Diagnosis of amyotrophic lateral sclerosis (ALS) depends on clinical evidence of combined upper motor neuron (UMN) and lower motor neuron (LMN) degeneration, although ALS patients can present with features predominantly of one or the other. Some UMN-predominant patients show hyperintense signal along the intracranial corticospinal tract (CST) on T2- and proton density (PD)-weighted images (ALS-CST +), and appear to have faster disease progression when compared to those without CST hyperintensity (ALS-CST -). The reason for this is unknown. We hypothesized that diffusion tensor tractography (DTT) would reveal differences in DTI abnormalities along the intracranial CST between these two patient subgroups. Clinical DTI scans were obtained at 1.5T in 14 neurologic controls and 45 ALS patients categorized into two UMN phenotypes based on clinical measures and MRI. DTT was used to quantitatively assess the CST in control and ALS groups. DTT revealed subcortical loss (\'truncation\') of virtual motor CST fibers (presumably) projecting from the precentral gyrus (PrG) in ALS patients but not in controls; in contrast, virtual fibers (presumably) projecting to the adjacent postcentral gyrus (PoG) were spared. No significant differences in virtual CST fiber length were observed between controls and ALS patients. However, the frequency of CST truncation was significantly higher in the ALS-CST + subgroup (9 of 21) than in the ALS-CST - subgroup (4 of 24; p = 0.049), suggesting this finding could differentiate these ALS subgroups. Also, because virtual CST truncation occurred only in the ALS patient group and not in the control group (p = 0.018), this DTT finding could prove to be a diagnostic biomarker of ALS. Significantly shorter disease duration and faster disease progression rate were observed in ALS patients with CST fiber truncation than in those without (p < 0.05). DTI metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were also determined in four regions of interest (ROIs) along the CST, namely: cerebral peduncle (CP), posterior limb of internal capsule (PLIC), centrum semiovale at top of lateral ventricle (CSoLV) and subcortical to primary motor cortex (subPMC). Of note, FA values along the left hemisphere virtual CST tract were significantly different between controls and ALS-CST + patients (p < 0.05) only at the PLIC level, but not at the CSoLV or subPMC level. Also, no significant differences in FA values were observed between ALS subgroups or between control and ALS-CST - groups (p > 0.05) in any of the ROIs. In addition, comparing FA values between ALS patients with CST truncation and those without in the aforementioned four ROIs, revealed no significant differences in either hemisphere. However, visual evaluation of DTT was able to identify UMN degeneration in patients with ALS, particularly in those with a more aggressive clinical disease course and possibly different pathologic processes.

The mechanism of motor recovery after stroke may involve reorganization of the surviving networks. However, details of adaptive changes in structural connectivity are not well understood. Here, we show long-term changes in white matter microstructure that relate to motor recovery in stroke patients. We studied ten subcortical ischemic stroke patients who showed motor hemiparesis at the initial clinical examination and an infarcted lesion centered in the posterior limb of internal capsule of the unilateral hemisphere at the initial diffusion-weighted magnetic resonance imaging scan. The participants underwent serial diffusion tensor imaging and motor function assessments at three consecutive time points; within 2 weeks, and at 1 and 3 months after the onset. Fractional anisotropy (FA) was analyzed for regional differences between hemispheres and time points, as well as for correlation with motor recovery using a tract-based spatial statistics analysis. The results showed significantly increased FA in the red nucleus and dorsal pons in the ipsi-lesional side at 3 months, and significantly decreased FA in the ipsi-lesional internal capsule at all time points, and in the cerebral peduncle, corona radiata, and corpus callosum at 3 months. In the correlation analysis, FA values of clusters in the red nucleus, dorsal pons, midbody of corpus callosum, and cingulum were positively correlated with recovery of motor function. Our study suggests that changes in white matter microstructure in alternative descending motor tracts including the rubro-spinal pathway, and interhemispheric callosal connections may play a key role in compensating for motor impairment after subcortical stroke.

Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD.