Extramotor Damage Is Associated with Cognition in Primary Lateral Sclerosis Patients

Elisa Canu,Massimo Filippi,Giancarlo Comi,Federica Agosta,Sebastiano Galantucci,Adriano Chiò,Nilo Riva,Vincenzo Silani,Andrea Falini,Jan Kassubek

doi:10.1371/journal.pone.0082017

Abstract

ObjectivesThis is a cross-sectional study aimed at investigating cognitive performances in patients with primary lateral sclerosis (PLS) and using diffusion tensor (DT) magnetic resonance imaging (MRI) to determine the topographical distribution of microstructural white matter (WM) damage in patients with or without cognitive deficits.MethodsDT MRI scans were obtained from 21 PLS patients and 35 age- and sex-matched healthy controls. All PLS patients underwent a comprehensive neuropsychological battery. Tract-based-spatial-statistics (TBSS) was used to perform a whole-brain voxel-wise analysis of fractional anisotropy (FA), axial, radial (radD) and mean diffusivity (MD).ResultsTen PLS patients had abnormal scores in at least one neuropsychological test (PLS with cognitive deficits, PLS-cd). Compared with healthy controls and cognitively unimpaired PLS patients (PLS-cu), PLS-cd cases showed decreased FA and increased MD and radD in the corticospinal tract (CST), corpus callosum, brainstem, anterior limb of internal capsule, superior and inferior longitudinal fasciculi, fornix, thalamic radiations, and parietal lobes, bilaterally. Compared with healthy controls, PLS-cd patients showed further decreased FA and increased radD in the cerebellar WM, bilaterally. Compared with controls, PLS-cu patients showed decreased FA in the mid-body of corpus callosum. In PLS, executive and language test scores correlated with WM damage.ConclusionsThis is the first study evaluating the relationship between cognitive performance and WM tract damage in PLS patients. PLS can be associated with a multi-domain cognitive impairment. WM damage to interhemispheric, limbic and major associative WM tracts seem to be the structural correlate of cognitive abnormalities in these patients.

Highlights

Primary lateral sclerosis (PLS) is a rare, progressive disorder characterised by an isolated degeneration of the upper motor neurons (UMN) in the absence of lower motor neuron (LMN) signs [1]
A few studies so far have investigated the cognitive status of PLS patients and findings are controversial with some authors reporting no cognitive abnormalities [1] and others describing the occurrence of cognitive impairment which extends beyond the executive functions to involve memory and language [2,5,6,7,8]
Demographic and neuropsychological findings Subject groups did not differ in terms of age at magnetic resonance imaging (MRI), gender, education and WM hyperintensities (WMH) load (Table 1)

Summary

Introduction

Primary lateral sclerosis (PLS) is a rare, progressive disorder characterised by an isolated degeneration of the upper motor neurons (UMN) in the absence of lower motor neuron (LMN) signs [1]. Compared with amyotrophic lateral sclerosis (ALS), PLS has a slower rate of progression and a more benign prognosis with a survival of more than 10 years from symptom onset [2]. The language domain is affected in ALS (especially confrontation naming), and memory deficits, less studied, have been reported in encoding rather than in retrieval [4]. A few studies so far have investigated the cognitive status of PLS patients and findings are controversial with some authors reporting no cognitive abnormalities [1] and others describing the occurrence of cognitive impairment which extends beyond the executive functions to involve memory and language [2,5,6,7,8]

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