Brain Functional And Structural Characteristics Of Sporadic Amyotrophic Lateral Sclerosis Patients Based On Multimodal Neuroimaging

Background Previous studies have found that amyotrophic lateral sclerosis (ALS) is a multisystem disorder. About 10% patients were familial ALS, and the rest of them are sporadic ALS. About 50% of ALS patients have cognitive impairment. Until now, there are no effective therapeutic measures. But unfortunately, there is an obvious delay in the diagnosis of ALS. Our research combined multimodal MRI scans to explore the structural and functional characteristics in sALS patients and to identify a feasible method or easily accessible biomarker to detect cognition impairment in ALS.Part 1 The brain structural and functional characteristics in sALS patientsObjective Investigating brain structural characteristics in sALS patients.Methods Selecting 22 sporadic ALS patients during 2013 December-2014 June in the Department of Neurology. Psychological assessment scales and clinical data were collected. DTI and three-dimensional T1-weighted anatomical imaging were performed on all participants.Results Compared to healthy controls, (1) decreased grey matter (GM) volume wre found in the bilateral precentral gyri and they had no relationship with clinical data; (2) decreased cortical thickness were found in bilateral precentral gyri, right superior frontal gyrus, right insula, left superior temporal gyrus and left supramarginal gyrus; (3) decreased FA value in bilateral splenium/body of corpus callosum, corticospinal tract, posterior limb of internal capsule, superior longitudinal fasciculus, superior corona radiate. Increased MD value in bilateral posterior limb of internal capsule, corticospinal tract, posterior/superior corona radiata, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, splenium/body/genu of corpus callosum, anterior/posterior thalamic radiation. (4) Cortical thickness of right precentral gyrus negatively correlated with UMN scores(r=-0.506, p=0.023) and positively correlated with ALSFRS-R scores (r=0.534, p=0.015). Cortical thickness of left supramarginal gyrus negatively correlated with SCWT(C-B) (r=-0.538, p=0.014). (5) FA value positively correlated with executive test (r=0.662, p=0.002), and MD value negatively correlated with the progression rate of ALS (r=-0.551, p=0.01).Conclusion Widespread brain structural changes existed in sALS patients and related with cognitive impairment or disease progression rate.Part 2 Correlation analysis between clinical data and MRI metrics in sALS patientsObjective Investigating brain functional characteristics in sALS patients.Methods In the present study, all participants completed a series of neuropsychological tests. Rs-fMRI was performed on 22 sporadic ALS patients and 22 healthy controls. Amplitude of low-frequency fluctuation (ALFF) methods was used to conduct group comparisons and correlation analyses with clinical data.Results Compared to healthy controls, (1) increased ALFF values were found in the right parahippocampal gyrus, left inferior temporal gyrus, left anterior cingulate gyrus, right superior frontal gyrus, and left middle occipital gyrus were identified in the sporadic ALS group; (2) the increased ALFF in the right parahippocampal gyrus was positively correlated with ALS progression rate(r=0.473, p=0.026); (3) increased ALFF value in right parahippocampal gyrus (r=0.514, p=0.014) left inferior temporal gyrus (r=0.469, p=0.028) and right superior frontal gyrus (r=0.506, p=0.016) positively correlated with serum creatinine, and (4) the ALS patients exhibited poor performances on cognitive and executive tests. Visuospatial/executive function and the ALFF value in the left anterior cingulate gyrus was negatively correlated (r=-0.454, p= 0.044). And there was a positive correlation between the Stroop B and the ALFF value in the left inferior temporal gyrus (r= 0.459, p=0.032).Conclusion These findings provide evidence of an extramotor involvement and suggest that the ALFF value in the right parahippocampal gyrus could represent a potential marker to monitor disease progression.