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AUTHORS’ AFFILIATIONS
From INSERM (E.L., S.L., Y.A., A.B.), UMR_S679 Neurologie & Thérapeutique Expérimentale, Paris; AP-HP (E.L., B.D., Y.A., A.B.), Pitié-Salpêtrière Hospital, Department of the Nervous System Disorders, Paris; UPMC Univ Paris 06 (E.L., S.L., Y.A., A.B.), UMR_S679, Paris; University of Lyon I and INSERM UMR 864 and The Pierre Wertheimer Neurological Hospital (S.T., E.B.), Department of Neurology, Lyon; AP-HP (S.T.d.M.), Pitié-Salpêtrière Hospital, Department of Public Health, Unit of de Biostatistics and Medical Information and Unit of Medical Research, Paris; UPMC Univ Paris 06 (S.T.d.M.), EA3974 Modelisation in Clinical Research, Paris; CEA (M.-J.R.), I2BM, Service Hospitalier Frédéric Joliot, Orsay; CEA (P.R.), I2BM, URA-CEA-CNRS 2210, Orsay; CHU Henri Mondor (P.R.), AP-HP et Faculté de Médecine Paris 12, Créteil; AP-HP (A.P.), Pitié-Salpêtrière Hospital, Department of Psychiatry, Paris; INSERM UMR 610 Neuroanatomie Fonctionnelle du Comportement et de ses Troubles (B.D.), Paris; AP-HP (B.D.), Pitié-Salpêtrière Hospital, Centre de Référence sur la Maladie de Pick, Paris; Inserm Avenir Group IFR 70 Behaviour (L.M.), Emotion and Basal Ganglia, Center of Clinical Investigation, Paris; Department of Clinical and Biological Neurosciences (P.P.), University Hospital of Grenoble; AP-HP (Y.A.), Pitié-Salpêtrière Hospital, Clinical Investigation Center, Paris; and AP-HP (A.B.), Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France.
Address correspondence and reprint requests to Prof. Alexis Brice, INSERM UMR S_679, Hôpital Pitié-Salpêtrière, 47 boulevard de l'Hôpital, F-75013 Paris, France alexis.brice{at}upmc.fr
Objective: To establish phenotype–genotype correlations in early-onset Parkinson disease (EOPD), we performed neurologic, neuropsychological, and psychiatric evaluations in a series of patients with and without parkin mutations.
Background: Parkin (PARK2) gene mutations are the major cause of autosomal recessive parkinsonism. The usual clinical features are early-onset typical PD with a slow clinical course, an excellent response to low doses of levodopa, frequent treatment-induced dyskinesias, and the absence of dementia.
Methods: A total of 44 patients with EOPD (21 with and 23 without parkin mutations) and 9 unaffected single heterozygous carriers of parkin mutations underwent extensive clinical, neuropsychological, and psychiatric examinations.
Results: The neurologic, neuropsychological, and psychiatric features were similar in all patients, except for significantly lower daily doses of dopaminergic treatment and greater delay in the development of levodopa-related fluctuations (p < 0.05) in parkin mutation carriers compared to noncarriers. There was no major difference between the two groups in terms of general cognitive efficiency. Psychiatric manifestations (depression) were more frequent in patients than in healthy single heterozygous parkin carriers but did not differ between the two groups of patients.
Conclusion: Carriers of parkin mutations are clinically indistinguishable from other patients with young-onset Parkinson disease (PD) on an individual basis. Severe generalized loss of dopaminergic neurons in the substantia nigra pars compacta in these patients is associated with an excellent response to low doses of dopa-equivalent and delayed fluctuations, but cognitive impairment and special behavioral or psychiatric symptoms were not more severe than in other patients with early-onset PD.
Abbreviations: CPRS = Comprehensive Psychopathological Rating Scale; EOPD = early-onset Parkinson disease; FAB = Frontal Assessment Battery; MADRS = Montgomery-Asberg Depression Rating Scale; MDRS = Mattis Dementia Rating Scale; MINI = Mini International Neuropsychiatric Interview; MMSE = Mini-Mental State Examination; TMT = Trail Making Test; UPDRS = Unified Parkinson's Disease Rating Scale; WCST = Wisconsin Card Sorting Test.
Received March 10, 2008. Accepted in final form June 27, 2008.
Editorial, page 106
e-Pub ahead of print on November 5, 2008, at www.neurology.org.
*The French Parkinson's Disease Genetics Study Group members are listed in the appendix.
Authors' affiliations are listed at the end of the article.
Supported by INSERM/AP-HP (PCR02006-P011104), the NIH grant NS41723-01A1, and the European commission (EU Contract No.LSHM-CT-2003-503330/APOPIS).
Disclosure: The authors report no disclosures.
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