Determinants of disability in multiple sclerosis at various disease stages: a multiparametric magnetic resonance study.
OBJECTIVE
To investigate whether diffusion-tensor magnetic resonance imaging and whole brain N-acetylaspartate (WBNAA) proton magnetic resonance spectroscopy can provide complementary pieces of information to achieve a better understanding of the factors associated with disability in multiple sclerosis (MS).


METHODS
Cross-sectional survey.


METHODS
Referral hospital-based MS center.


METHODS
Ten healthy control subjects, 27 patients with a clinically isolated neurological syndrome, 21 patients with relapsing-remitting MS, and 29 patients with secondary progressive MS.


METHODS
Conventional and diffusion-tensor magnetic resonance imaging, as well as WBNAA proton magnetic resonance spectroscopy, of the brain was performed. T2-hyperintense lesion volumes were measured. The mean values of mean diffusivity (MD) and fractional anisotropy of T2-visible lesions were computed. Histograms of MD and fractional anisotropy values were produced for normal-appearing white matter and gray matter (GM).


RESULTS
Patients with a clinically isolated neurological syndrome had a significantly (P=.002) lower WBNAA concentration than control subjects. Patients with relapsing-remitting MS had significantly higher T2 lesion volume (P=.007), mean lesion MD (P=.003), normal-appearing white matter fractional anisotropy peak height (P=.03), and a lower WBNAA concentration (P<.001) than patients with a clinically isolated neurological syndrome. Patients with secondary progressive MS had significantly higher T2 lesion volume (P=.01), lower mean normal-appearing white matter fractional anisotropy (P=.003), higher mean GM MD (P=.004), and lower GM MD peak height (P=.01) than patients with relapsing-remitting MS. Disease duration, GM MD peak height, and WBNAA concentration entered a multivariate model, explaining nearly 70% of the disability variance.


CONCLUSIONS
The accumulation of macroscopic lesions and normal-appearing white matter damage seems to occur mainly during the earliest clinical phases of MS, whereas pathological features of GM may be a hallmark of the late progressive stage of the disease. This supports the notion of MS as a "2-stage" disease.
Pulizzi
Annalisa
A
Neuroimaging Research Unit, Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
Rovaris
Marco
M
Judica
Elda
E
Sormani
Maria Pia
MP
Martinelli
Vittorio
V
Comi
Giancarlo
G
Filippi
Massimo
M
D000328:Adult; D000368:Aged; D016880:Anisotropy; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D010487:Periaqueductal Gray / Q000378:metabolism; D013577:Syndrome; D013997:Time Factors
D001224:Aspartic Acid; C000179:N-acetylaspartate