Challenges Assessing Clinical Endpoints in Early Huntington Disease
Identifieur interne : 000B67 ( PascalFrancis/Checkpoint ); précédent : 000B66; suivant : 000B68Challenges Assessing Clinical Endpoints in Early Huntington Disease
Auteurs : Jane S. Paulsen [États-Unis] ; CHIACHI WANG [États-Unis] ; Kevin Duff [États-Unis] ; Roger Barker [Royaume-Uni] ; Martha Nance [États-Unis] ; Leigh Beglinger [États-Unis] ; David Moser [États-Unis] ; Janet K. Williams [États-Unis] ; Sheila Simpson [Royaume-Uni] ; Douglas Langbehn [États-Unis] ; Daniel P. Van Kammen [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
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Abstract
The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow-up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life funtion. © 2010 Movement Disorder Society.
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Paulsen</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Neurology, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Chiachi Wang" sort="Chiachi Wang" uniqKey="Chiachi Wang" last="Chiachi Wang">CHIACHI WANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Duff, Kevin" sort="Duff, Kevin" uniqKey="Duff K" first="Kevin" last="Duff">Kevin Duff</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Barker, Roger" sort="Barker, Roger" uniqKey="Barker R" first="Roger" last="Barker">Roger Barker</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Cambridge Center for Brain Repair</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>4 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge Center for Brain Repair</wicri:noRegion></affiliation></author><author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Neurology, Park Nicollet Clinic</s1><s2>St. Louis Park, Minnesota</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Beglinger, Leigh" sort="Beglinger, Leigh" uniqKey="Beglinger L" first="Leigh" last="Beglinger">Leigh Beglinger</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Moser, David" sort="Moser, David" uniqKey="Moser D" first="David" last="Moser">David Moser</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Williams, Janet K" sort="Williams, Janet K" uniqKey="Williams J" first="Janet K." last="Williams">Janet K. Williams</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>College of Nursing, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Simpson, Sheila" sort="Simpson, Sheila" uniqKey="Simpson S" first="Sheila" last="Simpson">Sheila Simpson</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>North of Scotland Clinical Genetics Service</s1><s2>Aberdeen, Scotland</s2><s3>GBR</s3><sZ>9 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>North of Scotland Clinical Genetics Service</wicri:noRegion></affiliation></author><author><name sortKey="Langbehn, Douglas" sort="Langbehn, Douglas" uniqKey="Langbehn D" first="Douglas" last="Langbehn">Douglas Langbehn</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Biostatistics, University of Iowa College of Public Health</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Van Kammen, Daniel P" sort="Van Kammen, Daniel P" uniqKey="Van Kammen D" first="Daniel P." last="Van Kammen">Daniel P. Van Kammen</name><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>CHDI Management, Inc., CHDI Foundation</s1><s2>Princeton, New Jersey</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0512938</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0512938 INIST</idno><idno type="RBID">Pascal:10-0512938</idno><idno type="wicri:Area/PascalFrancis/Corpus">000808</idno><idno type="wicri:Area/PascalFrancis/Curation">002511</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000B67</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Challenges Assessing Clinical Endpoints in Early Huntington Disease</title><author><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S." last="Paulsen">Jane S. Paulsen</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Neurology, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Chiachi Wang" sort="Chiachi Wang" uniqKey="Chiachi Wang" last="Chiachi Wang">CHIACHI WANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Duff, Kevin" sort="Duff, Kevin" uniqKey="Duff K" first="Kevin" last="Duff">Kevin Duff</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Barker, Roger" sort="Barker, Roger" uniqKey="Barker R" first="Roger" last="Barker">Roger Barker</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Cambridge Center for Brain Repair</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>4 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge Center for Brain Repair</wicri:noRegion></affiliation></author><author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Neurology, Park Nicollet Clinic</s1><s2>St. Louis Park, Minnesota</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Beglinger, Leigh" sort="Beglinger, Leigh" uniqKey="Beglinger L" first="Leigh" last="Beglinger">Leigh Beglinger</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Moser, David" sort="Moser, David" uniqKey="Moser D" first="David" last="Moser">David Moser</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Williams, Janet K" sort="Williams, Janet K" uniqKey="Williams J" first="Janet K." last="Williams">Janet K. Williams</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>College of Nursing, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Simpson, Sheila" sort="Simpson, Sheila" uniqKey="Simpson S" first="Sheila" last="Simpson">Sheila Simpson</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>North of Scotland Clinical Genetics Service</s1><s2>Aberdeen, Scotland</s2><s3>GBR</s3><sZ>9 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>North of Scotland Clinical Genetics Service</wicri:noRegion></affiliation></author><author><name sortKey="Langbehn, Douglas" sort="Langbehn, Douglas" uniqKey="Langbehn D" first="Douglas" last="Langbehn">Douglas Langbehn</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Biostatistics, University of Iowa College of Public Health</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Van Kammen, Daniel P" sort="Van Kammen, Daniel P" uniqKey="Van Kammen D" first="Daniel P." last="Van Kammen">Daniel P. Van Kammen</name><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>CHDI Management, Inc., CHDI Foundation</s1><s2>Princeton, New Jersey</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Functional capacity</term><term>Huntington disease</term><term>Nervous system diseases</term><term>Prodrome</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Chorée de Huntington</term><term>Pathologie du système nerveux</term><term>Capacité fonctionnelle</term><term>Prodrome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow-up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life funtion. © 2010 Movement Disorder Society.