The effect of somatic mutations in mitochondrial DNA on the survival of patients with primary brain tumors.

AIM: To assess the presence of mitochondrial (mt) DNA somatic mutations, determine the relationship between clinicopathological characteristics and mutations, and assess the survival outcomes in Malay patients with primary brain tumors. METHODS: The study enrolled 54 patients with primary brain tumors. DNA extracted from paired tissue and blood samples was subjected to Sanger sequencing to identify alterations in the entire mtDNA. The associations between clinicopathological characteristics and mutations were evaluated. Cox-regression multivariate analysis was conducted to identify factors significantly associated with survival, and Kaplan-Meier analysis was used to compare the survival of patients with and without mutations. RESULTS: Overall, 29.6% of the patients harbored 19 somatic mutations distributed across 15 loci within the mtDNA. Notably, 36.8% of these mutations were not previously documented in MITOMAP. One newly identified mutation caused a frameshift in the ATPase6 gene, resulting in a premature stop codon. Three mutations were classified as deleterious in the MitImpact2 database. Overall, 1097 mtDNA polymorphisms were identified across 331 different locations. Patients with mutations exhibited significantly shorter survival than patients without mutations. CONCLUSIONS: mtDNA mutations negatively affected the survival outcomes of Malaysian patients with primary brain tumors. However, studies with larger samples are needed to confirm the association between mutation burden and survival rates.

Neuroradiological Correlation of the Lateral Third Periventricular, Pituitary Gland and Stalk, Pineal Gland, Cerebral Aqueduct, and Foramen Magendie and Luschka With Intraventricular Neuroendoscopic Images: A Case Series.

Neuroendoscopy procedures in pediatrics have expanded beyond the endoscopic third ventriculostomy. As such, a direct and angled endoscope allows further visualization around the corner, capturing the surrounding anatomy. Intraoperative live images look different than radiological images. Hence, in this single institutional experience, we correlate neuroradiology images with intraoperative intraventricular endoscopic views of the third-fourth ventricle, pituitary, pineal gland, cerebral aqueduct, and foramen magendie and luschka. Our collective case series reveals a few interesting case scenarios of normal and abnormal findings during the procedure. Careful navigation of the neuroendoscope is crucial to prevent injury to the neurovascular bundle. A close relationship with normal anatomy from radiological imaging is necessary to prevent it from getting lost once inside the ventricular cavity.

Light and the Brain: A Clinical Case Depicting the Effects of Light on Brainwaves and Possible Presence of Plasma-like Brain Energy.

Light is an electromagnetic radiation that has visible and invisible wavelength spectrums. Visible light can only be detected by the eyes through the optic pathways. With the presence of the scalp, cranium, and meninges, the brain is seen as being protected from direct exposure to light. For that reason, the brain can be viewed as a black body lying inside a black box. In physics, a black body tends to be in thermal equilibrium with its environment and can tightly regulate its temperature via thermodynamic principles. Therefore, a healthy brain inside a black box should not be exposed to light. On the contrary, photobiomodulation, a form of light therapy for the brain, has been shown to have beneficial effects on some neurological conditions. The proposed underlying mechanisms are multiple. Herein, we present our intraoperative findings of rapid electrocorticographic brainwave changes when the brain was shone directly with different wavelengths of light during awake brain surgery. Our findings provide literature evidence for light's ability to influence human brain energy and function. Our proposed mechanism for these rapid changes is the presence of plasma-like energy inside the brain, which causes fast brain activities that are akin to lightning strikes.

An Approach to the Examination of the Lumbar Plexus for Neurosurgical Residents: A Video Manuscript.

The lumbar plexus provides innervation to the lower limbs and is essential in enabling motor movement and sensation in the lower limbs. Some of its branches also innervate the muscles in the pelvic girdle. Compared to the brachial plexus in the upper limbs, the lumbar plexus appears to garner less recognition among physicians and surgeons. However, it is important to understand the anatomy of the lumbar plexus and its branches along with the innervation they enable, as injury to them can cause plexopathies and pathologies that should be recognised by any treating clinician. Lumbar disc herniation, trauma and entrapment by muscles or hypertrophic ligaments are common causes of lumbar plexus or nerve injuries. A video was produced to demonstrate the examination techniques explained in this article. To provide comprehensive examination of the lower limbs, the sciatic nerve and its branches are also included in the examination video.

Structured Manual Muscle Testing of the Lower Limbs.

An accurate and reliable neurological examination is pivotal in diagnosing patients with neurological and neurosurgical conditions. Despite the advancement of neuroscientific knowledge and the ever-progressing technologies and modalities that are being adopted to help achieve the challenge of accurate diagnosis, the neurologic examination is still crucial in both ambulatory and emergency settings. It provides the physician a tool to recognise neurologic involvement in certain disease states, and thereby allow proper work-up and treatment for patients. A basic neurologic examination can be performed rapidly with practice. Manual muscle testing of the lower limbs was carried out in accordance with a bedside clinical examination involving a clinical personnel examiner and a patient. This testing was performed in a rostro-caudal manner, starting from the hip and progressing to the toes. The neurological exam can be intimidating to perform for a lot of physicians. Deficiencies in accurate muscle testing have always presented a challenge for medical students and clinicians. By referring to the examination methods mentioned in our text and with the help of related video, it is our aim to improve the quality of neurological examination among medical personnel so that diseases may be recognised and managed earlier in their course.

Pain as a Guide in Glasgow Coma Scale Status for Neurological Assessment.

Neurological status is essential and often challenging for neurosurgical residents and also for neurosurgeons to determine surgical management. Pain as a component of the Glasgow Coma Scale (GCS) can be used as a tool in patients, especially an unconscious or comatose patient. In order to elicit this adequate noxious stimulus, a certain amount of pressure-pain threshold is required upon performing either as the central or peripheral technique. The scientific explanation behind each technique is required and needs to be well understood to aid the localisation of the defect in the neurological system. This paper will briefly review the aid of pain as a neurological guide in GCS status assessment.

Door-to-Skin Time in Patient Undergoing Emergency Trauma Craniotomy.

Background: Traumatic brain injury (TBI) is the third leading cause of death and disability worldwide in 2020. For patients with TBI with significant intracranial bleeds, urgent surgical intervention remains the mainstay treatment. This study aims to evaluate the time to definite surgical intervention since admission and its association with patient outcomes in a neurosurgery referral centre in Malaysia. Methods: This retrospective study was conducted at Hospital Sultanah Aminah Johor Bahru from 1 January 2019 to 31 December 2019. All patients with TBI requiring urgent craniotomy were identified from the operating theatre registry, and the required data were extracted from their clinical notes, including the Glasgow Outcome Score (GCS) at discharge and 6 months later. Logistic regression was performed to identify the factors associated with poor outcomes. Results: A total of 154 patients were included in this study. The median door-to-skin time was 605 (interquartile range = 494-766) min. At discharge, 105 patients (68.2%) had poor outcomes. At the 6-month follow-up, only 58 patients (37.7%) remained to have poor outcomes. Simple logistic regression showed that polytrauma, hypotensive episode, ventilation, severe TBI, and the door-to-skin time were significantly associated with poor outcomes. After adjustments for the clinical characteristics in the analysis, the likelihood of having poor outcomes for every minute delay in the door-to-skin time increased at discharge (adjusted odds ratio [AOR] = 1.005; 95% confidence interval [CI] = 1.002-1.008) and the 6-month follow-up (AOR = 1.008; 95% CI = 1.005-1.011). Conclusion: The door-to-skin time is directly proportional to poor outcomes in patients with TBI. Concerted efforts from all parties involved in trauma care are essential in eliminating delays in surgical interventions and improving outcomes.

The Brain-Gut Clinic in Hospital Universiti Sains Malaysia: Pioneering New Service to Advance Neuro-Gastroenterology and Motility in Malaysia.

