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Burning and stabbing pain in the feet and lower limbs can have a significant impact on the activities of daily living, including walking, climbing stairs and sleeping. Peripheral neuropathy in particular is often misdiagnosed or underdiagnosed because of a lack of awareness amongst both patients and physicians. Furthermore, crude screening tools, such as the 10‐g monofilament, only detect advanced neuropathy and a normal test will lead to false reassurance of those with small fiber mediated painful neuropathy. The underestimation of peripheral neuropathy is highly prevalent in the South‐East Asia region due to a lack of consensus guidance on routine screening and diagnostic pathways. Although neuropathy as a result of diabetes is the most common cause in the region, other causes due to infections (human immunodeficiency virus, hepatitis B or C virus), chronic inflammatory demyelinating polyneuropathy, drug‐induced neuropathy (cancer chemotherapy, antiretrovirals and antituberculous drugs) and vitamin deficiencies (vitamin B1, B6, B12, D) should be actively excluded. [ABSTRACT FROM AUTHOR]

Aim. Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population. Methods. PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals. Results. Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel (n=14,293) or aspirin (n=15,064) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53–0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups. Conclusions. The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model.Methods: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year.Results: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004).Interpretation: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764. [ABSTRACT FROM AUTHOR]

Objective: Success in clinical trials of intracranial atherosclerosis (ICAS) is related to accurate identification of high-risk patients. Noninvasive computational fluid dynamics (CFD) of stenotic lesions may enhance therapeutic decision-making. We determined whether physiologic parameters change downstream cerebral hemodynamics in patients with ICAS.Methods: Consecutive ICAS patients who underwent both CT angiography (CTA) and digital subtraction angiography were enrolled. CFD models were made using CTA source images. Inlet boundary conditions were defined using three ranges of systolic blood pressure (BP) (109.2, 158, and 225 mmHg) and hematocrit (27.3, 40.2, and 48.8). Ratios of pressure, shear strain rates (SSR), and flow velocity across the lesion were calculated using CFD simulations. A linear mixed model was used for the statistical analysis of repeated simulations.Results: Among the 56 patients, 32 had moderate stenosis (50-69%) and 24 had severe stenosis (70-99%). A linear mixed model revealed that the ratio of pressure was predicted by systolic BP and stenosis group interaction (P = .036). These pressure decreases were associated with systolic BP (P < .001) and stenosis group (P < .001), but not with hematocrit (P = .337). Post-hoc analysis revealed that pressure decreases were more profound in the severe stenosis than the moderate stenosis group when comparing high and low systolic BP (P = .0108). Ratios of SSR and velocity were only associated in the stenosis group.Conclusions: Our study showed that systolic BP along with the degree of stenosis was associated with pressure decreases across stenotic lesions. Physiologic conditions may superimpose further changes in post-stenotic or downstream blood flow. [ABSTRACT FROM AUTHOR]

Background and Purpose: Increased cerebral blood flow velocity of basilar artery (BA) is common but often neglected. By using digital subtraction angiography (DSA) to detect intracranial large artery stenosis, we performed transcranial Doppler (TCD) to evaluate cerebral hemodynamic changes of stroke patients. Methods: Acute stroke patients with TCD-detected raised peak systolic velocity (PSV) in BA (≥100 cm/second) were recruited. Results: Among 91 recruited patients, BA stenosis (>50%) was confirmed by using DSA in 29 patients (32%), among which 20 patients (70.0%) had coexistent internal carotid artery (ICA) and vertebral artery (VA) stenoses. Among patients without BA stenosis (n = 62, 68%), severe stenosis or occlusion of ICA was evaluated in 22 patients (22/62, 35.4%) and severe stenosis or occlusion of VA was detected in 22 patients (22/62, 35.4%). Among the values of PSV (120, 140, 160, and 180 cm/second) and the stenotic-to-prestenotic ratio (SPR) (1.5, 2.0, 2.5, and 3.0), 160 cm/second was found to show the highest predictive value (area under the receiver operator characteristic curve: .75, 95% CI: .65-.86), with a sensitivity of .70 and a specificity of .81. Conclusions: Apart from an intrinsic BA stenosis, high-grade steno-occlusion of ICA or VA may contribute a lot to induce an elevated flow velocity in BA. A higher value of cutoff point may increase the accuracy of diagnosing BA stenosis. [ABSTRACT FROM AUTHOR]

