White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis

Abstract

Primary lateral sclerosis is a sporadic disorder characterized by slowly progressive corticospinal dysfunction. Primary lateral sclerosis differs from amyotrophic lateral sclerosis by its lack of lower motor neuron signs and long survival. Few pathological studies have been carried out on patients with primary lateral sclerosis, and the relationship between primary lateral sclerosis and amyotrophic lateral sclerosis remains uncertain. To detect in vivo structural differences between the two disorders, diffusion tensor imaging of white matter tracts was carried out in 19 patients with primary lateral sclerosis, 18 patients with amyotrophic lateral sclerosis and 19 age-matched controls. Fibre tracking was used to reconstruct the intracranial portion of the corticospinal tract and three regions of the corpus callosum: the genu, splenium and callosal fibres connecting the motor cortices. Both patient groups had reduced fractional anisotropy, a measure associated with axonal organization, and increased mean diffusivity of the reconstructed corticospinal and callosal motor fibres compared with controls, without changes in the genu or splenium. Voxelwise comparison of the whole brain white matter using tract-based spatial statistics confirmed the differences between patients and controls in the diffusion properties of the corticospinal tracts and motor fibres of the callosum. This analysis further revealed differences in the regional distribution of white matter alterations between the patient groups. In patients with amyotrophic lateral sclerosis, the greatest reduction in fractional anisotropy occurred in the distal portions of the intracranial corticospinal tract, consistent with a distal axonal degeneration. In patients with primary lateral sclerosis, the greatest loss of fractional anisotropy and mean diffusivity occurred in the subcortical white matter underlying the motor cortex, with reduced volume, suggesting tissue loss. Clinical measures of upper motor neuron dysfunction correlated with reductions in fractional anisotropy in the corticospinal tract in patients with amyotrophic lateral sclerosis and increased mean diffusivity and volume loss of the corticospinal tract in patients with primary lateral sclerosis. Changes in the diffusion properties of the motor fibres of the corpus callosum were strongly correlated with changes in corticospinal fibres in patients, but not in controls. These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders.

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

“…Involvement of the corpus callosum (CC) is a consistent feature of ALS [Filippini et al, 2010], thought to contribute to a functional impairment of interhemispheric inhibition, as evidenced by both TMS [Karandreas et al, 2007; Wittstock et al, 2007] and clinically evident mirror movements [Wittstock et al, 2011]. The CC appears to be a particularly vulnerable structure in PLS [Agosta et al, 2014; Ciccarelli et al, 2009; Iwata et al, 2011; Kolind et al, 2013] and a finding of delayed lateralization of PMBR is in keeping with this observation. Preserved hemispheric autonomy is still demonstrated by the time that PMBR peaks, suggesting still adequate CC functionality, although partial mirror movements during response epochs were also noted in some patients' EMG.…”

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

“…The affected regions included the subcortical white matter, internal capsule, and the corpus callosum, consistent with other studies. 26,28,29 In the second step, to identify white matter regions associated with PBA, white matter voxels that differed from controls were compared between PBA1 and PBA2 patients, with ALSFRS-R and diagnosis (ALS vs PLS) as covariates. This analysis revealed a small region of white matter underlying the left motor cortex with reduced FA in PBA1 compared with PBA2 patients ( figure 3, row A).…”

“…Voxel-wise statistical analysis of the FA skeletons was performed using tract-based spatial statistics (version 1.2; http://www.fmrib.ox.ac.uk/fsl/), 25 with methods previously described. 26 Imaging analysis. A 2-step process was used to identify white matter tracts associated with PBA.…”

Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS

“…32 However, it is perhaps surprising that DTI studies have not consistently demonstrated a relationship between FA (or MD) and disability (studies reviewed in reference 5). An apparent paradox has also emerged whereby higher FA values (thought to reflect greater WM tract integrity) have been noted in patients with the longest disease duration, 3,33 despite evidence of decreasing FA values in some, but not all longitudinal studies. 34,35 There are also data specifically supporting a role for baseline FA in prognostication.…”