Similarities And Differences Of Idiopathic Parkinson's Disease And Multiple System Atrophy:Multi-modal Magnetic Resonance Imaging Studies

Objective: Idiopathic Parkinson's disease(IPD)and multiple system atrophy(MSA)are adult-onset,progressive neurodegenerative disorders that manifest with many overlapping symptoms,including motor and cognitive impairment.Contrast to IPD,MSA patients are not suitable candidates for deep brain stimulation procedures and have a shorter lifespan and poorer prognosis.Therefore,clinical separation is particular important.MSA is still commonly misdiagnosed as IPD because effective biomarkers and well understanding pathophysiological mechanisms are still challenging.Neurobiological investigations comparing MSA and IPD are warranted and could support improved diagnosis and treatment in the early stage of illness.Multi-mode magnetic resonance imaging is an important part in radiology,including the blood oxygenation level dependent functional magnetic resonance(f MRI)technology,the three-dimensional T1 imaging(3D-T1)and susceptibility weighted imaging(SWI).It could be used to explore the structural and functional change in vivo.Recently,the multi-mode magnetic resonance imaging technology has been widely applied in neuropathological mechanism and clinical research in IPD,and has made a series of achievements.However,most of the studies mainly focused on the single disease unit,and the results are controversial.Taken together,a comparative study was warranted to understand the pathophysiological mechanisms between the two diseases.Therefore,this study will combine the resting state f MRI(rs-f MRI),3D-T1 and SWI technology to investigate the similarities and differences in functional and structural alteration between the IPD and MSA,and to find reliable markers for differential diagnosis.Methods: Rs-f MR,3D-T1 and SWI scans were obtained from 38 IPD,62 MSA,and 59 HC.IPD patients met the UK PD Society Brain Bank diagnostic criteria and MSA patients fulfilled the second consensus clinical criteria.HC were recruited by advertisement from the community.All participants underwent a neuropsychological testing battery that included the Mini Mental State Examination(MMSE)and Montreal Cognitive Assessment(Mo CA).Unified Parkinson's Disease Rating Scale(UPDRS-III) and Hoehn and Yahr(H-Y)stage were conducted for movement ratings.HC did not show cognitive decline based on a MMSE score > 27,Mo CA score > 26,or > 25 for secondary school(12 years education).1.The amplitude of Low-Frequency Fluctuations(ALFF)was compared between patient groups.2.Seed-based connectivity analysis and voxel-based morphometry analysis were performed to assess the changes of cerebellar GMV and FC between the patient groups.3.The volumes of hippocampal subfields and the whole hippocampus were automatically segmented using Free Surfer 6.0 and compared between the patient groups.4.Putaminal hypointensity and ‘swallow-tail' sign was rated using visual scales from 0 to 2 and 0 to 3 scores,respectively.The diagnostic accuracy of the two signs separately and combined was calculated using a receiver operating characteristic curve,with clinical diagnosis as the gold standard.Results: 1.Lower ALFF in bilateral basal ganglion,bilateral ventrolateral prefrontal cortex and right amygdala,as well as higher ALFF in parieto-temporo-occipital cortex and right cerebellum was shared between both patient groups to compare with HC.In contrast to IPD,decreased or increased ALFF in different regions of visual associative cortices and decreased ALFF in right cerebellum were found in MSA group.2.Decreased cerebellar GMV were found in the motor cerebellum in both patient groups relative to HC,and broader reduction of GMV were observed in both cognitive and motor cerebellum in MSA compared with IPD and HC.Compared with IPD,MSA group exhibited decreased FC between bilateral dentate nucleus(DN)and default mode network(DMN),as well as decreased intracerebellar FC were shared in both patient groups relative to HC.Cerebellar GMV was positively correlated with FC of intracerebellum and DN-DMN in MSA.Motor/cognitive scores were associated with DN-DMN FC with considerable cerebellar GMV loss in MSA patients.3.Compared with HC,the volumes of the right Cornu Ammonis 1(CA1),right molecular layer(ML),bilateral presubiculum,bilateral hippocampus–amygdala transition area(HATA),and whole right hippocampus were reduced in the MSA-MCI group,while the volume of the bilateral hippocampal fissure was enlarged in PD-MCI patients.The MSA-MCI group had significant volumetric reduction in the right CA1,left fimbria,left HATA,and whole right hippocampus relative to the PD-MCI group.Moreover,positive correlations between orientation function and the volumes of the bilateral HATA were found in MSA-MCI patients,while visuospatial/executive function were positively correlated with volume of the left presubiculum,left ML and left fimbria in IPD-MCI patients.4.The scores of ‘swallow-tail' sign was lower in IPD than in MSA or in HCs,as well as for putaminal hypointensity in IPD or HCs than in MSA.The sensitivity and specificity of ‘swallow-tail' sign and putaminal hypointensity were 87.9% and 83.3%,and 35.9% and 100%,respectively,in the respective patient groups.The area under the curve of combined signs was increased from 0.85(‘swallow tail')or 0.68(putaminal hypointensity)to 0.93.Conclusion: Our findings suggested shared and distinct spontaneous brain activity abnormalities or GMV in motor network,DMN and hippocampus were present in MSA and IPD,which may help to explain similar clinical symptoms in both disorders but a more severe illness prognosis in MSA.The combination of ‘swallow-tail' sign and putaminal hypointensity can increase the accuracy of discriminating between MSA and IPD.In addition,further research is needed to better describe the functional role of the cerebellum,hippocampus and visual associative cortices in early stages of MSA and IPD.