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      Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

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          Abstract

          Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

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          Most cited references58

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          Analysis of missed cases of abusive head trauma.

          Abusive head trauma (AHT) is a dangerous form of child abuse that can be difficult to diagnose in young children. To determine how frequently AHT was previously missed by physicians in a group of abused children with head injuries and to determine factors associated with the unrecognized diagnosis. Retrospective chart review of cases of head trauma presenting between January 1, 1990, and December 31, 1995. Academic children's hospital. One hundred seventy-three children younger than 3 years with head injuries caused by abuse. Characteristics of head-injured children in whom diagnosis of AHT was unrecognized and the consequences of the missed diagnoses. Fifty-four (31.2%) of 173 abused children with head injuries had been seen by physicians after AHT and the diagnosis was not recognized. The mean time to correct diagnosis among these children was 7 days (range, 0-189 days). Abusive head trauma was more likely to be unrecognized in very young white children from intact families and in children without respiratory compromise or seizures. In 7 of the children with unrecognized AHT, misinterpretation of radiological studies contributed to the delay in diagnosis. Fifteen children (27.8%) were reinjured after the missed diagnosis. Twenty-two (40.7%) experienced medical complications related to the missed diagnosis. Four of 5 deaths in the group with unrecognized AHT might have been prevented by earlier recognition of abuse. Although diagnosing head trauma can be difficult in the absence of a history, it is important to consider inflicted head trauma in infants and young children presenting with nonspecific clinical signs.
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            Spatial navigational strategies correlate with gray matter in the hippocampus of healthy older adults tested in a virtual maze

            Healthy young adults use different strategies when navigating in a virtual maze. Spatial strategies involve using environmental landmarks while response strategies involve executing a series of movements from specific stimuli. Neuroimaging studies previously confirmed that people who use spatial strategies show increased activity and gray matter in the hippocampus, while those who use response strategies show increased activity and gray matter in caudate nucleus (Iaria et al., 2003; Bohbot et al., 2007). A growing number of studies report that cognitive decline that occurs with normal aging is correlated with a decrease in volume of the hippocampus. Here, we used voxel-based morphometry (VBM) to examine whether spatial strategies in aging are correlated with greater gray matter in the hippocampus, as found in our previous study with healthy young participants. Forty-five healthy older adults were tested on a virtual navigation task that allows spatial and response strategies. All participants learn the task to criterion after which a special “probe” trial that assesses spatial and response strategies is given. Results show that spontaneous spatial memory strategies, and not performance on the navigation task, positively correlate with gray matter in the hippocampus. Since numerous studies have shown that a decrease in the volume of the hippocampus correlates with cognitive deficits during normal aging and increases the risks of ensuing dementia, the current results suggest that older people who use their spatial memory strategies in their everyday lives may have increased gray matter in the hippocampus and enhance their probability of healthy and successful aging.
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              Molecular mechanisms of cognitive dysfunction following traumatic brain injury

              Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                31 July 2015
                August 2015
                : 4
                : 8
                : 1536-1560
                Affiliations
                [1 ]Children’s Hospital of The Kings Daughters, Eastern Virginia Medical School, Norfolk, Virginia, VA 23507, USA; E-Mail: Kent.Reifschneider@ 123456chkd.org
                [2 ]Children’s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226, USA; E-Mail: bauble@ 123456mcw.edu
                [3 ]Cincinnati Children’s Hospital Medical Center and College of Medicine, University of Cincinnati, MD, 3333 Burnet Avenue, MLC 7012, Cincinnati, OH 45229, USA
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: susan.rose@ 123456cchmc.org ; Tel.: +1-513-636-4744; Fax: +1-513-636-7486.
                Article
                jcm-04-01536
                10.3390/jcm4081536
                4555075
                26287247
                7ee4fdea-0564-4318-8605-1da140231206
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 February 2015
                : 17 July 2015
                Categories
                Review

                traumatic brain injury,hypopituitarism,precocious puberty,hypogonadotropic hypogonadism,central hypothyroidism,growth hormone deficiency,adrenal insufficiency,hyperprolactinemia,adult,pediatric

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