Neurological Complications during Treatment of Middle East Respiratory Syndrome
Identifieur interne : 000649 ( Ncbi/Merge ); précédent : 000648; suivant : 000650Neurological Complications during Treatment of Middle East Respiratory Syndrome
Auteurs : Jee-Eun Kim [Corée du Sud] ; Jae-Hyeok Heo [Corée du Sud] ; Hye-Ok Kim [Corée du Sud] ; Sook-Hee Song [Corée du Sud] ; Sang-Soon Park [Corée du Sud] ; Tai-Hwan Park [Corée du Sud] ; Jin-Young Ahn [Corée du Sud] ; Min-Ky Kim [Corée du Sud] ; Jae-Phil Choi [Corée du Sud]Source :
- Journal of Clinical Neurology (Seoul, Korea) [ 1738-6586 ] ; 2017.
Abstract
Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012.
We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described.
Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks.
Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.
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DOI: 10.3988/jcn.2017.13.3.227
PubMed: 28748673
PubMed Central: 5532318
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last="Heo">Jae-Hyeok Heo</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Neurology, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Neurology, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Hye Ok" sort="Kim, Hye Ok" uniqKey="Kim H" first="Hye-Ok" last="Kim">Hye-Ok Kim</name><affiliation wicri:level="3"><nlm:aff id="A2">Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Song, Sook Hee" sort="Song, Sook Hee" uniqKey="Song S" first="Sook-Hee" last="Song">Sook-Hee Song</name><affiliation wicri:level="3"><nlm:aff id="A2">Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Park, Sang Soon" sort="Park, Sang Soon" uniqKey="Park S" first="Sang-Soon" last="Park">Sang-Soon Park</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Neurology, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Neurology, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Park, Tai Hwan" sort="Park, Tai Hwan" uniqKey="Park T" first="Tai-Hwan" last="Park">Tai-Hwan Park</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Neurology, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Neurology, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Ahn, Jin Young" sort="Ahn, Jin Young" uniqKey="Ahn J" first="Jin-Young" last="Ahn">Jin-Young Ahn</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Neurology, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Neurology, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Min Ky" sort="Kim, Min Ky" uniqKey="Kim M" first="Min-Ky" last="Kim">Min-Ky Kim</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Neurology, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Neurology, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Choi, Jae Phil" sort="Choi, Jae Phil" uniqKey="Choi J" first="Jae-Phil" last="Choi">Jae-Phil Choi</name><affiliation wicri:level="3"><nlm:aff id="A3">Division of Infectious Diseases, Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Seoul Medical Center, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author></analytic><series><title level="j">Journal of Clinical Neurology (Seoul, Korea)</title><idno type="ISSN">1738-6586</idno><idno type="eISSN">2005-5013</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background and Purpose</title><p>Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012.</p></sec><sec><title>Methods</title><p>We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described.</p></sec><sec><title>Results</title><p>Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks.</p></sec><sec><title>Conclusions</title><p>Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Desforges, M" uniqKey="Desforges M">M Desforges</name></author><author><name sortKey="Le 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Neurol</journal-id><journal-id journal-id-type="iso-abbrev">J Clin Neurol</journal-id><journal-id journal-id-type="publisher-id">JCN</journal-id><journal-title-group><journal-title>Journal of Clinical Neurology (Seoul, Korea)</journal-title></journal-title-group><issn pub-type="ppub">1738-6586</issn><issn pub-type="epub">2005-5013</issn><publisher><publisher-name>Korean Neurological Association</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28748673</article-id><article-id pub-id-type="pmc">5532318</article-id><article-id pub-id-type="doi">10.3988/jcn.2017.13.3.227</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Neurological Complications during Treatment of Middle East Respiratory Syndrome</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Kim</surname><given-names>Jee-Eun</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Heo</surname><given-names>Jae-Hyeok</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Hye-ok</given-names></name><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Sook-hee</given-names></name><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Sang-Soon</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Tai-Hwan</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Ahn</surname><given-names>Jin-Young</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Min-Ky</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Choi</surname><given-names>Jae-Phil</given-names></name><xref ref-type="aff" rid="A3">c</xref></contrib></contrib-group><aff id="A1"><label>a</label>Department of Neurology, Seoul Medical Center, Seoul, Korea.</aff><aff id="A2"><label>b</label>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.</aff><aff id="A3"><label>c</label>Division of Infectious Diseases, Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.