Study On The Motor Dysfunction,Imaging,Biomarker And Genetics Of Cerebral Small Vessel Disease

BackgroundIncidence rate of cerebral small vessel disease(CSVD)is higher,which can be acute or chronic occult onset.Acute onset of CSVD is mainly manifested as acute stroke,while chronic CSVD can lead to cognitive dysfunction,affective disorder,motor dysfunction,etc.At present,there are more researches on cognitive dysfunction and less researches on motor dysfunction.The motor dysfunction of CSVD is mainly manifested as gait disorder,balance disorder,Parkinson-like symptoms,etc.At present,the research on motor dysfunction of CSVD is mostly focused on gait abnormality and balance disorder,but there are few studies on upper limb symptoms.There is no unified standard score scale for motor dysfunction of CSVD.Therefore,in order to understand the characteristics of CSVD dyskinesias,this study used multiple motor function score scales to comprehensively evaluate upper and lower limb dyskinesias in patients with chronic cerebral small vessel disease.CSVD has diverse performances at 3.0T magnetic resonance.In recent years,there have been more new imaging techniques used for CSVD research.However,most of researches are related to cognitive dysfunction.There are relatively few studies on the relationship between motor dysfunction and imaging performance.In order to investigate the imaging features of CSVD patients with motor dysfunction,multimode MRI was performed on these patients.The pathophysiological mechanism of GSVD is relatively complex,and it is not very clear.At present,it may be related to chronic cerebral ischemia and hypoxia,endothelial dysfunction,blood-brain barrier destruction,inflammatory response and genetic factors.In the third part of this study,serum sICAM-1 and GDF-15 levels,polymorphisms of ICAM-1 K469E gene and GDF-15 C3148G gene were detected to discover biological markers and genetic risk factors of CSVD.Part I Analysis on the characteristics of motor dysfunction in cerebral small vessel diseaseObjective:To analyze the characteristics of motor dysfunction in cerebral small vessel disease and explore a unified standard score scale for motor dysfunction of CSVD.Materials and methods:1.A total of 158 patients with cerebral small vessel disease diagnosed in the Department of Neurology of the Fifth Affiliated Hospital of Zhengzhou University were selected as the research subjects.All the subjects have symptoms related to chronic cerebral small vessel disease.2.The selected subjects were scored by the MOCA,HAMD,HAMA,TMT,and ADL scales.Patients with a TMT score less than 24 points were considered to have motor dysfunction,further,the TUG test,SPPB,SARA,and UPDRS(part Ⅲ)scores were performed.3.SPSS 17.0 software was used for statistical analysis,and P<0.05 was considered statistically significant.Results:1.The clinical manifestations of CSVD were diverse,and 58.9%of the patients had motor dysfunction.2.There were two main manifestations of lower limb dyskinesia in patients with CSVD:Gait anomalies that were mainly characterized by step width,step height,gait symmetry change,and slowing pace;Balance obstacles that were characterized by the instability of nudging with elbow,turning 360 degrees and standing with eyes closed.Upper limb dyskinesia was characterized by abnormal ataxia,awkward upper limb movement,and impaired fine movements.3.Motor dysfunction lead to further decline in patients’ daily living ability.4.The TMT scale and TUG scale are suitable for assessing lower limb dyskinesia in patients with CSVD,and the UPDRS scale(upper limb part)score is suitable for assessing upper limb dyskinesia in patients with CSVD.Conclusions:Motor dysfunction is a common clinical manifestation of CSVD,and lower limb symptoms are relatively severe.Motor dysfunction in patients with CSVD can be assessed by the TMT,TUG,and UPDRS(upper limb)scales.Part Ⅱ Study on multimode magnetic resonance imaging in patients with CSVD-related dyskinesiaObjective:To analyze the characteristics of multimode magnetic resonance imaging in patients with CSVD-related dyskinesia.Materials and methods:1.The subjects of this part were the 158 patients with CSVD in the first part.93 patients with motor dysfunction were treated as dyskinesia group,and the remaining 65 patients as non-dyskinesia group.2.All the selected subjects underwent 3.0T MRI,MRA,SWI and DTI for imaging evaluation.The differences of lacunar,white matter high signal,micro hemorrhage,enlarged perivascular space,total imaging burden score,fiber bundle damage,FA value and ADC value between the two groups were compared.3.SPSS 17.0 software was used for statistical analysis,and P<0.05 was considered