Diagnosis of Adult Onset Leukodystrophy in a Consecutive Study of 156 Patients (S60.006)

OBJECTIVE: To determine relative frequencies of different leukodystrophies in a cohort of patients with adult-onset and the rentability of a systematic diagnostic approach. BACKGROUND: Leukodystrophies are a rare and heterogeneous group of inherited disorders which usually occur during infancy. Patients with adult-onset are increasingly recognized. Systematic investigations of these patients are not clearly reported in the literature. DESIGN/METHODS: We have conducted a systematic study including all MS centers in France between January 2007 and July 2012. Inclusion criteria were: 1) symetrical involvement of white matter on the first available brain MRI, 2) age of onset above 16, 3) absence of acquired diseases. Classification was based on MRI patterns as vascular, metabolic, cavitary and unclassified. In each group, a systematic genetic and/or biochemical testing was realized. RESULTS: Among 400 files, 156 patients with adult-onset leukodystrophy were identified. The mean age of onset was 39.3 (range 16-75) and a sex ratio imbalance was noted (male/female = 60/96). Main initial clinical symptoms were paraparesis (n=33), ataxia (n=31), cognitive decline (n=27), psychiatric symptoms (n=24) and stroke (n=20). Based on MRI findings, 54/156 were vascular, 17/156 cavitary, 52/156 metabolic. 33 patients were unclassified. A final diagnosis was made in 39/54 vascular cases (72.2 %). Main causes were CADASIL (n=30) and COL4A1 mutation (n=7). 9/17 (52.9 %) patients with a cavitary MRI had a diagnosis of CACH syndrome, with a pathogenic eIF2B mutation. 30/52 (57.7 %) of patients with metabolic MRI had a diagnosis. Main causes were X-linked adrenoleukodystrophy (n=11/52), cerebrotendinous xanthomatosis (n=4/52), Krabbe disease (n= 2/52) and SPG 11 mutation (n=2/52). Among 33 patients with unclassified MRI pattern, a diagnosis was made in 39.4% (n=13 / 33). CONCLUSIONS: Adult-onset leukodystrophies are considered as rare. Utility of MRI classification is confirmed by our study with a final diagnosis rate of 58.3 % (91/156) cases. Disclosure: Dr. Labauge has nothing to disclose. Dr. Carra-Dalliere has nothing to disclose. Dr. Ayrignac has nothing to disclose. Dr. Menjot de Champfleur has nothing to disclose. Dr. Aubourg has nothing to disclose. Dr. Bellesme has nothing to disclose. Dr. Pelletier has received personal compensation for activities with Allergan, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, Teva, and Genzyme. Dr Pelletier has received research support from Bayer Schering, Biogen Idec, BMS, GSK, Merck Serono, Novartis, Peptimmune, Roche, Sanofi, Teva and Wyeth. Dr. Audoin has nothing to disclose. Dr. De Seze has received personal compensation for activities with Allergan, Inc., Almirall, Bayer Schering, Biogen Idec, Genzyme Corporation, LFB, Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Collongues has received personal compensation for activities with Biogen Idec, Bayer Schering, Teva Neuroscience, Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Magnin has nothing to disclose. Dr. Rumbach has nothing to disclose. Dr. Confavreux has received personal compensation for activities with Biogen Dompe, Biogen Idec, Gemacbio, Genzyme Corporation, Hertie Foundation, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, UCB Pharma, Bayer Schering, and Merck Serono. Dr. Confavreux has received research support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Vukusic has nothing to disclose. Dr. Camdessanche has nothing to disclose. Dr. Cohen has received personal compensation for activities with Schering, Biogen Idec, Serono, Inc., Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Lebrun has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Schering, Biogen Idec, Merck Serono, Genzyme, Almirall, Allergan, Inc., Novartis, and Sanofi as a speaker. Dr. Lebrun has received personal compensation in an editorial capacity from Elsevier. Dr. Brassat has received personal compensation from Schering, Biogen Idec, Serono and Sanofi for speaking in symposia. Dr. Clanet has received personal compensation for activities with Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Teva Neuroscience, and Genzyme Corporation. Dr. Vermersch has received personal compensation for activities with Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., Bayer, Novartis, Merck Serono, GlaxoSmithKline, Inc., and Almirall. Dr. Vermersch has received research support from Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., Bayer, and Merck Serono. Dr. Zephir has nothing to disclose. Dr. Outteryck has received personal compensation for activities with Biogen Idec, Bayer, Teva Neuroscience, Merck & Co., Inc., and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Wiertlevski has nothing to disclose. Dr. Ouallet has nothing to disclose. Dr. Brochet has received personal compensation from BayerHealthcare, Novartis Pharma, Merck-Serono and Biogen-Idec. Dr. Brochet received personal compensation for serving as associate editor for a journal published by LEN (publisher). This journal is supported by Biogen-Idec. ....Dr. Brochet has received research support from Merck-Serono, Biogen-Idec and Bayer Healthcare. Dr. Goizet has nothing to disclose. Dr. Denier has nothing to disclose. Dr. Debouverie has received personal compensation for activities with Biogen Idec, Bayer, Merck Serono, Novartis, Sanofi-Aventis Pharmaceutials, and Teva Neuroscience. Dr. Pittion has nothing to disclose. Dr. Edan has received personal compensation for activities with Biogen Idec, Teva Neuroscience, BENEFIT, and LFB. Dr. Edan has received research support from Bayer and Serono, Inc. Dr. Deburghgraeve has nothing to disclose. Dr. Verny has nothing to disclose. Dr. Amati-Bonneau has nothing to disclose. Dr. Bonneau has nothing to disclose. Dr. Hannequin has nothing to disclose. Dr. Guyant-Marchal has nothing to disclose. Dr. Derache has received personal compensation for activities with Merck Serono, Biogen Idec and Novartis as a speaker. Dr. Moreau has received research support from Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, Bayer, Merck Serono, and Novartis. Dr. Giroud has nothing to disclose. Dr. Guennoc has nothing to disclose. Dr. Clavelou has received personal compensation for activities with Schering, Biogen Idec, Serono, Inc., and Sanofi-Aventis Pharmaceuticals, Inc. as a speaker. Dr. Taithe has nothing to disclose. Dr. Mathis has nothing to disclose. Dr. Magy has received personal compensation for activities with Biogen Idec and LFB as a consultant. Dr. Devoize has nothing to disclose. Dr. Bataillard has nothing to disclose. Dr. Boespflug Tanguy has nothing to disclose. Dr. Tournier-Lasserve has nothing to disclose. Dr. Levade has nothing to disclose.