</aff><author-notes><corresp>Correspondence: Jee-Eun Kim, MD, PhD. Department of Neurology, Seoul Medical Center, 156 Sinnae-ro, Jungnang-gu, Seoul 02053, Korea. Tel +82-2-2276-8637, Fax +82-2-2276-8509, <email>junenr@gmail.com</email></corresp><corresp>Correspondence: Jae-Phil Choi, MD. Division of Infectious Diseases, Department of Internal Medicine, Seoul Medical Center, 156 Sinnae-ro, Jungnang-gu, Seoul 02053, Korea. Tel +82-2-2276-8663, Fax +82-2-2276-7820, <email>dasole@hanmail.net</email></corresp></author-notes><pub-date pub-type="ppub"><month>7</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>30</day><month>6</month><year>2017</year></pub-date><volume>13</volume><issue>3</issue><fpage>227</fpage><lpage>233</lpage><history><date date-type="received"><day>15</day><month>2</month><year>2017</year></date><date date-type="rev-recd"><day>16</day><month>5</month><year>2017</year></date><date date-type="accepted"><day>18</day><month>5</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017 Korean Neurological Association</copyright-statement><copyright-year>2017</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><sec><title>Background and Purpose</title><p>Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012.</p></sec><sec><title>Methods</title><p>We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described.</p></sec><sec><title>Results</title><p>Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks.</p></sec><sec><title>Conclusions</title><p>Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.</p></sec></abstract><kwd-group><kwd>Guillain-Barré syndrome</kwd><kwd>Middle East respiratory syndrome</kwd><kwd>neurological complications</kwd><kwd>peripheral neuropathy</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" orientation="portrait" position="float"><label>Fig. 1</label><caption><title>Timeline of clinical events and virological results in patient 1. The onset of neurological symptoms and their course during the sedative state were uncertain, and are indicated by the dotted lines. HD: hospital day, IVIG: intravenous immunoglobulin, MV: mechanical ventilator, TA: tracheal aspirate.</title></caption><graphic xlink:href="jcn-13-227-g001"></graphic></fig><table-wrap id="T1" orientation="portrait" position="float"><label>Table 1</label><caption><title>Demographic features of patients with laboratory-confirmed MERS coronavirus infection</title></caption><alternatives><graphic xlink:href="jcn-13-227-i001"></graphic><table frame="hsides" rules="rows"><col width="70%" span="1"></col><col width="30%" span="1"></col><thead><tr><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Variable</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Value (<italic>n</italic>=23)</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Sex, male</td><td valign="top" align="center" rowspan="1" colspan="1">14 (60.9)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Age, years</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">46 (39–69)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Incubation period, days<sup>*</sup></td><td valign="top" align="center" rowspan="1" colspan="1">7 (3–14)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Time from symptom onset to antiviral therapy, days</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">6 (2–8)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Comorbid illness</td><td valign="top" align="center" rowspan="1" colspan="1">12 (52.2)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Diabetes mellitus</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">3 (13.0)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Hypertension</td><td valign="top" align="center" rowspan="1" colspan="1">1 (4.3)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Chronic heart disease</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">2 (8.7)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Chronic renal disease</td><td valign="top" align="center" rowspan="1" colspan="1">1 (4.3)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Bronchiectasis</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">1 (4.3)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Malignancy<sup>†</sup></td><td valign="top" align="center" rowspan="1" colspan="1">1 (4.3)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Psychiatric disorder</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">2 (8.7)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Ankylosing spondylitis</td><td valign="top" align="center" rowspan="1" colspan="1">1 (4.3)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Symptoms during the disease course</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Fever≥38°C</td><td valign="top" align="center" rowspan="1" colspan="1">13 (56.5)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Cough/sputum</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">17 (73.9)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Dyspnea</td><td valign="top" align="center" rowspan="1" colspan="1">9 (39.1)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Myalgia or arthralgia</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">6 (26.9)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Headache</td><td valign="top" align="center" rowspan="1" colspan="1">2 (8.7)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Confusion</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">5 (21.7)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Seizure</td><td valign="top" align="center" rowspan="1" colspan="1">0 (0)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> GI symptoms (nausea, vomiting, or diarrhea)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">18 (78.26)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Asymptomatic</td><td valign="top" align="center" rowspan="1" colspan="1">0 (0)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Chest radiography abnormalities</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">23 (100)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Outcomes</td><td valign="top" align="center" rowspan="1" colspan="1"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Need for oxygen supply</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">9 (39.1)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Need for high-flow nasal cannula</td><td valign="top" align="center" rowspan="1" colspan="1">3 (13.0)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Need for mechanical ventilation</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">5 (21.7)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Need for ECMO</td><td valign="top" align="center" rowspan="1" colspan="1">1 (4.3)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Time from hospital admission to discharge of survivors, days</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">13 (5–17)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">In-hospital mortality</td><td valign="top" align="center" rowspan="1" colspan="1">4 (17.4)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Time from hospital admission to death of nonsurvivors, days, median (range)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">13 (5–26)</td></tr></tbody></table></alternatives><table-wrap-foot><fn><p>Except where indicated otherwise, data are median (interquartile range) or <italic>n</italic> (%) values.