Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough.
Identifieur interne : 002B93 ( Main/Exploration ); précédent : 002B92; suivant : 002B94Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough.
Auteurs : Anthony E. Lang [Canada] ; Jose A. ObesoSource :
- The Lancet. Neurology [ 1474-4422 ] ; 2004.
English descriptors
- KwdEn :
- Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Dopamine (metabolism), Drug Therapy, Combination, Humans, Levodopa (adverse effects), Levodopa (therapeutic use), Neurologic Examination, Neurosurgery (methods), Parkinson Disease (drug therapy), Parkinson Disease (pathology), Parkinson Disease (surgery), Substantia Nigra (drug effects), Substantia Nigra (pathology).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemical , metabolism : Dopamine.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- drug effects : Substantia Nigra.
- drug therapy : Parkinson Disease.
- methods : Neurosurgery.
- pathology : Parkinson Disease, Substantia Nigra.
- surgery : Parkinson Disease.
- Drug Therapy, Combination, Humans, Neurologic Examination.
Abstract
Levodopa remains the most effective treatment for Parkinson's disease (PD). However, the drug is complicated by a wide range of adverse effects, most notably motor fluctuations and dyskinesias. Long-acting dopamine agonists are associated with a reduced incidence of these complications and modern surgical approaches and pharmacological methods of providing more continuous dopaminergic stimulation have a substantial ameliorative effect on these problems. Despite these advances, disease progression remains unaffected. For this reason there has been much enthusiasm for cellular therapies designed to replace degenerating nigrostriatal dopaminergic neurons. However, recent fetal transplant trials have failed to show expected benefit and have been complicated by medication dyskinesias". Even if successful, such treatment may be predestined to provide no better outcome than available treatments given current medical and surgical experience that emphasises the increasingly critical role of "non-dopaminergic" symptoms to quality of life in late-stage PD. Knowledge of the widespread, multisystem nature of the neurodegeneration that accounts for these problems suggests that restoration of the nigrostriatal dopamine system should not be the ultimate goal of future research.
DOI: 10.1016/S1474-4422(04)00740-9
PubMed: 15099546
Affiliations:
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Lang</name><affiliation wicri:level="4"><nlm:affiliation>Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. lang@uhnres.utoronto.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="Jose A" last="Obeso">Jose A. Obeso</name></author></analytic><series><title level="j">The Lancet. Neurology</title><idno type="ISSN">1474-4422</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Dopamine (metabolism)</term><term>Drug Therapy, Combination</term><term>Humans</term><term>Levodopa (adverse effects)</term><term>Levodopa (therapeutic use)</term><term>Neurologic Examination</term><term>Neurosurgery (methods)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (pathology)</term><term>Parkinson Disease (surgery)</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (pathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Neurosurgery</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Drug Therapy, Combination</term><term>Humans</term><term>Neurologic Examination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Levodopa remains the most effective treatment for Parkinson's disease (PD). However, the drug is complicated by a wide range of adverse effects, most notably motor fluctuations and dyskinesias. Long-acting dopamine agonists are associated with a reduced incidence of these complications and modern surgical approaches and pharmacological methods of providing more continuous dopaminergic stimulation have a substantial ameliorative effect on these problems. Despite these advances, disease progression remains unaffected. For this reason there has been much enthusiasm for cellular therapies designed to replace degenerating nigrostriatal dopaminergic neurons. However, recent fetal transplant trials have failed to show expected benefit and have been complicated by medication dyskinesias". Even if successful, such treatment may be predestined to provide no better outcome than available treatments given current medical and surgical experience that emphasises the increasingly critical role of "non-dopaminergic" symptoms to quality of life in late-stage PD. Knowledge of the widespread, multisystem nature of the neurodegeneration that accounts for these problems suggests that restoration of the nigrostriatal dopamine system should not be the ultimate goal of future research.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="Jose A" last="Obeso">Jose A. Obeso</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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