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Background: In multiple sclerosis (MS), the ∈4 allele of apolipoprotein E (APOE ∈4) has been associated with more rapid clinical worsening and more severe tissue damage on magnetic resonance imaging. Objective: To use proton magnetic resonance spectroscopy (¹H-MRS) to further explore the biochemical changes in the brains of patients with MS associated with APOE ∈4. Design: A 2-year clinical and ¹H-MRS follow-up cohort study. Setting: The MS outpatient clinic, Department of Neurology, and Magnetic Resonance Center of KarlFranzens University. Patients: We performed ¹H-MRS of the central portion of both hemispheres and APOE genotyping in 72 patients (52 women and 20 men; mean ±SD age, 34.8 ±8.8 years) with clinically definite relapsing-remitting MS. Repeated studies were performed in 44 patients after a mean ±SD interval of 34± 9 months. Main Outcome Measure: Levels of N-acetylaspartare as measured by 1H-MRS. Results: Patients with MS and an 4 allele (n: 19) had a significantly lower mean+SD N-acetylaspartatecreatine ratio than those without an 4 allele (n:53) (1.73+ 0.26 vs 1.89 + 0.24; P: .04) despite the absence of significant differences in age at onset, disease duration, Expanded Disability Status Scale score, and number of previous relapses between subgroups. During followup, the drop in the N-acetylaspartate-creatine ratio of 4 carriers was also significantly larger (-0.31 vs -0.10; P:.01). This was paralleled by a higher number of relapses (mean + SD, 4.1 + 2.7 vs 1.7 + 1.6; P: .02) and a faster although nonsignificant progression of disability (mean+SD AExpanded Disability Status Scale score, 0.9+ 1.8 vs 0.3+ 1.1; P=.19). Conclusions: The APOE 4 allele has a negative effect on the course of MS, and increasing axonal damage may be an important mechanism. [ABSTRACT FROM AUTHOR]

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.

Background: In multiple sclerosis (MS), the epsilon4 allele of apolipoprotein E (APOE epsilon4) has been associated with more rapid clinical worsening and more severe tissue damage on magnetic resonance imaging., Objective: To use proton magnetic resonance spectroscopy ((1)H-MRS) to further explore the biochemical changes in the brains of patients with MS associated with APOE epsilon4., Design: A 2-year clinical and (1)H-MRS follow-up cohort study., Setting: The MS outpatient clinic, Department of Neurology, and Magnetic Resonance Center of Karl-Franzens University., Patients: We performed (1)H-MRS of the central portion of both hemispheres and APOE genotyping in 72 patients (52 women and 20 men; mean +/- SD age, 34.8 +/- 8.8 years) with clinically definite relapsing-remitting MS. Repeated studies were performed in 44 patients after a mean +/- SD interval of 34 +/- 9 months., Main Outcome Measure: Levels of N-acetylaspartate as measured by (1)H-MRS., Results: Patients with MS and an epsilon4 allele (n = 19) had a significantly lower mean +/- SD N-acetylaspartate-creatine ratio than those without an epsilon4 allele (n = 53) (1.73 +/- 0.26 vs 1.89 +/- 0.24; P =.04) despite the absence of significant differences in age at onset, disease duration, Expanded Disability Status Scale score, and number of previous relapses between subgroups. During follow-up, the drop in the N-acetylaspartate-creatine ratio of epsilon4 carriers was also significantly larger (-0.31 vs -0.10; P =.01). This was paralleled by a higher number of relapses (mean +/- SD, 4.1 +/- 2.7 vs 1.7 +/- 1.6; P =.02) and a faster although nonsignificant progression of disability (mean +/- SD (Delta)Expanded Disability Status Scale score, 0.9 +/- 1.8 vs 0.3 +/- 1.1; P =.19)., Conclusions: The APOE epsilon4 allele has a negative effect on the course of MS, and increasing axonal damage may be an important mechanism.