Robust graft survival and normalized dopaminergic innervation do not obligate recovery in a Parkinson disease patient.
Identifieur interne : 000029 ( PubMed/Checkpoint ); précédent : 000028; suivant : 000030Robust graft survival and normalized dopaminergic innervation do not obligate recovery in a Parkinson disease patient.
Auteurs : Jeffrey H. Kordower [États-Unis] ; Christopher G. Goetz [États-Unis] ; Yaping Chu [États-Unis] ; Glenda M. Halliday [Australie] ; Daniel A. Nicholson [États-Unis] ; Timothy F. Musial [États-Unis] ; David J. Marmion [États-Unis] ; A Jon Stoessl [Canada] ; Vesna Sossi [Canada] ; Thomas B. Freeman [États-Unis] ; C Warren Olanow [États-Unis]Source :
- Annals of neurology [ 1531-8249 ] ; 2017.
Abstract
The main goal of dopamine cell replacement therapy in Parkinson disease (PD) is to provide clinical benefit mediated by graft survival with nigrostriatal reinnervation. We report a dichotomy between graft structure and clinical function in a patient dying 16 years following fetal nigral grafting.
DOI: 10.1002/ana.24820
PubMed: 27900791
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Goetz</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Neurological Sciences, Rush University Medical Center, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Chu, Yaping" sort="Chu, Yaping" uniqKey="Chu Y" first="Yaping" last="Chu">Yaping Chu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Neurological Sciences, Rush University Medical Center, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M" last="Halliday">Glenda M. 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Musial</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Neurological Sciences, Rush University Medical Center, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Marmion, David J" sort="Marmion, David J" uniqKey="Marmion D" first="David J" last="Marmion">David J. Marmion</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Neurological Sciences, Rush University Medical Center, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Freeman, Thomas B" sort="Freeman, Thomas B" uniqKey="Freeman T" first="Thomas B" last="Freeman">Thomas B. Freeman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Department of Neurosurgery and Brain Repair, University of South Florida, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C Warren" last="Olanow">C Warren Olanow</name><affiliation wicri:level="2"><nlm:affiliation>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author></analytic><series><title level="j">Annals of neurology</title><idno type="eISSN">1531-8249</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The main goal of dopamine cell replacement therapy in Parkinson disease (PD) is to provide clinical benefit mediated by graft survival with nigrostriatal reinnervation. We report a dichotomy between graft structure and clinical function in a patient dying 16 years following fetal nigral grafting.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">27900791</PMID><DateCreated><Year>2016</Year><Month>11</Month><Day>30</Day></DateCreated><DateRevised><Year>2017</Year><Month>01</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8249</ISSN><JournalIssue CitedMedium="Internet"><Volume>81</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Annals of neurology</Title><ISOAbbreviation>Ann. Neurol.</ISOAbbreviation></Journal><ArticleTitle>Robust graft survival and normalized dopaminergic innervation do not obligate recovery in a Parkinson disease patient.</ArticleTitle><Pagination><MedlinePgn>46-57</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/ana.24820</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">The main goal of dopamine cell replacement therapy in Parkinson disease (PD) is to provide clinical benefit mediated by graft survival with nigrostriatal reinnervation. We report a dichotomy between graft structure and clinical function in a patient dying 16 years following fetal nigral grafting.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">A 55-year-old levodopa-responsive woman with PD received bilateral putaminal fetal mesencephalic grafts as part of an NIH-sponsored double-blind sham-controlled trial. The patient never experienced clinical benefit, and her course was complicated by the development of graft-related dyskinesias. Fluorodopa positron emission tomography demonstrated significant increases postgrafting bilaterally. She experienced worsening of parkinsonism with severe dyskinesias, and underwent subthalamic nucleus deep brain stimulation 8 years after grafting. She died 16 years after transplantation.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Postmortem analyses confirmed the diagnosis of PD and demonstrated >300,000 tyrosine hydroxylase (TH)-positive grafted cells per side with normalized striatal TH-immunoreactive fiber innervation and bidirectional synaptic connectivity. Twenty-seven percent and 17% of grafted neurons were serine 129-phosphorylated α-synuclein positive in the left and right putamen, respectively.</AbstractText><AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">These findings represent the largest number of surviving dopamine neurons and the densest and most widespread graft-mediated striatal dopamine reinnervation following a transplant procedure reported to date. Despite this, clinical recovery was not observed. Furthermore, the grafts were associated with a form of dyskinesias that resembled diphasic dyskinesia and persisted in the off-medication state. We hypothesize that the grafted cells produced a low level of dopamine sufficient to cause a levodopa-independent continuous form of diphasic dyskinesias, but insufficient to provide an antiparkinsonian benefit. ANN NEUROL 2017;81:46-57.</AbstractText><CopyrightInformation>© 2017 American Neurological Association.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kordower</LastName><ForeName>Jeffrey H</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Van Andel Institute, Grand Rapids, MI.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goetz</LastName><ForeName>Christopher G</ForeName><Initials>CG</Initials><AffiliationInfo><Affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chu</LastName><ForeName>Yaping</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Halliday</LastName><ForeName>Glenda M</ForeName><Initials>GM</Initials><AffiliationInfo><Affiliation>Neuroscience Research Australia and Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nicholson</LastName><ForeName>Daniel A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Musial</LastName><ForeName>Timothy F</ForeName><Initials>TF</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-0533-7967</Identifier><AffiliationInfo><Affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marmion</LastName><ForeName>David J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stoessl</LastName><ForeName>A Jon</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sossi</LastName><ForeName>Vesna</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Freeman</LastName><ForeName>Thomas B</ForeName><Initials>TB</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Olanow</LastName><ForeName>C Warren</ForeName><Initials>CW</Initials><AffiliationInfo><Affiliation>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>01</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Ann Neurol</MedlineTA><NlmUniqueID>7707449</NlmUniqueID><ISSNLinking>0364-5134</ISSNLinking></MedlineJournalInfo></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>05</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>11</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>11</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>12</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>12</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>12</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27900791</ArticleId><ArticleId IdType="doi">10.1002/ana.24820</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>Canada</li><li>États-Unis</li></country><region><li>Floride</li><li>Illinois</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Kordower, Jeffrey H" sort="Kordower, Jeffrey H" uniqKey="Kordower J" first="Jeffrey H" last="Kordower">Jeffrey H. 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