Innovations in detecting skull fractures: A review of computer-aided techniques in CT imaging.

BACKGROUND/INTRODUCTION: Traumatic brain injury (TBI) remains a leading cause of disability and mortality, with skull fractures being a frequent and serious consequence. Accurate and rapid diagnosis of these fractures is crucial, yet current manual methods via cranial CT scans are time-consuming and prone to error. METHODS: This review paper focuses on the evolution of computer-aided diagnosis (CAD) systems for detecting skull fractures in TBI patients. It critically assesses advancements from feature-based algorithms to modern machine learning and deep learning techniques. We examine current approaches to data acquisition, the use of public datasets, algorithmic strategies, and performance metrics RESULTS: The review highlights the potential of CAD systems to provide quick and reliable diagnostics, particularly outside regular clinical hours and in under-resourced settings. Our discussion encapsulates the challenges inherent in automated skull fracture assessment and suggests directions for future research to enhance diagnostic accuracy and patient care. CONCLUSION: With CAD systems, we stand on the cusp of significantly improving TBI management, underscoring the need for continued innovation in this field.

Study of the Practice of Surgical Antibiotic Prophylaxis Use for Elective Neurosurgical Cases in a Tertiary Hospital and Understanding the Rationale.

BACKGROUND: This study aims to evaluate the adherence to surgical antibiotic prophylaxis (SAP) guidelines in elective neurosurgery and assess the impact on surgical site infection (SSI) rates in a tertiary teaching hospital in Malaysia. METHOD: A retrospective review was conducted on patients who underwent elective neurosurgical procedures from January 1, 2021, to December 31, 2021, in a 1600-bed tertiary teaching hospital. The study assessed adherence to national and hospital SAP guidelines, focusing on the choice of antibiotic, dosage, timing, and duration. Additionally, a survey was conducted among neurosurgeons to evaluate their knowledge, attitudes and practices (KAP) regarding SAP. RESULT: Out of 202 patients included, there was a 99% compliance rate with antibiotic choice and 69.8% with the antibiotic duration. The SSI rate was identified at 6.4%. The KAP survey highlighted a strong awareness of SAP guidelines among surgeons, albeit with variations in practice, particularly in antibiotic duration and choice of antibiotics. CONCLUSION: While there is high adherence to the correct choice of antibiotic for SAP in elective neurosurgery, there are gaps in compliance with the recommended duration of antibiotic use. The study highlights the need for targeted interventions to improve adherence to SAP guidelines, which could potentially reduce the incidence of SSI in neurosurgery. Ongoing education and auditing are essential to optimize SAP practices and enhance patient outcomes in neurosurgery.

The use of intraoperative CT navigation for posterior cervical spine foraminotomy.

OBJECTIVES: Posterior cervical foraminotomy is a surgical procedure used to treat unilateral cervical radiculopathy. It provides direct decompression of the nerve root without the necessity of fusion while maintaining cervical mobility. With the advancement in image-guidance technology and minimal access techniques, intra-operative CT has provided a safer, more accurate instrumentation placement with less radiation exposure to operative staff and provides better anatomical visualization quality compared to traditional intra-operative imaging techniques. This case series aims to address the applications of advanced image guidance in posterior cervical foraminotomy and describe the nuances. METHOD: A technical report on a series of seven cases on intraoperative CT navigation for posterior cervical foraminotomy surgery. Posterior cervical foraminotomy was performed in all patients under CT guided navigation system without an image intensifier. In one case after the foraminotomy, the extruded disc was carefully removed by gentle retraction. RESULT: From 1 January 2020 to 31 December 2021, a total of seven patients with nine cervical foraminotomy procedures were performed using the aid of CT-guided navigation. The series comprised five women and two men whose mean age was 50.6 years. In all cases, the radiculopathy symptoms were diminished significantly. There were no cases of instability on the dynamic cervical radiograph. There were no complications during the surgical procedure. CONCLUSION: The navigation also allows the surgeon to localise the index level accurately and appraise the adequacy of the intended decompression in three planes of the CT scan image. The ability to perform accurate spine navigation would be the precursor for robotic spinal surgery.

Development of a Novel Retrospective Instrument to Gauge the General Well-Being Index and Lumbar-Specific Disability Index Post-intervention in Lumbar Degenerative Disease.

