Sequel Of Traumatic Brain Injury Research Articles

A prospective study to determine the risk factors associated with post traumatic seizures: A single institution experience.

Post traumatic seizures (PTS) are a known sequel of traumatic brain injury (TBI). Incidence of PTS is dependent on many factors including study design and characteristics of the study population. As incidence of TBI increases and death due to TBI decreases, more individuals will be at risk of developing and living with chronic complications. The objective of the present study was to determine the frequency and risk factors for PTS following TBI. A prospective study was conducted on patients admitted with TBI from April 1, 2019, to May 31, 2020, to determine the frequency, time to event, and risk factors for PTS following TBI. We classified the severity of head injury using a standard criterion, into mild, moderate and severe injury. Follow-up of 3 months was undertaken for all patients. Variables include age, sex, trauma severity, Glasgow coma scale, onset of PTS, and neuroradiological finding. We enrolled 450 post traumatic subjects, out of which 36 (8%) developed seizures. Of the total of 36 patients detected to have hemorrhagic contusion on computerized tomography scan, 12 patients developed seizures. We found that the independent risk factors associated with occurrence of PTS were frontal- temporal lobar contusion and severity of head injury. All these findings were statistically significant. We found that the independent risk factors associated with occurrence of PTS were frontal-temporal lobar contusion and severity of head injury. Type of management (Operative vs. Non operative) does not affect the outcome of PTS.

Chronic hypometabolism in striatum and hippocampal network after traumatic brain injury and their relation with memory impairment – [18F]-FDG-PET and MRI 4 months after fluid percussion injury in rat

Hippocampal and thalamo-cortico-striatal networks are critical for memory function as well as execution of a variety of learning strategies. In subjects with memory impairment as a sequel of traumatic brain injury (TBI), the contribution of late metabolic depression across these networks to memory deficit is poorly understood. We used [18F]-FDG-PET to measure chronic post-TBI glucose uptake in the striatum and connected brain areas (septal and temporal hippocampus, thalamus, entorhinal cortex, frontoparietal cortex and amygdala) in rats with lateral fluid-percussion injury (LFPI). Then we assessed a link between network hypometabolism and memory impairment. At 4 months post TBI, glucose uptake was decreased in ipsilateral striatum (10%, p = 0.027), frontoparietal cortex (17%, p = 0.00009), and hippocampus (22%, p = 0.027) as compared to sham operated controls. Thalamic uptake was 6% lower ipsilaterally than contralaterally, p = 0.00004). At 5 months, Morris water maze (MWM) showed memory impairment in 83% of the rats with TBI. The lower the hippocampal or striatal [18F]-FDG uptake, the poorer the MWM performance (hippocampus: r = −0.471, p < 0.05; striatum: r = −0.696, p < 0.001). Striatal [18F]-FDG-PET identified the injured animals with memory impairment with 100% specificity and sensitivity (AUC = 1.000, p = 0.009). Interestingly, the low striatal glucose uptake was a better diagnostic biomarker for memory impairment than the reduced hippocampal (AUC = 0.806, p = 0.112) or entorhinal (AUC = 0.528, p = 0.885) glucose uptake. The volumetric atrophy assessed in T2 weighted MRI or the gliotic area in Nissl staining did not correlate with glucose uptake. Arterial spin labeling did not indicate any reduction in the striatal blood flow. Our study suggests that TBI-induced chronic hypometabolism in striatum contributes to the cognitive deficits.

Medico-legal study of post-traumatic seizures and epilepsy in patients with traumatic brain injury in El Demerdash and Ain Shams Specialized Hospitals (2017 -2018)

Background: Traumatic brain injury (TBI) is one of the most leading causes of deaths and disability among youth worldwide. Post-traumatic seizures (PTS) and post-traumatic epilepsy (PTE) are important catastrophic complications of TBI. Epilepsy has important medico-legal aspects for both the patient and the physician. Aim of the study: to identify forms of post traumatic seizures (generalized, focal, or focal followed by secondary generalized), site of epileptic focus, nature of brain injury that caused their occurrence, risk factors for epilepsy occurrence and medico-legal importance of PTS. Methods: A prospective cross-sectional study was conducted including patients with PTS and PTE who presented to El Demerdash and Ain shams Specialized Hospitals during the study period. Data were collected from patients by a questionnaire and from clinical sheets. Patients were classified into three groups according to time of occurrence of PTS. Results: A total of 77 patients were included. Cases were mostly in the age group less than 45 years old. Male patients were more represented in the study (64.9%). Transportation injuries were the most prominent pattern of TBI followed by blunt trauma (29.9%), open head injuries (13%), fall from height (13%) and polytrauma (1.3%). The most common affected site was frontal area of the brain (51.9%) followed by temporal region (45.5%). Associated complications included intra-cranial hemorrhage (87%) and skull fracture (35.1%). Immediate seizures were recorded in 9.1 % of the studied patients compared to 26% with early PTS. Patients with late PTS were the majority accounting for 64.9% of study patients of whom 50% with late PTS from the start. Most cases experienced generalized seizures attacks (59.7%) followed by focal with secondary generalization seizures attacks in (27.3%) and the least were with focal seizures attacks (13.0%). EEG showed abnormal activity in (62.3%) of patients and normal activity in (37.7%). Conclusion: Post-traumatic seizures and epilepsy are an important well-known sequel of traumatic brain injury with important medico-legal aspects. Pattern of head injury and site of traumatic area are important risk factors in occurrence of PTS and EEG abnormal activity is an important predictor for occurrence of PTS as well.

Post Traumatic Hydrocephalus: Incidence, Pathophysiology and Outcomes.

Post-traumatic hydrocephalus (PTH) is a sequel of traumatic brain injury (TBI) that is seen more often in patients undergoing decompressive craniectomy (DC). It is associated with prolonged hospital stay and unfavorable outcomes. To study the incidence and risk factors for development of PTH in patients undergoing DC in our institution and to review the literature on PTH with respect to incidence, risk factors, pathophysiology, and outcomes of management. Data from 95 patients (among 220 patients who underwent DC for TBI and fulfilled the inclusion criteria) over a 5-year period at Christian Medical College, Vellore were collected and analyzed to study the incidence and possible risk factors for development of PTH. A review of the literature on PTH was performed by searching PUBMED resources. Thirty (31.6%) out of 95 patients developed post-traumatic ventriculomegaly, of whom seven (7.3%) developed symptomatic PTH, necessitating placement of ventriculoperitoneal shunt (VPS). No risk factor for development of PTH could be identified. The reported incidence of PTH in the literature is from 0.07% to 29%, with patients undergoing DC having a higher incidence. Younger age, subarachnoid hemorrhage, severity of TBI, presence of subdural hygroma, and delayed cranioplasty after DC are the main risk factors reported in the literature. PTH occurs in a significant proportion of patients with TBI and can lead to unfavorable outcomes. PTH has to be distinguished from asymptomatic ventriculomegaly as early as possible so that a CSF diversion procedure can be planned early during development of PTH.

Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury: A PET Study

To investigate quantitative positron emission tomography (PET) findings and to study whether the cholinergic function differs between respondents to cholinergic medication versus nonrespondents. Outpatient clinic and university PET imaging center. We studied 17 subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity of the acetylcholinesterase (AChE) enzyme. The subjects were PET scanned twice: without medication and after a 4-week treatment with rivastigmine 1.5 mg twice a day. Regional cerebral AChE activity was measured with PET. At baseline Statistical Parametric Mapping analyses showed significantly lower AChE activity in respondents bilaterally in the frontal cortex as compared with nonrespondents. Region of interest (ROI) analysis revealed that the difference was most pronounced in the lateral frontal cortex (-9.4%, P = .034) and anterior cingulate (-6.0%, P = .049). After rivastigmine treatment, AChE activity was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury.

