The aim of this research was to obtain an absolute quantification of the N-acetyl-aspartate, choline, creatine and phosphocreatine levels in normal-appearing white matter by means of 1H magnetic resonance spectroscopy in a group of multiple sclerosis patients (27 with the relapsing-remitting form and 13 with the secondary progressive form). These values were compared with those of a group of 12 age-matched healthy control subjects. A significant decrease in the N-acetyl-aspartate concentration was found in normal-appearing white matter of frontal and parietal brain areas in multiple sclerosis patients compared with the same areas in control subjects. This reduction was more evident in progressive patients. The decrease in the N-acetyl-aspartate concentration in normal-appearing white matter significantly correlated with the Expanded Disability Status and the lesional load. No significant change was found in the concentration of creatine or choline. This finding concurs with previous evidence of heterogeneity in the multiple sclerosis pathological process which is not confined to the lesions and involves not only myelin, but also axons, even in white matter which appears normal on MRI.

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RIASSUNTO -Il presente studio e stato volto a verificare le modificazioni di alcuni metaboliti cerebrali in corso di SLA mediante RM spettroscopica cerebrale e quantificazione assoluta dei metaboliti. Sono stati studiati 12 pazienti affetti da sclerosi laterale amiotrofica, di sesso maschile ed eta media: 53,0 ± 5,32 anni , 7 nella forma definita e 5 nella forma probabile.Lo studio ha evidenziato, a livello della sostanza grigia dell'area motoria primaria, una riduzione significativa dei livelli di N-Acetil-Aspartato rispetto ai soggetti di controllo (8,5 ± 0,6 mM vs 10,4 ± 0,7 mM, p< 0,001), piu marcata nei pazienti ad esordio bulbare ed in quelli con evidenze neuroradiologiche di ipointensita di segnale a carico della corteccia motoria. Non erano evidenti differenze significative relativamente ai valori di N-Acetil-Aspartato tra pazienti con diagnosi definita e quelli con forma probabile.SUMMARY -This study assessed changes in some brain metabolites in amyotrophic lateral sclerosis using cerebral magnetic resonance spectroscopy and absolute quantification of metabolites. We studied 12 men with an average age of 53.0 ± 5.32 years. Seven had definite and five probable amyotrophic lateral sclerosis. Investigations were performed with a 1.5 T system (Signa Advantage, GE Medical Systems) using a standard head coil. Spectra were acquired with STEAM sequences and CHESS presequence to suppress the water peak. Acquisitions were made in a localised region of the motor cortex with a typical volume 6 cc.The study disclosed a significant reduction inN-acetyl-aspartate levels in the grey matter of the primary motor area compared with control subjects (8.5 ± 0.6 mM vs 10.4 ± 0.7 mM, p < 0.001), more pronounced in patients with bulbar onset and those with neuroradiological evidence of signal hypointensity in the motor cortex. There were no significant differences in N -acetyl-aspartate values among patients with a definite diagnosis and probable cases.Our findings support histopathological evidence of axonal loss in the grey matter of the motor cortex in the course of amyotrophic lateral sclerosis as shown by the marked decrease in N-acetyl-aspartate, a marker of neural integrity. This finding was significantly correlated with clinical deterioration. 61

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