Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease
Identifieur interne : 000663 ( Main/Corpus ); précédent : 000662; suivant : 000664Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease
Auteurs : M. U. Ferraye ; B. Deb ; V. Fraix ; L. Goetz ; C. Ardouin ; J. Yelnik ; C. Henry-Lagrange ; E. Seigneuret ; B. Piallat ; P. Krack ; J.-F. Le Bas ; A.-L. Benabid ; S. Chabards ; P. PollakSource :
- Brain [ 0006-8950 ] ; 2010-01.
Abstract
Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable riskbenefit ratio.
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DOI: 10.1093/brain/awp229
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U." last="Ferraye">M. U. Ferraye</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation></author><author><name sortKey="Deb, B" sort="Deb, B" uniqKey="Deb B" first="B." last="Deb">B. Deb</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: Bettina.Debu@ujf-grenoble.fr</mods:affiliation></affiliation></author><author><name sortKey="Fraix, V" sort="Fraix, V" uniqKey="Fraix V" first="V." last="Fraix">V. Fraix</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation></author><author><name sortKey="Goetz, L" sort="Goetz, L" uniqKey="Goetz L" first="L." last="Goetz">L. Goetz</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation></author><author><name sortKey="Ardouin, C" sort="Ardouin, C" uniqKey="Ardouin C" first="C." last="Ardouin">C. Ardouin</name><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Yelnik, J" sort="Yelnik, J" uniqKey="Yelnik J" first="J." last="Yelnik">J. Yelnik</name><affiliation><mods:affiliation>4 INSERM UMR_S975, Fdration de Neurologie, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>5 University Pierre et Marie Curie, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>6 Hpital de la Piti-Salptrire, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Henry Lagrange, C" sort="Henry Lagrange, C" uniqKey="Henry Lagrange C" first="C." last="Henry-Lagrange">C. Henry-Lagrange</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation></author><author><name sortKey="Seigneuret, E" sort="Seigneuret, E" uniqKey="Seigneuret E" first="E." last="Seigneuret">E. Seigneuret</name><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Piallat, B" sort="Piallat, B" uniqKey="Piallat B" first="B." last="Piallat">B. Piallat</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation></author><author><name sortKey="Krack, P" sort="Krack, P" uniqKey="Krack P" first="P." last="Krack">P. Krack</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Le Bas, J F" sort="Le Bas, J F" uniqKey="Le Bas J" first="J.-F." last="Le Bas">J.-F. Le Bas</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Benabid, A L" sort="Benabid, A L" uniqKey="Benabid A" first="A.-L." last="Benabid">A.-L. Benabid</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Chabards, S" sort="Chabards, S" uniqKey="Chabards S" first="S." last="Chabards">S. Chabards</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Pollak, P" sort="Pollak, P" uniqKey="Pollak P" first="P." last="Pollak">P. Pollak</name><affiliation><mods:affiliation>1 University of Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</mods:affiliation></affiliation><affiliation><mods:affiliation>3 University Hospital of Grenoble, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-01">2010-01</date><biblScope unit="volume">133</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="205">205</biblScope><biblScope unit="page" to="214">214</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E</idno><idno type="DOI">10.1093/brain/awp229</idno><idno type="ArticleID">awp229</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable riskbenefit ratio.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>M. U. Ferraye</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string></affiliations></json:item><json:item><name>B. Deb</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string><json:string>E-mail: Bettina.Debu@ujf-grenoble.fr</json:string></affiliations></json:item><json:item><name>V. Fraix</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string></affiliations></json:item><json:item><name>L. Goetz</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string></affiliations></json:item><json:item><name>C. Ardouin</name><affiliations><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item><json:item><name>J. Yelnik</name><affiliations><json:string>4 INSERM UMR_S975, Fdration de Neurologie, Paris, France</json:string><json:string>5 University Pierre et Marie Curie, Paris, France</json:string><json:string>6 Hpital de la Piti-Salptrire, Paris, France</json:string></affiliations></json:item><json:item><name>C. Henry-Lagrange</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string></affiliations></json:item><json:item><name>E. Seigneuret</name><affiliations><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item><json:item><name>B. Piallat</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string></affiliations></json:item><json:item><name>P. Krack</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item><json:item><name>J.-F. Le Bas</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item><json:item><name>A.-L. Benabid</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item><json:item><name>S. Chabards</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item><json:item><name>P. Pollak</name><affiliations><json:string>1 University of Grenoble, France</json:string><json:string>2 INSERM, U836, Grenoble Institute of Neuroscience, France</json:string><json:string>3 University Hospital of Grenoble, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Original Articles</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable riskbenefit ratio.</abstract><qualityIndicators><score>8.5</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612.68 x 790.866 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>1</keywordCount><abstractCharCount>2033</abstractCharCount><pdfWordCount>5420</pdfWordCount><pdfCharCount>35605</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>287</abstractWordCount></qualityIndicators><title>Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease</title><genre><json:string>research-article</json:string></genre><host><volume>133</volume><pages><last>214</last><first>205</first></pages><issn><json:string>0006-8950</json:string></issn><issue>1</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2156</json:string></eissn><title>Brain</title></host><categories><wos><json:string>CLINICAL NEUROLOGY</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>2010</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1093/brain/awp229</json:string></doi><id>8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2009-09-22</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease</title><author><persName><forename type="first">M. U.</forename><surname>Ferraye</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation></author><author corresp="yes"><persName><forename type="first">B.</forename><surname>Deb</surname></persName><email>Bettina.Debu@ujf-grenoble.fr</email><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation></author><author><persName><forename type="first">V.</forename><surname>Fraix</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation></author><author><persName><forename type="first">L.</forename><surname>Goetz</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation></author><author><persName><forename type="first">C.