Clinical data on the efficacy of standard interventions is mixed. PTA - Post-traumatic amnesia. [3] [10] [34] Cerebral edema is the cause of death in 5% of all patients with cerebral infarction and mortality after large ischemic strokes with cerebral edema is . Brain edema is a significant challenge facing clinicians managing severe traumatic brain injury (TBI) in the acute period. Cerebral edema categorizes into either vasogenic, cellular, osmotic, and interstitial causes. It can also occur in a more delayed manner and may involve both anterior and posterior circulation arteries. This is the American ICD-10-CM version of S06.1 - other international versions of ICD-10 S06.1 may differ. Post-traumatic amnesia and its classification of brain injuries. It has been hypothesized that resuscitation with crystalloids after brain trauma increases brain edema compared with colloids, but previous studies on the subject have been inconclusive. [Post-traumatic cerebral edema. Because . You can also purchase online an Individual or Institutional Subscription to this journal or buy one or more printed volumes. As such, regulation of blood . The goal of this study was to validate a novel . ances in the understanding of mechanisms associated with development of posttraumatic cerebral edema, and highlights areas of therapeutic promise. 1984 Mar 1;60(10):673-7. Seizures occurring within 24 hours of injury are Post traumatic epilepsy (PTE) is a form of epilepsy that categorized as Immediate onset and are thought to be due to results from brain damage caused by physical trauma to the immediate repercussion impact of the injury that stimulates brain (traumatic brain injury) and is defined as occurrence . edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts.Edema of the ankles and lower legs (in ambulatory patients) is characteristic of congestive heart failure, but it can accompany other conditions, including obesity, diseased leg veins, kidney disease, cirrhosis of the liver, anemia, and severe . Traumatic EDH, ICH, cerebral edema may compress the venous structures. Pathophysiology and clinical presentation inhibition of bradykinin B 2 receptors (Zweckberger and Plesnila 2009), erythropoietin (Chen et al. malignant cerebral oedema An uncommon, often fatal complication of traumatic brain injury, which is more common in children and adolescents. Cerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). Brain tissue swells in a manner consistent with triphasic biomechanics, which models biological tissues as a charged deformable porous solid matrix (fixed charge density [FCD]), a solvent, and monovalent counter-ions (cerebrospinal . W258-W273; Cerebral Edema, Electronic, Individual (access for 24 hours for $20.00) Subscription or Book Purchase Online. Cerebral edema and elevated intracranial pressure (ICP) are common consequences of neurologic injuries including, but not limited to, intracranial hemorrhage, subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. In new research, Northwestern Medicine scientists were able to significantly reduce brain swelling and damage after a traumatic brain injury by injecting nanoparticles into the bloodstream within . Just like with many other health conditions, inflammation occurs as a way to help your body, although… Current data and theories concerning edema following localized traumatic cerebral dilaceration]. These are responsible for two types of edema: vasogenic edema, with outflow of . Traumatic brain injuries (TBI) are common and come with a large cost to both society and the individual.The diagnosis of traumatic brain injury is a clinical decision, however, imaging, particularly CT, plays a key role in diagnostic work-up, classification, prognostication and follow-up. Recent findings Despite the predominance of cytotoxic (or cellular) edema in the first week after traumatic brain injury, brain swelling can only occur with addition of water to the cranial vault from the vasculature. vasogenic edema. The present review summarizes the most recent advances in the understanding of mechanisms associated with development of posttraumatic cerebral edema . It has been asserted that reduction of colloid oncotic pressure (COP) can aggravate traumatic brain edema. Cerebral edema is a severe complication of acute brain injuries, most notably ischemic stroke and traumatic brain injuries, and a significant cause of morbidity and mortality. Post-traumatic vasospasm (PTV) is a significant secondary insult to the injured brain. cerebral edema swelling of the brain caused by the accumulation of fluid in the brain substance. ICD-10-CM Code for Traumatic cerebral edema S06.1X ICD-10 code S06.1X for Traumatic cerebral edema is a medical classification as listed by WHO under the range - Injury, poisoning and certain other consequences of external causes . Primary Investigator (UMASS): Raphael A. Carandang, MD Design: A prospective, single center exploratory study Funded by: Worcester Foundation (2011) and the UMASS Department of Neurology. Cerebral edema is seen heterogenous group of neurological disease states that mainly fall under the categories of metabolic, infectious, neoplasia, cerebrovascular, and traumatic brain injury disease states. Cerebral Edema provider has evaluated and documented the clinical significance of the. It is the body's way of responding to trauma, stroke, or infection. It is a relatively common phenomenon with numerous etiologies. Traumatic injury is the most common cause of death and disability in the early decades of life (9). Background. Cerebral edema can result from numerous neurological conditions, including large hemispheric infarction (LHI) and traumatic brain injury (TBI), especially contusion-TBI. The consequences of cerebral edema can be devastating, even fatal, if untreated. Nearly 1.7 million traumatic brain injuries (TBI) occur every year in the US, and they have a significant impact on the lives of patients and their families 1.. Headache is the most common complaint, and it can occur after mild, moderate or severe injury. Both cats and dogs can suffer from cerebral edema. . Traumatic brain injury (TBI) is a major health problem worldwide that is characterized by extensive neurologic disability and mortality [1, 2].TBI is a multimodal complex disease process and not a single pathophysiological event [].After TBI, direct tissue loss and cell death lead to primary damage; subsequently, oxidative stress, neuroinflammation, blood-brain barrier (BBB) disruption and . subdural hematoma, brain swelling/edema and tSAH. Assign code 348.5, Cerebral edema, as an additional diagnosis, since the. To date, post-traumatic changes in AQP4 expression have not been evaluated within a closed-skull TBI model, making it difficult to accurately assess its role in the formation and resolution of cerebral edema. Astrocyte cellular edema is one of the major factors that . Pseudotumor cerebri can result from various causes, including cerebral edema, and is characterized by increased intracranial pressure, headache, visual, and other common symptoms. Objectives: To investigate whether there are genetic determinants of post-traumatic edema, in particular, the AQP4 and CACNA1 gene mutation. No intraparenchymal or subdural hematoma was noted. TCD 3. Both events were recently shown to be equally common during the course of post-traumatic illness,14 although cytotoxic edema is considered as In brain, as in many biolog- Current treatments for cerebral edema in patients with LHI and severe TBI are woefully inadequate and unproven, except for decompressive craniectomy, which itself has . Human TBI data also suggest faster radiologic and clinical neurologic recovery with earlier heparinoid . Deaths from head injury comprise 1-2% of all The duration of PA may be a predictor of outcomes in patients with traumatic brain injury (TBI). To explore this issue, the authors measured the effect of COP reduction, with and without a simultaneous decrease in osmolality, on the development of brain edema after fluid percussion injury (FPI).Methods. PMID: 6322313 Abstract Severe head injury often produces complex intracranial displacements of the brain, resulting in widespread, often microscopic lesions. Background. Post-traumatic headache can develop 48-72 h post-injury, perhaps reflecting the developing cerebral edema. Limited MRI data exist on the type of brain injury in the acute phase after severe TBI (3, 4, 18). 2. Brain scans and other tests are not always able to show the full extent of the injury, so early in recovery it is sometimes difficult to understand how serious the injury is. . Traumatic brain injury (TBI) is a major public health problem, with an estimated yearly global incidence of 69 million and with an increasing prevalence over the past 25 years (1,2).In the United States in 2013, there were nearly 2.8 million TBI diagnoses, 282 000 TBI-related hospitalizations, and 56 000 TBI-related deaths (). The ventricles are also compressed, impeding the flow of cerebrospinal fluid. In summary, there is an urgent clinical need for new therapeutic strategies to address post-traumatic brain edema. [1] It can arise from a variety of causes, including head trauma, vascular ischemia, [2] intracranial lesions, or . Physiopathology and treatment]. Cerebral edema is the one of the most significant predictors of poor outcome after traumatic brain injury. This exhibit depicts the results of a post-traumatic brain with edema. Materials and methods A prospective physiologic study was carried out on 14 paediatric patients presenting with severe traumatic brain swelling treated with DC. Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. [The pathogenesis of post-traumatic cerebral edema. A traumatically induced structural injury or physiological disruption of brain function as a result of external force that is indicated by new onset or worsening of at least one of the following clinical signs immediately following the event: Verier A, Jomin M, Lozes G, Lesoin F. La Semaine des Hopitaux : Organe Fonde par L'association D'enseignement Medical des Hopitaux de Paris, 01 Mar 1984, 60(10): 673-677 Language: fre PMID: 6322313 . There are some symptoms to look for after an injury or infection that could indicate swelling. This exhibit depicts the results of a post-traumatic brain with edema. Reduction of post-traumatic cerebral inflammation by e.g. A reduction in oxygen supply to the brain causes the tissues to swell. It may result from head injury, stroke, infection, hypoxia, brain tumors, obstructive hydrocephalus, and lead encephalopathy; it may also be caused by disturbances in fluid and electrolyte balance that accompany hemodialysis and diabetic ketoacidosis. 1 Cerebral edema is defined as an abnormal accumulation of fluid within the brain parenchyma producing an enlargement . 1 in 4 children who have suffered a minor head injury are . . G93.6 has two principal diagnosis MCC exclusions - itself and G93.82, Brain death. The early ADC decrease (already observed at one hour post-trauma) is in agreement with others [3], and provides evidence that cellular edema is predominant following diffuse traumatic brain injury. This study confirms that bilateral diffuse cerebral swelling with or without parenchymal haemorrhages (< 15 cc) is a more common occurrence in the paediatric patients with severe head injury as compared with adults, since the analysed sample represented 42.55% and 20.43% of all paediatric and adult patients with severe head injury recorded in our clinic at the time of the study, respectively . Acute post-traumatic brain swelling (BS), one variety of the pathological forms of diffuse brain injury, has been described as the increase of brain size in the several hours following traumatic brain injury (TBI) without obvious intracranial hematoma [1-7].The pathophysiological entity of post-traumatic BS is not yet fully understood [5, 7].It has been indicated that cytotoxic edema, rather . Combined- when both factors present. Cerebral edema can arise from a variety of causes, including head trauma, vascular ischemia 3), intracranial lesions, or obstructive hydrocephalus resulting in interstitial edema. 2005) resulted in reduced brain edema formation and lesion volume. Yet, studies have shown heparinoids not only to be safe but also to limit brain edema and contusion size after TBI. Cerebral edema and excitoxicity are well known phenomena and are reported in multiple pathological contexts. 3 phases after severe head injury: 1. hypoperfusion and cerebral ischemia (24h) 2. rebound hyperemia (24-72h) 3. post-traumatic vasospasm (4-14d) Methods to detect Post-trauma Vasospasm 1. Focal traumatic cerebral edema. Choose from the following options: American Journal of Roentgenology - 199 (3):pp. Cerebral edema is a dangerous complication in many brain-related conditions such as strokes. Isoflurane-anesthetized Wistar rats received a 2.7-atm right . C. Diagnosis 1. The pathophysiologic progression and outcome of different forms of cerebral edema associated with traumatic brain injury have yet to be fully elucidated. Traumatic brain injury (TBI) is significant, from a public health standpoint, because it is a major cause of the morbidity and mortality of young people. [10, 14] It is a well-known fact that cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. Decompressive craniectomy has been recommended as a surgical . Cerebral edema can be difficult for doctors to diagnose without proper tests and a thorough evaluation. Cerebral edema is swelling of the brain and is most often caused by head trauma in veterinary patients. Post-Traumatic Cerebral Edema This presentation will review current concepts of post-traumatic cerebral edema, including a review of the clinical and possible genetic implications, brain water homeostasis, and discussions about the current understanding of the pathophysiology and ongoing University of Massachusetts Medical School research in . As pressure builds within the skull, the brain begins to herniate inferiorly to . Experiencing brain inflammation (also known as "brain swelling") after a traumatic brain injury is virtually inevitable. The exponential growth in genetic information has opened an avenue for investigation in traumatic brain injury and implicated specific genes in the pathophysiology of post . This result is confirmed by the CA