In-vivo evidence for stable neuroaxonal damage in the brain of patients with benign multiple sclerosis.
OBJECTIVE
The term benign multiple sclerosis (BMS) is referred to patients who have a mild or absent disability several years after disease clinical onset. Axonal damage can be measured in vivo using proton MR spectroscopy ((1)H-MRS). In this study, we quantified the severity of "global" axonal damage in BMS and early relapsing-remitting (RR) MS patients, using whole brain N-acetylaspartate (WBNAA) (1)H-MRS, to better elucidate the structural correlates of a non-disabling disease evolution.


METHODS
WBNAA concentration was measured in 37 patients with BMS (mean disease duration 22.3 years) and 17 patients with early RRMS (mean disease duration 4.0 years), using an unlocalized (1)H-MRS sequence. Dual echo and T1-weighted scans were also obtained to measure T2-hyperintense lesion volume (TLV) and normalized brain volume (NBV).


RESULTS
TLV was higher in BMS (mean TLV = 13.1 mL) than in early RRMS patients (mean TLV = 7.2 mL) (P = 0.018), whereas neither NBV (mean NBV: 1491.0 mL in BMS vs 1520.3 mL in RRMS) nor WBNAA concentration (mean WBNAA: 10.5 mmol in BMS vs 11.4 mmol in RRMS) significantly differed between the two groups. In MS patients, no correlation was found between WBNAA concentration and Expanded Disability Status Scale (EDSS), TLV and NBV.


CONCLUSIONS
The similar WBNAA concentrations seen in BMS and early RRMS patients fit with the notion that a non-disabling long-term evolution of MS may be due, at least in part, to non-progression of pathology. Such a condition seems to be independent from MRI-visible lesions burden.
Benedetti
B
B
Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
Rovaris
M
M
Rocca
M A
MA
Caputo
D
D
Zaffaroni
M
M
Capra
R
R
Bertolotto
A
A
Martinelli
V
V
Comi
G
G
Filippi
M
M
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001369:Axons / Q000737:chemistry / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001923:Brain Chemistry; D002470:Cell Survival; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D055815:Young Adult
D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate