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Time course of wallerian degeneration after ischaemic stroke revealed by diffusion tensor imaging
  1. G Thomalla,
  2. V Glauche,
  3. C Weiller,
  4. J Röther
  1. Neuroimage Nord, Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  1. Correspondence to:
 G Thomalla
 Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany;


Wallerian degeneration (WD) after ischaemic stroke is a well known phenomenon following a stereotypical time course. Whereas conventional magnetic resonance imaging fails to detect signal intensity changes until four weeks after stroke, diffusion tensor imaging (DTI) reveals changes related to WD only after days. DTI was used to monitor the time course of Wallerian degeneration of the pyramidal tract from the early subacute to the late chronic stage of ischaemic stroke in two patients. A progressive decrease of fractional anisotropy was found along the pyramidal tract in the cerebral peduncle below the primary lesion resulting from progressive changes in the principal diffusivities, as well as a slight increase in the orientationally averaged diffusivity in the chronic phase. These signal changes reflect the progressive disintegration of fibre structures resulting from WD.

  • Dav, averaged diffusivity
  • DTI, diffusion tensor imaging
  • FA, fractional anisotropy
  • WD, wallerian degeneration
  • wallerian degeneration
  • ischemic stroke
  • diffusion tensor imaging

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Wallerian degeneration (WD) of descending fibre tracts after ischaemic stroke is a well known phenomenon reflecting severe fibre tract damage. WD represents a uniform answer to injury within the central and peripheral nervous systems, and disintegration of axonal structures within the first days after injury is followed by infiltration of macrophages, degradation of myelin after several weeks, and finally, fibrosis and atrophy of the affected fibre tracts.1,2 After ischaemic stroke it usually takes two to four weeks before WD can be detected by conventional magnetic resonance imaging (MRI), where the main pathological finding is a hyperintensity on T2-weighted images along the affected tracts in the chronic stage, weeks to months after stroke.3

Recently, diffusion tensor imaging (DTI) has opened up new possibilities of imaging fibre tracts in the brain by estimation of the whole diffusion tensor—which provides information on the predominant direction and degree of water diffusion and thus allows conclusions to be drawn about the microstructural properties of tissue.4 The degree of anisotropy of diffusion reflects the integrity and the degree of organisation of the fibre tracts within the brain.5 DTI has been used to study WD in the chronic stage of stroke and it has been shown that fractional anisotropy (FA) was reduced along the pyramidal tract on the affected side below the primary lesion months to years after stroke.6,7 In a previous study, we used DTI to study early WD of the pyramidal tract after acute ischaemic stroke. We found decreases in FA and characteristic changes in the principal diffusivities (eigenvalues), reflecting early WD in the cerebral peduncle of the affected side as early as 2–16 days after ischaemic stroke; at the same time T2-weighted images and maps of the orientationally averaged diffusivity did not reveal obvious changes.8

No longitudinal DTI studies of WD have been published. Here we report the findings from diffusion tensor images obtained for two of our patients at three different time points during the time course from the early subacute to the chronic stage of stroke.


Magnetic resonance images were acquired on a 1.5 Tesla MR system (Magnetom Vision, Siemens, Erlangen/Germany). A high resolution T1-weighted image data set (voxel size 1×1×1 mm) was acquired. For DTI we used a single shot STEAM sequence9 with matrix size 56×64, field of view 192×192 mm, slice thickness 3 mm without interslice gap, and voxel size 3×3×3 mm. Diffusion sensitising gradients (b = 750 s/mm2) were applied along six directions, and one image without diffusion weighting (b = 0 s/mm2) was obtained. The diffusion tensor (D) for each voxel was calculated, and maps of eigenvalues, averaged diffusivity (Dav), and FA were generated4 using SPM99 in Matlab 5.3 (The MathWorks, Natick, MA). Three dimensional regions of interest (ROIs) were manually defined for each side covering the medial anterior cerebral peduncle between the hypothalamus and the pons. Eigenvalues (λ1, λ2, λ3), FA, and Dav were calculated within the ROI, and ratios between values of the affected and unaffected side were determined (rλ1, rλ2, rλ3, rFA, rDav). Details of the MRI protocol and postprocessing have been reported elsewhere.8


Two patients with striatocapsular infarction were examined at three time points after stroke (case 1: 12, 104, and 288 days after stroke; and case 2: 5, 35, and 92 days after stroke). DTI revealed a clear pattern of progressive structural changes, which corresponded well with histological findings on the temporal evolution of WD and with DTI findings of WD in the chronic stage after stroke as described above. In both patients the rFA decreased continuously (from 0.84 to 0.75 and from 0.83 to 0.62) and the rDav increased slightly (from 0.98 to 1.11 and from 0.96 to 1.02). Ratios for the second (rλ2) and third (rλ3) eigenvalues markedly increased over time in both patients (rλ2: from 1.07 to 1.29 and from 1.02 to 1.10; rλ3: from 1.05 to 1.27 and from 1.06 to 1.28).

An example of progressive FA decrease along the pyramidal tract below the primary lesion over time is shown in fig 1. Corresponding structural changes are clearly visible on the coregistered high resolution T1-weighted image in the late chronic stage, where a hypointensity resulting from degeneration of descending tracts in the mediolateral cerebral peduncle is easily identified.

Figure 1

 Time course of wallerian degeneration (WD). A slight decrease in fractional anisotropy (FA) was found along the affected pyramidal tract below the lesion 12 days after stroke on coronal as well as on transverse sections at the level of the cerebral peduncle. The decrease in FA became more pronounced after 104 and 288 days (small white arrows). On the T1-weighted (T1-w) images the area of the primary lesion shows the typical progression from a slight hypointensity in subacute infarction to a well defined structural defect in the chronic stage (large black arrows). Although after 12 days no pathological signal changes along the pyramidal tract were found, after 104 days, and even more definitely after 288 days, a clear hypointensity became visible along the descending pyramidal tract (small black arrows) representing typical signal alterations found in the chronic stage of WD. Transverse sections through the cerebral peduncle reveal limiting of WD to lateral parts of the pyramidal tract on both T1-w and FA images at days 104 and 288.


We longitudinally studied the course of WD in two patients by DTI and found a pattern of progressive structural degeneration which corresponds well to findings from experimental studies of WD. From these studies we know that anisotropy of diffusion in white matter mainly results from oriented membranes, such as axonal structures and myelin.5 Disintegration of axonal structures and myelin, as occurs in WD, results in loss of anisotropy, which is detected by DTI.5 Signal changes resulting from WD after ischaemic stroke have been detected by DTI in the early subacute stage8 as well as in chronic stroke.6,7

Structural changes in WD evolve over time with progressive destruction of fibre structures followed by gliosis.1,2 We found progressive loss of anisotropy resulting from reduced first eigenvalue and increased second and third eigenvalues. We interpret these changes as a reflection of the progressive structural alterations resulting from WD. Moreover, although in the early subacute stage no clear changes of the orientationally averaged diffusivity can be detected,8 in the chronic stage, with progression of structural degradation due to WD, an increase in the Dav becomes obvious.

The findings of the present report have to be interpreted with caution as they are based on only two cases. In previous DTI studies, a 15% decrease in FA was found in the cerebral peduncle two to six months after stroke in one study,6 and a 32% decrease in FA was found in the cerebral peduncle below the lesion in patients more than one year after stroke in another study.7 Although these findings are from different populations in different studies, they also appear to indicate a pattern of more pronounced loss of FA at later time points after stroke. In any case, the extent of WD after stroke may vary over a wide range in different patients, depending on the extent of the primary lesion and its location in relation to the affected fibre tracts. In our two patients the decrease in FA advanced from 16% to 25% in case 1 and from 17% to 48% in case 2, during a time course covering more than nine months and three months, respectively.

WD of the pyramidal tract after ischaemic stroke is known to reflect severe pyramidal tract damage associated with persisting impairment of motor functions.10,11 In patients with ischaemic stroke and motor impairment, the degree of WD of the pyramidal tract has been shown to be correlated to motor scales at different time points.8 In both our patients the DTI findings of a typical pattern of progressive WD were associated with persisting moderate to severe hemiparesis.

DTI allows evaluation of the time course of WD from the early subacute to the chronic stage. The findings on imaging reflect the different stages of WD that are well known from experimental and histological studies. Thus, DTI offers a way to detect and monitor the time course of severe degeneration of the pyramidal tract and may be a helpful tool in forecasting and monitoring recovery in patients with ischaemic stroke.



  • Competing interests: none declared

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