STUDY DESIGN: Validation of a novel retrospective comparative questionnaire to obtain post-intervention outcome data in patients with lumbar degenerative spinal disease. PURPOSE: Acquiring prospective outcome data for spinal intervention is not frequently feasible in resource-depleted units in certain developing countries. Therefore, a novel retrospective instrument is being validated for clinical use, which can act as a standard method to describe outcomes when data are retrospectively collected. OVERVIEW OF LITERATURE: The standard method of collecting outcome data after a spinal intervention has been prospective, including the Oswestry Disability Index, Roland-Morris Questionnaire, and Short Form-36. The process of content validation and reliability of the novel retrospective spinal questionnaires is highlighted. METHODS: Questionnaire items were created based on a literature review, followed by a process of content validation by experts and modification based on expert opinions to achieve an acceptable content validity index (CVI, 0.70-1.00). To calculate factor loadings for each question, a pilot test was subsequently conducted from a pool of patients who underwent lumbar spine surgeries for degenerative spine diseases. RESULTS: All items achieved a CVI of >0.85 for both relevancy and clarity and were successfully validated after appropriate corrections were made before the second validation phase. Except for Q9 and Q10, which showed low-loading factors in the pooled sample, the remainder of the items had acceptable loading factors across different subgroups, indicating that the passage of time did not affect the results of the exploratory factor analysis. CONCLUSIONS: The retrospective questionnaire that encompasses the general well-being and lumbar-specific symptoms is a valid and reliable instrument to provide an impression of the outcome after intervention in a patient with a degenerative lumbar spinal disease. A summative score will indicate the overall outcome.

Postnatal Posterior Fossa Arachnoid Cyst: A Developmental Etiology to Be Considered.

Intracranial arachnoid cyst is the most common cystic congenital anomaly in the brain. In this study, we discuss a pregnancy that had serial fetal ultrasound scans throughout the pregnancy and a fetal anomaly scan at 24 weeks of gestation that was normal. The child was born healthy with normal development, but 12 months onward the head began to enlarge. The magnetic resonance imaging of the brain showed a large posterior fossa arachnoid cyst with hydrocephalus. We discuss the postulation to explain this pathogenesis of the cyst. This case highlights that not all symptomatic arachnoid cysts are congenital despite the manifestation being as early as infancy.

Survey on Untethering of the Spinal Cord and Urological Manifestations among Spina Bifida Patients in Malaysia.

The incidence and severity of urinary tract infections (UTIs) due to spina bifida is poorly understood in Malaysia. Tethering of the spinal cord is a pathological fixation of the cord in the vertebral column that can result in neurogenic bladder dysfunction and other neurological problems. It occurs in patients with spina bifida, and the authors of this study sought to investigate the impact of untethering on the urological manifestations of children with a tethered cord, thereby consolidating a previously known understanding that untethering improves bladder and bowel function. Demographic and clinical data were collected via an online questionnaire and convenient sampling techniques were used. A total of 49 individuals affected by spina bifida participated in this study. UTIs were reported based on patients' observation of cloudy and smelly urine (67%) as well as urine validation (60%). UTI is defined as the combination of symptoms and factoring in urine culture results that eventually affects the UTI diagnosis in spina bifida individuals irrespective of CISC status. Furthermore, 18% of the respondents reported being prescribed antibiotics even though they had no history of UTI. Therefore, indiscriminate prescription of antibiotics by healthcare workers further compounds the severity of future UTIs. Employing CISC (73%) including stringent usage of sterile catheters (71%) did not prevent patients from getting UTI. Overall, 33% of our respondents reported manageable control of UTI (0-35 years of age). All individuals below the age of 5 (100%, n = 14) were seen to have improved urologically after the untethering surgery under the guidance of the Malaysia NTD support group. Improvement was scored and observed using KUB (Kidneys, Ureters and Bladder) ultrasound surveillance before untethering and continued thereafter. Spina bifida individuals may procure healthy bladder and bowel continence for the rest of their lives provided that neurosurgical and urological treatments were sought soon after birth and continues into adulthood.

Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia.

BACKGROUND: A higher incidence of pediatric intracranial germ cell tumors (iGCTs) in Asian countries compared with Western countries has been reported. In Malaysia, the literature regarding pediatric iGCTs have been nonexistent. The aim of this study was to review the management, survival, and long-term outcomes of pediatric iGCTs at a single tertiary center in Malaysia. PATIENTS AND METHODS: We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017. RESULTS: Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status. CONCLUSIONS: The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.

Conduct of neuro-oncology multidisciplinary team meetings and closing the "gaps" in the clinical management of childhood central nervous system tumors in a middle-income country.

