| Background:Stroke is the second leading cause of death and a major cause of disability worldwide.In china,it has become the leading cause of death and a principal cause of long-term disability in recent years.After stroke,only 20 to 30% of patients are independent,and motor impairment is the most common impairments,leading to major disability and poor quality of life.The recovery of motor function after stroke directly correlates with functional disability and quality of life.Therefore,providing accurate prognosis of long-term motor impairment within the first few days after an insult is highly desirable.However,making accurate predictions about motor outcome and recovery potential continues to be challenging for stroke clinicians.The corticospinal tract(CST)is the primary descending motor pathway connecting cortical motor regions with neurons in the spinalcord.Previous research demonstrated that the degree of injury to the CST is closely related to long-term neurological function and use this to predict motor recovery.In addition,animal experiments and post-mortem examinations revealed that a focal cerebral infarct could cause secondary degeneration in fiber pathways far away from the primary lesion.Delayed disintegration of such a fibre tract is called Wallerian degeneration(WD),which by definition is the anterograde degeneration of a nerve tract distal to an injury.WD is a common pathological process occurring both in the peripheral and central nervous systems,and many studies from animal experiment to human imaging all have shown such process after stroke,especially in stroke patients with impaired motor pathways.Therefore,early detection and quantitative evaluation of WD are of great clinical significance in preventing motor function injury and promoting functional recovery.In the past few decades,MRI has become one of the most important examination methods for central nervous system diseases.Sawlani et al found that patients with WD in the corticospinal tract had a corresponding hypointense signal in the tract on T2-weighted images at least one month after onset of disease,which then turned to hyperintense signal at 4 months.Moreover,many studies have reported hyperintense signals referred to WD along the affected CST fiber on T2-weighted images weeks or even months after stroke,and the duration of which was well correlated with the persistent functional disability.However,such slight change in signal intensity is difficult to detect by the conventional MRI.DTI,an imaging tool which can provide information on the predominant direction and degree of tissue water diffusion,has recently become a great focus in stroke diagnosis,especially in the aspect of in vivo quantification of microstructural damage to cerebral white matter.In the white matter,water diffuses quickly lengthwise along the fibers and slowly perpendicular to fibers,resulting in a form of anisotropic diffusion.The degree of anisotropy depends on the level of organization and integrity of the white matter tract and on the degree of freedom of water diffusion movements by oriented axonal membranes and myelin sheaths.The fractional anisotropy(FA)derived from DTI could reflect the direction of diffusion of water molecules in tissues,and indirectly reflect the integrity of brain fiber microstructure.Previous research have demonstrated that a reduced FA along the CST fiber remote from a cerebral infarct,interpreted as WD,was associated with greater motor deficit weeks after stroke onset and a worse motor recovery at 3 months.But most of the positive results were found during the subacute and chronic phase of stroke.It was believed that the change of FA value could only be detected in the late phase of stroke,and it might be too small to be seen and quantified in the acute phase,excluding it from a useful prognostic tool for stroke.In consideration of all above,this study is aimed to detect early changes in the CST fiber below the lesion after acute ischemic stroke and explored its changing pattern and the relationship with short-term and long-term clinical outcome.Most importantly,we plan to screen out the factors associated with such early changes,in order to provide theoretical guidance and practical basis for the clinical intervention in the future.Part one Investigation of early changing pattern of the corticospinal tract fiber below the lesion following acute ischemic strokeAims: The aim of this study is to elucidate the early changing pattern of the CST fiber below the lesion following acute ischemic strok with DTI.Methods: We reviewed our prospectively collected imaging data of AIS patients in our center between June 2016 and September 2019.We included those patients who were firsttime,acute,hemispheric ischemic stroke and had motor neurologic deficit with 24-hour multimodal MRI,including diffusion-weighted imaging(DWI),fluid attenuation inversion recovery(FLAIR)sequences,susceptibility weighted imaging(SWI)and diffusion tensor imaging(DTI)at 3 days and 7 days after stroke onset.The FA maps were generated from DTI,and the FA values of 5 consecutive slices of CST below the lesions were measured.In