Structural MRI reveals distributed cortical thinning in patients with pure lower motor neuron disease variants (P6.091)

Objective. To define the pattern of cortical thickness and white matter (WM) tract damage in patients with pure lower motor neuron (PLMN) disease variants relative to classic amyotrophic lateral sclerosis (ALS) and healthy controls. Background. There is an increasing awareness that ALS is a clinically and pathologically heterogeneous disease, including under the same general umbrella phenotypes ranging from pure upper motor neuron disease to PLMN disease. Methods. Twenty-eight patients with PLMN (18 progressive muscular atrophy, 2 respiratory ALS, 5 flail arm, and 3 flail leg) were compared with 57 classic ALS patients and 59 healthy controls. All subjects underwent T1-weighted and diffusion tensor (DT) MRI. Surface-based morphometry analysis was used to assess cortical thickness. Both vertex-wise and regions of interest-based analyses were applied. Using tractography, DT MRI metrics from corticospinal tract (CST), corpus callosum (CC), uncinate, cingulum, inferior longitudinal, and superior longitudinal fasciculi bilaterally were obtained. Results. Relative to controls, classic ALS patients showed cortical thinning of the motor-related cortices as well as a distributed involvement of the prefrontal, temporal and occipito-parietal gyri. Although less severe, a similar cortical involvement was found in patients with PLMN variants. Classic ALS showed WM damage along motor and extra-motor tracts compared with controls and patients with PLMN. No WM abnormalities were found in PLMN patients relative to controls. Conclusions. Cortical thickness is reduced in patients with PLMN not only in motor areas but also in widespread non-motor cortical areas, with a topographical distribution similar to that of classic ALS. Longitudinal studies are warranted to explore whether the cortical pattern of degeneration depicted in PLMN variants is able to identify those subjects who will develop UMN signs and/or cognitive deficits. Study Supported by: Italian Ministry of Health (#RF-2010-2313220).