Aims The purpose of this study was to discuss the relationship between blood pressure and prognosis of patients with symptomatic intracranial arterial stenosis. Methods Data on 2426 patients with symptomatic intracranial large artery stenosis and occlusion who participated in the Chinese Intracranial Atherosclerosis ( CICAS) study were analyzed. According to the JNC 7 criteria, blood pressure of all patients was classified into one of the four subgroups: normal, prehypertension, hypertension stage I, and hypertension stage II. Poor outcomes were defined as death and functional dependency ( mRS 3-5) at discharge or at 1 year. Results For patients with intracranial stenosis of 70% to 99%, the rate of poor outcome at discharge was 19.3%, 23.5%, 26.8%, and 39.8% ( P = 0.001) for each blood pressure subgroup. For patients with intracranial large artery occlusion, the rates were 17.6%, 22.1%, 29.5%, and 49.8%, respectively ( P < 0.0001). The rate of poor outcome at 12-month follow-up was 12.6%, 15.3%, 28.5%, and 27.9% ( P = 0.0038) in patients with stenosis of 70% to 99% for each blood pressure subgroup and 11.6%, 21.5%, 23.9%, 35.1% ( P < 0.0001) in patients with occlusion. Conclusions For patients with severe intracranial arterial stenosis or occlusion, higher hypertension stages are associated with an increased risk of poor outcome at discharge and 12-month follow-up. [ABSTRACT FROM AUTHOR]

Objective Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. Methods In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. Results Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year ( p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. Interpretation A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence. Ann Neurol 2015;77:478-486 [ABSTRACT FROM AUTHOR]

Aim High serum bilirubin predicts depression in non-stroke subjects, but it is unknown whether it also predicts post-stroke depression ( PSD). This study examined the association between the risk of PSD and bilirubin level. Methods Six hundred and thirty-five patients with acute ischemic stroke in Hong Kong were recruited. Serum total bilirubin, alanine transaminase and alkaline phosphatase levels were measured in all patients during their hospital stay. A psychiatrist gave the Structured Clinical Interview for DSM-IV to all patients 3 months after the index stroke, with 61 patients diagnosed with PSD: 27 with major depression, 24 with minor depression and 10 with dysthymia. Results In the full sample, the 25%, 50% and 75% percentile bilirubin levels were 7.0, 10.0 and 14.0 μmol/L, respectively. Significant differences were found between the PSD and non- PSD groups in terms of bilirubin level ( P = 0.006). In post-hoc comparisons, the proportion of patients with bilirubin ≥14.1 μmol/L was significantly higher in the PSD group (37.7% vs 19.7%, P = 0.001). In the final regression model, bilirubin level (≥14.1 μmol/L) remained a significant independent predictor of PSD, with an odds ratio of 2.4. Conclusions High bilirubin level is associated with PSD. Further investigations are needed to clarify the underlying pathophysiological link between bilirubin level and PSD. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND Age-related white matter changes (WMC) increase risk of cognitive and functional decline. They are considered as target for preventive trials. However, using magnetic resonance imaging (MRI) to screen for subclinical WMC is not cost-effective. We explored the clinical utility of transcranial Doppler ultrasound (TCD) in the evaluation of WMC. We hypothesized that the pulsatility index (PI) of TCD correlates with severity of WMC. METHODS Among 100 stroke patients with WMC, we obtained the mean PI of middle cerebral artery (MCA) and vertebral basilar artery (VB). We investigated the association between PI and WMC volume. We also obtained PI of 50 subjects who had no WMC on MRI and explored the ability of PI values in differentiating subjects with and without WMC. RESULTS Multivariate linear regressions found that mean MCA PI and mean VB PI were independent predictors for total WMC volume (beta = .43, P < .001 and beta = .37, P < .001, respectively). Mean MCA PI significantly differentiated patients with WMC from those without WMC (area under curve [AUC] .85 [95% confidence interval .78-.91]) with an optimal cut-off value at 1.15 that yielded sensitivity and specificity of 73.7% and 82%, respectively. AUC for mean VB PI was .81 (95% confidence interval .74-.88) with cut-off value at 1.06 that yielded sensitivity and specificity of 70% and 75%, respectively. CONCLUSIONS PI correlates with volume of WMC. It may help to differentiate those with and without WMC in stroke patients. Further study evaluating the clinical utility of TCD in screening for subclinical WMC among community elderly is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Insomnia is a common complaint in stroke survivors. The purpose of this study was to investigate the clinical and magnetic resonance imaging (MRI) correlates of insomnia symptoms in Chinese ischemic stroke survivors. Methods: A comprehensive psychiatric assessment was performed involving 508 ischemic stroke patients 3 months after their first-ever or recurrent acute stroke. Insomnia symptoms were evaluated with a standard insomnia questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS).The evaluation of the MRI scans focused on infarctions, white matter lesions, and microbleeds. Results: One hundred and eight-six patients (36.6% of the sample) had insomnia symptoms. Sixty-four patients (12.6%) had insomnia symptoms with daytime consequences. In the multivariate logistic regression analysis, GDS score (OR = 1.157, p<0.001) and acute frontal lobe infarction (OR = 1.933, p = 0.039) were significant predictors of insomnia symptoms, while the GDS score (OR = 1.251, p<0.001) and diabetes mellitus (OR = 1.959, p¼0.017) were significant predictors of insomnia symptoms with daytime consequences. Conclusions: Insomnia symptoms have a multi-factorial origin in stroke. Besides depressive symptoms, frontal lobe infarction and diabetes mellitus predict insomnia symptoms. [ABSTRACT FROM AUTHOR]