addition,FA values of corresponding layers of CST on the unaffected hemisphere were also measured and a following paired t test was done to compare the affected hemisphere and unaffected hemisphere.Results: 76 patients were finally included,30(39.4)% were female with mean age(68.0± 11.7).At 3 days after onset,the FA values for CST of nearest-5-slices below lesions of affected and unaffected hemisphere were as follows: Slice-1(0.6022±0.0902 vs 0.7039± 0.0524,P<0.001),Slice-2(0.6588±0.0751 vs 0.7184±0.0453,P<0.001),Slice-3(0.7137 ±0.0683 vs 0.7209±0.0452,P=0.132),Slice-4(0.7247±0.0591 vs 0.7305±0.0492,P=0.200),Slice-5(0.7302±0.0518 vs 0.7352±0.0471,P=0.368).At 7 days after onset,the FA values of nearest-5-slices below lesions of affected and unaffected hemisphere were as follows: Slice-1(0.5675±0.0571 vs 0.7040±0.0535,P<0.001),Slice-2(0.6125± 0.0952 vs 0.7181±0.0439,P<0.001),Slice-3(0.6604±0.0724 vs 0.7250±0.0465,P<0.001),Slice-4(0.7017±0.0646 vs 0.7315±0.0504,P<0.001),Slice-5(0.7375±0.0468 vs 0.7436±0.0508,P=0.146).Conclusions: In the acute phase of ischemic stroke,the most pronounced FA reduction was found in the slice closest to the ischemic lesion,and the reduction gradually decreased as moving away from this slice.Overall,the FA reduction tended to grow bigger over time.We found that early changes in the CST fiber below the lesion following acute ischemic stroke are time-dependent and distance-dependent.Part two Impact of early changes in the corticospinal tract fiber below the lesion on acute ischemic stroke outcomeAims: The aim of this study is to figure out impact of early changes in the corticospinal tract fiber below the lesion on acute ischemic stroke outcome.Methods: We reviewed our prospectively collected data of AIS patients in our stroke center between June 2016 and September 2019.We included patients who were first-time,acute,hemispheric ischemic stroke and had motor neurologic deficit with 24-hour multimodal MRI including diffusion-weighted imaging(DWI),fluid attenuation inversion recovery(FLAIR)sequences,susceptibility weighted imaging(SWI)and diffusion tensor imaging(DTI)at 3 days and 7 days after stroke onset.FA maps were generated from DTI,and FA values of 5 consecutive slices of CST below the lesions were measured.The ratio of FA on the affected hemisphere over the unaffected(r FA= FAaffected side / FAunaffected side)and the difference of FA value between 3 to 7 days on the affected side(ΔFA)were also calculated.Early neurological improvement(ENI)was defined as a reduction in the NIHSS of ≥2 points from the 24-hour to 7-day assessment after stroke or a NIHSS score of 0 on one week assessment.Clinical outcome at 3 months was assessed with modified Rankin Scale(m RS)score and was dichotomized into good outcome(0-2)and poor outcome(3-6).The differences of 5 slices FA,r FA and ΔFA in CST between the groups with different neurological outcomes were analyzed.We performed logistic regression analysis to investigate the impact of changes in CST,represented by 5 slices FA,r FA andΔFA,on ENI and long-term clinical outcome,respectively.Results: 75 patients were finally included,30(40.0%)were female with mean age(68.0± 11.7).Baseline m NIHSS was 6(IQR 2-8).Among them,47(62.7%)patients met criteria for ENI and 32(42.6%)patients had poor outcome at 3-month.Binary logistic regression analysis showed that at 3 days,affected side FAslice-1(OR 1.117,95%CI 1.037-1.024,P=0.004)and r FAslice-1(OR 1.078,95%CI 1.018-1.141,P=0.010);affected side FAslice-2(OR 1.086,95%CI 1.006-1.173,P=0.035)were independently associated with ENI.At 7 days,affected side FAslice-1(OR 1.189,95%CI 1.077-1.313,P=0.001)and r FAslice-1(OR 1.113,95%CI 1.044-1.187,P=0.001);affected side FAslice-2(OR 1.134,95%CI 1.045-1.230,P=0.002)and r FAslice-2(OR 1.101,95%CI 1.033-1.174,P=0.003);affected side FAslice-3(OR 1.132,95%CI 1.034-1.240,P=0.007)and r FAslice-3(OR 1.139,95%CI 1.042-1.244,P=0.004);affected side FAslice-4(OR 1.127,95%CI 1.021-1.243,P=0.017)and r FAslice-4(OR 1.212,95%CI 1.054-1.392,P=0.007)were independently associated with ENI.Besides,ΔFAslice-1(OR 0.814,95%CI 0.705-0.936,P=0.004),ΔFAslice-2(OR 0.812,95%CI 0.671-0.959,P=0.015),ΔFAslice-3(OR 0.802,95%CI 0.667-0.994,P=0.043)were also independently associated with ENI,respectively.In addition,3-day affected side FAslice-1(OR 0.921,95%CI 0.852-0.994,P=0.035);7-day affected side FAslice-1(OR 0.882,95%CI 0.797-0.975,P=0.014)and r FAslice-1(OR 0.907,95%CI 0.841-0.979,P=0.012);7-day affected side FAslice-2(OR 0.912,95%CI 0.837-0.992,P=0.033)and r FAslice-2(OR 0.920,95%CI 0.738-0.964,P=0.021);7-day affected side FAslice-3(OR 0.896,95%CI 0.805-0.998,P=0.046)and r FAslice-3(OR 0.934,95%CI 0.745-0.958,P=0.037);7-day r FAslice-4(OR 0.956,95%CI 0.721-0.970,P=0.045)were independently associated with poor outcome at 3-month.Moreover,ΔFAslice-1(OR 1.476,95%CI 1.103-1.975,P=0.009);and ΔFAslice-2(OR 1.268,95%CI 1.029-1.562,P=0.026)were also independently associated with poor outcome at 3-month,respectively.Conclusions: Early changes in the CST below the lesion revealed by DTI correlates with ENI and poor outcome at 3-month after acute ischemic stroke.This