Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study
Identifieur interne : 001105 ( Main/Exploration ); précédent : 001104; suivant : 001106Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study
Auteurs : Adolfo Mínguez-Castellanos [Espagne] ; Francisco Escamilla-Sevilla [Espagne] ; Gary R. Hotton [Royaume-Uni] ; Juan J. Toledo-Aral [Espagne] ; Ángel Ortega-Moreno [Espagne] ; Sim N Méndez-Ferrer [Espagne] ; José M. Martín-Linares [Espagne] ; Majed J. Katati [Espagne] ; Pablo Mir [Espagne] ; Javier Villadiego [Espagne] ; Miguel Meersmans [Espagne] ; Miguel Pérez-García [Espagne] ; David J. Brooks [Royaume-Uni] ; Ventura Arjona [Espagne] ; José L Pez-Barneo [Espagne]Source :
- Journal of Neurology, Neurosurgery & Psychiatry [ 0022-3050 ] ; 2007-08.
English descriptors
- KwdEn :
- CAPIT, Core Assessment Programme for Intracerebral Transplantation, CAPSIT-PD, Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease, CB, carotid body, GDNF, glial cell line derived neurotrophic factor, PD, Parkinson disease, PET, positron emission tomography, TH, tyrosine hydroxylase, UPDRS, Unified Parkinson’s Disease Rating Scale.
Abstract
Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD). Objective: We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD. Methods: Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson’s Disease Rating Scale III score in the off-medication state. Seven patients had 18F-dopa positron emission tomography scans before and 1 year after transplantation. Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off-period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non-significant 5% increase in mean putaminal 18F-dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal 18F-dopa uptake (r = −0.829; p = 0.042). Conclusions: CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.
Url:
DOI: 10.1136/jnnp.2006.106021
Affiliations:
- Espagne, Royaume-Uni
- Andalousie, Angleterre, Grand Londres
- Grenade (Espagne), Londres
- Université de Grenade
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Brooks</name><affiliation wicri:level="3"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Arjona, Ventura" sort="Arjona, Ventura" uniqKey="Arjona V" first="Ventura" last="Arjona">Ventura Arjona</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Neurocirugía, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada</wicri:regionArea><wicri:noRegion>Granada</wicri:noRegion></affiliation></author><author><name sortKey="L Pez Barneo, Jose" sort="L Pez Barneo, Jose" uniqKey="L Pez Barneo J" first="José" last="L Pez-Barneo">José L Pez-Barneo</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Laboratorio de Investigaciones Biomédicas, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla</wicri:regionArea><wicri:noRegion>Sevilla</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neurology, Neurosurgery & Psychiatry</title><title level="j" type="abbrev">J Neurol Neurosurg Psychiatry</title><idno type="ISSN">0022-3050</idno><idno type="eISSN">1468-330X</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2007-08">2007-08</date><biblScope unit="volume">78</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="825">825</biblScope></imprint><idno type="ISSN">0022-3050</idno></series><idno type="istex">B3A39B161A1B7B7E5CFF67D04FBF430965A48510</idno><idno type="DOI">10.1136/jnnp.2006.106021</idno><idno type="href">jnnp-78-825.pdf</idno><idno type="PMID">17220289</idno><idno type="local">0780825</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3050</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CAPIT, Core Assessment Programme for Intracerebral Transplantation</term><term>CAPSIT-PD, Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease</term><term>CB, carotid body</term><term>GDNF, glial cell line derived neurotrophic factor</term><term>PD, Parkinson disease</term><term>PET, positron emission tomography</term><term>TH, tyrosine hydroxylase</term><term>UPDRS, Unified Parkinson’s Disease Rating Scale</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD). Objective: We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD. Methods: Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson’s Disease Rating Scale III score in the off-medication state. Seven patients had 18F-dopa positron emission tomography scans before and 1 year after transplantation. Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off-period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non-significant 5% increase in mean putaminal 18F-dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal 18F-dopa uptake (r = −0.829; p = 0.042). Conclusions: CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.</div></front></TEI><affiliations><list><country><li>Espagne</li><li>Royaume-Uni</li></country><region><li>Andalousie</li><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Grenade (Espagne)</li><li>Londres</li></settlement><orgName><li>Université de Grenade</li></orgName></list><tree><country name="Espagne"><noRegion><name sortKey="Minguez Castellanos, Adolfo" sort="Minguez Castellanos, Adolfo" uniqKey="Minguez Castellanos A" first="Adolfo" last="Mínguez-Castellanos">Adolfo Mínguez-Castellanos</name></noRegion><name sortKey="Arjona, Ventura" sort="Arjona, Ventura" uniqKey="Arjona V" first="Ventura" last="Arjona">Ventura Arjona</name><name sortKey="Escamilla Sevilla, Francisco" sort="Escamilla Sevilla, Francisco" uniqKey="Escamilla Sevilla F" first="Francisco" last="Escamilla-Sevilla">Francisco Escamilla-Sevilla</name><name sortKey="Katati, Majed J" sort="Katati, Majed J" uniqKey="Katati M" first="Majed J" last="Katati">Majed J. Katati</name><name sortKey="L Pez Barneo, Jose" sort="L Pez Barneo, Jose" uniqKey="L Pez Barneo J" first="José" last="L Pez-Barneo">José L Pez-Barneo</name><name sortKey="Martin Linares, Jose M" sort="Martin Linares, Jose M" uniqKey="Martin Linares J" first="José M" last="Martín-Linares">José M. Martín-Linares</name><name sortKey="Meersmans, Miguel" sort="Meersmans, Miguel" uniqKey="Meersmans M" first="Miguel" last="Meersmans">Miguel Meersmans</name><name sortKey="Mendez Ferrer, Sim N" sort="Mendez Ferrer, Sim N" uniqKey="Mendez Ferrer S" first="Sim N" last="Méndez-Ferrer">Sim N Méndez-Ferrer</name><name sortKey="Mir, Pablo" sort="Mir, Pablo" uniqKey="Mir P" first="Pablo" last="Mir">Pablo Mir</name><name sortKey="Ortega Moreno, Angel" sort="Ortega Moreno, Angel" uniqKey="Ortega Moreno A" first="Ángel" last="Ortega-Moreno">Ángel Ortega-Moreno</name><name sortKey="Perez Garcia, Miguel" sort="Perez Garcia, Miguel" uniqKey="Perez Garcia M" first="Miguel" last="Pérez-García">Miguel Pérez-García</name><name sortKey="Toledo Aral, Juan J" sort="Toledo Aral, Juan J" uniqKey="Toledo Aral J" first="Juan J" last="Toledo-Aral">Juan J. Toledo-Aral</name><name sortKey="Villadiego, Javier" sort="Villadiego, Javier" uniqKey="Villadiego J" first="Javier" last="Villadiego">Javier Villadiego</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Hotton, Gary R" sort="Hotton, Gary R" uniqKey="Hotton G" first="Gary R" last="Hotton">Gary R. Hotton</name></noRegion><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J" last="Brooks">David J. Brooks</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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