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      Concussion and the autonomic nervous system: An introduction to the field and the results of a systematic review

      review-article
      a , * , b , c , c , d , e , e
      Neurorehabilitation
      IOS Press
      Concussion, mild traumatic brain injury, post-concussion syndrome, autonomic dysfunction, orthostatic intolerance

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          Abstract

          BACKGROUND:

          Recent evidence suggests that autonomic nervous dysfunction may be one of many potential factors contributing to persisting post-concussion symptoms.

          OBJECTIVE:

          This is the first systematic review to explore the impact of concussion on multiple aspects of autonomic nervous system functioning.

          METHODS:

          The methods employed are in compliance with the American Academy of Neurology (AAN) and PRISMA standards. Embase, MEDLINE, PsychINFO, and Science Citation Index literature searches were performed using relevant indexing terms for articles published prior to the end of December 2016. Data extraction was performed by two independent groups, including study quality indicators to determine potential risk for bias according to the 4-tiered classification scheme of the AAN.

          RESULTS:

          Thirty-six articles qualified for inclusion in the analysis. Only three studies (one Class II and two Class IV) did not identify anomalies in measures of ANS functioning in concussed populations.

          CONCLUSIONS:

          The evidence supports the conclusion that it is likely that concussion causes autonomic nervous system anomalies. An awareness of this relationship increases our understanding of the physical impact of concussion, partially explains the overlap of concussion symptoms with other medical conditions, presents opportunities for further research, and has the potential to powerfully inform treatment decisions.

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          Most cited references199

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          The neuroscience of mindfulness meditation.

          Research over the past two decades broadly supports the claim that mindfulness meditation - practiced widely for the reduction of stress and promotion of health - exerts beneficial effects on physical and mental health, and cognitive performance. Recent neuroimaging studies have begun to uncover the brain areas and networks that mediate these positive effects. However, the underlying neural mechanisms remain unclear, and it is apparent that more methodologically rigorous studies are required if we are to gain a full understanding of the neuronal and molecular bases of the changes in the brain that accompany mindfulness meditation.
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            Heart rate variability: a review.

            Heart rate variability (HRV) is a reliable reflection of the many physiological factors modulating the normal rhythm of the heart. In fact, they provide a powerful means of observing the interplay between the sympathetic and parasympathetic nervous systems. It shows that the structure generating the signal is not only simply linear, but also involves nonlinear contributions. Heart rate (HR) is a nonstationary signal; its variation may contain indicators of current disease, or warnings about impending cardiac diseases. The indicators may be present at all times or may occur at random-during certain intervals of the day. It is strenuous and time consuming to study and pinpoint abnormalities in voluminous data collected over several hours. Hence, HR variation analysis (instantaneous HR against time axis) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system. Computer based analytical tools for in-depth study of data over daylong intervals can be very useful in diagnostics. Therefore, the HRV signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. In this paper, we have discussed the various applications of HRV and different linear, frequency domain, wavelet domain, nonlinear techniques used for the analysis of the HRV.
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              The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system.

              The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis. Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest. In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta. Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production. Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages. The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth. Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.
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                Author and article information

                Journal
                NeuroRehabilitation
                NeuroRehabilitation
                NRE
                Neurorehabilitation
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1053-8135
                1878-6448
                7 April 2018
                29 June 2018
                2018
                : 42
                : 4
                : 397-427
                Affiliations
                [a ]Neurosciences Institute , Intermountain Healthcare, Murray, UT, USA
                [b ]Department of Clinical Neuropsychology, Barrow Neurological Institute , Phoenix, AZ, USA
                [c ]Summit Neuropsychology , Reno, NV, USA
                [d ]VA Sierra Nevada Healthcare System, Reno, NV, USA
                [e ] Hauenstein Neurosciences of Mercy Health and Department of Translational Science and Molecular Medicine, Michigan State University , MI, USA
                Author notes
                [* ]Address for correspondence: Jon L. Pertab, Ph.D., Neurosciences Institute, Intermountain Healthcare, 5171S Cottonwood St. Ste. 810, Murray, UT 84107, USA. Tel.: +1 801 507 9800; Fax: +1 801 507 9801; E-mail: jon.pertab@ 123456imail.org .
                Article
                NRE172298
                10.3233/NRE-172298
                6027940
                29660949
                2cbacc25-6ea9-45bf-b9ed-1e820ad595b9
                © 2018 – IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Review Article

                concussion,mild traumatic brain injury,post-concussion syndrome,autonomic dysfunction,orthostatic intolerance

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