PURPOSE: Multidisciplinary team meetings (MDTMs) are essential in the clinical management of pediatric central nervous system (CNS) tumors. Evaluations of the impact of MDTMs on childhood CNS tumors and clinicians' perspectives on their effectiveness are scarce. METHODS: We retrospectively reviewed the clinical data of pediatric patients (aged <18 years) with CNS tumors diagnosed and treated in the Pediatric Hematology-Oncology Division at the University Malaya Medical Center from 2008 to 2019. We also conducted a web-based survey of the core members of the multidisciplinary team to evaluate the impact of the MDTMs. RESULTS: During the pre-MDTM era (2008-2012), 29 CNS tumors were diagnosed and treated, and during the MDTM era (2014-2019), 49 CNS tumors were diagnosed and treated. The interval for histologic diagnosis was significantly shorter during the MDTM era (p=0.04), but the interval from diagnosis to chemotherapy or radiotherapy and the 5-year overall survival of the 78 patients did not improve (62.1% ± 9.0% vs. 68.8% ± 9.1%; p=0.184). However, the 5-year overall survival of patients with medulloblastoma or rare tumors significantly improved in the MDTM era (p=0.01). Key factors that contributed to delayed treatment and poor outcomes were postoperative complications, the facility's lack of infrastructure, poor parental education about early treatment, cultural beliefs in alternative medicine, and infection during chemotherapy. Eighteen clinicians responded to the survey; they felt that the MDTMs were beneficial in decision-making and enhanced the continuity of coordinated care. CONCLUSION: MDTMs significantly reduced the diagnostic interval and improved the overall outcomes. However, delayed treatment remains a major challenge that requires further attention.

Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma.

INTRODUCTION: Malignant astrocytomas are composed of heterogeneous cell populations. Compared to grade IV glioblastoma, low-grade astrocytomas have more differentiated cells and are associated with a better prognosis. Therefore, inducing cellular differentiation to alter the behaviour of high-grade astrocytomas may serve as a therapeutic strategy. The nuclear factor one (NFI) transcription factors are essential for normal astrocytic differentiation. Here, we investigate whether family members NFIA and NFIB act as effectors of cellular differentiation in glioblastoma. METHODS: We analysed expression of NFIA and NFIB in mRNA expression data of high-grade astrocytoma and with immunofluorescence co-staining. Furthermore, we induced NFI expression in patient-derived subcutaneous glioblastoma xenografts via in vivo electroporation. RESULTS: The expression of NFIA and NFIB is reduced in glioblastoma as compared to lower grade astrocytomas. At a cellular level, their expression is associated with differentiated and mature astrocyte-like tumour cells. In vivo analyses consistently demonstrate that expression of either NFIA or NFIB is sufficient to promote tumour cell differentiation in glioblastoma xenografts. CONCLUSION: Our findings indicate that both NFIA and NFIB may have an endogenous pro-differentiative function in astrocytomas, similar to their role in normal astrocyte differentiation. Overall, our study establishes a basis for further investigation of targeting NFI-mediated differentiation as a potential differentiation therapy.

Cranial neural tube defect after trimethoprim exposure.

OBJECTIVES: The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation. RESULTS: Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%, *P < 0.0001), in all litters. The TELSE tablet-treated females subsequently given folic acid did not result in pregnancies despite there being evidence of possible resorption. Furthermore, after multiple rounds of mating which did not yield viable pregnancies, eventually, 2 embryos with exencephaly were harvested in a litter of 6 at 0.05% w/v pure trimethoprim once. The use of trimethoprim, a folic acid antagonist, peri-conceptionally increased the risk of exencephaly in the mouse.

Panel of serum protein biomarkers to grade the severity of traumatic brain injury.

The Glasgow Coma Scale (GCS), which classifies patients into mild, moderate or severe traumatic brain injury (TBI), is a system used to prioritize treatment and prognosticate the severity of head injury. In this study, sera of patients with various stages of TBI, as well as control subjects, were analyzed to screen for proteins that may be used to complement the GCS system. By subjecting pooled serum samples to iTRAQ analysis for quantitative comparison of protein abundance, and attesting their altered levels using ELISA, we have detected increased levels of serum amyloid A, C-reactive protein, leucine-rich alpha-2-glycoprotein, lipopolysaccharide-binding protein, fibronectin, vitronectin and alpha-1-antichymotrypsin in patients across all strata of TBI relative to the controls. However, kininogen was decreased only in moderate and severe TBI, whereas apolipoprotein E and zinc-alpha-2-glycoprotein were only increased in severe TBI. Hence, we propose a panel of serum biomarkers, which if analyzed within 24 h of the injury, can be used to diagnose patients with TBI into mild, moderate or severe stratification objectively, thus complementing the traditional GCS.

