Case Report: Progressive Asymmetric Parkinsonism Secondary to CADASIL Without Dementia

Parkinsonism is a rare phenotype of cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL), all of which involve cognitive decline. Normal cognition has not been reported in previous disease studies. Here we report the case of a 60-year-old female patient with a 2-year history of progressive asymmetric parkinsonism. On examination, she showed severe parkinsonism featuring bradykinesia and axial and limb rigidity with preserved cognition. Magnetic resonance imaging (MRI) revealed white matter hyperintensity in the external capsule and periventricular region. Dopaminergic response was limited. A missense mutation c.1630C>T (p.R544C) on the NOTCH3 gene was identified on whole-exome sequencing, which confirmed the diagnosis of vascular parkinsonism secondary to CADASIL. A diagnosis of CADASIL should be considered in asymmetric parkinsonism without dementia. Characteristic MRI findings support the diagnosis.

Machine Learning for Predicting Motor Improvement After Acute Subcortical Infarction Using Baseline Whole Brain Volumes

Background. Neuroimaging biomarkers are valuable predictors of motor improvement after stroke, but there is a gap between published evidence and clinical usage. Objective. In this work, we aimed to investigate whether machine learning techniques, when applied to a combination of baseline whole brain volumes and clinical data, can accurately predict individual motor outcome after stroke. Methods. Upper extremity Fugl-Meyer Assessments (FMA-UE) were conducted 1 week and 12 weeks, and structural MRI was performed 1 week, after onset in 56 patients with subcortical infarction. Proportional recovery model residuals were employed to assign patients to proportional and poor recovery groups (34 vs 22). A sophisticated machine learning scheme, consisting of conditional infomax feature extraction, synthetic minority over-sampling technique for nominal and continuous, and bagging classification, was employed to predict motor outcomes, with the input features being a combination of baseline whole brain volumes and clinical data (FMA-UE scores). Results. The proposed machine learning scheme yielded an overall balanced accuracy of 87.71% in predicting proportional vs poor recovery outcomes, a sensitivity of 93.77% in correctly identifying poor recovery outcomes, and a ROC AUC of 89.74%. Compared with only using clinical data, adding whole brain volumes can significantly improve the classification performance, especially in terms of the overall balanced accuracy (from 80.88% to 87.71%) and the sensitivity (from 92.23% to 93.77%). Conclusions. Experimental results suggest that a combination of baseline whole brain volumes and clinical data, when equipped with appropriate machine learning techniques, may provide valuable information for personalized rehabilitation planning after subcortical infarction.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

The Relationship Between ADAMTS13 Activity and Overall Cerebral Small Vessel Disease Burden: A Cross-Sectional Study Based on CSVD

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden.Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model.Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [β = −7.31; 95% confidence interval (CI) (−9.40, −4.93); p&lt;0.01; β = 0.17; 95% confidence interval (0.11, 0.23); p&lt;0.01], subcortical infarction (SI) [(β = −9.22; 95% CI (−11.37, −7.06); p&lt;0.01); β = 0.21; 95% confidence interval (0.15, 0.27); p&lt;0.01] independently, but not cerebral microbleed (CMB) [(β = −2.3; 95% CI (−4.95, 0.05); p = 0.22); β = 0.02; 95% confidence interval (−0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p &lt; 0.01) after adjustment for age, history of hypertension, and current smoking.Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.

Longitudinal changes in the inferior cerebellar peduncle and lower limb motor recovery following subcortical infarction

