Immediate Neurological Recovery Following Perispinal Etanercept Years After Brain Injury
Positron emission tomographic brain imaging and pathological examination have revealed that a chronic, intracerebral neuroinflammatory response lasting for years after a single brain injury may occur in humans. Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrall...
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| Veröffentlicht in: | Clinical drug investigation 2014-05, Vol.34 (5), p.361-366 |
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| creator | Tobinick, Edward Rodriguez-Romanacce, Helen Levine, Arthur Ignatowski, Tracey A. Spengler, Robert N. |
| description | Positron emission tomographic brain imaging and pathological examination have revealed that a chronic, intracerebral neuroinflammatory response lasting for years after a single brain injury may occur in humans. Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrally involved in this pathology through its modulation of microglial activation, role in synaptic dysfunction, and induction of depressive symptoms and neuropathic pain. Etanercept is a recombinant TNF receptor fusion protein and potent TNF inhibitor that has been found to reduce microglial activation and neuropathic pain in multiple experimental models. We report that a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury. These results indicate that acute brain injury-induced pathologic levels of TNF may provide a therapeutic target that can be addressed years after injury. Perispinal administration of etanercept is capable of producing immediate relief from brain injury-mediated neurological dysfunction. |
| doi_str_mv | 10.1007/s40261-014-0186-1 |
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Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrally involved in this pathology through its modulation of microglial activation, role in synaptic dysfunction, and induction of depressive symptoms and neuropathic pain. Etanercept is a recombinant TNF receptor fusion protein and potent TNF inhibitor that has been found to reduce microglial activation and neuropathic pain in multiple experimental models. We report that a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury. These results indicate that acute brain injury-induced pathologic levels of TNF may provide a therapeutic target that can be addressed years after injury. Perispinal administration of etanercept is capable of producing immediate relief from brain injury-mediated neurological dysfunction.</description><identifier>ISSN: 1173-2563</identifier><identifier>EISSN: 1179-1918</identifier><identifier>DOI: 10.1007/s40261-014-0186-1</identifier><identifier>PMID: 24647830</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Brain Injuries - drug therapy ; Brain Injuries - immunology ; Brain Injuries - pathology ; Brain Injuries - physiopathology ; Case Report ; Etanercept ; Female ; Humans ; Immunoglobulin G - administration & dosage ; Immunoglobulin G - pharmacology ; Immunoglobulin G - therapeutic use ; Internal Medicine ; Medicine ; Medicine & Public Health ; Middle Aged ; Pharmacology/Toxicology ; Pharmacotherapy ; Receptors, Tumor Necrosis Factor - administration & dosage ; Receptors, Tumor Necrosis Factor - therapeutic use ; Recovery of Function - drug effects ; Tumor Necrosis Factor-alpha - antagonists & inhibitors ; Tumor Necrosis Factor-alpha - immunology ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Clinical drug investigation, 2014-05, Vol.34 (5), p.361-366</ispartof><rights>Springer International Publishing Switzerland 2014</rights><rights>Copyright Wolters Kluwer Health Adis International May 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-f04663af6003a828ce8244eeeec254af7b4cc07b3f031b69e0415cd9c4be25a43</citedby><cites>FETCH-LOGICAL-c372t-f04663af6003a828ce8244eeeec254af7b4cc07b3f031b69e0415cd9c4be25a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40261-014-0186-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40261-014-0186-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24647830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tobinick, Edward</creatorcontrib><creatorcontrib>Rodriguez-Romanacce, Helen</creatorcontrib><creatorcontrib>Levine, Arthur</creatorcontrib><creatorcontrib>Ignatowski, Tracey A.</creatorcontrib><creatorcontrib>Spengler, Robert N.</creatorcontrib><title>Immediate Neurological Recovery Following Perispinal Etanercept Years After Brain Injury</title><title>Clinical drug investigation</title><addtitle>Clin Drug Investig</addtitle><addtitle>Clin Drug Investig</addtitle><description>Positron emission tomographic brain imaging and pathological examination have revealed that a chronic, intracerebral neuroinflammatory response lasting for years after a single brain injury may occur in humans. Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrally involved in this pathology through its modulation of microglial activation, role in synaptic dysfunction, and induction of depressive symptoms and neuropathic pain. Etanercept is a recombinant TNF receptor fusion protein and potent TNF inhibitor that has been found to reduce microglial activation and neuropathic pain in multiple experimental models. We report that a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury. These results indicate that acute brain injury-induced pathologic levels of TNF may provide a therapeutic target that can be addressed years after injury. Perispinal administration of etanercept is capable of producing immediate relief from brain injury-mediated neurological dysfunction.