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Use of MR Imaging in Detection of Retrograde Wallerian Degeneration/”Die-Back Phenomenon” 2003

Saigal G, Pattany P, Quencer R, Pasquale-Styles M, Norenberg M, Marcillo A, Post MJD
University of Miami, Florida

Purpose and Background:
Spinal cord injuries can be both devastating and debilitating. About 11,000 spinal cord injuries occur in the US alone, each year. The ultimate objective of research in spinal cord injury is being able to find more effective treatments, the eventual goal being able to find a cure for paralysis following spinal cord injury. Various therapies are being developed to combat this injury and help in restoration of neurological function. One of these includes administration of steroids in the spinal cord immediately following injury. Other promising strategies being explored at the present time include treatment with growth factors and transplantation with nerve cells, Schwann cells and stem cells. Complete understanding of spinal cord injury is key to guiding development of new treatment strategies. Remarkably much is still unknown about pathology to the spinal cord following injury.

Wallerian degeneration is a post injury phenomenon which begins almost immediately following spinal cord injury. It can be divided into antegrade and retrograde (Wallerian) degeneration, with anterograde degeneration proceeding distally towards the axon terminals and retrograde degeneration proceeding proximally towards the cell body. Antegrade Wallerian degeneration has been extensively studied by pathology as well as imaging. It is thought to occur almost immediately following injury and evidence of early antegrade Wallerian degeneration has been demonstrated as early as 12 days after injury. The complete process is however slow and complete breakdown and removal of debris may take up to 2 years. Retrograde Wallerian degeneration also known as ‘dieback’ phenomenon is a less well understood entity. Although retrograde changes in the corticospinal tracts have been demonstrated on histopathology studies, this concept has not gained widespread acceptance. Some researchers have postulated the presence of ascending fibers in the corticospinal tract thus hypothesizing that changes seen in the corticospinal tracts above the level of injury actually represent antegrade Wallerian degeneration of these tracts. MR imaging has been useful in demonstrating changes seen in the spinal cord due to antegrade Wallerian degeneration. These changes were initially studied with conventional imaging MR techniques. More recently, though diffusion imaging has been found to be more sensitive in evaluating these changes. To our knowledge, retrograde Wallerian degeneration or ‘dieback’ phenomenon has not been studied using MR. We believe that demonstration of retrograde Wallerian degeneration would be important in determining the extent of axonal loss following injury to the spinal cord and would provide vital information in evaluating treatment strategies.

Materials & Methods:
Post mortem specimens of 6 patients were evaluated by histopathology and MR. The cross sectional images of the cord were acquired using a T1-weighted spin-echo sequence with the following imaging parameters: 800/20/4 (TR/TE/NEX) with a 3 mm slice thickness, 4 cm field of view (FOV), and 256 X 256 matrix, and 12 to 17 contiguous slices. Similarly, the T2-weighted images were acquired using spin-echo sequence with the following imaging parameters: 2000/80/6 (TR/TE/NEX).

Cross sectional DWI of the cord were acquired with diffusion encoding being applied along the slice-select, frequency-encoding, and phase-encoding axes. Five different b values of 0, 250, 500, 750, 1000 s/mm2 were used along each of the three orthogonal axes to obtain calculated ADC images. The diffusion-weighted image parameters were 3000/100/1 (TR/TE/Nex) with 256x256 image matrix; 12 to 17 contiguous slices, each 3 mm thick and FOV of 40 mm. Injury to death intervals varied from 12 to 40 years. Following this, the spinal cords were examined histopathologically following fixation. They were then sectioned and grossly examined. Sections were processed by routine histologic methods and embedded in paraffin. They were then stained using hematoxylin and eosin and special stains specifically luxol fast blue for myelin and silver stain for axons. The histopathology and the imaging findings were then correlated.

Results:
Histopathological examinations demonstrated definite evidence of axonal loss in all specimens above the level of injury consistent with retrograde wallerian degeneration. MR imaging was useful in corroborating these findings. We found that diffusion imaging was more useful than conventional imaging in the detection of these changes.

Conclusion:
Retrograde wallerian degeneration does occur. Our study demonstrated that diffusion imaging may be more sensitive than other conventional MR imaging in detecting these changes. Based on our findings in post mortem spinal cords, we believe that MR imaging may serve as a promising tool in the evaluation of Wallerian degeneration non-invasively in vivo. This information could prove critical in the use of future treatment strategies such as cord transplantation.