Neurogastroenterology and motility is a new but advanced subspecialty within gasteroenterology that cater to difficult, persistent and refractory gut-brain symptoms. Hospital USM has the country's first and new state-of-the art motility lab that was recently launched on the 25 May 2023, and is covered in nationwide media. Another first is the Brain-Gut Clinic, established on the 16 November 2022. The clinic is a new concept that builds on unique multiple disciplines in relation to the gut-brain axis. It is hoped that there will be more awareness on the existence of neurogastroenterology and motility among doctors and community, and that more research can be forthcoming to reduce the disease burden.

Tranexamic Acid in Non-Traumatic Intracerebral Haemorrhage (TANICH II): Introducing the Potential Role of 3 g Tranexamic Acid in Haematoma Reduction.

Background: Intracerebral haemorrhage (ICH) can be devastating, particularly if haematoma expansion occurs. The efficacy of tranexamic acid (TXA), an anti-fibrinolytic agent, in reducing haematoma expansion is now being studied worldwide. However, the optimal dosage of TXA has yet to be determined. This study was designed to further establish the potential of different doses of TXA. Methods: A double-blinded, randomised, placebo-controlled study was carried out among adults with non-traumatic ICH. Eligible study subjects were randomly assigned to receive placebo, 2-g TXA treatment or 3-g TXA treatment. Haematoma volumes before and after intervention were measured using the planimetric method. Results: A total of 60 subjects with 20 subjects in each treatment group were recruited for this study. Among the 60 subjects, the majority were male (n = 36, 60%), had known cases of hypertension (n = 43, 71.7%) and presented with full Glasgow coma scale (GCS) (n = 41, 68.3%). The results showed that there was no statistically significant difference (P = 0.315) in the mean changes of haematoma volume when compared with three study groups using ANCOVA, although the 3-g TXA group was the only group that showed haematoma volume reduction (mean reduction of 0.2 cm3) instead of expansion as in placebo (mean expansion 1.8 cm3) and 2-g TXA (mean expansion 0.3 cm3) groups. Good recovery was observed in all study groups, with only three subjects being moderately disabled. No adverse effects were reported in any of the study groups. Conclusion: To the best of our knowledge, this is the first clinical study using 3 g of TXA in the management of non-traumatic ICH. From our study, 3 g of TXA may potentially be helpful in reducing haematoma volume. Nonetheless, a larger-scale randomised controlled trial should be carried out to further establish the role of 3 g of TXA in non-traumatic ICH.

The Assessment of White Matter Integrity Alteration Pattern in Patients with Brain Tumor Utilizing Diffusion Tensor Imaging: A Systematic Review.

Alteration in the surrounding brain tissue may occur in the presence of a brain tumor. The present study aims to assess the characteristics and criteria of the pattern of white matter tract microstructure integrity alteration in brain tumor patients. The Scopus, PubMed/Medline, and Web of Science electronic databases were searched for related articles based on the guidelines established by PRISMA. Twenty-five studies were selected on the morphological changes of white matter tract integrity based on the differential classification of white matter tract (WMT) patterns in brain tumor patients through diffusion tensor imaging (DTI). The characterization was based on two criteria: the visualization of the tract-its orientation and position-and the DTI parameters, which were the fractional anisotropy and apparent diffusion coefficient. Individual evaluations revealed no absolute, mutually exclusive type of tumor in relation to morphological WMT microstructure integrity changes. In most cases, different types and grades of tumors have shown displacement or infiltration. Characterizing morphological changes in the integrity of the white matter tract microstructures is vital in the diagnostic and prognostic evaluation of the tumor's progression and could be a potential assessment for the early detection of possible neurological defects that may affect the patient, as well as aiding in surgery decision-making.

Big Brain Data Initiatives in Universiti Sains Malaysia: Data Stewardship to Data Repository and Data Sharing.

