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Assessment of Normal-Appearing White and Gray Matter in Patients With Primary Progressive Multiple Sclerosis
A Diffusion-Tensor Magnetic Resonance Imaging Study
Marco Rovaris, MD;
Marco Bozzali, MD;
Giuseppe Iannucci, MD;
Angelo Ghezzi, MD;
Domenico Caputo, MD;
Enrico Montanari, MD;
Antonio Bertolotto, MD;
Roberto Bergamaschi, MD;
Ruggero Capra, MD;
Giovanni Luigi Mancardi, MD;
Vittorio Martinelli, MD;
Giancarlo Comi, MD;
Massimo Filippi, MD
Arch Neurol. 2002;59:1406-1412.
Background Diffusion-tensor magnetic resonance imaging is sensitive to the more
destructive aspects of multiple sclerosis (MS) evolution occurring outside
and within T2-visible lesions and, as a consequence, holds promise for providing
a more complete picture of primary progressive (PP) MSrelated tissue
damage than conventional magnetic resonance imaging.
Objective To improve our understanding of PPMS by assessing the extent of occult
pathological features in the normal-appearing white and gray matter of the
brain using diffusion-tensor magnetic resonance imaging.
Methods Ninety-six patients with PPMS, 47 patients with secondary progressive
(SP) MS, and 44 healthy control subjects were studied. T2-hyperintense and
T1-hypointense lesion volumes were calculated, and the volume of the whole
brain tissue was measured. Diffusion-tensor magnetic resonance imaging scans
were postprocessed and analyzed to obtain the mean diffusivity and fractional
anisotropy histograms from the brain and from the normal-appearing white and
gray matter in isolation.
Results The mean T2-hyperintense and T1-hypointense lesion volumes were lower
in patients with PPMS than in patients with SPMS, while the mean absolute
brain volumes were similar in the 2 groups. The average lesion diffusivity
was significantly higher in patients with SPMS than in patients with PPMS
(P<.001). Histogram-derived metrics of the brain
tissue and normal-appearing white and gray matter were significantly different
between patients with PPMS and healthy subjects (range, P = .004 to <.001). Average diffusivity values were significantly
higher in patients with SPMS than in patients with PPMS for all the tissues
studied (range, P = .001 to <.001). Fractional
anisotropy histogramderived quantities did not significantly differ
between the 2 patient groups (range, P = .94 to .03).
Conclusion This study confirms that, in patients with PPMS, normal-appearing white
and gray matter are not spared by disease-related pathological processes,
although they are affected to a lesser degree than in patients with SPMS.
From the Neuroimaging Research Unit (Drs Rovaris, Bozzali, Iannucci,
and Filippi) and the Clinical Trials Unit (Drs Martinelli and Comi), Department
of Neuroscience, Scientific Institute and University Ospedale San Raffaele,
Milan; the Multiple Sclerosis Center, Ospedale di Gallarate, Gallarate (Dr
Ghezzi); the Departments of Neurology, Scientific Institute Don Gnocchi, University
of Milan, Milan (Dr Caputo), Ospedale di Orbassano, Orbassano (Dr Bertolotto),
and Spedali Civili, University of Brescia, Brescia (Dr Capra); the Multiple
Sclerosis Center, Ospedale di Fidenza, Fidenza (Dr Montanari); and the Departments
of Neurological Sciences, Scientific Institute C. Mondino, University of Pavia,
Pavia (Dr Bergamaschi), and University of Genoa, Genoa (Dr Mancardi), Italy.
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