Crouzon Syndrome: A Case Series of Craniomaxillofacial Distraction Osteogenesis for Functional Rehabilitation.

Crouzon syndrome (CS) is the most common craniosynostosis syndrome and requires a comprehensive management strategy for the optimization of care and functional rehabilitation. This report presents a case series of 6 pediatric patients diagnosed with CS who were treated with distraction osteogenesis (DO) to treat serious functional issues involving severe orbital proptosis, an obstructed nasopharyngeal airway, and increased intracranial pressure (ICP). Three boy and 3 girls were 8 months to 6 years old at the time of the operation. The mean skeletal advancement was 16.1 mm (range, 10 to 27 mm) with a mean follow-up of 31.7 months (range, 13 to 48 months). Reasonable and successful outcomes were achieved in most patients as evidenced by adequate eye protection, absence of signs and symptoms of increased ICP, and tracheostomy tube decannulation except in 1 patient. Complications were difficult fixation of external stabilizing pins in the distraction device (n = 1) and related to surgery (n = 4). Although DO can be considered very technical and can have potentially serious complications, the technique produces favorable functional and clinical outcomes in treating severe CS.

Intractable intraoperative brain herniation secondary to tension pneumocephalus: a rare life-threatening complication during drainage of subdural empyema / Herniação cerebral intratável secundária a pneumoencéfalo hipertensivo no intraoperatório: uma complicação rara com risco para a vida durante a drenagem de empiema subdural

Abstract Tension pneumocephalus is rare but has been well documented following trauma and neurosurgical procedures. It is a surgical emergency as it can lead to neurological deterioration, brainstem herniation and death. Unlike previous cases where tension pneumocephalus developed postoperatively, we describe a case of intraoperative tension pneumocephalus leading to sudden, massive open brain herniation out of the craniotomy site. The possible causative factors are outlined. It is imperative to rapidly identify possible causes of acute intraoperative brain herniation, including tension pneumocephalus, and institute appropriate measures to minimize neurological damage.

Resumo O pneumoencéfalo hipertensivo é raro, mas foi bem documentado após trauma e procedimentos neurocirúrgicos. Trata-se de uma emergência cirúrgica porque pode levar à deterioração neurológica, herniação do tronco cerebral e morte. Ao contrário de casos anteriores, nos quais o pneumoencéfalo hipertensivo se desenvolveu no pós-operatório, descrevemos um caso de pneumoencéfalo hipertensivo desenvolvido no período intraoperatório que levou a uma herniação cerebral súbita, maciça e aberta para fora do local da craniotomia. Os possíveis fatores causais são destacados. É imperativo identificar rapidamente as possíveis causas da herniação cerebral aguda no intraoperatório, incluindo o pneumoencéfalo hipertensivo, e instituir medidas apropriadas para minimizar os danos neurológicos.

The Prevalence and Distribution of Spina Bifida in a Single Major Referral Center in Malaysia.

BACKGROUND: The aim of this study is to review the medical history of patients with spina bifida, encompassing both aperta and occulta types born between the years 2003 until 2016, spanning a 13-year time period. We assessed each patient and maternal parent information, details of the defects, and conditions associated with the primary defect. We also include information on patients' ambulation and education level (where available). METHODS: Data from the Department of Patient Information University of Malaya Medical Centre (UMMC), Malaysia was captured from spina bifida patients (ICD10: Q05 spina bifida). Data involved patients referred to UMMC between 2003 and 2016 and/or born in UMMC within that particular time frame. We filtered and extracted the information according to the data of clinical examination, medical review, and social history provided in the medical records. RESULTS: A total of 86 patient records with spina bifida were analyzed. Spina bifida prevalence rate in this study ranged from 1.87 to 8.9 per 1,000 live births depending on weightage. We note that ethnicity was a factor whereby the highest numbers of spina bifida were from Malays (n = 36, 41.86%), followed by equal numbers of Chinese and Indians (n = 24, 27.91%). The highest number of diagnoses reported was myelomeningocele type-spina bifida (n = 39, 45.35%). The most common site of the spina bifida lesion was located at the lumbar region irrespective of aperta or occulta types (n = 23, 26.74%). Data on other associated phenotypes of spina bifida such as hydrocephalus and encephalocele was also captured at 37.21% (n = 32) and 1.16% (n = 1), respectively. In terms of mobility, 32.84% (n = 22/67) of patients between the ages 4 and 16 years old were found to be mobile. As many as 36.07% of patients ranging from 5 to 16 years of age (n = 22/61) received formal education ranging from preschool to secondary school. CONCLUSION: The prevalence of spina bifida in UMMC is as according to international statistics which is in the range of 0.5-10 per 1,000 live births. Majority of the reported cases were males, Malays, full term babies, and of the myelomeningocele phenotype located at the lumbar region.

