Lawrence S. Chin

Chronic traumatic encephalopathy – neuropathology in athletes and war veterans

Abstract Objective: The neuropathologic findings of chronic traumatic encephalopathy (CTE) were first described almost 40 years after the first clinical reports. We reviewed the literature and describe the neuropathological findings seen primarily in professional athletes and more recently, in war veterans. Methods: We reviewed the literature of CTE concentrating on references that focused on the correlation of clinical findings with the neuropathologic changes. The pathobiology and proposed mechanisms of injury are described. Diagnostic modalities and various diagnostic criteria of CTE are reviewed. Results: We are beginning to understand the neuropathologic basis of CTE, which appears to be a consequence of repetitive mild brain injuries. There appear to be reproducible criteria for the post-mortem diagnosis of CTE and the neuropathologic findings are becoming more widely accepted. More research is required to elucidate the risk factors that predispose athletes and war veterans to CTE. There is also a need for more diagnostic markers and a method to assess CTE in patients prior to death. The neuropathologic findings of a progressive tauopathy including the presence of numerous neurofibrillary tangles (NFTs), rare neuritic plaques, and widespread expression of TDP-43 (transactive response [TAR] DNA binding protein 43) also require further study. Discussion: The potential prevalence of CTE, as well as the vulnerable populations involved, makes research into this topic crucial. Currently, a comprehensive neurological exam, neuropsychiatric assessment, and standard radiographic techniques such as conventional MRI are the mainstay of diagnosis. There is a pressing need for the prevention of CTE and the development of non-invasive diagnostic tests in order to develop therapies that may be of clinical use to athletes and blast injury veterans during their lifetimes.

Treatment of penetrating nonmissile traumatic brain injury. Case series and review of the literature

INTRODUCTION Penetrating traumatic brain injuries (TBIs), with the exception of gunshot wounds, are relatively rare occurrences and affect all ages. Clinical presentation varies depending on the mechanism of the injury. Prompt surgical treatment is often indicated and is influenced by patient clinical examination, anatomic trajectory, and the penetrating objects size, shape, and velocity. METHODS We present 3 cases of penetrating TBI. Their similarities and differences affecting operative and medical management are compared. We relate our experience with management of penetrating intracranial foreign bodies in general and discuss the relevant literature. RESULTS Our first case was a 12-year-old male who presented with a self-inflicted transfacial transcranial injury by a crossbow. The arrow passed through the left sphenoid and cavernous sinus and exited through the parietal calvarium. Our second case was a 37-year-old man with a transoral intracranial stab wound by a knife. In our third case, we present a 46-year-old male who accidentally fired a nail gun into his right ear. The nail traversed the posterior wall of the external auditory canal into the posterior fossa, ending in the cerebellar vermis. Each case was treated with craniotomy and foreign body removal. All resulted in good outcomes after surgical treatment. CONCLUSION Surgery in penetrating TBI is the treatment of choice. Our cases demonstrate how certain principles applied to individual patient scenarios may optimize clinical results. Severity of the injury and operative approach are among the most important considerations to achieve the best patient outcomes.

Traumatic Brain Injury: Current Treatment Strategies and Future Endeavors

Traumatic brain injury (TBI) presents in various forms ranging from mild alterations of consciousness to an unrelenting comatose state and death. In the most severe form of TBI, the entirety of the brain is affected by a diffuse type of injury and swelling. Treatment modalities vary extensively based on the severity of the injury and range from daily cognitive therapy sessions to radical surgery such as bilateral decompressive craniectomies. Guidelines have been set forth regarding the optimal management of TBI, but they must be taken in context of the situation and cannot be used in every individual circumstance. In this review article, we have summarized the current status of treatment for TBI in both clinical practice and basic research. We have put forth a brief overview of the various subtypes of traumatic injuries, optimal medical management, and both the noninvasive and invasive monitoring modalities, in addition to the surgical interventions necessary in particular instances. We have overviewed the main achievements in searching for therapeutic strategies of TBI in basic science. We have also discussed the future direction for developing TBI treatment from an experimental perspective.

Effect of Hypernatremia on Outcomes After severe Traumatic Brain Injury: A Nationwide Inpatient Sample analysis

OBJECTIVE Induced hypernatremia is frequently used to reduce intracranial pressure in patients with severe traumatic brain injury (TBI). This technique is controversial, and some studies have independently associated hypernatremia with worse outcomes after TBI. We sought to investigate this potential association in a large healthcare database. METHODS The Nationwide Inpatient Sample was used to obtain data on all adults who had been discharged from 2002 to 2011 with a primary diagnosis of TBI who required mechanical ventilation, intracranial pressure monitoring, or craniotomy/craniectomy. Patients with diabetes insipidus were excluded. The patients with hypernatremia were assigned to the hypernatremia group, and the rest were assigned to the control group. The primary outcome was in-hospital mortality, and the secondary outcomes included the length of stay, nonroutine hospital discharge, total hospital charges, tracheostomy, and gastrostomy placement. RESULTS A total of 85,579 patients without a diagnosis of hypernatremia (control group) and 4542 patients with a diagnosis of hypernatremia (hypernatremia group) were identified. When controlling for age, comorbidities, gender, and cerebral edema, hypernatremia was associated with an increased rate of in-hospital mortality (odds ratio, 1.51; 95% confidence interval, 1.39-1.65), a longer mean length of stay (23.65 vs. 12.12 days; P < 0.001), an increased rate of nonroutine hospital discharge (odds ratio, 2.58; 95% confidence interval, 2.28-2.92), and greater mean total hospital cost (

Brain repair by hematopoietic growth factors in the subacute phase of traumatic brain injury

227,112 vs.

Chromatin run-on reveals nascent RNAs that differentiate normal and malignant brain tissue

112,507; P < 0.001). The patients with hypernatremia also had greater rates of tracheostomy and gastrostomy placement. CONCLUSIONS Hypernatremia was associated with poorer outcomes in patients with severe TBI. This finding warrants further investigation in a prospective, randomized study.

Affinity of Mucormycosis for Basal Ganglia in Intravenous Drug Users: Case Illustration and Review of Literature

OBJECTIVETraumatic brain injury (TBI) is a major cause of long-term disability and death in young adults. The lack of pharmaceutical therapy for post-acute TBI recovery remains a crucial medical challenge. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF), which are 2 key hematopoietic growth factors, have shown neuroprotective and neurorestorative effects in experimental stroke. The objective of this study was to determine the therapeutic efficacy of combined treatment (SCF + G-CSF) in subacute TBI.METHODSYoung-adult male C57BL mice were subject to TBI in the cortex of the right hemisphere. After TBI induction, mice were randomly divided into 2 groups: a vehicle control group and an SCF + G-CSF treatment group. Mice without TBI served as sham operative controls. Treatment was initiated 2 weeks after TBI induction. SCF (200 μg/kg) and G-CSF (50 μg/kg) or an equal volume of vehicle solution was subcutaneously injected daily for 7 days. A battery of neurobehavioral tests for evaluation of memory and cognitive function (water maze and novel object recognition tests), anxiety (elevated plus maze test), and motor function (Rota-Rod test) was performed during the period of 2-9 weeks after treatment. Neurodegeneration and dendritic density in both hemispheres were determined through histochemistry and immunohistochemistry at 11 weeks posttreatment.RESULTSWater maze testing showed that TBI-impaired spatial learning and memory was restored by SCF + G-CSF treatment. The findings from the elevated plus maze tests revealed that SCF + G-CSF treatment recovered TBI-caused anxiety and risk-taking behavior. There were no significant differences between the treated and nontreated TBI mice in both the Rota-Rod test and novel object recognition test. In the brain sections, the authors observed that widespread degenerating neurons were significantly increased in both hemispheres in the TBI-vehicle control mice. TBI-induced increases in neurodegeneration were significantly reduced by SCF + G-CSF treatment in the contralateral hemisphere, making it no different from that of the sham controls. Dendritic density in the frontal cortex of the contralateral hemisphere was significantly reduced in the TBI-vehicle control mice, whereas SCF + G-CSF-treated TBI mice showed significant increases of the dendritic density in the same brain region. SCF + G-CSF-treated TBI mice also showed a trend toward increasing dendritic density in the contralateral hippocampus.CONCLUSIONSSCF + G-CSF treatment in the subacute phase of TBI restored TBI-impaired spatial learning and memory, prevented posttraumatic anxiety and risk-taking behavior, inhibited TBI-induced neurodegeneration, and enhanced neural network remodeling. These findings suggest the therapeutic potential of hematopoietic growth factors for brain repair in the subacute phase of TBI.

Combined Transzygomatic and Pterional Approach for Resection of a Dermoid Cyst of the Foreman Ovale

Non-coding elements in our genomes that play critical roles in complex disease are frequently marked by highly unstable RNA species. Sequencing nascent RNAs attached to an actively transcribing RNA polymerase complex can identify unstable RNAs, including those templated from gene-distal enhancers (eRNAs). However, nascent RNA sequencing techniques remain challenging to apply in some cell lines and especially to intact tissues, limiting broad applications in fields such as cancer genomics and personalized medicine. Here we report the development of chromatin run-on and sequencing (ChRO-seq), a novel run-on technology that maps the location of RNA polymerase using virtually any frozen tissue sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in 23 human glioblastoma (GBM) brain tumors and patient derived xenografts. Remarkably, >90,000 distal enhancers discovered using the signature of eRNA biogenesis within primary GBMs closely resemble those found in the normal human brain, and diverge substantially from GBM cell models. Despite extensive overall similarity, 12% of enhancers in each GBM distinguish normal and malignant brain tissue. These enhancers drive regulatory programs similar to the developing nervous system and are enriched for transcription factor binding sites that specify a stem-like cell fate. These results demonstrate that GBMs largely retain the enhancer landscape associated with their tissue of origin, but selectively adopt regulatory programs that are responsible for driving stem-like cell properties.The human genome encodes a variety of poorly understood RNA species that remain challenging to identify using existing genomic tools. We developed chromatin run-on and sequencing (ChRO-seq) to map the location of RNA polymerase using virtually any input sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in primary human glioblastoma (GBM) brain tumors. Whereas enhancers discovered in primary GBMs resemble open chromatin in the normal human brain, rare enhancers activated in malignant tissue drive regulatory programs similar to the developing nervous system. We identified enhancers that regulate genes characteristic of each known GBM subtype, identified transcription factors that drive them, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.

Full Recovery After a Bihemispheric Gunshot Wound to the Head: Case Report, Clinical Management, and Literature Review

Central nervous system mucormycosis is an aggressive fungal infection often ending in fatality. The usual circumstance is an immunocompromised individual presenting with rapidly progressive rhinocerebral involvement. An extremely rare variant of central nervous system mucormycosis isolated to the basal ganglia in an immunocompetent intravenous drug user is detailed in this manuscript. The patient was aggressively treated with aspiration of the fungal abscess and long-term intravenous antifungal agents.

Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme

Dermoid cysts are rare, benign intracranial lesions commonly located in the posterior fossa. We describe a uniquely located dermoid cyst in the foreman ovale resected via a combined pterional and transzygomatic approach.