Background The cerebellum receives afferent signals from spinocerebellar pathways regulating lower limb movements. However, the longitudinal changes in the spinocerebellar pathway in the early stage of unilateral supratentorial stroke and their potential clinical significance have received little attention. Methods Diffusion tensor imaging and Fugl-Meyer assessment of lower limb were performed 1, 4, and 12 weeks after onset in 33 patients with acute subcortical infarction involving the supratentorial areas, and in 33 healthy subjects. We evaluated group differences in diffusion metrics in the bilateral inferior cerebellar peduncle (ICP) and analyzed the correlation between ICP diffusion metrics and changes to the Fugl-Meyer scores of the affected lower limb within 12 weeks after stroke. Results Significantly decreased fractional anisotropy and increased mean diffusivity were found in the contralesional ICP at week 12 after stroke compared to controls (all P < 0.01) and those at week 1 (all P < 0.05). There were significant fractional anisotropy decreases in the ipsilesional ICP at week 4 (P = 0.008) and week 12 (P = 0.004) compared to controls. Both fractional anisotropy (rs = 0.416, P = 0.025) and mean diffusivity (rs = -0.507, P = 0.005) changes in the contralesional ICP correlated with changes in Fugl-Meyer scores of the affected lower limb in all patients. Conclusions Bilateral ICP degeneration occurs in the early phase of supratentorial stroke, and diffusion metric values of the contralesional ICP are useful indicators of affected lower limb function after supratentorial stroke.

Different Predictive Factors for Early Neurological Deterioration Based on the Location of Single Subcortical Infarction: Early Prognosis in Single Subcortical Infarction

Background and Purpose: Patients with single subcortical infarctions (SSIs) have relatively a favorable prognosis, but they often experience early neurological deterioration (END). In this study, we compared the predictors for END in patients with SSI according to the location of the lesion. Methods: We included consecutive patients with SSIs within 72 hours of symptom onset presenting between 2010 and 2016. END was defined as an increase of ≥2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 in the motor NIHSS score within the first 72 hours of admission. Along with the analysis of all patients with SSI, we also analyzed the predictors for END in proximal/distal SSI patients and anterior/posterior circulation SSI patients. Results: A total of 438 patients with SSI were evaluated. In multivariable analysis, initial NIHSS score (adjusted odds ratio, 1.36 [95% CI, 1.15–1.60]), pulsatility index (adjusted odds ratio, 1.25 [95% CI, 1.03–1.52]), parent artery disease (adjusted odds ratio, 2.14 [95% CI, 1.06–4.33]), and neutrophil-to-lymphocyte ratio (adjusted odds ratio, 1.24 [95% CI, 1.04–1.49]) were positively associated with END. In patients with proximal SSI, initial NIHSS score, pulsatility index, parent artery disease, and neutrophil-to-lymphocyte ratio showed positive associations with END. Meanwhile, no variable related to END was found in the distal SSI group. When we compared the predictors for END based on the involved vascular territory, higher initial NIHSS score and neutrophil-to-lymphocyte ratio were significantly associated with END in patients with anterior circulation SSIs. On the contrary, higher pulsatility index values and the presence of parent artery disease were independent predictors for END in patients with SSIs in the posterior circulation. Conclusions: Initial NIHSS score, pulsatility index, parent artery disease, and neutrophil-to-lymphocyte ratio are associated with END in patients with SSIs. The frequency and predictors for END differ depending on the location of the SSI.

Clopidogrel Plus Aspirin in Patients With Different Types of Single Small Subcortical Infarction

Background: We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction (SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.Methods: SSSI was defined as single DWI lesion of ≤2.0 cm. Patients with SSSI were divided into SSSI + PAD (parent artery disease) and SSSI – PAD, according to the stenosis of the parent artery. The efficacy outcome was stroke recurrence during 90-day follow-up. Cox proportional hazards models or logistic regression models were used to assess the interaction of the treatment effects of clopidogrel plus aspirin vs. aspirin alone among patients with and without PAD.Results: Among 338 patients with SSSI included in the subanalysis, 105 were with PAD and 233 without. The efficacy of clopidogrel plus aspirin compared with aspirin alone on any stroke was consistent between patients with [adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI), 0.25–2.75] and without PAD (adjusted HR 1.03; 95% CI, 0.40–2.68, interaction P = 0.83). In patients with SSSI + PAD, the rate of stroke recurrence in those treated with dual antiplatelet therapy and mono antiplatelet therapy was not significantly different (10.9 vs. 13.6%, P = 0.77). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI + PAD or SSSI – PAD.Conclusions: There was no significant difference in the efficacy of clopidogrel plus aspirin compared with aspirin alone between patients with SSSI + PAD and SSSI – PAD in the CHANCE trial. Studies in other populations and with adequate power are needed to further verify such findings.