study highlights the utility of DTI during acute phase of ischemic stroke and the potential of FA as a surrogate imaging marker for prognosis.Part three Investigating the factors associated with early changes in the corticospinal tract fiber below the lesion following acute ischemic strokeⅠ Related factors with early changes in the corticospinal tract fiber below the lesion following acute ischemic strokeAims: The aim of this study is to investigate the factors associated with early changes in the CST below the lesion following acute ischemic stroke.Methods: We reviewed the data of AIS patients in our stroke center between June 2016 and September 2019.We included patients who were first-time,acute,hemispheric ischemic stroke and had motor neurologic deficit with 24-hour multimodal MRI including diffusion-weighted imaging(DWI),fluid attenuation inversion recovery(FLAIR)sequences,susceptibility weighted imaging(SWI)and diffusion tensor imaging(DTI)at 3 days and 7 days after stroke onset.Reperfusion was defined as a reduction in the lesion volume of Tmax>6 s over 70% between the baseline and 24 hours.Hemorrhagic transformation(HT)was defined according to European Cooperative Acute Stroke Study(ECASS)II trial.Total lesion volume and CST lesion volume were also calculated respectively.We investigated the impacts of reperfusion,HT,and the size of the infarct on early changes in CST below the lesion following acute ischemic strokeResults: 75 patients were finally included,30(40.0%)were female with mean age(68.0± 11.7).Among them,44(58.6%)patients achieve reperfusion and 23(30.6%)patients had HT at 24-hour.The mean 24-hour lesion volume was 35.2±42.9ml and CST lesion volume was 3.9±2.6ml.The severity of WMH was positive correlated with ΔFAslice-1(r=0.229,P=0.048).Pearson correlation analysis indicated that 24-hour lesion volume was correlated with ΔFAslice-1(r=0.331,P=0.004),ΔFAslice-2(r=0.317,P=0.006),ΔFAslice-3(r=0.263,P=0.023),and ΔFAslice-4(r=0.247,P=0.033)but not correlated with ΔFAslice-5(r=0.139,P=0.058).24-hour CST lesion volume was significantly correlated with ΔFAslice-1(r=0.472,P<0.001),ΔFAslice-2(r=0.464,P<0.001),ΔFAslice-3(r=0.437,P<0.001),ΔFAslice-4(r=0.399,P<0.001),and ΔFAslice-5(r=0.393,P<0.001).Multiple linear regression analysis indicated that 24-hour CST lesion volume was independent correlated with ΔFAslice-1(B=0.572,95%CI 0.192-0.952,P=0.004),ΔFAslice-2(B=0.785,95%CI 0.099-1.471,P=0.026),and ΔFAslice-3(B=0.646,95%CI 0.049-1.243,P=0.034).Conclusions: Early changes in the CST below the lesion following acute ischemic stroke at 3-7 days were associated with 24-hour hemorrhage transformation,which might result in the aggravation of CST degeneration.Moreover,those changes were positively correlated with the volume of CST infarction that the larger the volume of CST infarction involved,the severer the downstream CST fiber degeneration.Ⅱ Early prediction of corticospinal tract infarct volume and hemorrhage transformation after reperfusion therapyAims: The aim of this study is to figure out the baseline associated factors with corticospinal tract(CST)infarct volume and hemorrhage transformation at 24-hour after reperfusion therapy.Methods: We reviewed the data of AIS patients with LVO of anterior circulation in our stroke center between January 2014 and September 2018.We enrolled patients who underwent post-interventional NCCT immediately after MT and had a follow-up MR scan at 24-hour.Metallic hyperdensity sign was defined as non-petechial intracerebral hyperdense lesion(diameter≥1cm)in basal ganglia and a maximum CT unit >90 Hounsfield unit(HU).The sensitivity,specificity,and positive and negative predictive values of metallic hyperdensity sign in predicting PH were calculated.Correlation analysis and multiple linear regression analysis were used to assess the relation between baseline clinical factors and 24-hour CST infarct volume.Results: A total of 95 patients were included.The mean age was 69.0±11.1 years and 47(49.4%)were female.The median baseline NIHSS was 13(IQR,11-17).58(61.0%)patients had HT and 27(28.4%)patients had PH at 24-hour.Intracerebral hyperdense lesion was found in 74(77.8%)patients,among whom 28(37.8%)patients had metallic hyperdensity sign and the remaining 67(62.2%)patients had non-metallic hyperdensity sign.The sensitivity,specificity,positive predictive value,and negative predictive value of metallic hyperdensity sign in predicting PH were 88.9%,94.1%,85.7%,and 95.5%,respectively.24-hour CST infarct volume was independent positive correlated with baseline NIHSS score(β=0.303,P=0.023),baseline infarct volume(β=0.458,P<0.001),baseline hypoperfusion volume(β=0.540,P<0.001)and onset to puncture time(β=0.240,P=0.035).Conclusions: NCCT-based metallic hyperdensity sign immediately after MT in LVO patients may indicate the high risk of PH at 24 hours with high specificity and negative predictive value,which may be helpful in post-interventional management in 24 hours after mechanical thrombectomy.Early reperfusion treatment is beneficial to reduce the degree of 24-hour motor function injury. |
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