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.

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.

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.

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.

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.

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.

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.

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.

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.

Examination Approaches to Brachial Plexus Injury for Neurosurgical Residents.

Background: Brachial plexus injury is a severe peripheral nerve injury that affects the upper extremities and causes functional damage and disability. A detailed and accurate clinical examination is required to accurately localise the site of injury. This video manuscript aims to provide guidelines for the structured assessment of a patient with brachial plexus injury, specifically tailored to Malaysian medical students and trainees. Methods: A video demonstrating the examination of the brachial plexus was made. This video, created at the School of Medical Sciences at Universiti Sains Malaysia (USM), demonstrates the proper examination technique for brachial plexus. Conclusion: We hope that this video will help students and young doctors evaluate patients with brachial plexus injury and reach accurate localisation of the injury.

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.

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.

Neural alterations in working memory of mild-moderate TBI: An fMRI study in Malaysia.

Working memory (WM) encompasses crucial cognitive processes or abilities to retain and manipulate temporary information for immediate execution of complex cognitive tasks in daily functioning such as reasoning and decision-making. The WM of individuals sustaining traumatic brain injury (TBI) was commonly compromised, especially in the domain of WM. The current study investigated the brain responses of WM in a group of participants with mild-moderate TBI compared to their healthy counterparts employing functional magnetic resonance imaging. All consented participants (healthy: n = 26 and TBI: n = 15) performed two variations of the n-back WM task with four load conditions (0-, 1-, 2-, and 3-back). The respective within-group effects showed a right hemisphere-dominance activation and slower reaction in performance for the TBI group. Random-effects analysis revealed activation difference between the two groups in the right occipital lobe in the guided n-back with cues, and in the bilateral occipital lobe, superior parietal region, and cingulate cortices in the n-back without cues. The left middle frontal gyrus was implicated in the load-dependent processing of WM in both groups. Further group analysis identified that the notable activation changes in the frontal gyri and anterior cingulate cortex are according to low and high loads. Though relatively smaller in scale, this study was eminent as it clarified the neural alterations in WM in the mild-moderate TBI group compared to healthy controls. It confirmed the robustness of the phenomenon in TBI with the reproducibility of the results in a heterogeneous non-Western sample.

Risk Factors Associated with Outcome of Spontaneous Intracerebral Haemorrhage: Hospital Kuala Lumpur Experience.

Background: Stroke is the third leading cause of death in Malaysia. This study aims to evaluate the mortality risk factors of spontaneous intracerebral haemorrhage (ICH) in Hospital Kuala Lumpur, Malaysia. Methods: A single centre prospective cohort study was performed between 1 May 2017 and 30 April 2018 for patients above 18 years old with spontaneous ICH. Patients exhibiting haemorrhage due to tumours and ruptured arteriovenous malformations were excluded. The demographics, clinical parameters, radiology findings, surgical intervention, mortality at 30 days and outcome based on modified Rankin score (MRS) grading were recorded. Selected variables were incorporated into a binary logistic regression to determine the outcome predictors of mortality. Results: A total of 292 patients were recruited into the study. The findings showed that the mean age of ICH patients was 48.9 years old. Most of the lesions were located in the putamen (45.9%). More than half (61.0%) of the patients presented with a good outcome whereas 39.0% of the patients presented with a poor outcome. The mortality rate at 30 days was 29.1%. The important predictors for mortality were male (odds ratio [OR] = 0.343; P = 0.043), concomitant use of warfarin and aspirin (OR = 14.696; P = 0.007), ischaemic heart disease [IHD] (OR = 0.007; P = 0.003), brainstem bleed (OR = 0.001; P = 0.001), the presence of intraventricular haemorrhage [IVH] (OR = 0.198; P = 0.049) and surgery. Conclusion: Most diagnosed ICH patients in Malaysia were at a younger age (mean of 48.9 years old) with the significant mortality predictors were IVH, IHD, surgery and brainstem bleed.

Preliminary Comparison of Transseptal Microscopic Versus Endoscopic Transsphenoidal Surgery in a University Teaching Hospital.

Background: Transsphenoidal surgery (TSS) is an increasing preferred treatment for sella lesions. In a university teaching hospital, the novel endoscopic TSS was adopted with ongoing resident teaching. We evaluated a single institutional series of preliminary comparisons of transseptal microscopic with endoscopic TSS. Methods: A retrospective data analysis included 37 patients and 19 patients who underwent microscopic and endoscopic TSS, respectively. The demographic characteristics of the patients, intra-operative analyses, morbidity, mortality and visual assessments were included in this analysis. Results: The study included 31 men and 25 women, and median age at surgery was 49 years old (range 14-70 years old). There were no differences between the rates of cerebrospinal fluid (CSF) fistula, sinus complications, anterior pituitary hormone deficiency and diabetes insipidus between the groups. Total length of stay and intensive care unit stay were similar between the groups. Patients who underwent endoscopic TSS were at significantly increased risk of epistaxis (P = 0.010), respiratory event (P = 0.014) and post-operative visual deterioration prior to discharge (P = 0.032). Conclusion: Endoscopic TSS is a promising procedure that allows sufficient visualisation of the surgical field and adequate tumour removal. It is comparable to microscopic TSS but has a higher complication rate notably due to steep learning curve required to gain the expertise.

Cognitive Impairment and Neuropsychiatry Manifestation Following Mild and Moderate Traumatic Brain Injury at 3 Months and 6 Months.

Background: Cognitive impairment (CI) and neuropsychiatry manifestation (NM) are known complications among patients with traumatic brain injury (TBI). However, the clinical correlation between mild and moderate TBI with the above have not been extensively studied. Methods: The patients (n = 54) were divided into mild and moderate TBI. Both groups were assessed at 3 months and 6 months post-trauma for the same measures. Diagnosis of CI was done using the Montreal cognitive assessment (MoCA) questionnaire while NM screening was performed using the 12-items General Health Questionnaire (GHQ-12) followed by MINI International Neuropsychiatry Interview (MINI). Results: We found five patients (19.2%) with mild TBI had CI and five patients (19.2%) had NM at 3 months. Only one patient (3.8%) persistently has CI at 6 months while the rest recovered. As for moderate TBI, 11 patients (39.3%) had CI and seven patients (25%) had NM at 3 months but none had persistent CI or NM at 6 months. Age (P < 0.05) and blood pressure were significant risks (P < 0.05) for CI and NM at 3 months. Conclusion: This study highlighted the importance of screening following mild and moderate TBI at 3 months and 6 months. Early recognition facilitates effective rehabilitation programmes planning hence improve prognosis in the future.

Disconnecting surgery at alveus and cornu ammonis of hippocampus, amygdala superficialis, and amygdala medial nuclei for epilepsy associated with attention deficit hyperactivity disorder.

The neural basis for epilepsy and attention deficit hyperactivity disorder (ADHD) is currently incompletely known. We reported a young girl with both epilepsy and ADHD, who had a calcified lesion in the right basolateral amygdalo-hippocampal region extending to the ventral striatum. The child underwent disconnecting surgery and biopsy of the lesion. Fascinatingly, the child's behavior changed immediately after the surgery from inattentive and impulsive to nearly normal behavior experiencing no more breakthrough seizures since after 3 years of surgery. The Schaltenbrand Wahren Brain Atlas revealed alveus, cornu ammonis, amygdala superficialis, and medium as the disconnected region in this surgery.

Role of the Neurons, Astrocytes and Particle-Wave Duality in Conventional Electromagnetic Field, Plasma Brain Dynamics and Quantum Brain Dynamics.

The brain is regarded as the most complex anatomical structure in the human body that executes various functions. The electromagnetic brainwaves or energy with its discrete network is commonly thought of as the sole contributor to various brain functions. However, the discrete pattern of the brain network seems insufficient to explain consciousness, binding problems in neural communication, brain heat, psychiatric manifestations and higher-order of thinking. Therefore, it seems that the brain must possess additional energy for it to have a much higher degree of functional freedom. Plasma brain dynamics (PBD) and quantum brain dynamics (QBD) are two hypothetical brain energies that have a strong scientific basis to exist together with the conventional brain electromagnetic energy. The presence of these energies may explain the puzzling brain functions, thus creating an opportunity to correct any abnormalities arising from them.

What are Your Eyes Revealing? The Contemporary Bedside Neuro-Ophthalmological Examination.

The neuro-ophthalmological evaluation is done to assess the integrity of cranial nerves II, III, IV, VI. This work does not intend to substitute the examination in a fully equipped ophthalmology suite. The aim of this manuscript is to describe bedside examination of the eye by using simple apparatus that are easily available. This work incorporates the usage of smartphone application, as smartphone is deemed an accessory in almost every resident's pocket during review of patients as a consult in the emergency department. However, the essence of traditional physical examination remains the fundamental. Understanding of neuroanatomy and neurophysiology of the eye and the central nervous system can enhance the clinician's performance at the bedside.