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The etiology of concurrent stenoses of extracranial and intracranial vessels in patients with ischemic stroke is poorly understood, but hereditary factors are believed to be important. We aimed to determine whether genetic polymorphisms affecting homocysteine and lipid metabolism are associated with concurrent stenoses. The genotypes of 191 Han Chinese patients with acute ischemic stroke, of whom 47 (25%) had concurrent stenoses, and 167 healthy control patients in Hong Kong were examined for the following polymorphisms: paraoxonase 1 (PON1) Q192R, methylenetetrahydrofolate reductase (MTHFR) A222V, glutamate-cysteine ligase catalytic-subunit (GCLC)-129C > T, and oxidized low-density lipoprotein receptor (OLR) 3′ untranslated region C > T (rs1050283). The genotype distributions of PON1 Q192R and MTHFR A222V, which affect lipid and homocysteine metabolism, differed significantly between patients with stroke and healthy controls. The presence of at least one R allele in PON1 Q192R and a TT allele in OLR rs1050283 were associated with concurrent stenoses. We also identified a possible association between the presence of at least one V allele in MTHFR A222V and concurrent stenoses. This study shows that genetic polymorphisms affecting homocysteine and lipid metabolism are possible risk factors for stroke and concurrent stenoses.

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

The objective of this cross-sectional study was to identify the factors associated with health-related quality of life (HRQOL) of family caregivers of Chinese stroke patients. One hundred and twenty-three stroke patients consecutively admitted to a stroke clinic and their 123 family caregivers were recruited. The caregivers' HRQOLs were assessed with the Short Form 36 (SF-36). Two subscores of the SF-36, the Physical Component Summary and the Mental Component Summary Scores served as the dependent variables. Independent variables comprised patients and caregivers' demographic data and physical and psychological conditions in relation to caregivers' HRQOL. The severity of coexisting illnesses of both the patients and their caregivers was assessed using the Cumulative Illness Rating Scale. The Geriatric Depression Scale (GDS) was administered to rate both the patients and their caregivers' depressive symptoms. The extent of the patients' functional disability was assessed using the Barthel Index and the Instrumental Activities of Daily Living. Global cognition of the patients was measured using the Mini Mental State Examination. The level of social support and recent life events of the caregivers were rated using Lubben Social Network Scale and the Modified Life Event Scale, respectively. The multiple linear regression revealed caregivers' Cumulative Illness Rating Scale and GDS score were associated with Physical Component Summary Score of SF-36. The patients and caregivers' GDS score were associated with Mental Component Summary Score of SF-36. Severity of depressive symptoms in Chinese stroke patients and their caregivers is an important factor associated with the caregivers' HRQOL. Further studies evaluating interventions on caregivers' HRQOL should include the assessment and management of mood disorders.

Surgery is recommended for pharmacoresistant temporal lobe epilepsy (TLE), but seizures recur in approximately one third of patients postsurgery. P-glycoprotein is an efflux multidrug transporter that is overexpressed in a range of epileptogenic pathologies. We hypothesized that increased expression of P-glycoprotein in the epileptogenic temporal lobe might be a marker for recurrence of pharmacoresistant seizures postsurgery. We performed immunohistochemistry on temporal lobe tissues resected from 69 patients who underwent anterior temporal lobectomy for pharmacoresistant TLE with histopathological proven hippocampal sclerosis. P-glycoprotein expression was rated by three pathologists independently. Patients with seizure recurrence (n=22) had greater number of positively stained capillaries (p=0.001) and higher P-glycoprotein immunoreactive score in capillaries (p=0.002) in the white matter of resected temporal lobe. The differences remained significant in multivariate analysis (p=0.002 and 0.006, respectively). The results suggest that P-glycoprotein expression in temporal lobe may be associated with seizure recurrence after surgery for pharmacoresistant TLE.

Arecent study in Caucasians found an association between the single nucleotide polymorphism (SNP) of SCN1A, IVS5N +5 G>A (rs3812718), and febrile seizures (FS). We examined whether this and other tagging SNPs of SCN1A were associated with an increased risk of FS in Han Chinese. A total of 728 Han Chinese patients with focal epilepsy were recruited: 97 had a history of FS (58% male, mean age 35 ± 12 years) and 631 did not (50% male, mean age 40 ± 15 years). Genotyping was performed for IVS5N +5 G>A and seven other tagging SNPs selected from the HapMap database. Genotyping was also performed in 848 ethnically matched population controls (50% male, mean age 37 ± 17 years). There was no statistically significant difference in either allele or genotype frequency of any of the SNPs studied between epilepsy patients with and without FS, and between epilepsy patients with FS and controls. The results do not suggest that SCN1A SNPs are susceptibility factors for FS in Han Chinese.

BACKGROUND AND PURPOSE Microemboli signal (MES) detected by transcranial Doppler (TCD) may represent ongoing embolic phenomenon and is a predictor of recurrent stroke or transient ischemic attack. We sought to study the frequency of MES in stroke patients with large artery occlusive diseases treated with low molecular weight heparin (LMWH) or aspirin. METHODS Patients participating in the Fraxiparine in Ischemic Stroke (FISS)-tris study were recruited. MES detection was performed from middle cerebral artery on the 1st, 3rd, and 7th days after randomization. The correlation between the presence of MES and the treatment was determined by the χ2 test. RESULTS Among 47 patients, 26 were randomized to LMWH and 21 to aspirin. On day 1, MES were detected in 10 patients (7/26 on LMWH, 3/21 on aspirin; P= .475). On day 3, 12 patients had MES (7/25 on LMWH, 5/20 on aspirin; P= .821). On day 7, 11 patients had MES (6/25 on LMWH, 5/20 on aspirin; P= .938). The median of the number of MES on days 1, 3, and 7 was 4 (range 1-10), 5 (range 1-42), and 3 (range 1-33) for the LMWH group and 1 (range 1-15), 4 (range 1-10), and 2 (range 1-4) for the aspirin group. CONCLUSIONS There were no significant differences in the frequency of MES between patients with large artery occlusive disease treated with LMWH and aspirin.

BACKGROUND AND PURPOSE Current criteria for middle cerebral artery (MCA) stenosis by transcranial Doppler were mainly based on the flow velocity acceleration, ignoring other useful parameters. We tested the accuracy of new criteria using magnetic resonance angiography (MRA) as the confirmative method. METHODS A compositive score for each MCA was calculated according to following parameters: Velocity Scale (score 0-6 for peak systolic velocity

Objective: Anxiety disorders (ANDI) commonly occur in patients with Parkinson's disease (PD) but their socio-demographic and clinical correlates have not yet been unequivocally determined. This study aimed to assess the frequency of ANDI and their correlates in Chinese PD patients. Methods: A cohort of 133 patients of PD were recruited from three neurology outpatient clinics. Participants' neurological, cognitive, and psychiatric status was assessed using standardized rating instruments. ANDI were diagnosed by qualified psychiatrists using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders–4th Edition (SCID-DSM IV). Results: Thirty-six patients (27.1%) were diagnosed with some types of ANDI; Generalized Anxiety Disorder, Agoraphobia, and Social Phobia were the commonest subtypes of ANDI in PD ( n = 11, 8.3%, in each of the three subtypes). Nine patients had more than one subtype of ANDI. In multivariate logistic regression, younger age of onset of PD [odds ratio (OR) =2.654, 95% confident intervals (CI) = 1.120–6.289, p = 0.027), Geriatric Depression Scale score (OR = 1.179, 95% CI = 1.056–1.316, p = 0.003) and muscle cramps (≥ 1/week) (OR = 2.605, 95% CI = 1.098–6.184, p = 0.030) were independent correlates of ANDI. Conclusions: ANDI are common in Chinese PD patients. Younger age of onset of PD, severity of depressive symptoms, and muscle cramps may be independent correlates of ANDI suggesting that anxiety in PD has multifactorial origin.

Background: Early neurological deterioration is common in the acute phase after stroke. We sought to investigate the correlation between the progression of microembolic signal (MES), ischemic infarcts and the neurological deficits in the acute phase of stroke patients with large artery occlusive disease. Methods: Transient ischemic attack or stroke patients with relevant significant large artery stenosis (≧50% diameter reduction) and admitted within 7 days of the symptom onset were recruited in this study. MES, infarcts on diffusion-weighted imaging and National Institutes of Health Stroke Scale (NIHSS) score were assessed on days 1 and 7 of recruitment. Results: Among 67 patients, 50.7% (34 of 67) had MES on day 1. Presence of MES correlated with both a higher number of infarcts (p = 0.006) and the incidence of multiple infarcts (χ2 test, p = 0.002), but not with the NIHSS score. On day 7, MES was detected in 25.4% of the patients (17 of 67), 11.8% of them (2 of 17) displayed new or extended infarct on DWI (p = 0.14) and 29.4% (5 of 17) showed neurological improvement (p = 0.039). Among the patients with positive MES at baseline, NIHSS reduction was positively correlated with disappearance of MES on day 7 (MES disappearance vs. persistence group, 2.05 vs. 0.73, p = 0.023). Conclusions: Neither the disappearance of MES nor the changes in NIHSS score correlated with the progression of infarct. Disappearance of MES indicated better neurological improvement in the acute phase.

Background and Purpose: Coexisting ischemic heart disease (IHD) and concurrent atherosclerosis of intracranial and extracranial vessels is common in Asians. This study aims to investigate the long-term outcomes of ischemic stroke patients with concurrent stenoses and IHD. Methods: This was a prospective cohort study in Hong Kong. Consecutive Chinese patients with acute ischemic stroke underwent MRI, magnetic resonance angiography and carotid duplex sonography. Results: A total of 428 patients were included. The mean follow-up period was 65 months (up to 87 months). Ninety-three patients (22%) died of any cause and 104 patients (22%) suffered from nonfatal vascular events. Fifty-four patients (13%) had IHD. Among them, 27 patients (50%) had concurrent stenoses. In patients with concurrent stenoses and IHD, only 3 (11%) were free of death and recurrent vascular events. Eight (30%) had recurrent nonfatal stroke, 7 (26%) had nonfatal myocardial infarct (MI) and 11 (41%) died, 6 (22%) of them due to fatal MI. The overall 5-year cumulative rates of mortality, recurrent vascular events and combined poor outcomes were 21, 23 and 43%, respectively. In patients with concurrent stenoses and IHD, these rates were 40, 50 and 83%, respectively. More deaths (log rank: 6.56; p = 0.01), recurrent vascular events (log rank: 25.24; p < 0.001) and poor outcomes (log rank: 27.50; p < 0.001) were found among patients with concurrent stenoses and IHD. Conclusions: Ischemic stroke patients with concurrent stenoses and IHD had high risks of death and recurrent vascular events. Future studies on aggressive medical therapy and early cardiac interventions in this high-risk group of stroke patients are warranted.

Inflammatory endothelial activation mediated by intercellular adhesion molecule-1 (ICAM-1) plays a role in the pathogenesis of large- and small-vessel disease. We explored the association between soluble ICAM-1 (sICAM-1) and white matter lesion (WML) as a manifestation of cerebral small-vessel disease.One hundred and seventy-five elderly individuals agedor= 60 without neurological deficits were studied. Subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH) were rated separately. Lesions in each category were then divided into three groups (grade 0-I, grade II, grade III) according to the Fazekas scale.Plasma sICAM-1 levels were positively associated with grades of WML (for SDWMH: 297.4+/-135.6ng/mL in grade 0-I, 391.3+/-145.5ng/mL in grade II, and 450.2+/-232.9ng/mL in grade III, p0.001; for PVH: 282.5+/-116.5ng/mL in grade 0-I, 402.3+/-160.4ng/mL in grade II, and 428.1+/-227.7ng/mL in grade III, p0.001). Multivariate analysis showed higher sICAM-1 levels, age and hypertension were the independent risk factors associated with the presence and severity of WML. More than 4-fold increased risk of WML was observed in patients with the highest quartile of sICAM-1 (all WML OR=4.694, 95% CI: 1.805-12.204; moderate WML OR=4.618, 95% CI: 1.543-13.825; severe WML OR=4.893, 95% CI: 1.236-19.368).Increased plasma sICAM-1 suggests inflammatory process may be involved in the pathogenesis of WML.

Objective In ictal scalp electroencephalogram (EEG) the presence of artefacts and the wide ranging patterns of discharges are hurdles to good diagnostic accuracy. Quantitative EEG aids the lateralization and/or localization process of epileptiform activity. Methods Twelve patients achieving Engel Class I/IIa outcome following temporal lobe surgery (1 year) were selected with ∼1–3 ictal EEGs analyzed/patient. The EEG signals were denoised with discrete wavelet transform (DWT), followed by computing the normalized absolute slopes and spatial interpolation of scalp topography associated to detection of local maxima. For localization, the region with the highest normalized absolute slopes at the time when epileptiform activities were registered (>2.5 times standard deviation) was designated as the region of onset. For lateralization, the cerebral hemisphere registering the first appearance of normalized absolute slopes >2.5 times the standard deviation was designated as the side of onset. As comparison, all the EEG episodes were reviewed by two neurologists blinded to clinical information to determine the localization and lateralization of seizure onset by visual analysis. Results 16/25 seizures (64%) were correctly localized by the visual method and 21/25 seizures (84%) by the quantitative EEG method. 12/25 seizures (48%) were correctly lateralized by the visual method and 23/25 seizures (92%) by the quantitative EEG method. The McNemar test showed p = 0.15 for localization and p = 0.0026 for lateralization when comparing the two methods. Conclusions The quantitative EEG method yielded significantly more seizure episodes that were correctly lateralized and there was a trend towards more correctly localized seizures. Significance Coupling DWT with the absolute slope method helps clinicians achieve a better EEG diagnostic accuracy.

Frontal and basal ganglia infarcts and executive dysfunction are thought to be involved in the pathophysiology of poststroke emotional incontinence (PSEI). The study examined whether patients with PSEI have more frontal and/or basal ganglia infarcts and impairment in executive function. A total of 516 Chinese patients with acute ischemic stroke consecutively admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong were screened for PSEI 3 months after the index stroke. According to Kim’s criteria, 39 (7.6%) had PSEI. Thirty-nine stroke patients without PSEI served as matched control group. The PSEI group had significantly more frontal and/or basal ganglia infarcts, had lower Chinese Frontal Assessment Battery scores, required more time to complete the Stroop Test, and made more omission and commission errors in the Go–NoGo test. There was no significant correlation between frontal or basal ganglia infarcts and executive function. The correlation between frontal infarct and severity of PSEI was .420. Further follow-up and functional imaging studies are warranted to explore the relationship between PSEI, brain infarcts, and executive dysfunction. (JINS, 2009, 15, 62–68.)

Background: Cerebral microbleeds (CMBs) were found in patients with and without hypertension. We aimed to investigate different distribution patterns of CMBs in patients with and without hypertension. Methods: We examined acute ischemic stroke patients using a standardized MRI protocol that included T1, T2 and gradient-echo T2*. Clinical and imaging characteristics were collected from all patients. Results: Among 998 patients, CMBs were detected in 273 patients (27.3%). Of these, 62 did not have hypertension (22.7%). The incidence of CMBs among patients without hypertension (62/335, 18.5%) was lower than among those with hypertension (211/663, 31.8%; p < 0.01). The location of CMBs in patients without hypertension was limited to the cortical-subcortical (CSC) region in 40.3% (25/62) compared to 20.4% of those with hypertension (43/211; p = 0.01). No significant difference was found between CMB locations within the intra-CSC region in both groups. The severity of white matter changes and systolic blood pressure on admission were found to be independent predictors for CMBs in patients without hypertension. Conclusions: CMBs in patients with and without hypertension have different distribution patterns and may have a different pathogenesis. Blood pressure controlling is important in both groups because systolic blood pressure is an independent predictor of CMBs in patients without hypertension.

Purpose: To determine the long-term outcome of ischemic stroke patients with concurrent intracranial and extracranial atherosclerosis using magnetic resonance angiography. Methods: A prospective cohort of patients in Hong Kong with acute ischemic stroke was studied with magnetic resonance angiography of the brain and carotid duplex. All patients were followed up regularly for the development of recurrent stroke, cardiac events, or death. Results: Totally 343 patients with acute ischemic stroke were included, of whom 104 (30%) had concurrent intracranial and extracranial lesions. The follow-up period was up to 76 months (mean 44.5 months). Overall, 55 patients (15.5%) died of any cause and 91 patients (26.5%) suffered a further nonfatal vascular event. The overall 5-year cumulative rates of mortality, restroke and poor outcomes (combined death and further vascular events) were 18, 27 and 37%, respectively. In patients with concurrent lesions, these rates were 31, 41 and 51%, respectively. The corresponding rates were 13, 22 and 31% in patients without concurrent lesions. The risks were highest in the first year after stroke. More deaths (log rank, 16.3; p = 0.0001), restrokes (log rank, 9.71; p = 0.002) and poor outcomes (log rank, 13.87; p = 0.0001) were found among patients with concurrent lesions. The presence of concurrent vascular lesions, advanced age, smoking, hyperlipidemia and previous history of stroke were independent predictors of poor outcomes. Conclusions: The long-term prognosis of ischemic stroke patients with concurrent atherosclerosis of intracranial and extracranial vessels is poor. They are at high risk of further vascular events or death.

Background Multiple sclerosis (MS) has a low prevalence in Hong Kong. Objective To reassess MS prevalence in Hong Kong and to examine associated risk factors for relapsing–remitting type MS patients to reach Kurtzke's Extended Disability Status Scale (EDSS) of 6.0, i.e. when walking aid was needed. Design Retrospective observational study on MS patients over 11 years. Setting Three tertiary hospitals in Hong Kong. Results A hundred and six patients were recruited. Female to male ratio was 3.2:1 and the prevalence was 4.8 per 100,000. 95 were relapsing–remitting (RR) type. The mean disease duration was 12.7 years (range: 1–45 years) and the duration of follow up was 11.0 +/− 0.8 (mean +/− SE) years. The initial mean EDSS was 1.59 and the latest mean EDSS was 4.26. 38 (40%) RR type MS patients progressed to EDSS 6.0 after a mean duration of 6.0 years. With Cox regression analysis, patients with older age (> 35y) of onset (HR 2.57; 95% CI:1.29–5.11), higher EDSS of 2.0 or more upon presentation (HR 2.19; 95%CI: 1.12–4.26) were associated with progression to EDSS of 6.0, while there was a tendency towards slower disease progression for patients initially presenting with optic symptoms (HR 0.52; 95%CI: 0.23–1.16). The number of relapses and use of interferon could not be shown to have significant effect on disease progression. Conclusions The local period prevalence ratio of MS was 4.8 per 100,000. Older age of onset and higher EDSS upon initial presentation were independent predictors for progression to EDSS of 6.0.

Vincent Mok1, Adrian Wong1, Simon Ho2, Thomas Leung1, Wynnie WM Lam2, Ka Sing Wong11Department of Medicine and Therapeutics; 2Department of Radiology and Organ Imaging, The Chinese University of Hong Kong, Shatin, Hong Kong, ChinaBackground: We explored the efficacy and tolerability of rivastigmine among Chinese patients with subcortical vascular dementia.Methods: Forty subjects were randomized to either placebo (n = 20) or rivastigmine (n = 20) in a double-blind 26-week trial. Outcome measures were cognition (mini-mental state examination, frontal assessment battery), neuropsychiatric inventory (NPI), instrumental activities of daily living, clinical dementia rating scale, and adverse events.Results: No statistical significant benefit could be observed in the active group in any of the efficacy measures. A trend favoring active group was observed only in the NPI subscore of irritability (p = 0.066) and aberrant motor behavior (p = 0.068). Withdrawal rate was 30% and 15% in the active and placebo group, respectively.Conclusion: Among Chinese subcortical vascular dementia patients, there was no apparent cognitive benefit associated with use of rivastigmine over the 6 months period. A trend favoring rivastigmine was observed in certain behavioral measures. Rivastigmine was associated with more withdrawals relative to placebo.Keywords: rivastigmine, subcortical vascular dementia, Chinese

Background: Despite the rapid progress in stroke prevention, effective acute stroke treatment except for thrombolysis is still lacking. Hypoperfusion is related to unfavorable functional outcome, further strokes and long-term mortality. Therefore, the need for a safe and effective way of increasing the cerebral blood flow seems obvious. Currently, there is a growing body of evidence to suggest that external counterpulsation (ECP) may enhance the blood supply to the brain and thus may be beneficial to patients with ischemic stroke. Methods: A MEDLINE search in combination with a search for papers in Chinese literature in the Wan Fang and China Academic Journal databases was carried out. Results: Preliminary investigations suggested that ECP may improve the clinical outcome of stroke patients. However, well-designed clinical studies exploring the therapeutic effects of ECP in ischemic stroke are very limited. Conclusions: Randomized-controlled trials with a large sample size are needed to further define the efficacy and safety of ECP in acute stroke management. Future studies should provide insight into the value of ECP in ischemic stroke as well as its possible mechanisms.

Background Collateral pathways are important in maintaining adequate cerebral blood flow in patients with carotid stenosis. We aimed to evaluate the hemodynamic patterns in relation to carotid stenosis in acute stroke patients. Methods Consecutive 586 stroke patients in a hospital based cohort were included in the present study. Carotid duplex was performed to identify patients with absolute minimal diameter reductions of 50 % or greater in their internal carotid arteries (ICAs). Color velocity imaging quantification ultrasound (CVIQ) was used to measure extracranial arterial blood flow volume (BFV) in bilateral common carotid arteries (CCAs) and bilateral vertebral arteries (VAs). The absolute values of BFV and the ratios were compared between patients with and without ICA stenosis. Results Among 586 acute ischemic stroke patients (mean age: 67.5 ± 12.4y), ICA stenosis was detected in 112 patients (19.1 %), including unilateral ICA stenosis in 81 patients (13.8 %) and bilateral ICA stenosis in 31 patients (5.3 %). Among patients with unilateral ICA stenosis, the BFV in contralateral CCA was significantly higher than that in ipsilateral CCA (325.5 ± 99.8 mL/min vs. 242.2 ± 112.2 mL/min, P

Introduction: In SAMMPRIS, the benefit of aggressive medical therapy over stenting persisted throughout the extended follow-up. It is uncertain how modern medical management could diminish stroke relapses. Method: In a prospective academic-initiated study, we recruited 40 patients (mean age 63.4±9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3D-rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein Results: Overall, the risk factor control reached the pre-specified intensity. Plaque thickness, and hence luminal narrowing, significantly diminished at one year (from 1.50±0.48 to 1.24±0.42mm; p Conclusion: Intracranial plaques might regress and positively remodel under intensive risk factor control. These morphologic changes might stabilise the plaques, alleviate unfavourable hemodynamics across the steno-occlusion, and hence reduce the risk of plaque rupture or platelet aggregation.

Background and Objectives: Blood pressure variability (BPV), heart rate variability (HRV) and baroreflex sensitivity (BRS) as measures of autonomic function might provide prognostic information in ischemic stroke. We aimed to study noninvasive beat-to-beat assessment of BPV, HRV and BRS in the acute phase of ischemic stroke to determine whether any of them predicted clinical outcome. Methods & Patients: Consecutive ischemic stroke patients within 7 days of symptom onset were enrolled. The frequency components of BPV and HRV by means of power spectral analysis [very low frequency (VLF; < 0.04 Hz); low frequency (LF; 0.04-0.15 Hz); high frequency (HF; 0.15-0.40 Hz); power spectral density (PSD; Results: 82 patients were recruited (mean age, 64.6 ± 9.9 years; 89.3% males). Univariate analysis showed that there were significant differences in National Institutes of Health Stroke Scale (NIHSS) at recruitment, VLF diastolic BPV, VLF, HF and PSD systolic BPV, and down ramp BEI between the good and poor outcome groups (all P < 0.05). After adjusting for NIHSS, multivariate logistic regression showed that only HF systolic BPV (OR 1.320; 95% CI, 1.050-1.659; P=0.017) and down BEI (OR 0.950; 95% CI, 0.912-0.990; P=0.014) were independently correlated with poor functional outcome. Conclusions: Beat-to beat highly variable systolic blood pressure and impaired BRS as evaluated by decreased down BEI are associated with an unfavorable functional outcome after acute ischemic stroke. Important prognostic information can be readily obtained from a short period of noninvasive hemodynamics monitoring in the acute stroke patient.

Objective: Although Magnetic Resonance Imaging (MRI) vessel wall imaging could visualize the pathology of intracranial arterial disease, signal changes are poorly interpreted due to lacking of cerebral artery specimens. Based on a MRI-histology comparison study on a series of post-mortem cerebral arteries, we aimed to examine the occurrence of hyper-, iso- and hypo-intensity on T1-weighted fat-suppressed images of MCA plaques, which might be suggestive of different plaque components. Methods: Fifty-eight pairs of MCAs were imaged at 1.5T MRI with T1-weighted Table 1: The distribution of different atherosclerotic phenotypes among MCA plaques with iso-, hyper- and hypo-intensity on T1-weighted fat-suppressed images fat-suppressed- and T2-weighted sequence. MRI was performed in the postmortem brains to scan the cross-sections of MCAs with barium expanding the artery lumen. The MCAs were then removed for histopathologic processing and atherosclerotic plaque classification, which was used as a reference standard to interpret the signal changes on MRI pictures. Results: A total of 76 MRI vessel wall images were adequate for signal changes interpretation. On T1-weighted fat-suppressed images of MCA plaques, hyper-intensity was revealed on 34 vessels (44.7%), iso-intensity on 24 vessels (31.6%) and hypo-intensity was revealed on 18 samples (23.7%). There was a trend that iso-intensity indicated lower grade atherosclerosis and hypo-intensity represented advanced atherosclerosis, while hyper-intensity was suggestive of median grade atherosclerotic plaques. Further analysis demonstrated that nearly all hypo-intensity was found to be histology-verified advanced atherosclerosis with lipid core formation. Interpretation: Signals of hypo-intensity on T1-weighted fat-suppressed images of MCA plaques may be useful in stratification of stroke patients with intracranial atherosclerosis.

Background: Intracranial arterial stenosis (ICAS) is a predominant cause of ischemic stroke in Asia. Changes of the signal intensities across ICAS lesions on time-of-flight magnetic resonance angiography (MRA) have been indicated to partially reflect the hemodynamic significance of the lesions, which we aimed to verify by correlating with cerebral perfusion features provided by CT perfusion imaging. Methods: Ischemic stroke or transient ischemic attack patients with unilateral symptomatic stenosis (≥50%) of intracranial internal carotid artery or middle cerebral artery were included in this study. Change of signal intensities across an ICAS lesion on time-of-flight MRA was calculated by the distal and proximal signal intensity ratio (SIR). Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) within the middle cerebral artery territory of ipsilateral and contralateral hemispheres were evaluated on the CT perfusion images at the basal ganglia level. Relative CBV, CBF and MTT were defined as the ratios of the parameters obtained from ipsilateral and contralateral hemispheres. The relationships between SIR and CT perfusion parameters were analyzed. Results: Fifty subjects (74% male, mean age 62.84) were recruited. Overall, mean SIR was 0.77 ± 0.17. SIR of ICAS significantly, linearly and negatively correlated with ipsilateral CBV (r = -0.335, P = 0.017), CBF (r = -0.312, P = 0.028), and MTT (r = -0.301, P = 0.034), and relative MTT (r = -0.443, P = 0.001). Conclusions: Changes of the signal intensities across ICAS lesions on time-of-flight MRA may be a simple marker to reflect cerebral perfusion changes in patients with symptomatic ICAS.

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Increasing our knowledge about intracranial atherosclerosis (ICAS) natural history and prognostic factors is essential to improve its preventive therapy and thus reduce the dramatic clinical consequences caused by this entity. ICAS is characterized by a chronic and progressive course until it becomes symptomatic, mostly through complication of an unstable intracranial atherosclerotic plaque. Population-based studies in healthy subjects have shown that the prevalence of asymptomatic ICAS is higher in Asian than in Caucasian populations. In both settings, asymptomatic ICAS is associated with classical vascular risk factors and with the metabolic syndrome, and it is burdened with an increasing risk of having incident stroke and cognitive impairment. When it reaches its symptomatic stage, ICAS is a dynamic and aggressive condition, and affected patients are at high risk of having recurrent stroke and other major vascular events. The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial has recently shown a robust impact of intensive medical therapy reducing the risk of clinical recurrence of symptomatic ICAS. However, even under best medical therapy and degree of risk factor control, symptomatic ICAS-related recurrence risk continues to be the highest among all stroke etiologic subtypes. The second part of the chapter reviews the current understanding of prognostic factors that may help discriminate the high-risk ICAS patients, divided into local factors (vulnerable ICAS plaque) and systemic factors (vulnerable ICAS patient). Regarding research on local factors, high-resolution magnetic resonance imaging (HRMRI) is an emerging technique that allows in vivo evaluation of intracranial arterial wall, which is displacing our research focus from intracranial stenosis degree towards intracranial atherosclerotic plaque composition and activity. Characterization of the vulnerable ICAS patient may be improved with biomarker research. The latest contributions in this field help support the hypothesis that inflammation determines the risk of progression and complication of this disease, as it occurs in atherosclerosis affecting extracranial arterial beds.

Wilson disease (WD), an autosomal recessive disorder of copper transport, is the most common inherited liver disorder in Hong Kong Chinese. This was the first local study to elucidate the molecular basis and establish an effective DNA-based diagnostic protocol. The ATP7B genes of 65 patients were amplified by polymerase chain reaction (PCR) and sequenced. Haplotype analysis was performed using D13S301, D13S314, and D13S316. The p.L770L/p.R778L status in 660 subjects was determined to estimate WD prevalence. Allele age of p.R778L was determined by the smallest homozygosity region between D13S301 and D13S270. We identified 42 different mutations with 17 being novel. p.R778L (17.3%) was the most prevalent. Exons 2, 8, 12, 13, and 16 harbored 70% mutations. Thirty-two haplotypes were associated with WD chromosomes. The estimated prevalence rate was 1 in 5,400. Three out of 660 normal subjects had p.L770L/p.R778L. In the remaining 657 individuals, neither p.L770L nor p.R778L was found. We characterized a Hong Kong Chinese-specific ATP7B mutation spectrum with great genetic diversity. Exons 2, 8, 12, 13, and 16 should be screened first. The perfect linkage disequilibrium suggested that p.R778L and its private polymorphism p.L770L originated from a single ancestor. This East-Asian-specific mutation p.R778L/p.L770L is aged at least 5,500 years.

To investigate the proportion of Chinese patients with intractable seizures and the risk factors leading to refractory epilepsy.Consecutive patients over 14 years of age attending a Neurology clinic were evaluated. Patients with epilepsy were classified into two groups according to their seizure control: refractory or seizure-free. Epilepsy was classified as idiopathic as defined by age-related onset and typical electroclinical characteristics, symptomatic if secondary to a structural abnormality and cryptogenic if the cause was unknown. Age, sex, epilepsy syndrome classification, aetiology, presence of mental retardation and the number of drugs used were compared between patients with refractory epilepsy and those in remission.Among 260 adolescent and adult patients with a mean age of 34 years (range 15-79), complete seizure control was achieved in 157 (60%) cases. Multivariate binomial logistic regression analysis showed that patients with mesial temporal sclerosis (OR=7.6, 95% CI 3.53-16.4, p0.01) and the presence of mental retardation (OR=9.39, 95% CI 3.98-22.12, p0.01) were more likely to develop pharmacoresistant epilepsy.In adults the underlying aetiology is an important factor as to whether patients develop intractable seizures. Poor control was also associated with the presence of mesial temporal sclerosis and mental retardation.

We studied 590 asymptomatic villagers aged > or =40 years in Liangbei County in central rural China and found 41 subjects (prevalence 6.9%) with intracranial atherosclerosis. In a multivariate analysis, the significant risk factors for intracranial stenosis were hypertension (OR 2.53; 95% CI 1.12 to 5.72), glycosuria (OR 3; 1.19 to 7.97), heart disease (OR 4; 1.39 to 11.6), and family history of stroke (OR 5.2; 1.38 to 20). Intracranial atherosclerosis is not uncommon among asymptomatic Chinese subjects.

Environmental and genetic factors may both affect the risk of vascular cognitive impairment developing after a stroke. To identify factors affecting this risk, the cognitive status of 121 patients was examined 3 months after an ischemic stroke. In all patients and in 270 control subjects, 7 polymorphisms reported to affect risk of vascular ischemic disease were genotyped. In 51 patients (42.1%), vascular cognitive impairment resulted, defined by a Mini-Mental State Examination score of less than 24. These patients were older and more likely to be women. Alleles of none of the polymorphisms differed between patients with or without vascular cognitive impairment, except for glutamate-cysteine ligase modifier (GCLM) (odds ratio = 2.8, P = .006). When all stroke patients were considered, the GCLM genotype did not affect Mini-Mental State Examination scores. Testing the GCLM genotype in an independent group of stroke patients may determine whether this association with vascular cognitive impairment is genuine. ( J Geriatr Psychiatry Neurol 2007;20:93-99)

Summary Background Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD. Methods Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0·4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80–300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493). Findings Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index ≥85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI −5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0–1 (odds ratio 1·55, 95% CI 1·02–2·35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78% vs 79% and 73% vs 75%, respectively). Interpretation Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.

This study aimed to compare changes in plasma beta-globin DNA and serum S100 protein to diagnose stroke and for predicting mortality and morbidity.Patients with stroke-like symptoms presenting to the emergency department of a Hong Kong hospital were recruited. Plasma DNA was analyzed for the beta-globin gene with fluorescent-based PCR. S100 concentrations were determined using ELISA. Primary outcomes were diagnosis of stroke, mortality, and modified Rankin Score (mRS) after 6 months.One hundred ninety-seven consecutive patients recruited, 118 (60%) ischemic stroke, 35 (18%) hemorrhage and 44 (22%) with no acute neuroimaging changes. Serum S100 and plasma DNA were increased in 126 (p0.0010) and 36 (p=0.21) stroke patients respectively vs. controls. Median plasma DNA was higher in hemorrhagic stroke than those without (1725 vs. 1050 kilogenome-equivalents/l, p=0.0104). Median plasma DNA was higher in mRS2 vs. mRSor=2 (1350 vs. 1025, p=0.0103), and higher in non-survivors vs. survivors (1625 vs. 1050, p=0.0070). Median serum S100 higher in mRS2 patients vs. mRSor=2 (0.152 vs. 0.131 microg/l, p=0.0003). The odds ratio (OR) of discriminating hemorrhagic from non-hemorrhagic stroke with DNA was 4.24 (95% CI 1.88-9.56); S100 and DNA together give an OR of 16.55.For stroke diagnosis, S100 performs better than DNA; DNA is a better marker for hemorrhage. For diagnosis of hemorrhagic stroke, combined S100 and DNA performs better than either alone. Plasma DNA and serum S100 predict morbidity and mortality in stroke.