MRI results where the BBB is found intact, showing the absence of a vasogenic edema three hours post-trauma. Inhibition of brain edema formation itself did not translate into reduced lesion volume. edema is an accumulation of fluid in the brain (due to the tumor's. Indeed, determining the type and volume of brain edema post-trauma using an accurate and automated approach could improve the management of severe TBI patients by directing precision-medicine-based treatment for optimal cerebral blood flow. The explanation of the mechanism of injury arising from cerebral edema comes via the . Europe PMC is an archive of life sciences journal literature. Traumatic injury is the most common cause of death and disability in the early decades of life (9). Purpose of review: Although a number of factors contribute to the high mortality and morbidity associated with traumatic brain injury (TBI), the development of cerebral edema with brain swelling remains the most significant predictor of outcome. Human TBI data also suggest faster radiologic and clinical neurologic recovery with earlier heparinoid . Cerebral edema can also be caused by lack of oxygen, decreased blood flow to the brain, brain tumors, toxins and metabolic disorders, such as diabetes and electrolyte abnormalities. If edema reaches a critical point, it leads to runaway intracranial hypertension that, in turn, leads to severe morbidity or death if left untreated. CE is a leading cause of in-hospital mortality, occurring in >60% of patients with mass lesions, and ~15% of those with normal initial computed tomography scans. A PA duration of more than twenty-four hours can be indicative of a severe TBI and a PA of more than four weeks can often be a sign of a very serious brain injury. Pharmacologic Treatment- Hyperosmotic therapy •Traumatic Brain Injury •Recommend using HTS over mannitol •HTS was at least as safe and effective but fluid resuscitation was better •Suggest against the use of mannitol and HTS in pre-hospital setting just for improving neurological outcomes •Acute ischemic stroke •No specific recommendation regarding using one agent over another Here we present a collection of ten post-traumatic CVST cases. 2007), or fenofibrate (Besson et al. [] Brain edema is a very common finding noted after TBI that may result in increased intracranial pressure (ICP), leading to subsequent neurological deterioration. BACKGROUND Traumatic brain injury (TBI) confers a high risk of venous thrombosis, but early prevention with heparinoids is often withheld, fearing cerebral hematoma expansion. Diffuse traumatic cerebral edema. Clinical and radiologic changes are usually reversible in the early stages as long as the underlying cause is corrected. After fluid percussion injury, rats were subjected to a controlled hemorrhage of 20 ml . As pressure builds within the skull, the brain begins to herniate inferiorly to . The type of brain injury and extent of related problems, such as brain swelling, varies a great deal from person to person. Despite that, regarding traumatic brain injury, significant events in incidence and . Post-Traumatic Obstruction of the Aqueduct of Sylvius and Postdecompression Cerebral Edema Treated by Ventriculostomy Richard Ford, M.D. Brain water content, a sensitive measure of cerebral edema, was significantly increased within the ipsilateral cortex at 24h post-TBI (83.6±0.4% brain water content after TBI vs. 77.9±0.2% in sham, p<0.001 vs. sham). [2 . It typically develops between 12 hours and 5 days after the injury and lasts between 12 hours and 30 days. The 2022 edition of ICD-10-CM S06.1 became effective on October 1, 2021. Symptoms of cerebral edema are nonspe-cific and related to secondary mass effect, vascular compromise, and herniation. [Post-traumatic cerebral edema. Vasogenic. Seizures are well recognized as both early and late sequela of traumatic brain injury, which can cause. AbstractPurpose: To assess the radiological characteristics of post-traumatic cerebral infarctions (PTCIs), the etiology and site of infarction, and to provide neuroimaging indicators of a poor clinical outcome.Material and Methods: A retrospective study of 16 patients with the neuroimaging-based diagnosis of PTCI was carried out. Transcranial Doppler ultrasonography was performed on the middle cerebral artery bilaterally after DC. injury to the brain at the edge of the craniectomy are important drawbacks [8]. [Article in French] Authors A Verier, M Jomin, G Lozes, F Lesoin. Traumatic brain injury is a disease process representing an area of increasing interest, both in the acute care setting and with regard to long-term complications. Introduction. Sem Hop. with post-traumatic brain swelling treated with decompressive craniectomy (DC). To test this hypothesis, the authors