The sharing of open-access neuroimaging data has increased significantly during the last few years. Sharing neuroimaging data is crucial to accelerating scientific advancement, particularly in the field of neuroscience. A number of big initiatives that will increase the amount of available neuroimaging data are currently in development. The Big Brain Data Initiative project was started by Universiti Sains Malaysia as the first neuroimaging data repository platform in Malaysia for the purpose of data sharing. In order to ensure that the neuroimaging data in this project is accessible, usable, and secure, as well as to offer users high-quality data that can be consistently accessed, we first came up with good data stewardship practices. Then, we developed MyneuroDB, an online repository database system for data sharing purposes. Here, we describe the Big Brain Data Initiative and MyneuroDB, a data repository that provides the ability to openly share neuroimaging data, currently including magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG), following the FAIR principles for data sharing.

Clinical outcomes and thermodynamics aspect of direct brain cooling in severe head injury.

Background: Brain cooling therapy is one of the subjects of interest, and currently, data on direct brain cooling are lacking. Hence, the objective is to investigate the clinical outcomes and discuss the thermodynamics aspect of direct brain cooling on severely injured brain patients. Methods: This pilot study recruited the severely injured brain patients who were then randomized to either a direct brain cooling therapy group using a constant cooling temperature system or a control group. All studied patients must be subjected to an emergency neurosurgical procedure of decompressive craniectomy and were monitored with intracranial pressure, brain oxygenation, and temperature. Further, comparison was made with our historical group of patients who had direct brain cooling therapy through the old technique. Results: The results disclosed the direct brain cooling treated patients through a newer technique obtained a better Extended Glasgow Outcome Score than a control group (P < 001). In addition, there is a significant outcome difference between the combined cooling treated patients (new and old technique) with the control group (P < 0.001). Focal brain oxygenation and temperature are likely factors that correlate with better outcomes. Conclusion: Direct brain cooling is feasible, safe, and affects the clinical outcomes of the severely traumatized brain, and physics of thermodynamics may play a role in its pathophysiology.

A mini-review on anticancer-related properties of azithromycin and its potential activities in overcoming the challenges of glioblastoma.

The resistance, plasticity and heterogeneity of cancer cells, including glioblastoma (GB) cells, have prompted the investigation of various agents for possible adjuncts and alternatives to existing therapies. This includes a macrolide antibiotic, azithromycin (AZI). It possesses intriguing anticancer properties in a range of cancer models in vitro, such as antiproliferative, pro-apoptotic, anti-autophagy and anti-angiogenic effects. In fact, AZI is renowned for its ability to eradicate cancer stem cells by inhibiting mitochondrial biogenesis and respiration. AZI-containing regimens in cancer patients for different purposes have shown favourable (i.e., attributed to its antibacterial activity) and unfavourable outcomes. Whilst its direct anticancer effects have yet to be clinically proven. To that end, this review provides a summary of AZI anticancer studies and delineates its potential activities in overcoming the challenges of GB.

Examination of Thoracic and Lumbosacral Spine Guide for Neurosurgery Residents.

Background: This paper outlines a summary of examination techniques for the thoracic and lumbosacral spine. It starts with observation, palpation and a range of movements followed by various special tests to identify thoracic and lumbosacral spine pathology. Methods: Bedside instruments used include a measuring tape, scoliometer and back range of motion instrument (BROM II). Discussion: Back flexion-extension, lateral flexion and rotation were assessed with bedside instruments. This would aid in increasing the accuracy and precision of objective measurement while conducting a clinical examination to determine the back range motion. Specific tests were used to localise specific anatomical locations and identify the spine pathology that can help the clinician to diagnose and treat the disease.

Dorsal Column Bedside Examination Test: Tips for the Neurosurgical Resident.

