title: Accelerated evolution of brain atrophy and "black holes" in MS patients with APOE-epsilon 4.
abstract: Apolipoprotein E (APOE)-epsilon4 has been associated with an unfavorable course of multiple sclerosis (MS). The mechanisms responsible for this are unclear, although cross-sectional MRI demonstrated a higher extent of "black holes" (BHs) in such patients. Here, we have studied the impact of the APOE genotype on both the longitudinal evolution of focal (BH ratio) and global (brain volume change [BVC]) brain tissue damage. Ninety-nine MS patients underwent ApoE genotyping, clinical examination, and magnetic resonance imaging at baseline and after 2.7 +/- 1.1 years to assess lesion load (LL) and BVC. In APOE-epsilon4 patients, the annual reduction in brain volume was fivefold higher (-0.65 +/- 0.61%) than in those without APOE-epsilon4 (-0.13 +/- 0.36%; p = 0.0001). At baseline, T(2) LL and T(1) LL were non-significantly higher in epsilon4 carriers, despite a shorter disease duration and absence of significant clinical differences. During follow-up, T(1) LL increased from 1.2 +/- 2.3 ccm to 1.7 +/- 2.7 ccm in the epsilon4 group, although T(2) LL did not change, leading to a significantly higher increase in the BH ratio [(T(1) LL/T(2) LL) x 100] from 5.5 to 12.4% (p = 0.005). BH ratio remained almost constant in non-epsilon4 patients (5.0 vs 5.7%). Accelerated brain tissue loss and a higher proportion of lesions evolving into BH therefore provide magnetic resonance imaging evidence for more pronounced tissue destruction in MS patients with APOE-epsilon4.
authors.affiliation: Department of Neurology, Karl-Franzens University, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.forename: Stephen
authors.initials: S
authors.lastname: Smith
authors.forename: Siegrid
authors.initials: S
authors.lastname: Strasser-Fuchs
authors.forename: Birgit
authors.initials: B
authors.lastname: Poltrum
authors.forename: Helena
authors.initials: H
authors.lastname: Schmidt
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D015999:Multivariate Analysis; D018709:Statistics, Nonparametric
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E