Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.

Xavier Ayrignac (1) , Clarisse Carra Dallière (1) , Nicolas Menjot de Champfleur (2, 1, 3) , Christian Denier (4) , Patrick Aubourg (5) , Celine Bellesme (5) , Giovanni Castelnovo (6) , Jean Pelletier (7) , Bertrand Audoin (8) , Elsa Kaphan (7) , Jerome de Seze (9) , Nicolas Collongues (10) , Frederic Blanc (10) , Jean-Baptiste Chanson (11) , Eloi Magnin (12) , Eric Berger (12) , Sandra Vukusic (8) , Francoise Durand-Dubief (13) , Jean-Philippe Camdessanche (14) , Mickael Cohen (15) , Christine Lebrun-Frenay (15) , David Brassat (16) , Michel Clanet (8) , Patrick Vermersch (17) , Helene Zephir (17) , Olivier Outteryck (18) , Sandrine Wiertlewski (19) , David-Axel Laplaud (19) , Jean-Christophe Ouallet (20) , Bruno Brochet (20) , Cyril Goizet (21) , Marc Debouverie (22, 23) , Sophie Pittion (23) , Gilles Edan (24, 25, 26) , Véronique Deburghgraeve (27) , Emmanuelle Le Page (27) , Christophe Verny (28) , Patrizia Amati-Bonneau (29, 30) , Dominique Bonneau (31, 32) , Didier Hannequin (33) , Lucie Guyant-Maréchal (34) , Nathalie Derache (35) , Gilles Louis Defer (35) , Thibault Moreau (36) , Maurice Giroud (37) , Anne Marie Guennoc (38) , Pierre Clavelou (39) , Frédérique Taithe (39) , Stephane Mathis (40) , Jean-Philippe Neau (40) , Laurent Magy (41) , Jean Louis Devoize (42) , Marc Bataillard (10) , Julien Masliah-Planchon (43) , Imen Dorboz (44) , Elisabeth Tournier-Lasserve (45) , Thierry Levade (46) , Odile Boespflug Tanguy (45) , Pierre Labauge (47, 48)

1 CHU Montpellier
2 UM1 - Université Montpellier 1
3 INM - Institut des Neurosciences de Montpellier
4 Department of Neuroradiology
5 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
6 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
7 CHU Marseille
8 CRMBM - Centre de résonance magnétique biologique et médicale
9 Service de neurologie [Strasbourg]
10 CHU Strasbourg
11 Laboratoire d'imagerie et de neurosciences cognitives (Strasbourg)
12 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
13 RMN et optique : De la mesure au biomarqueur
14 CHU Saint-Etienne
15 CHU Nice - Centre Hospitalier Universitaire de Nice
16 Pôle Neurosciences [CHU Toulouse]
17 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
18 EA 2686 - Laboratoire d'Immunologie
19 CHU Nantes - Centre hospitalier universitaire de Nantes
20 CHU Bordeaux [Bordeaux]
21 Service de génétique médicale
22 CIC - Centre d'investigation clinique [Nancy]
23 Service de neurologie [CHRU Nancy]
24 VisAGeS - Vision, Action et Gestion d'informations en Santé
25 Service de Neurologie [Rennes] = Neurology [Rennes]
26 CIC - Centre d'Investigation Clinique [Rennes]
27 CHU Pontchaillou [Rennes]
28 BICETRE - Géronto - Service de Gérontologie
29 CHU Angers - Centre Hospitalier Universitaire d'Angers
30 BNMI - Biologie Neurovasculaire et Mitochondriale Intégrée
31 Mitochondrie : Régulations et Pathologie
32 Service de génétique
33 GMFC - Génétique du cancer et des maladies neuropsychiatriques
34 Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
35 Service de Neurologie [CHU Caen]
36 CESP - Centre de recherche en épidémiologie et santé des populations
37 CHU Dijon
38 CHU Trousseau [Tours]
39 CHU Clermont-Ferrand
40 CHU Poitiers - Centre hospitalier universitaire de Poitiers
41 Service de Neurologie [CHU Limoges]
42 CH Angoulême - Centre Hospitalier d'Angoulême
43 Inserm U745 - Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux
44 PROTECT - Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies
45 USPC - Université Sorbonne Paris Cité
46 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
47 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
48 UM - Université de Montpellier

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.

Keywords: genetic; metabolic; leukoencephalopathies; leukodystrophy; MRI

Domains: Life Sciences [q-bio]

Xavier Ayrignac, Clarisse Carra Dallière, Nicolas Menjot de Champfleur, Christian Denier, Patrick Aubourg, et al.. Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.. Brain - A Journal of Neurology , 2015, 138 (Pt 2), pp.284-92. ⟨10.1093/brain/awu353⟩. ⟨hal-01138578⟩