Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.
Brain. 2014-12-19; 138(2): 284-292
DOI: 10.1093/brain/awu353
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1. Brain. 2015 Feb;138(Pt 2):284-92. doi: 10.1093/brain/awu353. Epub 2014 Dec 19.
Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a
comprehensive study of 154 patients.
Ayrignac X(1), Carra-Dalliere C(1), Menjot de Champfleur N(2), Denier C(3),
Aubourg P(4), Bellesme C(4), Castelnovo G(5), Pelletier J(6), Audoin B(6), Kaphan
E(6), de Seze J(7), Collongues N(7), Blanc F(7), Chanson JB(7), Magnin E(8),
Berger E(8), Vukusic S(9), Durand-Dubief F(9), Camdessanche JP(10), Cohen M(11),
Lebrun-Frenay C(11), Brassat D(12), Clanet M(13), Vermersch P(14), Zephir H(14),
Outteryck O(14), Wiertlewski S(15), Laplaud DA(15), Ouallet JC(16), Brochet
B(16), Goizet C(16), Debouverie M(17), Pittion S(17), Edan G(18), Deburghgraeve
V(18), Le Page E(18), Verny C(19), Amati-Bonneau P(19), Bonneau D(19), Hannequin
D(20), Guyant-Maréchal L(21), Derache N(22), Defer GL(22), Moreau T(23), Giroud
M(23), Guennoc AM(24), Clavelou P(25), Taithe F(25), Mathis S(26), Neau JP(26),
Magy L(27), Devoize JL(28), Bataillard M(7), Masliah-Planchon J(29), Dorboz
I(30), Tournier-Lasserve E(31), Levade T(32), Boespflug Tanguy O(30), Labauge
P(33).
Author information:
(1)1 Département de Neurologie, CHU de Montpellier, 34295 Montpellier, France.
(2)2 Département de Neuroradiologie, CHU de Montpellier, 34295 Montpellier,
France.
(3)3 Département de Neurologie, APHP, 94275 Hôpital Kremin-Bicêtre, Paris,
France.
(4)4 Département de Neuropédiatrie, INSERM UM475, 94275 Hôpital Bicêtre-Paris
Sud, Paris, France.
(5)5 Département de Neurologie, CHU de Nimes, 30029 Nimes, France.
(6)6 Département de Neurologie, CHU de Marseille, 13385 Marseille, France.
(7)7 Département de Neurologie, CHU de Strasbourg, 67000 Strasbourg, France.
(8)8 Département de Neurologie, CHU de Besançon, 25000 Besançon, France.
(9)9 Département de Neurologie, CHU de Lyon, 69677 Bron, France.
(10)10 Département de Neurologie, CHU de Saint-Etienne, 42100 Saint-Etienne,
France.
(11)11 Département de Neurologie, CHU de Nice, 06000 Nice, France.
(12)12 Pôle des neurosciences, INSERM UMR 1043 Université de Toulouse III, 31059
Toulouse, France.
(13)13 Département de Neurologie, CHU de Toulouse, 31059 Toulouse, France.
(14)14 Département de Neurologie, CHU de Lille, 59000 Lille, France.
(15)15 Département de Neurologie, CHU de Nantes, 44093 Nantes, France.
(16)16 Département de Neurologie, CHU de Bordeaux, 33076 Bordeaux, France.
(17)17 Département de Neurologie, CHU de Nancy, 54000 Nancy, France.
(18)18 Département de Neurologie, CHU de Rennes, 35000 Rennes, France.
(19)19 Département de Neurologie, CHU d’Angers, 49100 Angers, France.
(20)20 Inserm U1079, Université de Rouen, 76000 Rouen, France 21 Département de
Neurologie, CHU de Rouen, 76000 Rouen, France.
(21)20 Inserm U1079, Université de Rouen, 76000 Rouen, France.
(22)22 Département de Neurologie, CHU de Caen, 14033 Caen, France.
(23)23 Département de Neurologie, CHU de Dijon, 21079 Dijon, France.
(24)24 Département de Neurologie, CHU de Tours, 37000 Tours, France.
(25)25 Département de Neurologie, CHU de Clermont-Ferrand, 63000
Clermont-Ferrand, France.
(26)26 Département de Neurologie, CH de Poitiers, 86021 Poitiers, France.
(27)27 Département de Neurologie, CHU de Limoges, 87000 Limoges, France.
(28)28 Département de Neurologie, CH d’Angoulême, 16959 Angoulême, France.
(29)29 UF de Génétique moléculaire, Hôpital Robert Debré, AP-HP, Paris, France.
(30)30 Centre de référence maladies rares Leucodystrophies, Service de
Neuropédiatrie et des Maladies Métaboliques, AP-HP Hôpital Robert Debré, Paris,
France 31 NEUROPROTECT, Inserm U1141, Université Paris Diderot, Sorbonne Paris
Cité, Hôpital Robert Debré, Paris, France.
(31)32 Service de Génétique Neuro-vasculaire, Hopital Lariboisière, UMR-S 740,
Université Paris Diderot, Sorbonne Paris Cité, 75010 Paris, France.
(32)33 Centre de références des maladies lysosomiales, IFR de Biochimie, CHU de
Toulouse, 31059 Toulouse, France.
(33)1 Département de Neurologie, CHU de Montpellier, 34295 Montpellier, France
.
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.
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DOI: 10.1093/brain/awu353
PMID: 25527826 [Indexed for MEDLINE]