statistically significant.Results:1.Multiple imaging markers coexisted in patients with CSVD.2.The proportion of 3 and 4 scores of imaging burden in the dyskinesia group was higher than that in the non-dyskinesia group,with statistical difference(P<0.05).3.The proportion of patients with more than 3 basal.ganglia lacunas in the dyskinesia group was higher than that in the non-dyskinesia group,with statistical difference(P=0.044).The proportion of patients with 2 points of paraventricular white matter high signal score in the dyskinesia group was higher than that in the non-dyskinesia group,with a statistical difference(P=0.029);The proportion of patients with 4-6 points of frontal white matter high signal score in the dyskinesia group was higher than that in the non-dyskinesia group,with statistical difference(P=0.009).There was no statistical difference in the number of microbleeds and the number of enlarged perivascular spaces in different parts of the brain between the two groups.4.Most of the fiber bundle imaging in the dyskinesia group and the non-dyskinia group were normal images.The damaged fiber bundle showed sparse frontal fiber bundles,sparse frontal occipital fiber bundles,sparse fiber bundles in the corpus callosum,cortical spinal cord damaged and extensive fiber bundle sparseness.5.FA values in frontal lobe,left caudatus nucleus,corpus callosum and midbrain were significantly lower in the dyskinesia group than:in the non-dyskinesia group(P<0.05).ADC values in frontal lobe,corpus callosum and midbrain were significantly higher in the dyskinesia group than in the non-dyskinesia group(P<0.05).Conclusions:The higher the imaging burden score of patients with CSVD,the more likely they are to develop dyskinesias.Lacunar and white matter high signals are associated with dyskinesias.The degree of brain microstructural damage is higher in the dyskinesia group than in the non-dyskinesia group.The frontal lobe,corpus callosum,caudate nucleus,and midbrain microstructure damage may be related to dyskinesia.Part Ⅲ Study on biological markers and genetics of cerebral small vessel diseaseObjective:To explore the biological markers and genetic risk factors of CSVD,and analyze whether there were differences between the dyskinesia group and the non-dyskinesia group.Materials and methods:1.Research object:158 patients with CSVD in the first part of this paper were selected as the case group,and 150 people with no abnormality in cranial imaging examination were selected as the control group.2.Serum levels of sICAM-1 and GDF-15 were tested by ELISA.3.PCR-RFLP was used to detect and analyze the polymorphisms of ICAM-1 K469E gene and GDF-15 C3148G gene.4.SPSS 17.0 software was used for statistical analysis,and P<0.05 was considered statistically significant.Results:1.Serum levels of sICAM-1 and GDF-15 were significantly higher in CSVD group than that in control group(P<0.001).In the CSVD group,serum level of sICAM-1 and GDF-15 in the dyskinesia group was higher than that in the non-dyskinesia group,which was statistically different(P<0.05).By linear correlation analysis,serum level of GDF-15 exhibited a moderate relation to serum level of sIC AM-1.2.There were three genotypes of ICAM-1 K469E gene:KK,KE and EE.The frequencies of EE genotype and E allele of ICAM-1 K469E gene in CSVD group were significantly higher than that in control group(P<0.05).There was no significant difference in the frequencies of EE genotype and E allele of ICAM-1 K469E gene between the dyskinesia group and the non-dyskinesia group.3.Two types of GDF-15 C3148G genotypes were found:CC and CG.There was no significant difference in the frequencies of genotype and allele of GDF-15 C3148G gene between the CSVD group and the control group.There was also no significant difference in the frequencies of genotype and allele of GDF-15 C3148G gene between the dyskinesia group and the non-dyskinesia group.4.Comparison of serum sICAM-1 levels in patients with different genotypes was highest in patients with EE genotype,followed by patients with KE genotype,and lowest in patients with KK genotype.There was a statistical difference in serum sIC AM-1 levels among patients with three genotypes in the CSVD group and the control group(P<0.05).There was no statistically significant difference in serum GDF-15 levels between patients with two genotypes in the CSVD group and the control group.5.The relative risk of CSVD in the people with EE genotype of ICAM-1 K469E is 2.649 times higher than that in the people with non-EE genotype.Conclusions:Serum levels of sICAM-1 and GDF-15 may be used as biological marker of CSVD.The polymorphism of ICAM-1 K469E gene may be a genetic risk factor of CSVD.