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      Clinical Comparison of 99mTc Exametazime and 123I Ioflupane SPECT in Patients with Chronic Mild Traumatic Brain Injury

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          Abstract

          Background

          This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population.

          Methods and Findings

          Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both 99mTc exametazime to measure cerebral blood flow (CBF) and 123I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients.

          Conclusions

          Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

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          Most cited references44

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          Sensitization of the Trigeminovascular Pathway: Perspective and Implications to Migraine Pathophysiology

          Migraine headache is commonly associated with signs of exaggerated intracranial and extracranial mechanical sensitivities. Patients exhibiting signs of intracranial hypersensitivity testify that their headache throbs and that mundane physical activities that increase intracranial pressure (such as bending over or coughing) intensify the pain. Patients exhibiting signs of extracranial hypersensitivity testify that during migraine their facial skin hurts in response to otherwise innocuous activities such as combing, shaving, letting water run over their face in the shower, or wearing glasses or earrings (termed here cephalic cutaneous allodynia). Such patients often testify that during migraine their bodily skin is hypersensitive and that wearing tight cloth, bracelets, rings, necklaces and socks or using a heavy blanket can be uncomfortable and/or painful (termed her extracephalic cutaneous allodynia). This review summarizes the evidence that support the view that activation of the trigeminovascular pathway contribute to the headache phase of a migraine attack, that the development of throbbing in the initial phase of migraine is mediated by sensitization of peripheral trigeminovascular neurons that innervate the meninges, that the development of cephalic allodynia is propelled by sensitization of second-order trigeminovascular neurons in the spinal trigeminal nucleus which receive converging sensory input from the meninges as well as from the scalp and facial skin, and that the development of extracephalic allodynia is mediated by sensitization of third-order trigeminovascular neurons in the posterior thalamic nuclei which receive converging sensory input from the meninges, facial and body skin.
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            Timing and topography of cerebral blood flow, aura, and headache during migraine attacks.

            Ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura (classic migraine). In the present study, the number of repeatedly studied patients (n = 63) was large enough to determine statistically significant sequences of events and statistically significant spatial relations. The first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere. Further development of this pathological process was accompanied by the aura symptoms. Thereafter headache occurred while regional cerebral blood flow remained decreased. During the headache phase, regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache. In some patients headache disappeared while regional cerebral blood flow remained increased. Although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral, one-third had bilateral headache. Unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated (i.e., aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere). Our results suggest a simple model for migraine attacks: A pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay, it also causes the headache by stimulating local vascular nociceptors. Bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings.
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              Natural history of headache after traumatic brain injury.

              Headache is one of the most common persisting symptoms after traumatic brain injury (TBI). Yet there is a paucity of prospective longitudinal studies of the incidence and prevalence of headache in a sample with a range of injury severity. We sought to describe the natural history of headache in the first year after TBI, and to determine the roles of prior history of headache, sex, and severity of TBI as risk factors for post-traumatic headache. A cohort of 452 acute, consecutive patients admitted to inpatient rehabilitation services with TBI were enrolled during their inpatient rehabilitation from February 2008 to June 2009. Subjects were enrolled across 7 acute rehabilitation centers designated as TBI Model Systems centers. They were prospectively assessed by structured interviews prior to inpatient rehabilitation discharge, and at 3, 6, and 12 months after injury. Results of this natural history study suggest that 71% of participants reported headache during the first year after injury. The prevalence of headache remained high over the first year, with more than 41% of participants reporting headache at 3, 6, and 12 months post-injury. Persons with a pre-injury history of headache (p<0.001) and females (p<0.01) were significantly more likely to report headache. The incidence of headache had no relation to TBI severity (p=0.67). Overall, headache is common in the first year after TBI, independent of the severity of injury range examined in this study. Use of the International Classification of Headache Disorders criteria requiring onset of headache within 1 week of injury underestimates rates of post-traumatic headache. Better understanding of the natural history of headache including timing, type, and risk factors should aid in the design of treatment studies to prevent or reduce the chronicity of headache and its disruptive effects on quality of life.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                24 January 2014
                : 9
                : 1
                : e87009
                Affiliations
                [1 ]Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
                [2 ]Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
                [3 ]Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
                [4 ]Magee Rehabilitation Hospital, Philadelphia, Pennsylvania, United States of America
                [5 ]Amen Clinics, Inc., Newport Beach, California, United States of America
                [6 ]Institute for Neurodegenerative Disorders, New Haven, Connecticut, United States of America
                [7 ]Yale University School of Medicine, New Haven, Connecticut, United States of America
                University Of Cambridge, United Kingdom
                Author notes

                Competing Interests: Dr. Andrew Newberg’s Institution received a grant from GE Healthcare in order to perform the study reported in the paper. However, GE Healthcare had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Daniel Amen is employed by the commercial company, Amen Clinics, Inc. Dr. John Russell is employed by the commercial company, Molecular Neuroimaging. These affiliations do not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: ABN MS CI TL DA DR NW. Performed the experiments: ABN MS AG CI TL DA DR NW. Analyzed the data: ABN MS AG CI TL DA DR NW. Contributed reagents/materials/analysis tools: ABN MS AG CI TL DA DR NW. Wrote the paper: ABN MS AG CI TL DA DR NW.

                Article
                PONE-D-13-37527
                10.1371/journal.pone.0087009
                3901727
                be0aea02-c71a-47ac-83ac-2e9b83a013d8
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 September 2013
                : 17 December 2013
                Page count
                Pages: 9
                Funding
                This work was supported by a grant from GE Healthcare, Princeton, NJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Neuroanatomy
                Neuroscience
                Neuroanatomy
                Neuroimaging
                Medicine
                Anatomy and Physiology
                Neurological System
                Neuroanatomy
                Neurology
                Cerebrovascular Diseases
                Head Injury
                Neuroimaging
                Radiology
                Nuclear Medicine
                SPECT imaging

                Uncategorized
                Uncategorized

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