Whole brain‐based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging

Abstract

Different motor neuron disorders (MNDs) are mainly defined by the clinical presentation based on the predominance of upper or lower motor neuron impairment and the course of the disease. Magnetic resonance imaging (MRI) mostly serves as a tool to exclude other pathologies, but novel approaches such as diffusion tensor imaging (DTI) have begun to add information on the underlying pathophysiological processes of these disorders in vivo. The present study was designed to investigate three different rare MNDs, i.e., primary lateral sclerosis (PLS, N = 25), hereditary spastic paraparesis (HSP, N = 24), and X-linked spinobulbar muscular atrophy (X-SBMA, N = 20), by use of whole-brain-based DTI analysis in comparison with matched controls. This analysis of white matter (WM) impairment revealed widespread and characteristic patterns of alterations within the motor system with a predominant deterioration of the corticospinal tract (CST) in HSP and PLS patients according to the clinical presentation and also in patients with X-SBMA to a lesser degree, but also WM changes in projections to the limbic system and within distinct areas of the corpus callosum (CC), the latter both for HSP and PLS. In summary, DTI was able to define a characteristic WM pathoanatomy in motor and extra-motor brain areas, such as the CC and the limbic projectional system, for different MNDs via whole brain-based FA assessment and quantitative fiber tracking. Future advanced MRI-based investigations might help to provide a fingerprint-identification of MNDs.

Tract-based spatial statistics of diffusion tensor imaging in hereditary spastic paraplegia with thin corpus callosum reveals widespread white matter changes

“…One previous application of DTI in motor neuron diseases included 24 pure HSP patients and reported significant alterations in motor pathways and projections to the limbic system and corpus callosum (20). In our analysis, patients with HSP-TCC had additional widespread alterations in other areas, including the brain stem, cerebellum and anterior thalamic radiations, thalami, superior longitudinal fasciculi, uncinate fasciculi, and sagittal stratum.…”

A Distinct MR Imaging Phenotype in Amyotrophic Lateral Sclerosis: Correlation between T1 Magnetization Transfer Contrast Hyperintensity along the Corticospinal Tract and Diffusion Tensor Imaging Analysis

“…37 DTI studies of patients with hereditary spastic paraparesis have also demonstrated prominent posterior CC involvement, notably not detected in the LMN-only slowly progressive disorder (ie, X-linked spinobulbar muscular atrophy). 57 It has been reported that in ALS and PLS, there is a loss or shrinkage of Betz cells in the premotor cortex, but the cortical motor neurons seem to degenerate more in PLS than ALS. 58 Therefore, all these findings together support the hypothesis that the T1 MTC hyperintense signal intensity, when present, expresses a distinct ALS phenotype characterized by a more severe cortical motor neuron degeneration, with a more prominent "dying back" degeneration of neurons of the CST.…”

Kennedy disease (X-linked recessive bulbospinal neuronopathy): A comprehensive review from pathophysiology to therapy

“…More recently, magnetic resonance imaging (MRI) studies using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) reported widespread white matter and subtle gray matter changes in the frontal regions [40]. Further research [41] found widespread white matter changes in the corticospinal tract and in the limbic system, while another study [42] described multifocal white matter changes, mainly in the brainstem. A recent positron emission tomography (PET) [43] study also identified hypometabolism in the frontal regions, in ten patients with SBMA.…”