212 Hydrocephalus in Pediatric Traumatic Brain Injury

Abstract INTRODUCTION Hydrocephalus is a well-known and life-threatening sequel of traumatic brain injury (TBI) in adults, but is not as well characterized in children. We investigated the national incidence, risk factors, and outcomes associated with hydrocephalus in pediatric TBI. METHODS The Kids Inpatient Database (KID) is the largest pediatric hospital database in the U.S. and is sampled every 3 years. We queried the KID 2003, 2006, 2009, and 2012 using ICD-9-CM codes to identify all patients (age 0–20) with a primary diagnosis of TBI (850.xx 854.xx) and a secondary diagnosis code for hydrocephalus (331.3-331.5, excluding congenital hydrocephalus [742.3]. Variables included demographics, comorbidities, TBI severity (consciousness, type of wound) complications (medical or neurological), and discharge outcomes. Both univariate and multivariable analysis was utilized to identify factors associated with hydrocephalus and alpha was set at P &lt; 0.05. RESULTS &gt;In 124,444 patients hospitalized for TBI. The average rate of hydrocephalus was 1.0% but was affected by the type of TBI: subdural hematoma (2.4%), subarachnoid hemorrhage (1.4%), epidural hematoma (1.0%), cerebral laceration (0.9%), concussion (0.2%). The risk factors for hydrocephalus in multivariable analysis were age 0–5 (compared to other ages), Medicaid insurance, electrolyte disorder, chronic neurological condition, weight loss, subarachnoid hemorrhage, subdural hematoma, open wound, postoperative neurological complication, and septicemia (all P &lt; 0.05). The likelihood of hydrocephalus was increased among surgically managed patients (6.0% vs. 0.5%) but decreased among those who underwent operation on admission day (0.8% vs. 4.1%) (both P &lt; 0.05). The mortality rate for TBI patients without hydrocephalus was higher (5.4%) than those with hydrocephalus (1.1%). However, average LOS (25 vs. 5 days) and mean total hospital costs ($86,596 vs. $16,791) were greater among patients with hydrocephalus. CONCLUSION Hydrocephalus following TBI in children is relatively uncommon but is more likely in patients with certain demographics, pre-existing comorbidities, and injury patterns and attracts a higher total hospital cost.

Late onset of subdural hematoma after bifrontal contusion

Cerebral cortical contusions are one of the most common computed tomography findings in head-injured patients and common sequel of traumatic brain injury. These contusions tend to show a progressive increase in mass effect on repeated imaging, most small contusions do not require surgical evacuation. However, progression to subdural hematoma (SDH) in a late aspect is unique. Here we present a 71-year-old man with bifrontal contusion, who deteriorated 43 days after initial trauma with sudden onset of acute SDH. This unusual case suggests that neurosurgeons should be alert for the possibility of very late onset of acute SDH after bifrontal contusions.

Smoking and outcome of traumatic brain injury

Objective: There is evidence that the cholinergic system is involved in cognitive sequels of traumatic brain injury (TBI). Nicotinic acetylcholine receptors (nAChRs) are known to have a major role in cognitive functions. Smokers have up-regulation of these receptors. This study investigated whether smoking is associated with the outcome from TBI.Methods: A specific questionnaire was sent, after checking inclusion and exclusion criteria, to 1022 subjects with TBI who had visited the neurological outpatient clinic of a university hospital during a 14-year period. Of these, 689 (67.4%) responded, forming the final study population. Associations between demographic variables, injury severity and outcome and smoking history were analysed using multivariate methods.Results: Smokers were more often men (p < 0.001), younger at the time of the injury (p = 0.008) and had less education (p < 0.0001). In univariate analysis, non-smokers did not differ for outcome of TBI by GOS-E (p = 0.08). Furthermore, in multivariate analysis, no association was found between smoking history and TBI outcome.Conclusions: This study does not suggest that smoking affects the outcome of TBI.

Evaluation of late cognitive impairment and anxiety states following traumatic brain injury in mice: The effect of minocycline

Comorbidity of cognitive and stress disorders is a common clinical sequel of traumatic brain injury (TBI) that is essentially determined by the site and severity of the insult, but also by the extent of the ensuing neuroinflammatory response. The present study sought to examine the late effects of closed-head TBI on memory function and anxiety in mice, in order to further examine the potential efficacy of an acute anti-inflammatory treatment with minocycline. The mouse model of closed-head injury by mechanical percussion was applied on anesthetized Swiss mice. The treatment protocol included three injections of minocycline (i.p.) at 5min (90mg/kg), 3h and 9h (45mg/kg) post-TBI. The Novel Object Recognition Test as well as the Elevated Plus Maze (EPM) and Elevated Zero Maze (EZM) tasks were employed to assess post-TBI memory and anxiety respectively. Our results revealed a recognition memory deficit that was significant up to at least 13 weeks post-TBI. However, neither EPM nor EZM revealed any alteration in post-TBI anxiety levels albeit some mild disinhibition. Most importantly, minocycline was able to attenuate the memory impairment in an effective and lasting manner, highlighting its therapeutic potential in TBI.

Disfunción neuroendocrina y agresión cerebral. Reunión de consenso

This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

A randomized controlled trial of rivastigmine for chronic sequels of traumatic brain injury—What it showed and taught?

Primary objective: To evaluate the effectiveness of rivastigmine for chronic sequels of traumatic brain injury (TBI).Research design: Randomized, placebo-controlled, double-blind crossover trial.Methods and procedures: Of 772 outpatients with TBI treated during 1993–2002, all eligible patients were contacted and 102 patients volunteered. They were randomized to receive either rivastigmine (Exelon) or placebo. The study included two periods with titration to the highest tolerated or maximum dose (12 mg rivastigmine daily) and a maintenance period of 8 weeks, separated by a 4-week washout. Computerized neuropsychological testing and standardized clinical interviews were used to assess the outcome.Main outcomes and results: Sixty-nine patients completed the study and 17 withdrew because of adverse effects. In two measures of computerized testing (subtraction test, p = 0.034 and correct answers in the 10–15 minute vigilance test, p = 0.048) rivastigmine was better than placebo. The clinical interviews did not yield significant results. After the study, 45% of patients considered rivastigmine beneficial compared to 20% with placebo.Conclusions: A weak trend favouring rivastigmine for chronic symptoms of TBI was observed. The clinical significance of the results and the problems in conducting drug trials for chronic TBI symptoms are discussed.

Role of Vasopressin V1a and V2 Receptors for the Development of Secondary Brain Damage after Traumatic Brain Injury in Mice

Brain edema is still one of the most deleterious sequels of traumatic brain injury (TBI), and its pathophysiology is not sufficiently understood. The goal of the current study was to investigate the role of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), an important regulator of tissue water homeostasis, for the formation of post-traumatic brain edema, intracranial pressure (ICP), brain damage, and functional deficits following brain trauma. C57/B16 mice (n=112) were subjected to controlled cortical impact (CCI; 8m/s, 1 mm). At 3 min after trauma, animals received 500 ng of the AVP V(1a)-receptor antogonist (deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-Vasopressin) or 500 ng of the AVP V2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(2),Val(4), Abu(6),Arg(8,9)]-Vasopressin) by intracerebroventricular injection. After trauma, cerebral water content (24 h), ICP (24 h), contusion volume (24 h and 7 days), and functional outcome (1-7 days) were assessed (n=8 per experimental group). Post-traumatic inhibition of AVP V(1A) receptors reduced ICP by 29% (p < 0.05), brain water content by 45% (p < 0.05), and secondary contusion expansion by 37% (p < 0.05), and it significantly improved motor function 6 and 7 days after trauma (p < 0.05). Inhibition of AVP V2 receptors had no significant effect. The current results demonstrate that vasopressin V(1A) receptors are involved in the pathogenesis of brain edema formation and the subsequent development of secondary brain damage after traumatic brain injury. Accordingly, our study suggests that vasopressin V(1A) receptors may represent a novel therapeutic target for the treatment of post-traumatic brain edema and secondary brain damage.

Regional Differences in Cerebral Edema After Traumatic Brain Injury Identified by Impedance Analysis

Cerebral edema is a common and potentially devastating sequel of traumatic brain injury. We developed and validated a system capable of tissue impedance analysis, which was found to correlate with cerebral edema. Constant sinusoidal current (50 microA), at frequencies from 500 to 5000 Hz, was applied across a bipolar electrode unit superficially placed in a rat brain after traumatic brain injury. Rats were randomized to three groups: severe controlled cortical injury (CCI), mild CCI, or sham injury. At 60 h post-CCI, cerebral voltage and phase angle were measured at each frequency at the site of injury, at the penumbral region, at the ipsilateral frontal region, and in the contralateral hemisphere. Impedance measurements were also obtained in vivo. The electrical properties of varied injuries and specified locations were compared using a repeated measures analysis of variance (RMANOVA), were correlated with regional tissue water percentage using regression analyses, and were combined to generate polar coordinates. The measured voltage was significantly different at the site of injury (P<0.0001), in the penumbra (P=0.002), and in the contralateral hemisphere (P=0.005) when severe, mild, and sham CCI rats were compared. Severely injured rats had statistically different voltage measurements when the various sites were compared (P=0.002). The ex vivo measurements correlated with in vivo measurements. Further, the impedance measurements correlated with measured tissue water percentage at the site of injury (R2=0.69; P<0.0001). The creation of a polar coordinate graph, incorporating voltage and phase angle measurements, enabled the identification of impedance areas unique to normal, mild edema, and severe edema measurements in the rat brain. Electrical measurements and tissue water percentages quantified regional and severity differences in rat brain edema after CCI. Impedance was inversely proportional to the tissue water percentage. Thus, impedance measurement can be used to quantify severity of cerebral edema in real time at specific sites.