Challenges of Treating Childhood Medulloblastoma in a Country With Limited Resources: 20 Years of Experience at a Single Tertiary Center in Malaysia.

PURPOSE: Pediatric medulloblastoma (MB) treatment has evolved over the past few decades; however, treating children in countries with limited resources remains challenging. Until now, the literature regarding childhood MB in Malaysia has been nonexistent. Our objectives were to review the demographics and outcome of pediatric MB treated at the University Malaya Medical Center between January 1994 and December 2013 and describe the challenges encountered. METHODS: Fifty-one patients with childhood MB were seen at University Malaya Medical Center. Data from 43 patients were analyzed; eight patients were excluded because their families refused treatment after surgery. RESULTS: Headache and vomiting were the most common presenting symptoms, and the mean interval between symptom onset and diagnosis was 4 weeks. Fourteen patients presented with metastatic disease. Five-year progression-free survival (± SE) for patients ≥ 3 years old was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) in the high-risk group and 68.6% ± 18.6% (95% CI, 40.3% to 100%) in the average-risk group, and 5-year overall survival (± SE) in these two groups was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) and 58.3% ± 18.6% (95% CI, 31.3% to 100%), respectively. Children younger than 3 years old had 5-year progression-free and overall survival rates (± SE) of 47.6% ± 12.1% (95% CI, 28.9% to 78.4%) and 45.6% ± 11.7% (95% CI, 27.6% to 75.5%), respectively. Time to relapse ranged from 4 to 132 months. Most patients who experienced relapse died within 1 year. Febrile neutropenia, hearing loss, and endocrinopathy were the most common treatment-related complications. CONCLUSION: The survival rate of childhood MB in Malaysia is inferior to that usually reported in the literature. We postulate that the following factors contribute to this difference: lack of a multidisciplinary neuro-oncology team, limited health care facilities, inconsistent risk assessment, insufficient data in the National Cancer Registry and pathology reports, inadequate long-term follow-up, and cultural beliefs leading to treatment abandonment.

A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas.

The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.

[Intractable intraoperative brain herniation secondary to tension pneumocephalus: a rare life-threatening complication during drainage of subdural empyema]. / Herniação cerebral intratável secundária a pneumoencéfalo hipertensivo no intraoperatório: uma complicação rara com risco para a vida durante a drenagem de empiema subdural.

Tension pneumocephalus is rare but has been well documented following trauma and neurosurgical procedures. It is a surgical emergency as it can lead to neurological deterioration, brainstem herniation and death. Unlike previous cases where tension pneumocephalus developed postoperatively, we describe a case of intraoperative tension pneumocephalus leading to sudden, massive open brain herniation out of the craniotomy site. The possible causative factors are outlined. It is imperative to rapidly identify possible causes of acute intraoperative brain herniation, including tension pneumocephalus, and institute appropriate measures to minimize neurological damage.

Neuropsychological Outcomes in Patients with Complicated Versus Uncomplicated Mild Traumatic Brain Injury: 6-Month Follow-Up.

OBJECTIVE: To compare the extent of persistent neuropsychological impairment in patients with complicated mild traumatic brain injury (mTBI) and those with uncomplicated mTBI. METHODS: Sixty-one patients with mTBI (Glasgow Coma Scale score 13-15) were recruited prospectively, categorized according to baseline computed tomography findings, and subjected to neuropsychological assessment at initial admission (n = 61) as well as at a 6-month follow-up (n = 30). The paired t test, Cohen's d effect size calculation, and repeated-measures analysis of variance were used to establish the differences between the 2 groups in terms of neuropsychological performance. RESULTS: A trend toward poorer neuropsychological performance among the patients with complicated mTBI was observed during admission; however, performance in this group improved over time. In contrast, the uncomplicated mTBI group showed slower recovery, especially in tasks of memory, visuospatial processing, and executive functions, at follow-up. CONCLUSIONS: Our findings suggest that despite the broad umbrella designation of mTBI, the current classification schemes of injury severity for mild neurotrauma should be revisited. They also raise questions about the clinical relevance of both traumatic focal lesions and the absence of visible traumatic lesions on brain imaging studies in patients with milder forms of head trauma.

Missense Mutation of Brain Derived Neurotrophic Factor (BDNF) Alters Neurocognitive Performance in Patients with Mild Traumatic Brain Injury: A Longitudinal Study.

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen's d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers.