Mild Brain Research Articles

Quantitative proteomics of synaptosome S-nitrosylation in Alzheimer's disease.

Increasing evidence suggests that both synaptic loss and neuroinflammation constitute early pathologic hallmarks of Alzheimer's disease. A downstream event during inflammatory activation of microglia and astrocytes is the induction of nitric oxide synthase type 2, resulting in an increased release of nitric oxide and the post-translational S-nitrosylation of protein cysteine residues. Both early events, inflammation and synaptic dysfunction, could be connected if this excess nitrosylation occurs on synaptic proteins. In the long term, such changes could provide new insight into patho-mechanisms as well as biomarker candidates from the early stages of disease progression. This study investigated S-nitrosylation in synaptosomal proteins isolated from APP/PS1 model mice in comparison to wild type and NOS2-/- mice, as well as human control, mild cognitive impairment and Alzheimer's disease brain tissues. Proteomics data were obtained using an established protocol utilizing an isobaric mass tag method, followed by nanocapillary high performance liquid chromatography tandem mass spectrometry. Statistical analysis identified the S-nitrosylation sites most likely derived from an increase in nitric oxide (NO) in dependence of presence of AD pathology, age and the key enzyme NOS2. The resulting list of candidate proteins is discussed considering function, previous findings in the context of neurodegeneration, and the potential for further validation studies.

Neonatal hypoxic encephalopathy: Correlation between post-cooling brain MRI findings and 2 years neurodevelopmental outcome.

Objective:This study aims to evaluate the magnetic resonance imaging (MRI) brain patterns among hypoxic-ischemic encephalopathy (HIE) babies who underwent post-cooling MRI brain as well as to correlate the post-cooling brain scoring with patient's neurodevelopmental outcome at 2 years.Subjects and Methods:It was a retrospective cross sectional study carried out at a tertiary university hospital. Record of patients diagnosed with neonatal HIE from 2007 until 2016 who completed 72 h of cooling therapy and had MRI brain within 2 weeks of life were included in this study. A new scoring system by Trivedi et al. that emphasizes on subcortical deep gray matter and posterior limb internal capsule injury were utilized upon MRI assessment, using TW, T2W, and diffusion-weighted imaging (DWI) sequences. Cumulative MRI brain score was obtained and graded as none, mild, moderate, and severe brain injury. The MRI brain scoring was then correlated with patient's 2 years neurodevelopmental outcome using Fisher's Exact Test.Results:A total of 23 patients were eligible of which 19 term neonates were included. 13% of these neonates (n = 3) had mild MRI brain injury grading with 52.2% (n = 12) moderate and 34.8% (n = 8) severe. There was no significant correlation seen between MRI brain grading and developmental outcome at 2 years old (P > 0.05).Conclusion:There was no significant correlation between neonatal MRI brain injury grading and 2 years neurodevelopmental outcome. Nevertheless, the new MRI brain scoring by Trivedi et al. is reproducible and comprehensive as it involves various important brain structures, assessed from different MRI sequences.

Chronic traumatic encephalopathy: the nature, mechanisms and stages of development

The survey provides data on the history of discovery and the epidemiology of chronic traumatic encephalopathy, which can occur after a single or repeated mild traumatic brain injury. Chronic traumatic encephalopathy has a nearly century-long history and was first identified in boxing veterans. Initially, signs of progressive neurological disease (punch-drunk), which occurred after repeated multiple traumatic brain injury in boxers, were described. Other sport activities alongside with box, associated with repeated mild brain injuries may cause dementia and neurodegenerative diseases. That led to the use of the term “chronic traumatic encephalopathy” (CTE). The features of the disease are defined, namely, that it occurs many years after the injury and develops in very small percentage of persons experienced a head injury, and clinically it resembles such neurodegenerative disorders as Parkinson’s and Alzheimer’s diseases. The paper deals with the pathogenesis associated with the accumulation of beta amyloid, tau protein, the development of neuro-inflammation and immune-associated reactions, including intracerebral local and systemic immune processes. The review indicates the role of genetic susceptibility, resistance to injury, gender, physiological stress, environmental exposure and age in the development of CTE.The significance of immune responses and inflammation in the development of various forms of neurodegenerative diseases and CTE is widely recognized, but the mechanisms of the immunoprotective and immunodegenerative actions are still not well understood and require special experimental studies. The review notes different role of immune responses in the pathogenesis at certain stages of development of CTE.The protective and immunopathological mechanisms of chronic traumatic encephalopathy are analyzed in detail; three main periods of its development have been identified, and new approaches to the study and treatment have been outlined.

Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury

BackgroundTraumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. We hypothesized that TBI would lead to long-term changes in the transcriptional profile of microglial pathways associated with the development of subsequent neurologic impairment. Materials and methodsMale C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to Quantiseq 3′-biased RNA sequencing at 7, 30, and 90 d after TBI. K-means clustering on 396 differentially expressed genes was performed, and gene ontology enrichment analysis was used to determine corresponding enriched processes. ResultsDifferentially expressed genes in microglia exhibited four main patterns of expression over the course of TBI. In particular, we identified four gene clusters which corresponded to the host defense response, synaptic plasticity, lipid remodeling, and membrane polarization. ConclusionsTranscriptional profiling within individual populations of microglia after TBI remains a critical unmet research need within the field of TBI. This focused study identified several physiologic processes within microglia that may be associated with development of long-term neurologic impairment after TBI. These data demonstrate the capability of longitudinal transcriptional profiling to uncover potential cell-specific targets for the treatment of TBI.

Phase II Clinical Trial of Hippocampal-Sparing Whole Brain Irradiation and Simultaneous Integrated Boost Tomotherapy (SIB-TOMO) for Brain Metastases in Patients with Lung Cancer

To evaluate the clinical efficacy and feasibility of hippocampal-sparing whole brain irradiation and simultaneous integrated boost tomotherapy (SIB-TOMO) for brain metastases in patients with lung cancer. 39 patients with lung cancer receiving hippocampal-sparing whole brain irradiation and simultaneous integrated boost tomotherapy in National Cancer Centre/Cancer Hospital ,Chinese Academy of Medical Sciences between 2015 and 2019 were analyzed. All patients received brain MRI and with 1 to 10 brain metastatic lesions . The prescription dose of whole brain was 95% PTV brain 32.4(21.6∼40.0)Gy in 18(12∼20) fractions, The prescription dose of brain metastatic lesions was 95% PGTVBM 48.6(45.0∼60.0) Gy in 18 (15∼20) fractions ,and the limited dose of hippocampus was less than 15Gy .The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment and survival rate and brain metastasis rate were analyzed. As of February 15, 2019 , a total of 39 patients (median age 61 years )were treated with hippocampal-sparing whole brain irradiation and SIB-TOMO, the median follow-up was 13 months. The 1-year survival rate was 64.2%, and the median survival time was 15.6 months. Therapeutic effect of intracranial lesions after treatment as follows: CR:3 patients (7.6%); PR:12 patients (30.1%);SD: 9 patients (23.1%); PD: 10 patients (25.6%); 5 patients(12.8%) were not followed up or undergoing treatment. 8 patients (20.5%) had new extensive multiple brain metastases, but there was no metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was no significantly decreased. Hippocampal-sparing whole brain irradiation and simultaneous integrated boost tomotherapy (SIB-TOMO) for brain metastases in patients with lung cancer is feasible. It can obtain better local control rate for brain metastases lesions, reduce the probability of intracranial recurrence, and protect neurocognitive function.

Behavior, protein, and dendritic changes after model traumatic brain injury and treatment with nanocoffee particles

BackgroundTraumatic brain injury (TBI) is a widespread public health problem and a signature injury of our military in modern conflicts. Despite the long-term effects of even mild brain injuries, an effective treatment remains elusive. Coffee and several of its compounds, including caffeine, have been identified as having neuroprotective effects in studies of neurodegenerative disease. Given the molecular similarities between TBI and neurodegenerative disease, we have devised a study to test a nanocoffee extract in the treatment of a mouse model of mild TBI.ResultsAfter a single injury and two subsequent injections of nanocoffee, we identified treatment as being associated with improved behavioral outcomes, favorable molecular signaling changes, and dendritic changes suggestive of improved neuronal health.ConclusionsWe have identified coffee extracts as a potential viable multifaceted treatment approach to target the secondary injury associated with TBI.

Identifying an optimal epoch length for spectral analysis of heart rate of critically-ill infants

Background and objectiveTo identify the optimal epoch length for power spectral analysis of cardiac beat-to-beat intervals (BBi) in critically ill newborns. Materials and methodBBi of 49 term newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy with well-defined outcomes (good outcome (n = 28): no or mild brain injury and adverse outcome (n = 21): moderate or severe brain injury or death) served as test population. A power spectrum of BBi was calculated with an autoregressive model in three different epoch lengths: 2 min, 5 min, and 10 min. Spectral power was quantified in three different frequency bands: very low-frequency (0.016–0.04 Hz), low-frequency (0.05–0.25 Hz), and high-frequency (0.3–1 Hz). In each frequency band, the absolute power and the normalized power were calculated. Furthermore, standard deviation (SDNN) of BBi was calculated. These metrics were compared between the outcome groups with a receiver operator characteristic (ROC) analysis in 3-h windows. The ROC curve area >0.7 was regarded as a significant separation. ResultsThe absolute spectral powers in all three epoch lengths in all three frequency bands and SDNN distinguished the two outcome groups consistently for most time points. The spectral metrics calculated with a 2-min epoch length performed as well as the five- and 10-min epoch lengths (paired t−test P < 0.05). ConclusionSpectral analysis of BBi in 2-min epoch shows a similar discriminatory power as longer epoch lengths. A shorter epoch also has clinical advantages for translation into a continuous real-time bedside monitor of heart rate variability in the intensive care unit.

Response to Blast-like Shear Stresses Associated with Mild Blast-Induced Brain Injury

Toward the goal of understanding the pathophysiology of mild blast-induced traumatic brain injury and identifying the physical forces associated with the primary injury phase, we developed a system that couples a pneumatic blast to a microfluidic channel to precisely and reproducibly deliver shear transients to dissociated human central nervous system (CNS) cells, on a timescale comparable to an explosive blast but with minimal pressure transients. Using fluorescent beads, we have characterized the shear transients experienced by the cells and demonstrate that the system is capable of accurately and reproducibly delivering uniform shear transients with minimal pressure across the cell culture volume. This system is compatible with high-resolution, time-lapse optical microscopy. Using this system, we demonstrate that blast-like shear transients produced with minimal pressure transients and submillisecond rise times activate calcium responses in dissociated human CNS cultures. Cells respond with increased cytosolic free calcium to a threshold shear stress between 8 and 21 Pa; the propagation of this calcium response is a result of purinergic signaling. We propose that this system models, in vitro, the fundamental injury wave produced by shear forces consequent to blast shock waves passing through density inhomogeneity in human CNS cells.

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

Hypertension Exacerbates Cerebrovascular Oxidative Stress Induced by Mild Traumatic Brain Injury: Protective Effects of the Mitochondria-Targeted Antioxidative Peptide SS-31.

Traumatic brain injury (TBI) induces cerebrovascular oxidative stress, which is associated with neurovascular uncoupling, autoregulatory dysfunction, and persisting cognitive decline in both pre-clinical models and patients. However, single mild TBI (mTBI), the most frequent form of brain trauma, increases cerebral generation of reactive oxygen species (ROS) only transiently. We hypothesized that comorbid conditions might exacerbate long-term ROS generation in cerebral arteries after mTBI. Because hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive and spontaneously hypertensive rats (SHR) and assessed changes in cytoplasmic and mitochondrial superoxide (O2-) production by confocal microscopy in isolated middle cerebral arteries (MCA) 2 weeks after mTBI using dihydroethidine (DHE) and the mitochondria-targeted redox-sensitive fluorescent indicator dye MitoSox. We found that mTBI induced a significant increase in long-term cytoplasmic and mitochondrial O2- production in MCAs of SHRs and increased expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit Nox4, which were reversed to the normal level by treating the animals with the cell-permeable, mitochondria-targeted antioxidant peptide SS-31 (5.7 mg kg-1 day-1, i.p.). Persistent mTBI-induced oxidative stress in MCAs of SHRs was significantly decreased by inhibiting vascular NADPH oxidase (apocyinin). We propose that hypertension- and mTBI-induced cerebrovascular oxidative stress likely lead to persistent dysregulation of cerebral blood flow (CBF) and cognitive dysfunction, which might be reversed by SS-31 treatment.

The link between concussion and inflammation.

In their article “Acute elevation of serum inflammatory markers predicts symptom recovery after concussion,” Nitta and coauthors1 studied the connection between inflammation and head trauma. More specifically, they looked at the connection between inflammation and mild brain injury in American football players.

The Role of Potentially Malleable Factors in Post-Concussive Symptoms and Objective Cognitive Outcomes in Iraq and Afghanistan Veterans with History of Mild TBI

Abstract Objective We examined whether potentially malleable factors are associated with post-concussive symptoms (PCS) and cognition in Veterans with mild traumatic brain injury (mTBI) histories. Method Combat-exposed Iraq and Afghanistan Veterans with remote history of mTBI (N=48) completed a neuropsychological assessment and self-report questionnaires. Hierarchical linear regressions predicting PCS (Rivermead Post-Concussion Symptoms Questionnaire) and objective cognition included relevant demographic, injury, and psychiatric symptom variables in the first block and five malleable factors (TBI knowledge, self-efficacy, coping style, attribution of symptoms to mTBI, and uncommonly-endorsed symptoms [mild Brain Injury Atypical Symptoms (mBIAS) scale]) in the second block. Those with valid performance validity tests (n = 42) were included in the cognitive test analyses. Results With psychiatric symptoms and lifetime history of mTBIs entered first, malleable factors accounted for 14-17% of additional variance in PCS (p &lt; .001). Lower self-efficacy (B = -.53, p &lt; .001) and greater attribution of symptoms to mTBI (B = .21, p = .05) were associated with higher PCS, whereas an approach style of coping, TBI knowledge, and the mBIAS were not (p’s&gt;.05). Regarding cognition, the malleable factors block accounted for 25% of additional variance in executive functioning (p = .04) with premorbid intelligence entered first. Specifically, higher mBIAS scores significantly predicted worse executive functioning (B = -.50, p = .004). No significant associations emerged when predicting attention/processing speed or memory (p’s&gt;.05). Conclusions In combat-exposed Veterans with mTBI histories, potentially malleable factors contribute to clinical outcomes even after accounting for psychiatric symptoms. These malleable features are prime targets to augment during psychoeducation (e.g., uncommonly-endorsed symptoms, attribution of symptoms) and cognitive behavioral therapy (e.g., self-efficacy) in the context of chronic PCS.

Protein S100 sebagai Petanda Kerusakan Otak pada Cedera Otak Ringan dan Sedang

Brain injury becomes worldwide public health issue since it may cause disability and mortality. The diagnosis of brain injury is made based on clinical neurology examination, and CT scan or MRI. Serum S100 protein examination in mild and moderate brain injury patients is needed to detect and evaluate the presence of post traumatic brain injury. This research subject is healthy people and patients with mild and moderate brain injury, based on their GCS grade, clinical neurologic examination, and CT scan. On these patients, the blood for S100 protein examination is taken at admission, 6 and 24 hours post trauma, and last day of hospitalization. Examination of a serum S100 protein is conducted using ECLIA method. There is significant difference (p value 0,001) in mild or moderate brain injury patients in all serum S100 protein. The peak level of serum S100 protein reached at 6 hours post trauma. Serum S100 protein in moderate brain injury patients at admission is significantly higher than the mild ones, and serum S100 protein in mild brain injury patients is also significantly higher than healthy people. Serum S100 protein can be used as brain injury biomarker to detect and evaluate the presence of post traumatic brain injury.

Transcranial Magnetic Stimulation: A Tool for Quantifying Neurophysiological Changes in the Brain Following Concussion Injury in Sports

(1) Background: Sport-related concussion is a growing public health concern. Defined as a functional injury, concussion is characterised by a constellation of signs and symptoms. However, clinical imaging methods do not reveal any structural damage. Recently, neurophysiological techniques such as transcranial magnetic stimulation (TMS) are being applied to quantify functional changes following concussion, both from an acute perspective, but also to investigate chronic changes associated with concussion injuries. The aim of this review paper is to present a state of art review on studies using TMS to assess concussion. (2) Methods: Systematic searching of relevant databases for peer-reviewed literature between 1985 to present day. A qualitative synthesis of studies attaining the inclusion criteria was conducted. (3) Results: Twenty-two studies met the inclusion criteria. TMS study checklist rated studies of moderate to high methodological quality. Nine studies reported short-term data following concussion, while 13 studies reported long-term changes in those with persistent symptoms or chronic changes with history of head trauma. Majority of studies reported alterations or abnormalities in intracortical inhibition. (4) Conclusions: This review demonstrates that TMS is a reliable and sophisticated technique to measure the neurophysiology of concussion. While further studies are required to establish effectiveness TMS as a clinical tool for mild brain injury, the potential of TMS to reliably quantify cortical activity offers exciting opportunities to provide objective measures for concussion diagnosis and prognosis.

MILD TRAUMATIC BRAIN INJURY INDUCES VASCULAR IMPAIRMENT AND AMYLOID CLEARANCE DEFICITS IN MICE

TBI is considered the most robust environmental risk factor for Alzheimer's disease (AD), how exactly cerebrovascular impairment of TBI (especially mTBI) influences AD pathogenesis is still a big challenge in research field. Close-head mild brain injury mouse model was established; In vivo micro-dialysis and interstitial fluid (ISF) amyloid β (Aβ) half-life determination in TBI-affected hemisphere compared to unaffected contralateral; Immunohistochemistry and Cognitive impairment evaluation were performed after TBI. mTBI induced Blood-brain barrier dysfunction and cerebral blood flow reduction, and it also altered structural integrity of perivascular space and basement membrane, which contributed to the accelerated amyloid pathologies and cognitive impairment by impairing the brain β-amyloid (Aβ) clearance through vascular pathways. Vascular impairment plays a key role in mTBI pathogenesis and which is a potential risk for accelerating the progression of AD.

Clinical significance of posttraumatic intracranial hemorrhage in clinically mild brain injury: a retrospective cohort study.

Much attention has been focused on management of severe traumatic brain injury (TBI); however, comparatively little is known about management of traumatic hemorrhage in clinically mild TBI. We aimed to clarify the role of clinical observation and repeat radiography for patients with mild TBI and abnormal findings on initial computed tomography (CT) of the head. We queried the neurotrauma database of the Ontario Trauma Registry and the Sunnybrook institutional database to identify patients with CT findings of a traumatic hemorrhage or calvarial fracture between November 2014 and December 2016. Exclusionary criteria were age less than 16 years, Glasgow Coma Scale (GCS) score less than 13, anticoagulant use, bleeding diathesis and midline shift greater than 5 mm. The primary outcome was the need for neurosurgical intervention. A total of 607 patients were included. Most (374 [61.6%]) had a GCS score of 15; 185 (30.5%) and 48 (7.9%) had a GCS score of 14 and 13, respectively. Five patients (0.8%) required surgical intervention, all within the first 72 hours, owing to clinical deterioration with subsequently demonstrated radiographic evidence of expanding hemorrhage. Most patients (506 [83.4%]) had routine repeat imaging, without documented change in their neurologic status. The majority of patients in our cohort had repeat imaging, which did not influence surgical management, at substantial cost to the health care system. The findings suggest the need to reevaluate repeat imaging protocols for this subset of patients with TBI.

Single Mild Traumatic Brain Injury Induces Persistent Disruption of the Blood-Brain Barrier, Neuroinflammation and Cognitive Decline in Hypertensive Rats.

Traumatic brain injury (TBI) induces blood-brain barrier (BBB) disruption, which contributes to secondary injury of brain tissue and development of chronic cognitive decline. However, single mild (m)TBI, the most frequent form of brain trauma disrupts the BBB only transiently. We hypothesized, that co-morbid conditions exacerbate persistent BBB disruption after mTBI leading to long term cognitive dysfunction. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive Wistar and spontaneously hypertensive rats (SHR) and we assessed BBB permeability, extravasation of blood-borne substances, neuroinflammation and cognitive function two weeks after trauma. We found that mTBI induced a significant BBB disruption two weeks after trauma in SHRs but not in normotensive Wistar rats, which was associated with a significant accumulation of fibrin and increased neuronal expression of inflammatory cytokines TNFα, IL-1β and IL-6 in the cortex and hippocampus. SHRs showed impaired learning and memory two weeks after mild TBI, whereas cognitive function of normotensive Wistar rats remained intact. Future studies should establish the mechanisms through which hypertension and mild TBI interact to promote persistent BBB disruption, neuroinflammation and cognitive decline to provide neuroprotection and improve cognitive function in patients with mTBI.

Comparing two proposed protocols to test the oblique response of cycling helmets to fall impacts

In cycling, oblique head impacts from a fall cause rotational motion of a cyclist’s head and it is rotational kinematics that are most commonly associated with mild and severe brain injuries. This study aims to compare the head kinematics and brain strain response between two oblique test protocols for simulating fall impact events in cycling. (1) The Angular Launched Impact (ALI) protocol simulates a head impact for realistic and typical falling events in cycling such as falling over the bicycle handle bars or laterally falling, and (2) EN13087-11 is a currently proposed standard test that simulates a head impact from a vertical fall onto an angled surface. EN13087-11 reported greater rotational head kinematics and brain tissue strain than occurs in the more frequent and realistic falling events simulated by the ALI. Differences in response are attributed to the different vector of impact forces associated with the ALI and EN13087-11. When considering how best to test a helmet under oblique impact conditions, it is recommended that a certification test should closely mimic real-world kinematics of cycling accidents.

Treatable cause of hereditary spastic paraplegia: eight cases of combined homocysteinaemia with methylmalonic aciduria.

Combined homocysteinemia with methylmalonic aciduria (MMA/HCY) are genetic disorders of intracellular cobalamin (cbl) transport and processing that cause downstream deficiencies in methylcobalamin and adenosylcobalamin. Untreated disease is characterized biochemically by methylmalonic aciduria and hyperhomocysteinemia, while the clinical features are variable. When spastic paraplegia (SP) dominates, it is difficult to differentiate from hereditary spastic paraplegia (HSP). Clinical, biochemical and imaging features were reviewed in eight patients with MMA/HCY that mimicked HSP. Seven males and one female were enrolled. The median onset age was 13years old (range 7-26years old). The median time delay of diagnosis was 20.5months (range 2-60months). Spastic gait was the first symptom in four patients, while the other four patients presented with chronic emotional abnormalities or cognitive impairment. The main clinical manifestation was SP, and other neurological symptoms included cognitive impairment (5/8), spastic dysuria (3/8), personality change and depression (3/8), ataxia (2/8), seizures (2/8), limb numbness (2/8), and developmental delay (2/8). When patients were diagnosed, the mean serum homocysteine level, the methylmalonic acid level in urine, the serum propionylcarnitine (C3) level and the ratios of C3-to-acetylcarnitine (C2) and free carnitine (C0) were all dramatically elevated. Cranial MRIs showed nothing remarkable except mild brain atrophy. All spinal MRIs were normal except for case 8. Definite compound heterozygous mutations in MMACHC were detected in five cases. Follow-up indicated partial improvement in all the patients after intramuscular cbl, oral betaine and folate, supporting the diagnosis of MMA/HCY. Our data highlight the need for extensive investigation of intracellular cbl transport and processing, when spastic paraparesis is a prominent component of the clinical picture. Testing for urine methylmalonic acid and serum homocysteine levels is a simple but critical approach in suspected cases. Genetic testing, especially for MMACHC gene mutations, is needed. Raising awareness of this disorder could result in the timely initiation of targeted treatment, which may significantly improve patient outcomes.

Galveston Orientation &amp; Amnesia Test (GOAT) Score to Assess Degree of Severity in Mild Brain Injury

ABSTRACT&#x0D; Introduction. Most of the minor brain injuries will heal as usual, but around 10-15% even 58% experience a continuous or chronic disorder known as post-traumatic syndrome. Post traumatic syndrome has manifested in the first 7 days where the quality of life of patients has decreased significantly. This study aimed to assess post traumatic amnesia in minor traumatic brain injuries in Emergency, Inpatient, and Outpatient RSUP. Moh. Hoesin Palembang using GOAT to determine the classification of minor brain injuries based on post traumatic amnesia and determine the prognosis of mild traumatic brain injury according to the presence or absence of post-traumatic syndrome.&#x0D; Methods. This research is an analytic survey with cross sectional approach. The subjects of this study were patients who were admitted and treated at the Emergency Department, Inpatient Installation, and Outpatient Installation (Polyclinic) at the RSUP dr. Mohammad Hoesin Palembang with mild traumatic brain injury and met the inclusion criteria. Inclusion criteria were patients who present with mild brain injury (GCS EMV score 13-15), age ≥ 15 years, the time of the event lasts longer ≤ 24 hours, agreeing and signing informed consent&#x0D; Results. Amnesia assessment uses the GOAT (Galveston Orientation and Amnesia Test) which is divided into three categories, namely PTA free if results&gt; 75, and still in amnesia period if results &lt;66 and 66-75 are doubtful. Based on GOAT assessment the number of Amnesia respondents was 23 people (42.6%) with an average GOAT score or score of 67.6.&#x0D; Conclusion. There is a significant relationship between the incidence of amnesia and post-traumatic syndrome using the GOAT Score assessment.