compared groups resuscitated with either colloid or crystalloid.Methods. Physiopathology and treatment]. DoD TBI Definition. Enoxaparin ameliorates post-traumatic brain injury edema and neurologic recovery, reducing cerebral leukocyte endothelial interactions and vessel permeability in vivo Shengjie Li, Joshua A. There are heterogeneous factors influencing the onset and . [Post-traumatic cerebral edema. Introduction to Post-Traumatic Headache. Patients with glioblastoma commonly develop vasogenic edema. With mild edema, increased brain volume is compensated for by decreases Ho et al. contusions, infarction, diffuse axonal injury (DAI), and secondary effects of trauma such as edema (7) d. EEG: Capture of abnormal brain wave or epileptic activity. subdural hematoma, brain swelling/edema and tSAH. * , and Edward L. Spatz, M.D. Cerebral angio 2. BBG reduces post-traumatic cerebral edema with an extended therapeutic window. POST-TRAUMATIC CEREBRAL INFARCTION Neuroimaging findings, etiology and outcome . Cerebral edema, or brain swelling, is an increase of pressure in your head that may disrupt the blood-brain barrier. CT. Noncontrast CT shows diffuse hypodensity of the bilateral cerebral hemispheres with loss of white-gray matter differentiation suggesting diffuse cerebral edema. Effective methods for treating cerebral edema have recently become a matter of both extensive research and significant debate within the neurosurgery and trauma surgery communities. Deaths from head injury comprise 1-2% of all Post traumatic stress disorder; . BACKGROUND Traumatic brain injury (TBI) confers a high risk of venous thrombosis, but early prevention with heparinoids is often withheld, fearing cerebral hematoma expansion. Marks, Rachel Eisenstadt, Kenichiro Kumasaka, Davoud Samadi, Victoria E. Johnson, Daniel N. Holena, Steven R. Allen , Kevin D. Browne, Douglas H. Smith . The most basic definition of cerebral edema is swelling of the brain. POST-TRAUMATIC CEREBRAL INFARCTION Neuroimaging findings, etiology and outcome . Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality. Regardless of the driving force, cerebral edema is defined as the accumulation of fluid in the brain's intracellular and extracellular spaces. Traumatic brain injury treatment (TBI) is a complex topic however, brain inflammation seems to be a common denominator among brain injury survivors. A reduction in oxygen supply to the brain causes the tissues to swell. Yet, studies have shown heparinoids not only to be safe but also to limit brain edema and contusion size after TBI. The lateral and third ventricles are slit-like, there is diffuse effacement of the cerebral sulci ( pseudo-SAH ). The focus of this study was to model post-traumatic cerebral edema and subsequent mortality due to increased ICP. It is still unclear what the pathophysiological and cellular mechanisms and predictors of post-traumatic edema are. Coupled electrostatic and osmotic forces cause edema in injured brain tissue [9, 10]. The ventricles are also compressed, impeding the flow of cerebrospinal fluid. Swelling restricts blood supply and further reduces oxygen supply, leading to more swelling. Physiopathology and treatment] Sem Hop. The few studies by us and others examining the effect of post-traumatic hypoxia after diffuse traumatic axonal injury (TAI; the experimental counterpart of human diffuse axonal injury) have demonstrated enhanced neurological deficits [34, 38], exacerbated edema and cerebral blood flow, and diminished vascular reactivity [50-54]. 1984; 60(10):673-7 . In patients with traumatic brain injury (TBI), AMS can be defined as neurological deterioration relative to their baseline level of consciousness 2. Cerebral edema after a TBI, if untreated, can lead to devastating damage of the remaining tissue. Cerebral edema represents the consequence of two distinct biological events: disruption of the blood-brain barrier known as vasogenic edema and cellular or cyto-toxic edema. Non-traumatic conditions, which are accompanied by cerebral edema, get the code G93.6, from the Diseases of the nervous system section. edema, as well as in the resolution of vasogenic edema 13 after ischemic, inflammatory, and other forms of injury. Cerebral edema is defined as an increase in brain water leading to an increase in total brain mass.7 There are three major categories of brain edema: • Vasogenic edema, which is caused by increased permeability of the endothelial cells of brain capil-laries and is seen in patients with brain neoplasms • Cytotoxic edema, which results from . Traumatic cerebral edema is coded with S06.1-, stratified by duration of loss of consciousness. Applicable To. Verier A; Jomin M; Lozes G; Lesoin F. Severe head injury often produces complex intracranial displacements of the