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Fractional Anisotropy in the Posterior Limb of the Internal Capsule and Prognosis in Amyotrophic Lateral Sclerosis

Ricarda A. L. Menke, PhD; Ivy Abraham, BSc; Catherine S. Thiel; Nicola Filippini, DPhil; Steve Knight, BSc; Kevin Talbot, DPhil; Martin R. Turner, PhD
Arch Neurol. 2012;69(11):1493-1498. doi:10.1001/archneurol.2012.1122.
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Objective  To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarkers.

Design  Baseline clinical assessment and 3-T diffusion tensor imaging, repeated after approximately 6 months. Tract-based spatial statistics were used to assess voxelwise correlations of just the baseline diffusion tensor imaging indices with the progression rate (change in disability score/time interval) within the corticospinal tract and corpus callosum.

Patients  The study involved 21 patients with amyotrophic lateral sclerosis and 3 patients with primary lateral sclerosis.

Results  Correlation was observed between fractional anisotropy and progression rate for a region of the corticospinal tract spanning the posterior limb of the internal capsule, with a left hemisphere emphasis. Posterior limb of the internal capsule fractional anisotropy showed potential to distinguish those patients with rapid progression. Axial diffusivity significantly increased in this region in a paired t test analysis of baseline and follow-up diffusion tensor imaging, in keeping with axonal damage. No correlations were noted for the corpus callosum.

Conclusions  Posterior limb of the internal capsule fractional anisotropy is a candidate prognostic marker in amyotrophic lateral sclerosis, with potential to identify incident cases with more rapid progression.

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Figures

Place holder to copy figure label and caption
Grahic Jump Location

Figure 1. Tract-based spatial statistics results within the corticospinal tract (CST) in relation to progression rate. Significant tract-based spatial statistics results (P < .05, familywise error corrected) in sagittal, coronal, and axial views (top panel) overlaid onto the group's mean fractional anisotropy (FA) skeleton (green) and the FMRIB58 FA template showing those parts of the CSTs where baseline FA was associated with progression rate (age included as a covariate of no interest). This revealed a bilateral region through the posterior limb of the internal capsules (red). The left side remained correlated when disease duration was added as a further potential confounding variable (blue). Scatterplots are shown for average FA within the tract-based spatial statistics–significant masks in the left and right CST vs progression rate between the 2 points to demonstrate the correlation in this region (bottom panel; estimates subject to circularity bias). The dotted vertical line shows the median progression rate based on a median survival of 30 months from symptom onset in amyotrophic lateral sclerosis (ALS). The horizontal dotted line in the left posterior limb of the internal capsule shows that baseline FA less than 0.62 identified the 4 patients above the median in this study. A indicates anterior; FRS, Functional Rating Scale; L, left; P, posterior; PLS, primary lateral sclerosis; R, right.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Longitudinal tract-based spatial statistics changes within the corticospinal tract (CST). Significant tract-based spatial statistics paired t test results (P < .05, familywise error corrected) in sagittal, coronal, and axial views (left 3 panels) overlaid onto the group's mean fractional anisotropy skeleton (green) and the FMRIB58 fractional anisotropy template showing those parts of the CSTs where the L1 (axial diffusivity) values significantly increased between the baseline and follow-up scans. This suggests left posterior limb of the internal capsule region axonal damage. Box plot also shown (far right panel). A indicates anterior; L, left; P, posterior; R, right.

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