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From the Fédération de Neurologie and Faculté de Médecine Pitié-Salpêtrière (Paris VI) (Drs. Tourbah, Gout, Fontaine, Liblau, Lubetzki, and Lyon-Caen), Hôpital de la Salpêtrière, Paris; Service de Neuroradiologie (Drs. Tourbah, Stievenart, and Cabanis), Centre Hospitalier National d’Ophtalmologie des XV–XX, Paris; CJF 97-11 Pathologie de la Myéline (Drs. Tourbah, Fontaine, and Liblau), Hôpital de la Salpêtrière, Paris; Service de Biophysique et Médecine Nucléaire (Dr. Stievenart), Hôpital Beaujon, Clichy; Service de Neurologie (Dr. Gout), Fondation A. de Rotschild, Paris; and Laboratoire d’Immunologie Cellulaire (Dr. Liblau), Hôpital de la Salpêtrière, Paris, France.
Address correspondence and reprint requests to Dr. A. Tourbah, Fédération de Neurologie, Hôpital de la Salpêtrière, 47 Bld de l’Hôpital, 75651 Paris Cedex 13, France.
OBJECTIVE: To determine the efficacy of MRS in discriminating between relapsing remitting (RR) and secondary progressive (SP) MS.
METHODS: MRS at long and short echo times was carried out in 104 patients with MS stratified for clinical course (RR or SP), and the results were compared with those of 15 control subjects. Normal-appearing white matter (NAWM) was studied in 55 patients, and a high–T2-signal area on MRI in 49 others.
RESULTS: At long echo times, there was a highly significant decrease in the ratios N-acetyl-aspartate/creatine (NAA/Cr) and NAA/choline (Cho) in high–T2-signal areas and in the NAWM in patients with an SP course compared with control subjects and patients with an RR course. There was a significant negative correlation between these ratios and clinical disability measured by Expanded Disability Status Scale score, which was independent of disease duration. Discriminant values between patients with RR and SP courses were found in the NAWM (NAA/Cr = 1.75 and NAA/Cho = 1.5), but not in high–T2-signal areas. At short echo times, there was a significant increase in the ratio myoinositol/Cr in high-signal areas of patients with an SP course compared with control subjects, and the presence of abnormal resonances in the lesions and NAWM for free amino acids and lipids (in 30% and 8%, respectively) and GLX complex (glutamine, glutamate, 
-aminobutyric acid; 16% and 20%, respectively).
CONCLUSIONS: Studying normal-appearing white matter on MRI with MRS allows discrimination between relapsing remitting and secondary progressive patients. In the NAWM of patients with MS and an SP course, severe axonal loss/dysfunction is negatively correlated to clinical disability and independent of the duration of the disease.
Key words: Proton magnetic resonance spectroscopy—Relapsing-remitting MS—Secondary progressive MS—Normal-appearing white matter—Axonal damage.
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