Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke

Abstract

We used diffusion tensor imaging (DTI) to assess Wallerian degeneration of the pyramidal tract within the first 2 weeks after ischemic stroke, and correlated the extent of Wallerian degeneration with the motor deficit. Nine patients with middle cerebral artery stroke were examined 2–16 days after stroke by DTI and T2-weighted MRI. We measured fractional anisotropy (FA), averaged diffusivity (Dav), eigenvalues of the diffusion tensor and T2-weighted signal in the cerebral peduncle and compared these values between the affected and the unaffected side and between patients and six controls. FA was significantly reduced on the affected side compared to the unaffected side and compared to the control group. The largest eigenvalue was reduced, whereas the smallest eigenvalue was elevated on the affected side. There was no significant difference in T2-weighted signal and Dav. The decrease of anisotropy correlated positively with the motor deficit at the time of DTI study and 90 days after stroke. The reduction of anisotropy mirrors the disintegration of axonal structures, as it occurs in the early phase of Wallerian degeneration. DTI detects changes of water diffusion related to beginning pyramidal tract degeneration within the first 2 weeks after stroke that are not yet visible in conventional T2-weighted or orientationally averaged diffusion weighted MRI. We demonstrated for the first time a correlation of early DTI findings of pyramidal tract damage with the motor deficit. DTI can help prognosing recovery of motor function after stroke within the early subacute phase.

Introduction

The degeneration of distal parts of nerves after injury of the proximal axon or cell body is labelled Wallerian Degeneration (WD). Waller (1850) first reported this pattern of degeneration after cutting glossopharyngeal and hypoglossal nerves of the frog in 1850. WD represents a uniform answer to injury of the proximal nerve or cell body within the central and peripheral nervous system. It is characterised by a highly stereotypical course, starting with disintegration of axonal structures within days after injury, followed by degradation of myelin due to infiltration of macrophages and finally, fibrosis and atrophy of the affected fibre tracts Johnson et al., 1950, Lampert and Cressman, 1966, Lexa et al., 1994.

WD after ischemic stroke is a well-known phenomenon. After ischemic infarction of the motor cortex or descending motor pathways, WD of the pyramidal tract reflects severe pyramidal tract damage. In previous studies, severe damage of the pyramidal tract, proven either by MRI or transcranial magnetic stimulation, has been associated with persisting motor impairment Binkofski et al., 1996, Fukui et al., 1994, Watanabe and Tashiro, 1992, Watanabe et al., 2001. Evidence of severe pyramidal damage in the early phase after stroke would be of great value to assess the prognosis and rehabilitational potential of stroke patients.

In the chronic stage of WD, atrophy of the pyramidal tract can be detected by computed tomography (Stovring and Fernando, 1983). Conventional magnetic resonance imaging (MRI) detects signal intensity changes that vary during the time course of WD Fukui et al., 1994, Inoue et al., 1990, Kuhn et al., 1989, Orita et al., 1994a, Orita et al., 1994b, Sawlani et al., 1997, Uchino et al., 1990, Watanabe and Tashiro, 1992, but signal intensity changes are generally not detected until 4 weeks after stroke. After a short phase of hypointensity in T2-weighted (T2w) MRI Kuhn et al., 1989, Sawlani et al., 1997, a T2w hyperintensity along the affected tracts is usually found in the chronic stage that is most likely due to fibrosis of the pyramidal tract Fukui et al., 1994, Inoue et al., 1990, Kuhn et al., 1989, Orita et al., 1994a, Orita et al., 1994b, Sawlani et al., 1997, Uchino et al., 1990, Watanabe and Tashiro, 1992. However, in the first days and weeks, WD is not detectable by conventional MRI.

Diffusion Tensor Imaging (DTI) is a technique that uses diffusion sensitising gradients applied in at least six non-collinear directions to determine the full diffusion tensor (Basser et al., 1994). The diffusion tensor provides information on the predominant direction and degree of water diffusion and gives clues on the microstructural properties of tissue Basser and Pierpaoli, 1996, Le Bihan et al., 2001, Pierpaoli et al., 1996. DTI is particularly interesting for the in vivo visualisation of white matter tracts. In cerebral white matter, water diffusion is fast along the main fibre directions and slowed perpendicular to fibres, resulting in anisotropic diffusion. The degree of anisotropy depends on the level of organisation of the studied tract Le Bihan et al., 2001, Pierpaoli et al., 1996 and the degree of hindrance to water diffusion by oriented axonal membranes and myelin sheaths (Beaulieu and Allen, 1994a). DTI therefore appears well suited to study WD of long descending tracts after ischemic stroke.

Recent reports studied WD of the pyramidal tract by DTI in the chronic stage of stroke Pierpaoli et al., 2001, Werring et al., 2000. Heterogeneous populations were studied in the chronic phase months to years after stroke. Reduced anisotropy along the pyramidal tract of the affected side was found and interpreted as the equivalent of WD Pierpaoli et al., 2001, Werring et al., 2000. In another study, colour-coded contrast images obtained from diffusion weighted imaging along the three orthogonal axes were used to detect early WD in a sample of patients with intracerebral haemorrhage or ischemic stroke (Watanabe et al., 2001). Changes of colour intensity along the corticospinal tract were found 3 weeks after onset and interpreted as reflection of early WD.

To the best of our knowledge, no DTI data on WD in the early subacute stage after stroke at sites of the brain remote from the initial infarct is available. The purpose of this study is to evaluate whether DTI can detect changes of water diffusion that are reflective of early WD in the pyramidal tract within the first 2 weeks after ischemic stroke, and to test whether DTI findings of early WD correlate with measures of motor deficit and outcome.