Deep brain stimulation does not enhance neuroinflammation in multiple system atrophy
Neurobiology of Disease. 2018-10-01; 118: 155-160
DOI: 10.1016/j.nbd.2018.07.016
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1. Neurobiol Dis. 2018 Oct;118:155-160. doi: 10.1016/j.nbd.2018.07.016. Epub 2018
Jul 17.
Deep brain stimulation does not enhance neuroinflammation in multiple system
atrophy.
Lopez-Cuina M(1), Fernagut PO(2), Canron MH(1), Vital A(3), Lannes B(4), De Paula
AM(5), Streichenberger N(6), Guehl D(7), Damier P(8), Eusebio A(9), Houeto
JL(10), Tison F(11), Tranchant C(12), Viallet F(13), Witjas T(9), Thobois S(14),
Meissner WG(15).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Université de Poitiers, Laboratoire de Neurosciences
Expérimentales et Cliniques, UMR_S 1084, F-86000 Poitiers, France; INSERM,
Laboratoire de Neurosciences Expérimentales et Cliniques, UMR_S 1084, F-86000
Poitiers, France.
(3)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Department of Pathology, CHU de Bordeaux, Bordeaux,
France.
(4)Department of Pathology, CHU de Strasbourg, Strasbourg, France.
(5)Department of Pathology, CHU de la Timone, Marseille, France.
(6)Centre de Pathologie et Neuropathologie Est Hospices Civils de Lyon,
Université Claude Bernard Lyon1, Institut NeuroMyogène CNRS UMR 5310, INSERM
U1217, France.
(7)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Service des Explorations Fonctionnelles du Système
Nerveux, F-33000 Bordeaux, France.
(8)Centre d’Investigation Clinique, Department of Neurology, CHU, INSERM, Nantes,
France.
(9)APHM, CHU Timone, Department of Neurology and Movement Disorders, Institut de
Neurosciences de La Timone UMR 7289, Aix Marseille Université, CNRS, 13385
Marseille, France.
(10)Service de Neurologie, CIC-INSERM 1402, CHU de Poitiers, Poitiers, France.
(11)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France; Centre de Référence Maladie Rare AMS, CHU de
Bordeaux, F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux,
F-33000 Bordeaux, France.
(12)Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Hôpital de
Hautepierre, Strasbourg; Fédération de Médecine Translationnelle de Strasbourg
(FMTS), Université de Strasbourg; Strasbourg; Institut de Génétique et de
Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université
de Strasbourg, Illkirch, France.
(13)Service de Neurologie, CH intercommunal d’Aix-Pertuis; Laboratoire Parole et
Langage UMR 7309 CNRS and Université Aix-Marseille, 13616 Aix en Provence,
France.
(14)Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Expert
Parkinson’s disease Center, 69000 Lyon, France; Université de Lyon, Université
Claude Bernard Lyon 1, Faculté de Médecine Lyon Sud Charles Mérieux, 69000 Lyon,
France; Université de Lyon, CNRS, Institut des Sciences Cognitives Marc
Jeannerot, Centre de Neurosciences Cognitives, UMR5229, Bron, France.
(15)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France; Centre de Référence Maladie Rare AMS, CHU de
Bordeaux, F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux,
F-33000 Bordeaux, France. Electronic address: .
Slowly progressive, levodopa-responsive multiple system atrophy (MSA) may be
misdiagnosed as Parkinson’s disease (PD). Deep brain stimulation (DBS) is mostly
ineffective in these patients and may even worsen the clinical course. Here we
assessed whether neuropathological differences between patients with MSA who were
treated with DBS of the subthalamic nucleus because of a misleading clinical
presentation and typical disease cases may explain the more benign disease course
of the former, and also the rapid clinical decline after surgery. The post-mortem
assessment included the subthalamic nucleus, the globus pallidus, the thalamus
and the putamen in five patients with MSA who received DBS and nine typical
disease cases. There was no evidence for distinct neuroinflammatory profiles
between both groups that could be related to the surgical procedure or that could
explain the rapid clinical progression during DBS. Patients who received deep
brain stimulation displayed a higher proportion of α-synuclein bearing neuronal
cytoplasmic inclusions in the putamen compared with typical cases, while the
number of surviving neurons was not different between groups. Our findings
suggest that DBS does not induce neuroinflammatory changes in patients with MSA,
at least several years after the surgery. We further hypothesize that the
peculiar pattern of α-synuclein pathology may contribute to differences in the
clinical phenotype, with a greater proportion of neuronal inclusions in the
putamen being associated to a milder, “PD-like” phenotype with sustained levodopa
response and slower disease progression.
Copyright © 2018 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2018.07.016
PMID: 30026036