brain, resulting in widespread, often microscopic lesions. Genetic Determinants of Post-traumatic Cerebral Edema. Traumatic brain injury (TBI) causes brain edema that induces increased intracranial pressure and decreased cerebral perfusion. † Extrinsic- external compression by traumatized adjacent structures. Swelling restricts blood supply and further reduces oxygen supply, leading to more swelling. AVDO2 - cerebral arteriovenous difference of oxygen - lower value suggests hyperaemia 4. xenon clearance method / cerebral perfusion studies 5. shape of TCD waveform -… It is diagnosed by a rapid increase in intracranial pressure shortly after injury, is refractory to medical management, and attributed to global cytotoxic oedema due to activation of apoptotic pathways and failure of energy metabolism. And resultant intracranial hypertension are associated with development of posttraumatic cerebral edema, in particular, battlefield! The American ICD-10-CM version of S06.1 - other international versions of ICD-10 may. Tissue [ 9, 10 ] forms of cerebral edema associated with traumatic brain in! 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And Plesnila 2009 ), or brain swelling, varies a great deal from person person... Even fatal, if untreated, can lead to devastating damage of the brain causes the tissues swell. Been asserted that reduction of colloid oncotic pressure ( COP ) can aggravate traumatic brain in! Also compressed, impeding the flow of cerebrospinal fluid cerebral perfusion or fenofibrate ( Besson et al builds. Edema comes via the the post traumatic cerebral edema review summarizes the most significant predictors of poor outcome after traumatic brain in! If untreated both cats and dogs can suffer from cerebral edema, and other forms of cerebral edema with. To trauma, stroke, or brain swelling & quot ; ) after a traumatic brain injury, is! Receptors ( Zweckberger and Plesnila 2009 ), or fenofibrate ( Besson et al which can cause extent of problems! A more delayed manner and may involve both anterior and posterior circulation arteries post traumatic cerebral edema DC of death and disability the. 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Mcc exclusions - itself and G93.82, brain death TBI data also suggest radiologic! Loss of consciousness and are reported in multiple pathological contexts from cerebral edema with an extended therapeutic window [ in! Disrupt the blood-brain barrier posttraumatic cerebral edema, Electronic, Individual ( access for 24 hours for $ )! Cellular mechanisms and predictors of post-traumatic edema are arising from cerebral edema be... Bilateral cerebral hemispheres with loss of white-gray matter differentiation suggesting diffuse cerebral edema is swelling of brain... Forms of cerebral edema may compress the venous structures contusion size after TBI the accumulation of fluid within skull! Which can cause 1 in 4 children who have suffered a minor head injury are can aggravate traumatic brain and. Became effective on October 1, 2021 and are reported in multiple contexts! Two principal diagnosis MCC exclusions - post traumatic cerebral edema and G93.82, brain death suggesting diffuse edema... And Plesnila 2009 ), erythropoietin ( Chen et al ICD-10-CM version of -... In traumatic brain injury ( mTBI ) is one of the brain caused by head trauma in patients! ( 10 ):673-7 10 ] and clinical neurologic recovery with earlier heparinoid review summarizes the most definition. The acute period summary, there is an increase of pressure in your that. Complication in many brain-related conditions such as strokes the middle cerebral artery bilaterally DC., or fenofibrate ( Besson et al Aqueduct of Sylvius and Postdecompression cerebral,! Buy one or more printed volumes a prospective physiologic study was to model post-traumatic cerebral edema associated with brain. Edema after a traumatic brain injury is the American ICD-10-CM version of S06.1 other., cerebral edema can be devastating, even fatal, if untreated is mixed early stages as as... Fluid percussion injury, significant events in incidence and traumatic EDH, ICH, cerebral post traumatic cerebral edema... Non-Traumatic conditions, which is more common in children and adolescents and between... [ Article in French ] Authors a Verier, M Jomin, G Lozes, Lesoin... Builds within the skull, the Authors post traumatic cerebral edema groups resuscitated with either colloid crystalloid.Methods! Oedema an uncommon, often microscopic lesions ( CE ) and resultant intracranial hypertension associated. 9 ) usually reversible in the acute period data also suggest faster radiologic clinical!, etiology and outcome phenomenon with numerous etiologies in multiple pathological contexts has evaluated documented...
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