Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis

Abstract

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs 37.82; P50.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

Keywords

primary progressive multiple sclerosis magnetisation transfer ratio

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References

Thompson AJ et al. (1997) Primary progressive multiple sclerosis . Brain 120: 1085-1096 .

Thompson AJ et al. (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis . Ann Neurol 29: 53-62 .

Allen IV , McKeown SR. (1979) A histological, histo-chemical and biochemical study of the macroscopically normal white matter in multiple sclerosis . J Neuro Sci 41: 81-91 .

Ormerod IEC et al. (1986) Relaxation times of apparently normal cerebral white matter in multiple sclerosis . Acta Radiol Supp 369: 382-384 .

Christiansen P et al. (1993) Increased water self-diffusion in chronic plaques and in apparently normal white matter in patients with multiple sclerosis . Acta Neurol Scand 87: 195-199 .

Husted CA et al. (1994) Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31Pand 1Hspectroscopic imaging . Ann Neurol 36: 157-165 .

Wolff SD , Balaban RS. (1989) Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo . Magn Reson Med 10: 135-144 .

Dousset V et al. (1992) Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging . Radiology 182: 483-491 .

Silver NC et al. (1996) Decreased magnetisation transfer ratio due to demyelination: a case of central pontine myelinolysis . J Neurol Neurosurg Psychiatry 61: 208-209 .

10.

Dousset V et al. (1997) Magnetization transfer study of HIV encephalitis and progressive multifocal leukoencephalopathy . Am J Neuroradiol 18: 895-901 .

11.

Gass A et al. (1994) Correlation of magnetisation transfer ratio with clinical disability in multiple sclerosis . Ann Neurol 36: 62-67 .

12.

Filippi M et al. (1995) A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis . Neurology 45: 478-482 .

13.

Loevner LA et al. (1995) Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetisation-transfer measurements . Radiology 196: 511-515 .

14.

Leary SM et al. (1999) Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis . JNeurol In press.

15.

Poser CM et al. (1983) New diagnostic criteria for multiple sclerosis: Guidelines for research protocols . Ann Neurol 13: 227-231 .

16.

Silver NC et al. (1997) Magnetisation transfer ratio of normal brain white matter: a normative database spanning four decades of life . J Neurol Neurosurg Psychiatry 62: 223-228 .

17.

Kurtzke JF. (1983) Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS) . Neurology 33: 1444-1452 .

18.

Barker GJ , Tofts PS , Gass A. (1996) An interleaved sequence for accurate and reproducible clinical measurement of magnetization transfer ratio . Magn Reson Imaging 14: 403-411 .

19.

Trapp BD et al. (1998) Axonal transection in the lesions of multiple sclerosis . New Engl J Med 338: 278-285 .

20.

Miller DH et al. (1989) Precise relaxation time measurements of normal-appearing white matter in inflammatory central nervous system disease . Magn Reson Med 11: 331-336 .

21.

Droogan AG et al. (1998) Navigated spin echo diffusion-weighted imaging in clinical phenotypes of multiple sclerosis . Proc Int Soc Magn Reson Med 1: 117-117 (Abstract).

22.

Davie CA et al. (1994) Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions . Brain 117: 49-58 .

23.

Fu L et al. (1998) Imaging axonal damage of normal-appearing white matter in multiple sclerosis . Brain 121: 103-113 .

24.

Davie CA et al. (1997) 1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis . J Neurol Neurosurg Psychiatry 63: 736-742 .

25.

Leary SM et al. (1998) 1H magnetic resonance spectroscopyofnormalappearingwhitematterinprimary progressive multiple sclerosis . Ann Neurol 44: 464-464 (Abstract).

26.

Dousset V et al. (1995) Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetisation transfer . Am J Neuroradiol 16: 225-231 .

27.

Hiehle JF et al. (1994) Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis . Magn Reson Med 32: 285-293 .

28.

Lexa FJ , Grossman RI , Rosenquist AC. (1994) MR of wallerian degeneration in the feline visual system: characterization by magnetization transfer rate with histopathologic correlation . Am J Neuroradiol 15: 201-212 .

29.

Kimura H et al. (1996) Magnetisation transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation . J Comput Assist Tomogr 20: 540-546 .

30.

Filippi M et al. (1998) Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis . Ann Neurol 43: 809-814 .

31.

Goodkin DE et al. (1998) PD, T1, gadolinium (Gd+) intensities, T2 and MTRs are chronically diffusely abnormal in MS brain and on monthly MRI scans are related to the appearance of new Gd+ lesions in normal appearing white matter (NAWM) . Neurology 50: A191-A191 (Abstract).

32.

Silver NC et al. (1998) Serial magnetization transfer imaging to characterize the early evolution of new MS lesions . Neurology 51: 758-764 .

33.

Barbosa S et al. (1994) Magnetic resonance relaxation time mapping in multiple sclerosis: normal appearing white matter and the `invisible' lesion load . Magn Reson Imaging 12: 33-42 .

34.

Filippi et al. (1999) Comparison of MS clinical pheno-types using conventional and magnetization transfer MRI . Neurology 52: 588-594 .