</description><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Brain Injuries - drug therapy</subject><subject>Brain Injuries - immunology</subject><subject>Brain Injuries - pathology</subject><subject>Brain Injuries - physiopathology</subject><subject>Case Report</subject><subject>Etanercept</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G - administration & dosage</subject><subject>Immunoglobulin G - pharmacology</subject><subject>Immunoglobulin G - therapeutic use</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Receptors, Tumor Necrosis Factor - administration & dosage</subject><subject>Receptors, Tumor Necrosis Factor - therapeutic use</subject><subject>Recovery of Function - drug effects</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>1173-2563</issn><issn>1179-1918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kE1LxDAQhoMofv8AL1Lw4qWaSdIkPar4sSAqoqCnkMbp0qXbrEmr7L8366qIYCAkMM-8kzyE7AE9AkrVcRSUScgpiLS1zGGFbAKoMocS9OrnneeskHyDbMU4oRQkSLZONpiQQmlON8nTaDrFl8b2mN3gEHzrx42zbXaPzr9hmGcXvm39e9ONszsMTZw1Xaqe97bD4HDWZ89oQ8xO6h5Ddhps02WjbjKE-Q5Zq20bcffr3CaPF-cPZ1f59e3l6OzkOndcsT6vqZCS21pSyq1m2qFmQmBajhXC1qoSzlFV8ZpyqGSJVEDhXkonKmSFFXybHC5zZ8G_Dhh7M22iw7ZNL_RDNFCA0koLXSb04A868UNI_1lQUpaCK7oIhCXlgo8xYG1moZnaMDdAzUK7WWo3SbtZaDeQeva_kocq6fzp-PacALYEYip1Ywy_Rv-b-gFKUIz6</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Tobinick, Edward</creator><creator>Rodriguez-Romanacce, Helen</creator><creator>Levine, Arthur</creator><creator>Ignatowski, Tracey A.</creator><creator>Spengler, Robert N.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20140501</creationdate><title>Immediate Neurological Recovery Following Perispinal Etanercept Years After Brain Injury</title><author>Tobinick, Edward ; Rodriguez-Romanacce, Helen ; Levine, Arthur ; Ignatowski, Tracey A. ; Spengler, Robert N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-f04663af6003a828ce8244eeeec254af7b4cc07b3f031b69e0415cd9c4be25a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Brain Injuries - drug therapy</topic><topic>Brain Injuries - immunology</topic><topic>Brain Injuries - pathology</topic><topic>Brain Injuries - physiopathology</topic><topic>Case Report</topic><topic>Etanercept</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin G - administration & dosage</topic><topic>Immunoglobulin G - pharmacology</topic><topic>Immunoglobulin G - therapeutic use</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Receptors, Tumor Necrosis Factor - administration & dosage</topic><topic>Receptors, Tumor Necrosis Factor - therapeutic use</topic><topic>Recovery of Function - drug effects</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tobinick, Edward</creatorcontrib><creatorcontrib>Rodriguez-Romanacce, Helen</creatorcontrib><creatorcontrib>Levine, Arthur</creatorcontrib><creatorcontrib>Ignatowski, Tracey A.</creatorcontrib><creatorcontrib>Spengler, Robert N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical drug investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tobinick, Edward</au><au>Rodriguez-Romanacce, Helen</au><au>Levine, Arthur</au><au>Ignatowski, Tracey A.</au><au>Spengler, Robert N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immediate Neurological Recovery Following Perispinal Etanercept Years After Brain Injury</atitle><jtitle>Clinical drug investigation</jtitle><stitle>Clin Drug Investig</stitle><addtitle>Clin Drug Investig</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>34</volume><issue>5</issue><spage>361</spage><epage>366</epage><pages>361-366</pages><issn>1173-2563</issn><eissn>1179-1918</eissn><abstract>Positron emission tomographic brain imaging and pathological examination have revealed that a chronic, intracerebral neuroinflammatory response lasting for years after a single brain injury may occur in humans. Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrally involved in this pathology through its modulation of microglial activation, role in synaptic dysfunction, and induction of depressive symptoms and neuropathic pain. Etanercept is a recombinant TNF receptor fusion protein and potent TNF inhibitor that has been found to reduce microglial activation and neuropathic pain in multiple experimental models. We report that a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury. These results indicate that acute brain injury-induced pathologic levels of TNF may provide a therapeutic target that can be addressed years after injury. Perispinal administration of etanercept is capable of producing immediate relief from brain injury-mediated neurological dysfunction.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>24647830</pmid><doi>10.1007/s40261-014-0186-1</doi><tpages>6</tpages></addata></record> |
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| subjects | Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - pharmacology Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Brain Injuries - drug therapy Brain Injuries - immunology Brain Injuries - pathology Brain Injuries - physiopathology Case Report Etanercept Female Humans Immunoglobulin G - administration & dosage Immunoglobulin G - pharmacology Immunoglobulin G - therapeutic use Internal Medicine Medicine Medicine & Public Health Middle Aged Pharmacology/Toxicology Pharmacotherapy Receptors, Tumor Necrosis Factor - administration & dosage Receptors, Tumor Necrosis Factor - therapeutic use Recovery of Function - drug effects Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - metabolism |
| title | Immediate Neurological Recovery Following Perispinal Etanercept Years After Brain Injury |
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