Objective Although cerebral small vessel disease (SVD) is closely associated with late life depression, patients with even severe SVD may have no depressive symptoms. We postulate that concurrent brain atrophy may also involve in the pathogenesis of depressive symptoms in SVD. We aimed to investigate the relevance of brain atrophy in predicting depressive symptoms among patients with severe SVD. Methods We recruited 45 lacunar stroke patients who had diffuse white matter lesion (WML) and varying severity levels of depressive symptoms. We used a quantitative hybrid warping method to determine the volume of 99 brain regions for each patient. We assessed severity of depressive symptoms using the depression score of the hospital anxiety and depression scale (HADS-D). We first performed correlation analysis of each brain variable with the depression score. Significant variables were then entered separately into linear regression analysis to explore predictors of HADS-D, with adjustment of relevant clinical variables. Results The mean age (SD) of the 45 participants was 74.6 (8.3) years. The mean HADS-D score was 3.5, with score ranging from 0 to15. Variables that had a significant correlation coefficient with HADS-D were gender, hypertension, Oxford handicap scale, left inferior frontal gyrus, right subthalamic nucleus, left posterior limb of internal capsule, and right cerebellum. Regression analyses showed that only left inferior frontal gyrus atrophy (β = -0.354, p = 0.017) predicted HADS-D score after adjusted for other relevant clinical variables. Conclusion Concurrent atrophy of left inferior frontal gyrus is associated with depressive symptoms in elderly patients with severe SVD. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and purpose. To investigate the optimal values of flow velocity on transcranial Doppler (TCD) in grading the severity of middle cerebral artery (MCA) stenosis in comparison with magnetic resonance angiography (MRA). Methods. Both TCD and MRA examinations were performed on 148 asymptomatic patients. The peak flow velocities of each MCA were recorded. Severity of MCA stenosis on MRA was classified as normal-mild (< 50% lumen diameter reduction), moderate (50%-75%), and severe-void (> 75% and void of flow signal). Results. Among 296 MCAs evaluated, normal-mild stenosis was found in 75 (25%), moderate stenosis in 112 (38%), and severe stenosis in 109 (37%). The mean of systolic velocity (Vs) of MCA differed significantly among these three groups: mean Vs = 121.83 ± 22.52 cm/s in the normal-mild group; 155.96 ± 21.62 cm/s for the moderate group; and 199.39 ± 43.86 cm/s for the severe group ( P < .001). The optimal cutoff velocity for detection of MCA (> 50%) stenosis was found at Vs > 140 cm/s on TCD (area under the ROC curve is 0.87, P < 0.001). The best cutoff points for grading severity of on TCD were 140 cm/s and 180 cm/s. Conclusion. TCD enables grading of the severity of MCA stenosis according to the flow velocity. This method provides a noninvasive and reliable method for grading MCA stenosis and allows longitudinal monitoring of the relationship between clinical outcome and hemodynamic change. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH. Methods: We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini-Mental State Examination, Mattis dementia rating scale—initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters. Results: Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale—initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer’s disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline. Conclusions: Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer’s pathology. [Copyright &y& Elsevier]