</forename><surname>Ardouin</surname></persName><affiliation>3 University Hospital of Grenoble, France</affiliation></author><author><persName><forename type="first">J.</forename><surname>Yelnik</surname></persName><affiliation>4 INSERM UMR_S975, Fdration de Neurologie, Paris, France</affiliation><affiliation>5 University Pierre et Marie Curie, Paris, France</affiliation><affiliation>6 Hpital de la Piti-Salptrire, Paris, France</affiliation></author><author><persName><forename type="first">C.</forename><surname>Henry-Lagrange</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation></author><author><persName><forename type="first">E.</forename><surname>Seigneuret</surname></persName><affiliation>3 University Hospital of Grenoble, France</affiliation></author><author><persName><forename type="first">B.</forename><surname>Piallat</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation></author><author><persName><forename type="first">P.</forename><surname>Krack</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation></author><author><persName><forename type="first">J.-F.</forename><surname>Le Bas</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation></author><author><persName><forename type="first">A.-L.</forename><surname>Benabid</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation></author><author><persName><forename type="first">S.</forename><surname>Chabards</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation></author><author><persName><forename type="first">P.</forename><surname>Pollak</surname></persName><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation></author></analytic><monogr><title level="j">Brain</title><idno type="pISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-01"></date><biblScope unit="volume">133</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="205">205</biblScope><biblScope unit="page" to="214">214</biblScope></imprint></monogr><idno type="istex">8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E</idno><idno type="DOI">10.1093/brain/awp229</idno><idno type="ArticleID">awp229</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-09-22</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable riskbenefit ratio.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>Original Articles</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-09-22">Created</change><change when="2010-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/8CD3E269DDE0A53AB7BE2EBA33B1CF022C12187E/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-title>Brain</journal-title><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/brain/awp229</article-id><article-id pub-id-type="publisher-id">awp229</article-id><article-categories><subj-group><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ferraye</surname><given-names>M. U.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Debû</surname><given-names>B.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fraix</surname><given-names>V.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goetz</surname><given-names>L.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ardouin</surname><given-names>C.</given-names></name><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yelnik</surname><given-names>J.</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref><xref ref-type="aff" rid="AFF5"><sup>5</sup></xref><xref ref-type="aff" rid="AFF6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Henry-Lagrange</surname><given-names>C.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Seigneuret</surname><given-names>E.</given-names></name><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Piallat</surname><given-names>B.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Krack</surname><given-names>P.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Le Bas</surname><given-names>J.-F.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Benabid</surname><given-names>A.-L.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chabardès</surname><given-names>S.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pollak</surname><given-names>P.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib></contrib-group><aff id="AFF1">1 University of Grenoble, France</aff><aff id="AFF2">2 INSERM, U836, Grenoble Institute of Neuroscience, France</aff><aff id="AFF3">3 University Hospital of Grenoble, France</aff><aff id="AFF4">4 INSERM UMR_S975, Fédération de Neurologie, Paris, France</aff><aff id="AFF5">5 University Pierre et Marie Curie, Paris, France</aff><aff id="AFF6">6 Hôpital de la Pitié-Salpêtrière, Paris, France</aff><author-notes><corresp>Correspondence to: B. Debû, Université de Grenoble, INSERM U836, CHU de Grenoble, Pavillon de Neurologie, BP217, 38043 Grenoble Cedex 9, France E-mail: <email>Bettina.Debu@ujf-grenoble.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>1</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>22</day><month>9</month><year>2009</year></pub-date><volume>133</volume><issue>1</issue><fpage>205</fpage><lpage>214</lpage><history><date date-type="received"><day>29</day><month>5</month><year>2009</year></date><date date-type="rev-recd"><day>8</day><month>7</month><year>2009</year></date><date date-type="accepted"><day>20</day><month>7</month><year>2009</year></date></history><permissions><copyright-statement>© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2009</copyright-year></permissions><abstract><p>Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk–benefit ratio.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">M. U.</namePart><namePart type="family">Ferraye</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">B.</namePart><namePart type="family">Deb</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>E-mail: Bettina.Debu@ujf-grenoble.fr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V.</namePart><namePart type="family">Fraix</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Goetz</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Ardouin</namePart><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.</namePart><namePart type="family">Yelnik</namePart><affiliation>4 INSERM UMR_S975, Fdration de Neurologie, Paris, France</affiliation><affiliation>5 University Pierre et Marie Curie, Paris, France</affiliation><affiliation>6 Hpital de la Piti-Salptrire, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Henry-Lagrange</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Seigneuret</namePart><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B.</namePart><namePart type="family">Piallat</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Krack</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.-F.</namePart><namePart type="family">Le Bas</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.-L.</namePart><namePart type="family">Benabid</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S.</namePart><namePart type="family">Chabards</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Pollak</namePart><affiliation>1 University of Grenoble, France</affiliation><affiliation>2 INSERM, U836, Grenoble Institute of Neuroscience, France</affiliation><affiliation>3 University Hospital of Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>Original Articles</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2010-01</dateIssued><dateCreated 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The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. 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|texte= Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease
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