</p><p><sup>*</sup>Five patients with an obscure incubation period were not included in the calculation, <sup>†</sup>One of the patients had a malignancy, hepatocellular carcinoma.</p><p>ECMO: extracorporeal membrane oxygenation, GI: gastrointestinal, MERS: Middle East respiratory syndrome.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" orientation="portrait" position="float"><label>Table 2</label><caption><title>Clinical presentations of patients with MERS who experienced neurological complications, and the therapies applied to them</title></caption><alternatives><graphic xlink:href="jcn-13-227-i002"></graphic><table frame="hsides" rules="rows"><col width="20%" span="1"></col><col width="20%" span="1"></col><col width="20%" span="1"></col><col width="20%" span="1"></col><col width="20%" span="1"></col><thead><tr><th valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"></th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 1</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 2</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 3</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 4</th></tr></thead><tbody><tr><td valign="middle" align="left" rowspan="1" colspan="1">Sex/age, years</td><td valign="middle" align="center" rowspan="1" colspan="1">Male/55</td><td valign="middle" align="center" rowspan="1" colspan="1">Female/43</td><td valign="middle" align="center" rowspan="1" colspan="1">Male/46</td><td valign="middle" align="center" rowspan="1" colspan="1">Female/38</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Incubation period, days</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">5–18</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">10</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">4</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">3</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">Initial symptoms</td><td valign="middle" align="center" rowspan="1" colspan="1">Cough, dyspnea, and chest discomfort</td><td valign="middle" align="center" rowspan="1" colspan="1">Fever, myalgia, chills, cough, sputum, and headache</td><td valign="middle" align="center" rowspan="1" colspan="1">Fever, cough, dyspnea, and headache</td><td valign="middle" align="center" rowspan="1" colspan="1">Cough, sore throat, and fever</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">GI symptoms</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">-</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Vomiting and nausea</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">diarrhea</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">-</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">Hospital course and treatment</td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Respiratory support</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Mechanical ventilation</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">HFNC</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">5 L/min nasal oxygen</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">2 L/min nasal oxygen</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> PSI</td><td valign="middle" align="center" rowspan="1" colspan="1">104</td><td valign="middle" align="center" rowspan="1" colspan="1">63</td><td valign="middle" align="center" rowspan="1" colspan="1">56</td><td valign="middle" align="center" rowspan="1" colspan="1">48</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Sepsis severity<sup>*</sup></td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Septic shock</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Sepsis</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Sepsis</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Pneumonia</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> SAPS II</td><td valign="middle" align="center" rowspan="1" colspan="1">74</td><td valign="middle" align="center" rowspan="1" colspan="1">37</td><td valign="middle" align="center" rowspan="1" colspan="1">42</td><td valign="middle" align="center" rowspan="1" colspan="1">30</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Antiviral regimen</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">IFN, Rb, and LR</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">IFN, Rb, and LR</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">IFN, Rb, and LR</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">IFN, Rb, and LR</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> Antibiotics used before onset of neurological symptoms</td><td valign="middle" align="center" rowspan="1" colspan="1">Ceftazidime, teicoplanin, meropenem, and moxifloxacin</td><td valign="middle" align="center" rowspan="1" colspan="1">-</td><td valign="middle" align="center" rowspan="1" colspan="1">-</td><td valign="middle" align="center" rowspan="1" colspan="1">-</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> IVIG treatment</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Yes</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">No</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">No</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">No</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> Steroid treatment</td><td valign="middle" align="center" rowspan="1" colspan="1">No</td><td valign="middle" align="center" rowspan="1" colspan="1">No</td><td valign="middle" align="center" rowspan="1" colspan="1">No</td><td valign="middle" align="center" rowspan="1" colspan="1">No</td></tr></tbody></table></alternatives><table-wrap-foot><fn><p><sup>*</sup>Sepsis is defined as life-threatening organ dysfunction from a dysregulated host reaction to an infection. Septic shock represents a subtype of sepsis that is accompanied by severe circulatory, cellular, and metabolic abnormalities that increase mortality.