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Axonal Loss In Multiple Sclerosis Lesions:
MRI Insights Into Substrates Of Disability

van Waesberghe JH, Kamphorst W, De Groot CJ, van Walderveen MA, Castelijns JA, Ravid R, Lycklama a Nijeholt GJ, van der Valk P, Polman CH, Thompson AJ, Barkhof F
Ann Neurol 1999 Nov;46(5):747-54
Academic Hospital Vrije Universiteit, MS-MR Centre and Dept of Radiology, Amsterdam, The Netherlands
PMID# 10553992; UI# 20019420
Abstract

Magnetic Resonance Imaging (MRI) monitoring of disease progression in Multiple Sclerosis is limited by the lack of correlation of abnormalities seen on T2-weighted imaging, and disability.

We studied the HistoPathology of Multiple Sclerosis lesions, as depicted by MRI, in a large postmortem sample, focusing on Axonal Loss.

Tissue samples from 17 patients were selected immediately postmortem for HistoPathological analysis on the basis of T2-weighted imaging, including Normal-Appearing White Matter and T1 HypoIntense lesions.

In each region, we measured Magnetization Transfer Ratios (MTR), T1 contrast ratio, Myelin, and Axonal density.

T2 lesions (109 samples) were heterogeneous with regard to MRI appearance on T1 and MTR, whereas Axonal density ranged from 0% (no residual Axons) to 100% (normal Axonal density).

    Of 64 T2 Lesions:
  1. 17 were reactive
  2. 21 Active
  3. 15 Chronically active
  4. 11 Chronically inactive

MTR and T1 contrast ratio correlated strongly with Axonal density. Also in Normal-Appearing White Matter (24 samples), MTR correlated with Axonal density.

In conclusion, postmortem tissue sampling by using MRI revealed a range of pathology, illustrating the high sensitivity and low specificity of T2-weighted imaging.

T1 HypoIntensity and MTR were strongly associated with Axonal density, emphasizing their role in monitoring progression in Multiple Sclerosis.



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