Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson’s disease patients with GBA mutations
Parkinsonism & Related Disorders. 2020-07-01; 76: 56-62
DOI: 10.1016/j.parkreldis.2020.04.002
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Mangone G(1), Bekadar S(2), Cormier-Dequaire F(1), Tahiri K(2), Welaratne A(3),Czernecki V(4), Pineau F(4), Karachi C(5), Castrioto A(6), Durif F(7), Tranchant C(8), Devos D(9), Thobois S(10), Meissner WG(11), Navarro MS(5), Cornu P(5), Lesage S(1), Brice A(1), Welter ML(12), Corvol JC(13);
contributors/investigators.
Collaborators: Benchetrit E(1), Delaby L(4), Berthet D(4), Danjou F(2), Vidaihlet M(1), Krack P(6), Pelissier P(6), Morand D(7), Delaigue C(7), Barun N(8), Anheim M(8), Pleuvret M(9), Destée A(9), Defebvre L(9), Moreau C(9), Simonin C(9), Ryckewaert G(9), Kreisler A(9), Mutez E(9), Carrière N(9), Hopes L(9), Tard C(9), Grolez G(9), Dujardin K(9), Pecheux N(9), Delliaux M(9), Rolland AS(9), Broussolle E(10), Laurencin C(10), Tison F(14), Burbaud P(14).
Author information:
(1)Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la
Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Département de Neurologie, Clinical Research Center
Neurosciences, Paris, France.
(2)Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la
Moelle épinière, Paris, France.
(3)Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département
de Neurologie, Clinical Research Center Neurosciences, Paris, France.
(4)Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la
Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Département de Neurologie, Clinical Research Center
Neurosciences, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Département de Neurologie, Institut of Memory and Alzheimer’s
Disease (IM2A), Paris, France.
(5)Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la
Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Département de Neurochirurgie, Paris, France.
(6)Unité des Troubles du Mouvement, Département de Neurologie, CHU de Grenoble,
Université de Grenoble Alpes, INSERM U1216, F-38000, Grenoble, France.
(7)Service de Neurologie, CHU Clermont-Ferrand, Université Clermont Auvergne,
F-63000, Clermont-Ferrand, France.
(8)Département de Neurologie, Hôpitaux Universitaires de Strasbourg, Hôpital de
Hautepierre, Strasbourg, France; Institut de Génétique et de Biologie Moléculaire
et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg,
Illkirch, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS),
Université de Strasbourg, Strasbourg, France.
(9)Département de Neurologie, Centre Expert maladie de Parkinson, Département de
Pharmacologie Clinique et des Neurosciences, Université de Lille, Centre
Hospitalier Universitaire de Lille, INSERM UMR_S 1171, LICEND, France.
(10)Neurologie C, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de
Lyon, 69500, Bron, France; Univ Lyon, Université Claude Bernard Lyon 1, Faculté
de Médecine Lyon Sud, Lyon, France; Institut des Sciences Cognitives Marc
Jeannerod, UMR 5229, CNRS, Bron, France.
(11)Service de Neurologie, Centre Expert Parkinson, IMNc, CHU Bordeaux, 33000,
Bordeaux, France; Univ. de Bordeaux, Institut des Maladies Neurodégénératives,
CNRS, UMR 5293, 33000, Bordeaux, France; Dept. Medicine, University of Otago,
Christchurch, New Zealand; Brain Research Institute, Christchurch, New Zealand.
(12)Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de
la Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Département de Neurologie, Clinical Research Center
Neurosciences, Paris, France; Département de Neurophysiologie, CHU Rouen,
Université de Normandie, Rouen, France.
(13)Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de
la Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Département de Neurologie, Clinical Research Center
Neurosciences, Paris, France. Electronic address: .
(14)Service de Neurologie, Centre Expert Parkinson, IMNc, CHU Bordeaux, 33000,
Bordeaux, France; Univ. de Bordeaux, Institut des Maladies Neurodégénératives,
CNRS, UMR 5293, 33000, Bordeaux, France.
BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) has demonstrated
its efficacy on motor complications in advanced Parkinson’s disease (PD) but does
not modify disease progression. Genetic forms of PD have been associated with
different cognitive progression profiles.
OBJECTIVE: To assess the effect of PD-related genetic mutations on cognitive
outcome after STN-DBS.
METHODS: Patients with STN-DBS were screened for LRRK2, GBA, and PRKN mutations
at the Pitié-Salpêtrière Hospital between 1997 and 2009. Patients with known
monogenetic forms of PD from six other centers were also included. The Mattis
Dementia Rating Scale (MDRS) was used to evaluate cognition at baseline and
one-year post-surgery. The standardized Unified PD Rating Scale (UPDRS)
evaluation On and Off medication/DBS was also administered. A generalized linear
model adjusted for sex, ethnicity, age at onset, and disease duration was used to
evaluate the effect of genetic factors on MDRS changes.
RESULTS: We analyzed 208 patients (131 males, 77 females, 54.3 ± 8.8 years)
including 25 GBA, 18 LRRK2, 22 PRKN, and 143 PD patients without mutations. PRKN
patients were younger and had a longer disease duration at baseline. A GBA
mutation was the only significant genetic factor associated with MDRS change
(β = -2.51, p = 0.009). GBA mutation carriers had a more pronounced
post-operative MDRS decline (3.2 ± 5.1) than patients with LRRK2 (0.9 ± 4.8),
PRKN (0.5 ± 2.7) or controls (1.4 ± 4.4). The motor response to DBS was similar
between groups.
CONCLUSION: GBA mutations are associated with early cognitive decline following
STN-DBS. Neuropsychological assessment and discussions on the benefit/risk ratio
of DBS are particularly important for this population.
Copyright © 2020 Elsevier Ltd. All rights reserved.