<xref rid="B10" ref-type="bibr">10</xref></p><p>GI: gastrointestinal, HFNC: high-flow nasal cannula oxygen therapy, IFN: type 1 interferon, IVIG: intravenous immunoglobulin, LR: lopinavir/ritonavir, MERS: Middle East respiratory syndrome, PSI: Pneumonia Severity Index, Rb: ribavirin, SAPS II: Simplified Acute Physiology Score II.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T3" orientation="portrait" position="float"><label>Table 3</label><caption><title>Neurological manifestations and laboratory findings in patients with laboratory-confirmed MERS</title></caption><alternatives><graphic xlink:href="jcn-13-227-i003"></graphic><table frame="hsides" rules="rows"><col width="20%" span="1"></col><col width="20%" span="1"></col><col width="20%" span="1"></col><col width="20%" span="1"></col><col width="20%" span="1"></col><thead><tr><th valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"></th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 1</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 2</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 3</th><th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Patient 4</th></tr></thead><tbody><tr><td valign="middle" align="left" rowspan="1" colspan="1">Neurological symptoms</td><td valign="middle" align="center" rowspan="1" colspan="1">Hypersomnolence and weakness in all four limbs</td><td valign="middle" align="center" rowspan="1" colspan="1">Tingling/pain in both hands and below the knees, and weakness in both legs</td><td valign="middle" align="center" rowspan="1" colspan="1">Tingling in distal parts of both hands and feet</td><td valign="middle" align="center" rowspan="1" colspan="1">Tingling in both hands</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Days after MERS onset</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Unclear<sup>*</sup></td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">16</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">20</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">21</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">Neurological examination</td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Cranial nerves</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Ptosis and ophthalmoplegia</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> Motor</td><td valign="middle" align="center" rowspan="1" colspan="1">Weakness in all four limbs</td><td valign="middle" align="center" rowspan="1" colspan="1">Proximal dominant weakness in both legs</td><td valign="middle" align="center" rowspan="1" colspan="1">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1">Normal</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Sensory</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Hypesthesia in distal parts of all four limbs</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> Deep tendon reflex</td><td valign="middle" align="center" rowspan="1" colspan="1">Hyporeflexia in all four limbs</td><td valign="middle" align="center" rowspan="1" colspan="1">Hyporeflexia in both legs</td><td valign="middle" align="center" rowspan="1" colspan="1">Hyporeflexia in both legs</td><td valign="middle" align="center" rowspan="1" colspan="1">Normal</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Cerebellar function</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Limb ataxia</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">Laboratory findings</td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td><td valign="middle" align="center" rowspan="1" colspan="1"></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> CSF</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">NA</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">NA</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">NA</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"> NCS</td><td valign="middle" align="center" rowspan="1" colspan="1">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1">Normal</td><td valign="middle" align="center" rowspan="1" colspan="1">NA</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)"> Peak serum creatine kinase, U/L</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">45</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">48</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">99</td><td valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(241,230,225)">NA</td></tr></tbody></table></alternatives><table-wrap-foot><fn><p><sup>*</sup>Neurological symptoms were detected 24 days after the initial onset of respiratory symptoms.</p><p>CSF: cerebrospinal fluid, MERS: Middle East respiratory syndrome, NA: not available, NCS: nerve conduction study.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Jee Eun" sort="Kim, Jee Eun" uniqKey="Kim J" first="Jee-Eun" last="Kim">Jee-Eun Kim</name></region><name sortKey="Ahn, Jin Young" sort="Ahn, Jin Young" uniqKey="Ahn J" first="Jin-Young" last="Ahn">Jin-Young Ahn</name><name sortKey="Choi, Jae Phil" sort="Choi, Jae Phil" uniqKey="Choi J" first="Jae-Phil" last="Choi">Jae-Phil Choi</name><name sortKey="Heo, Jae Hyeok" sort="Heo, Jae Hyeok" uniqKey="Heo J" first="Jae-Hyeok" last="Heo">Jae-Hyeok Heo</name><name sortKey="Kim, Hye Ok" sort="Kim, Hye Ok" uniqKey="Kim H" first="Hye-Ok" last="Kim">Hye-Ok Kim</name><name sortKey="Kim, Min Ky" sort="Kim, Min Ky" uniqKey="Kim M" first="Min-Ky" last="Kim">Min-Ky Kim</name><name sortKey="Park, Sang Soon" sort="Park, Sang Soon" uniqKey="Park S" first="Sang-Soon" last="Park">Sang-Soon Park</name><name sortKey="Park, Tai Hwan" sort="Park, Tai Hwan" uniqKey="Park T" first="Tai-Hwan" last="Park">Tai-Hwan Park</name><name sortKey="Song, Sook Hee" sort="Song, Sook Hee" uniqKey="Song S" first="Sook-Hee" last="Song">Sook-Hee Song</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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