The dorsal column medial lemniscus (DCML) system is a sensory pathway of the central nervous system; it carries sensations of soft touch, vibration, proprioception, two-point discrimination, and pressure from the skin and joints. The clinical signs of the DCML pathway lesions include loss of soft touch, vibratory sense, proprioception, discrimination sense, and a positive Rhomberg test. Diseases that affect this pathway are usually degenerative, for example, spinal cord degeneration due to vitamin B12 deficiency; it can also be affected by trauma or infarction of the posterior spinal artery causing posterior cord syndrome. This video manuscript provides a step-by-step examination technique of the dorsal column examination, specially catered for Malaysian medical students and trainees. A series of videos show the techniques for soft touch sensation examination, examination of the vibratory sense, examination of the joint position sense, examination of two-point discrimination and the Rhomberg test. We hope that students can adhere to these techniques and apply them in their daily neurological assessments.

Chronic Anterior Pituitary Dysfunction Following Traumatic Head Injury: Prospective Study in Hospital Sultanah Aminah Johor Bahru, Malaysia.

Background: Hypopituitarism following traumatic brain injury (TBI) is not rare however most patients were left undiagnosed and untreated. Association of post TBI hypopituitarism causing neurobehavioural and quality of life impairment. The aim of the study is to determine the incidence of the chronic anterior pituitary deficiency in patients with traumatic brain injury. Subsequently determine the risk factor and the outcome of the patient with chronic anterior pituitary dysfunction. Methods: This is single centre cross-sectional study involved 105 traumatic head injury patients under the Neurosurgical Department Hospital Sultanah Aminah, Johor Bahru, Malaysia. The primary investigator will do an interview and the patients will be asked question to complete a questioner from SF-36 (36 questions). Subsequently, consent for participation will be taken and blood sampling will be done. Results: Thirty-three patients were noted to have anterior pituitary dysfunction. The mean age was 36.97 ± 12.96 years old. Twenty-seven patients (32.5%) were male and six patients were female (27.3%). Chronic anterior pituitary dysfunction in patients with a severe traumatic head injury around 47.1% (23 patients), as compared to a moderate head injury (8 patients, 38.1%) and 2 sustained mild head injury (5.6%). The mean duration after the onset of trauma was 10.3 ± 1.79 months. All patient with anterior pituitary dysfunction had positive CT brain findings with 22 had subarachnoid haemorrhage (SAH) at the basal cistern and 27 patients had a base of skull fracture, where 52.1% of the patient underwent surgical intervention, 84.8% involved one axis and another 5 patients had two axes involved. Severity of the head injury (P < 0.001), prolonged duration of hospital stay (P = 0.014), radiological findings of a base of skull fracture (P < 0.001) and presence of SAH at basal cistern (P < 0.001) was significantly associated with pituitary dysfunction. The patient with anterior pituitary dysfunction has the lower 36-item Short Form Survey (SF-36) marks 56.3 ± 10.3. Conclusion: The prevalence of hypopituitarism was 31%. Indicators are increased TBI severity, prolonged hospitalisation and positive finding in radiological assessment. Post-traumatic chronic anterior pituitary dysfunction also related with poor quality of life as showed by low SF-36 marks.

Manual Muscle Testing of the Scapula and the Upper Limb through Bedside Examination.

Neurological examination is an important tool in diagnosing patients with neurological and neurosurgical conditions. As the complexity and knowledge of neurological and neurosurgical conditions increases, we are now required to learn and indoctrinate our peers and students with the correct skills and methods of examination. Emphasis on the correct techniques of testing muscle strength is essential to avoid errors in recording muscle power and in testing specific muscles which may have overlapping functions. The manual muscle testing of muscles of scapula and upper limbs was performed as to mimic a bedside clinical examination and involved an examiner, a patient and a videographer. The manual muscle testing has been performed in rostrocaudal manner starting from the scapula and ending with the thumbs. A reliable and consistent method of manual muscle testing is lacking among students and clinicians. By adhering to the methods delineated in our text and accompanying video, we hope to reduce inter-examiner variability and increase the reliability and validity of this important examination.

Subthalamic Nucleus (STN)-Deep Brain Stimulation Reduces the Power of Mu and Beta Rhythms and Enhances Synchrony at the Motor Cortices in Parkinson's Disease: A Report of Two Cases.

