Detour ahead: possible causes of corticospinal tract truncation in upper motor neuron–predominant amyotrophic lateral sclerosis

Clinical diagnosis of amyotrophic lateral sclerosis (ALS) depends on finding evidence of combined of upper motor neuron (UMN) and lower motor neuron degeneration. T2- and proton density (PD)-weighted images reveal intracranial corticospinal tract (CST) hyperintensity in some UMN-predominant ALS patients who also exhibit faster disease progression compared to those without CST hyperintensity. Our previous study identified CST fibre tract truncation in a subset of UMN-predominant ALS patients, both with and without CST hyperintensity. In this study, we investigated the underlying cause(s) of CST fibre tract truncation in such ALS patients. Routine clinical diffusion tensor imaging (DTI) scans were acquired in 14 neurologic controls and 45 ALS patients using a 1.5 T magnetic resonance imaging (MRI) scanner. UMN-predominant ALS patients were categorized into two subgroups based on their clinically-acquired conventional MRI findings. DTI reconstruction was performed using both single-exponential and bi-exponential fitting approaches (the latter for free water [FW] estimation). DTI along the perivascular space (ALPS) index was also measured. CST fibres were reconstructed using tractography in both control and ALS subgroups. In CST-truncated ALS patients, the fibres deviated from their normal trajectory and entered the superior longitudinal fasciculus (SLF) at the level of the centrum semiovale, resulting in apparent truncation and overlap with the SLF. Axial diffusivity, radial diffusivity, FW content, and mean diffusivity values were normal along the expected CST pathway in cases of truncation, suggesting that axonal or myelin degeneration, inflammation, or oedema were unlikely to be responsible for CST truncation. ALPS index was significantly increased in CST-truncated patients compared to those without CST truncation. Based on these results, we hypothesize that impaired axonal guidance mechanisms or dysfunction of the glymphatic system may contribute to CST fibre tract truncation in ALS.