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>25</s2></fA05><fA06><s2>15</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Challenges Assessing Clinical Endpoints in Early Huntington Disease</s1></fA08><fA11 i1="01" i2="1"><s1>PAULSEN (Jane S.)</s1></fA11><fA11 i1="02" i2="1"><s1>CHIACHI WANG</s1></fA11><fA11 i1="03" i2="1"><s1>DUFF (Kevin)</s1></fA11><fA11 i1="04" i2="1"><s1>BARKER (Roger)</s1></fA11><fA11 i1="05" i2="1"><s1>NANCE (Martha)</s1></fA11><fA11 i1="06" i2="1"><s1>BEGLINGER (Leigh)</s1></fA11><fA11 i1="07" i2="1"><s1>MOSER (David)</s1></fA11><fA11 i1="08" i2="1"><s1>WILLIAMS (Janet K.)</s1></fA11><fA11 i1="09" i2="1"><s1>SIMPSON (Sheila)</s1></fA11><fA11 i1="10" i2="1"><s1>LANGBEHN (Douglas)</s1></fA11><fA11 i1="11" i2="1"><s1>VAN KAMMEN (Daniel P.)</s1></fA11><fA14 i1="01"><s1>Department of Psychiatry, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Neurology, University of Iowa Carver College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ></fA14><fA14 i1="03"><s1>Cambridge Center for Brain Repair</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>4 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Neurology, Park Nicollet Clinic</s1><s2>St. Louis Park, Minnesota</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="05"><s1>College of Nursing, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="06"><s1>North of Scotland Clinical Genetics Service</s1><s2>Aberdeen, Scotland</s2><s3>GBR</s3><sZ>9 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Biostatistics, University of Iowa College of Public Health</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>10 aut.</sZ></fA14><fA14 i1="08"><s1>CHDI Management, Inc., CHDI Foundation</s1><s2>Princeton, New Jersey</s2><s3>USA</s3><sZ>11 aut.</sZ></fA14><fA17 i1="01" i2="1"><s1>PREDICT-HD Investigators of the Huntington Study Group</s1><s3>INC</s3></fA17><fA20><s1>2595-2603</s1></fA20><fA21><s1>2010</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000191411680170</s5></fA43><fA44><s0>0000</s0><s1>© 2010 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>34 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>10-0512938</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow-up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life funtion. © 2010 Movement Disorder Society.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Chorée de Huntington</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Huntington disease</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Corea Huntington</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Capacité fonctionnelle</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Functional capacity</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Capacidad funcional</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Prodrome</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Prodrome</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Pródromo</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Maladie héréditaire</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Genetic disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Enfermedad hereditaria</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>41</s5></fC07><fN21><s1>347</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Iowa</li><li>Minnesota</li><li>New Jersey</li></region><settlement><li>Iowa City</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="États-Unis"><region name="Iowa"><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S." last="Paulsen">Jane S. Paulsen</name></region><name sortKey="Beglinger, Leigh" sort="Beglinger, Leigh" uniqKey="Beglinger L" first="Leigh" last="Beglinger">Leigh Beglinger</name><name sortKey="Chiachi Wang" sort="Chiachi Wang" uniqKey="Chiachi Wang" last="Chiachi Wang">CHIACHI WANG</name><name sortKey="Duff, Kevin" sort="Duff, Kevin" uniqKey="Duff K" first="Kevin" last="Duff">Kevin Duff</name><name sortKey="Langbehn, Douglas" sort="Langbehn, Douglas" uniqKey="Langbehn D" first="Douglas" last="Langbehn">Douglas Langbehn</name><name sortKey="Langbehn, Douglas" sort="Langbehn, Douglas" uniqKey="Langbehn D" first="Douglas" last="Langbehn">Douglas Langbehn</name><name sortKey="Moser, David" sort="Moser, David" uniqKey="Moser D" first="David" last="Moser">David Moser</name><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S." last="Paulsen">Jane S. Paulsen</name><name sortKey="Van Kammen, Daniel P" sort="Van Kammen, Daniel P" uniqKey="Van Kammen D" first="Daniel P." last="Van Kammen">Daniel P. Van Kammen</name><name sortKey="Williams, Janet K" sort="Williams, Janet K" uniqKey="Williams J" first="Janet K." last="Williams">Janet K. Williams</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Barker, Roger" sort="Barker, Roger" uniqKey="Barker R" first="Roger" last="Barker">Roger Barker</name></noRegion><name sortKey="Simpson, Sheila" sort="Simpson, Sheila" uniqKey="Simpson S" first="Sheila" last="Simpson">Sheila Simpson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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