The motor circuit in Parkinson's disease (PD) involves the basal ganglia, thalamus, motor cortex, and cerebellum. Hence, subthalamic nucleus (STN) or globus pallidus internus deep brain stimulation is commonly used in treating refractory Parkinson's patients. During the procedure, the local field potential (LPF) is commonly made along the trajectory of the STN. Two cases were assessed, where an electroencephalographic recording at the sensorimotor cortices was also performed with and without stimulation at the optimal STN electrode site. The 'on' stimulation state associated with clinical improvement correlated with a marked reduction in the late theta (7.5 Hz), alpha (10.5 Hz) (Mu wave), and beta (20 Hz) wave power. Besides, more synchronized and coherent brainwaves were noted when the stimulation was 'on'.

Introduction of a newly created AW stereotactic frame: a phantom-based accuracy evaluation and an initial experience in clinical usage.

BACKGROUND: A new stereotactic frame was created in 2015, based on a linear algorithm. It is called Albert Wong (AW) frame. A simple AW stereo-calculator was also designed based on Excel® (Microscoft Corporation, Redmond, WA) programme for the frame. OBJECTIVE: The aim of this study is to test the accuracy of the AW frame by a direct head to head comparison with CRW® frame (Integra Life Sciences, Plainsboro, NJ) on a phantom. METHODS: This is a prospective pilot cross-sectional phantom study with a total of 42 (21 for AW and 21 for CRW®) laboratory testings performed in 2017 at our institute to compare the accuracies of both frames in a consecutive manner. A phantom (BL phantom) was newly created, where targets can be placed at different heights and positions on a platform attached under the frame for accuracy testing comparing between the AW and CRW® frames. RESULTS: A comparable accuracy testing results were observed between the AW and CRW® frames of 0.64 mm versus 1.07 mm respectively. Approval from the local ethics committee for a clinical trial was obtained. We report on three case illustrations who had the AW frame-based biopsies with definitive diagnoses and without any post-biopsy related complication. CONCLUSION: AW frame successfully demonstrated a good accuracy of 0.64 mm in phantom testing using the BL phantom by a linear algorithmic calculation. The clinical trial with three patients demonstrated definitive diagnoses and safety with its use.

Prediction of outcomes in traumatic brain injury: The IMPACT and CRASH prognostic models in a single neurosurgical center, Malaysia.

BACKGROUND: Traumatic brain injury (TBI) has recently become a major concern for public health care and a socioeconomic burden internationally. Prognostic models are mathematical models developed from specific populations which are used to predict the mortality and unfavorable outcomes especially in trauma centers. Hence, we formulate a study to perform an external validation of the IMPACT and CRASH prognostic models; the CRASH model to predict 14-day mortality and 6-month unfavorable outcome and the IMPACT model to estimate 6-month mortality and unfavorable outcome in a single center cohort of TBI patients in Malaysia. METHODS: All patients with traumatic brain injury (mild, moderate, and severe) who were admitted to Queen Elizabeth Hospital from November 1, 2017, to January 31, 2019, were prospectively analyzed through a data collection sheet. The discriminatory power of the models was assessed as area under the receiver operating characteristic curve and calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. RESULTS: We analyzed 281 patients with significant TBI treated in a single neurosurgical center in Malaysia over a 2-year period. The overall observed 14-day mortality was 9.6%, a 6-month unfavorable outcome of 23.5%, and a 6-month mortality of 13.2%. Overall, both the CRASH and IMPACT models showed good discrimination with AUCs ranging from 0.88 to 0.94 and both models calibrating satisfactorily H-L GoF P>0.05 and calibration slopes >1.0 although IMPACT seemed to be slightly more superior compared to the CRASH model. CONCLUSIONS: The CRASH and IMPACT prognostic models displayed satisfactory overall performance in our cohort of TBI patients, but further investigations on factors contributing to TBI outcomes and continuous updating on both models remain crucial.