of a 10-year-old male, who had failure of fusion of anterior arch of atlas due to the failure of formation of the anterior midline synchondrosis, and this mimicked a Jefferson fracture. If it was not for the peculiar absence of any corresponding evidence to suggest spinal injury, we might have mistaken this extremely rare but benign anomaly for a Jefferson fracture and subjected the patient to needless surgical treatment. Hence, it is concluded that keen clinical acumen and clear understanding of the developmental anatomy of these patients may be necessary to adequately manage them.

Management Options and Outcome of Cerebral Arteriovenous Malformation in Pregnancy: Case Series.

Cerebral arteriovenous malformation (AVM) is a rare entity with an estimated prevalence of 0.01-0.05% in the general population. We reviewed hospital obstetric records during 2010-2017 and reported a case series of six patients with cerebral AVM in pregnancy, of which five patients had successful pregnancy, and one maternal mortality.

Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress.

The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.

Occurrence, distribution, and dechlorination of polychlorinated biphenyls and health risk assessment in Selangor River basin.

Polychlorinated biphenyls (PCBs) were monitored in surface water collected in the Selangor River basin, Malaysia, to identify the occurrence, distribution, and dechlorination process as well as to assess the potential adverse effects to the Malaysian population. Ten PCB homologs (i.e., mono-CBs to deca-CBs) were quantitated by using gas chromatography-mass spectrometry (GC/MS). The total concentration of PCBs in the 10 sampling sites ranged from limit of detection to 7.67 ng L-1. The higher chlorinated biphenyls (tetra-CBs to deca-CBs) were almost not detected in most of the sampling sites, whereas lower chlorinated biphenyls (mono-CBs, di-CBs, and tri-CBs) dominated more than 90 % of the 10 homologs in all the sampling sites. Therefore, the PCB load was estimated to be negligible during the sampling period because PCBs have an extremely long half-life. The PCBs, particularly higher chlorinated biphenyls, could be thoroughly dechlorinated to mono-CBs to tri-CBs by microbial decomposition in sediment or could still be accumulated in the sediment. The lower chlorinated biphenyls, however, could be resuspended or desorbed from the sediment because they have faster desorption rates and higher solubility, compared to the higher chlorinated biphenyls. The health risk for the Malaysia population by PCB intake that was estimated from the local fish consumption (7.2 ng kg-1 bw day-1) and tap water consumption (1.5 × 10-3-3.1 × 10-3 ng kg-1 bw day-1) based on the detected PCB levels in the surface water was considered to be minimal. The hazard quotient based on the tolerable daily intake (20 ng kg-1 bw day-1) was estimated at 0.36.

The NeuroAiD Safe Treatment (NeST) Registry: a protocol.

INTRODUCTION: NeuroAiD (MLC601, MLC901), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries. The NeuroAiD Safe Treatment (NeST) Registry aims to assess its use and safety in the real-world setting. METHODS AND ANALYSIS: The NeST Registry is designed as a product registry that would provide information on the use and safety of NeuroAiD in clinical practice. An online NeST Registry was set up to allow easy entry and retrieval of essential information including demographics, medical conditions, clinical assessments of neurological, functional and cognitive state, compliance, concomitant medications, and side effects, if any, among patients on NeuroAiD. Patients who are taking or have been prescribed NeuroAiD may be included. Participation is voluntary. Data collected are similar to information obtained during standard care and are prospectively entered by the participating physicians at baseline (before initialisation of NeuroAiD) and during subsequent visits. The primary outcome assessed is safety (ie, non-serious and serious adverse event), while compliance and neurological status over time are secondary outcomes. The in-person follow-up assessments are timed with clinical appointments. Anonymised data will be extracted and collectively analysed. Initial target sample size for the registry is 2000. Analysis will be performed after every 500 participants entered with completed follow-up information. ETHICS AND DISSEMINATION: Doctors who prescribe NeuroAiD will be introduced to the registry by local partners. The central coordinator of the registry will discuss the protocol and requirements for implementation with doctors who show interest. Currently, the registry has been approved by the Ethics Committees of Universiti Kebangsaan Malaysia (Malaysia) and National Brain Center (Indonesia). In addition, for other countries, Ethics Committee approval will be obtained in accordance with local requirements. TRIAL REGISTRATION NUMBER: NCT02536079.

The lower cheek flap combined with neurosurgical approach for infratemporal fossa tumour

p style=text-align: justify;strongOBJECTIVE:/strong To describe our experience in performing the lower cheek flap for access to the infratemporal fossa combined with the neurosurgical approach. br /br /strongMETHODS:/strongbr /strongDesign:/strong Case report br /strongSetting:/strong Tertiary Referral Center br /strongPatients:/strong Two br /br /strongRESULTS:/strong Two unusual tumours involving the infratemporal and middle cranial fossa were excised using this combined appoach. The infratemporal fossa tumour was accessed via the lower cheek flap while the intracranial portion was resected from above via craniotomy.br /br /strongCONCLUSION:/strong The lower cheek flap in combination with the neurosurgical approach allows optimal exposure to tumours involving the infratemporal and middle cranial fossae. It has less complications and better aesthetic outcome compared to other approaches./p