Effet de l’âge sur le fonctionnement exécutif après lésion cérébrale chez l’adulte

IntroductionExecutive functioning deficits have often been described in normal aging. They are also known to be a frequent sequel of traumatic brain injury, where patients may exhibit severe long-standing impairments in instrumental activities of daily living. One could therefore expect that cerebral lesions affecting executive functioning would result in more severe impairments in older patients. We previously developed an ecological assessment of executive functions, consisting of a cooking task, requiring multitasking abilities and known to be sensitive to a dysexecutive syndrome [Cortex 36 (2000) 649–669]. The aim of this study was to analyze the effect of age on the cognitive and ecological assessments of executive functions in a group of patients with acquired brain injury (ABI) resulting in a dysexecutive syndrome. Studies in this area usually focus on patients older than 60 or 65, but we chose to analyze the effect of age in a younger population. We hypothesized that older patients would have poorer performances on the cognitive and ecological tests of executive functioning, when compared to younger patients. MethodsForty-five patients with ABI resulting in frontal lesions and a dysexecutive syndrome participated in this study. Patients underwent a comprehensive battery of cognitive tests assessing executive functioning, as well as the cooking task. We also studied a group of 12 control subjects who performed the cooking task. ResultsNo effect of age was found on performance in the cooking task in the control group. Age was not related to demographic parameters or injury severity in the ABI group. Although the ABI group was relatively young (mean age: 40.3 years (S.D.=12.5), ranging from 17 to 63), results indicated a significant deleterious effect of age on the cognitive tests of executive functioning in the ABI group. We also highlighted a significant worsening of patients’ performance in the cooking task with age, and this effect was found on several variables of task analysis: the number of errors and occurrence of dangerous behaviors. ConclusionOur study demonstrates the deleterious effect of aging on cognitive and ecological assessment of executive functioning after ABI. The strength of this study is that it deviated from the traditional age considered in studies of elderly populations and focused on younger patients. It is therefore important to consider the implication that this may have on a patient's rehabilitation program and postinjury discharge.

Adults with Acquired Traumatic Brain Injury: A Theoretical Analysis from a Social Recognition Perspective

The purpose of this study is to illuminate the changeover process experienced by people with traumatic brain injury (TBI) and increase the understanding of social recognition occurring after injury. Fifteen persons, ages 28–56, with TBI have been in-depth interviewed. Data were first analyzed by latent-content analysis using a hermeneutic approach, and later re-contextualized within a matrix constructed from theories of social recognition. Results were initially structured into six themes and then re-described in terms of recognition, that is, the individual dimension, the legal dimension, and the value dimension. The conclusions suggest that people with TBI experience both recognition and non-recognition during the recovery process and later in life, living in society with the sequel of TBI. Such experiences are described on all dimensions.

Subarachnoid Hemorrhage As a Cause of Hypopituitarism

Common causes of pituitary insufficiency include pathologies such as pituitary adenomas, other intra- and parasellar tumors, as well inflammatory, surgical or radiation-induced destruction of pituitary tissue. More recently, hypopituitarism has also been identified as a frequent sequel of traumatic brain injury (TBI). Despite the close anatomical relationship between pituitary gland, hypothalamic structures and the arteries of the circle of Willis and the observation that many bodily and psychosocial long-term sequelae of survivors of aneurysmal subarachnoid hemorrhage (SAH) resemble those of patients with untreated hypopituitarism, aneurysmal SAH has so far been considered a rare cause of endocrine abnormalities. However, in recent clinical investigations partial hypopituitarism has been diagnosed in 37.5-55% of SAH survivors. At present, many questions concerning the most appropriate diagnostic work-up, the clinical implications of hormone deficiencies and relative importance of hormone replacement in this patient group are not yet satisfactorily clarified. This article gives an overview of the historical and current studies on hypopituitarism as a consequence of aneurysmal SAH, which show that neuroendocrine deficiency occurs more often than has so far been appreciated. Despite the still unresolved issues, endocrine abnormalities should be considered a cause for impaired recovery and long-term morbidity in SAH-survivors. Enhanced awareness of physicians treating SAH-patients for post-traumatic hypopituitarism is called for, so that screening for hormone deficiencies and appropriate replacement therapy can be initiated.

An Open-Label Trial of Donepezil (Aricept) in the Treatment of Persons With Mild Traumatic Brain Injury

An Open-Label Trial of Donepezil (Aricept) in the Treatment of Persons With Mild Traumatic Brain Injury