Abstract P665: Different Predictive Factors for Early Neurological Deterioration Based on the Location of Single Subcortical Infarction

Introduction: Patients with single subcortical infarction (SSI) have relatively favorable prognosis, but they often experience early neurological deterioration (END) in a clinical course. In addition, SSI is considered to differ in its prognosis and mechanism depending on the location of the lesion. Hypothesis: We compared the predictors for END in patients with SSI according to the location of the lesion. Methods: We included consecutive patients with SSI within 72 hours of symptom onset between 2010 and 2016. END was defined as an increase of ≥ 2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 hours of admission. Along with the analysis of the entire SSI patients, we also analyzed the predictors for END in the proximal/distal SSI patients and the anterior/posterior circulation SSI patients. Results: A total of 438 patients with SSI were evaluated. In multivariable analysis, initial NIHSS score [adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI): 1.15-1.60], pulsatility index (PI) (aOR = 1.25, 95% CI: 1.03-1.52), parent artery disease (PAD) (aOR = 2.14, 95% CI: 1.06-4.33), and neutrophil to lymphocyte ratio (NLR) (aOR = 1.24, 95% CI: 1.04-1.49) were positively associated with END. In patients with proximal SSI, initial NIHSS score, PI, PAD, and NLR showed positive associations with END. Meanwhile, no variable related to END was found in distal SSI. When we compared the predictors for END based on the involved vascular territory, initial NIHSS score and NLR were significantly associated with END in the anterior circulation. On the other hand, patient with SSI in the posterior circulation showed PI and PAD as independent predictors of END. Conclusions: Initial NIHSS score, PI, PAD, and NLR were associated with END in patients with SSI. The frequency and predictors for END were different depending on the location of SSI lesion.

Abstract P722: Triglyceride-Glucose Index is Associated With Early Neurological Deterioration in Single Subcortical Infarction

Introduction: Single subcortical infarction (SSI) has usually favorable prognosis, but early neurological deterioration (END) often occurs in their clinical courses. Fasting glucose and triglyceride are both risk factors for END. Therefore, the triglyceride-glucose (TyG) index that combines them can be a potent predictor of END. Hypothesis: We evaluated the relationship between TyG index and END in patients with SSI. Methods: We included consecutive patients with SSI within 72 hours of symptom onset between 2011 and 2015. END was defined as an increase of ≥ 2 on the total NIHSS score or ≥ 1 on the motor NIHSS score within the first 72 hours of admission. TyG index was calculated according to the following formula: TyG index = Ln [fasting triglyceride (mg/dL) x fasting glucose (mg/dL)/2]. Considering the effect directly on the formula, patients currently taking glucose- or lipid-lowering agents were excluded. Results: A total of 305 patients with SSI were included. In multivariable analysis, TyG index [adjusted odds ratio (aOR) = 2.94, 95% confidence interval (CI): 1.58-5.45] and age (aOR = 1.05, 95% CI: 1.01-1.09) were positively associated with END. In subgroup analysis based on the presence of diabetes, TyG index showed a meaningful association only in patients with diabetes history. In the analysis by type of SSI, TyG index and END were related only in patients with proximal SSI. When examined in accordance with the involved vascular territory, TyG index was associated with END in both the anterior circulation and posterior circulation. When examined in accordance with the involved vascular territory, TyG index was associated with END in both anterior circulation (aOR = 2.66, 95% CI: 1.24-5.68) and posterior circulation (aOR = 3.55, 95% CI: 1.03-12.26), but the posterior circulation had a larger aOR value. Conclusions: TyG index was associated with END in SSI patients. This tendency depends on the presence of diabetes and the location of the SSI lesion.