Background: Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic review and meta-analysis to synthesize relevant evidence currently available. Methods: Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT. Results: In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities. Conclusions: Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients.

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.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.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.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.

Acute symptomatic seizure (AS) after ischaemic stroke is defined as a seizure occurring ≤7 days of the stroke. There remains a lack of information on the prognosis of AS after ischaemic stroke and how it should be treated.We prospectively recruited patients after their incidents of ischaemic stroke from a population-based stroke registry. Stroke aetiology was defined according to Trial-of-ORG-10172 in acute-stroke treatment (TOAST). Patients were examined for any transient complete-occlusion with recanalisation (TCOR) and haemorrhagic transformation. The seizure outcomes were (1) acute clustering of seizures ≤7 days, (2) seizure recurrence associated with stroke recurrence beyond the 7-day period and (3) unprovoked seizure (US)7 days.104 patients (mean age 65 years/55% female) with AS after ischaemic stroke were identified (mean follow-up 6.17 years). Comparison of the group of patients with AS and those without seizures showed that patients with AS had significantly less large-vessel and small-vessel disease but more cardioembolisms (p0.05) and a higher proportion of TCOR (p0.01), multiple territory infarcts (p=0.007) and haemorrhagic transformations (p0.01). Using Kaplan-Meier statistics, the risk of acute clustering of seizures ≤7 days was 22%, with a statistical trend for TCOR as a predictive factor (p=0.06). The risk of seizure recurrence associated with worsening/recurrence of stroke beyond 7 days was 13.5% at 2 years, 16.4% at 4 years and 18% at 8 years. Presence of2 cardiovascular risk factors (p0.05) and status epilepticus (P0.05) are predictive risk factors on Cox regression model. The risk of US was 19% at 2 years, 25% at 4 years and 28% at 8 years with epileptiform EEG as a predictive factor (p0.05).Seizure recurrence following AS after ischaemic stroke may appear as acute clustering. Afterwards, seizures may occur as often with a recurrent stroke as without one within 4.2 years. We recommend the use of antiepileptic agents for up to 4 years if the underlying stroke aetiology cannot be fully treated.

The differences between initial and recurrent stroke plaques are not defined. Hence, a nested case-control study was conducted to evaluate the association of stroke recurrence with the echogenic characteristics of carotid plaques in patients with ischaemic stroke.One hundred and four patients with 1-year recurrent acute ischaemic stroke were enrolled and compared with 104 control patients (first-time ischaemic stroke) matched for age, gender, stroke severity and treatment allocation. Based on the Mannheim Carotid Intima-Media Thickness Consensus (2004-2006), the number of carotid plaques and echogenicity between the two groups of patients were compared.As compared to patients with first-time stroke, those with recurrent stroke showed significantly higher prevalence of heart disease (13.46 vs 28.85%, P = 0.0066) and presence of intracranial stenosis (55.77 vs 89.90%, P 0.0001). During the 1-year follow-up, patients with recurrent stroke had a significantly higher rate of unstable plaques (80.41%) than patients with first-time stroke (64.21%, P = 0.036). Also, patients with recurrent stroke had a significantly larger number of plaques than patients with first-time stroke (P = 0.0152). Multivariate conditional logistic regression analysis (after adjustment for heart disease and intracranial stenosis) identified an association between 1-year stroke recurrence and the presence of unstable plaques (hazard ratio 3.077; 95% CI: 1.133-8.355).Stroke recurrence is related to advanced atherosclerosis defined by carotid plaque and its characteristics.

Pain is common in stroke; however, its impacts on health-related quality of life (HRQoL) are unclear due to the limitations of previous studies.The current study aims to examine and compare the demographic and clinical characteristics of Chinese stroke patients with and without pain and explore the correlations between poststroke pain and HRQoL.Four hundreds and forty-one participants recruited in an acute stroke unit in a regional hospital. They were assessed 3 months after the index stroke with the following instruments. HRQoL was measured using the Short Form-12 (SF-12). The Chinese version of the Faces Pain Rating Scale-Revised (FPS-R) was used to determine the presence and intensity of pain. The demographic and clinical characteristics of patients were obtained using Barthel Index (BI), Fatigue Severity Scale (FSS), Geriatric Depression Scale (GDS), Anxiety subscale of the Hospital Anxiety and Depression Scale (HADSA), Instrumental Activities of Daily Living (IADL), Mini Mental State Examination (MMSE), Modified Rankin Scale (MRS), and National Institutes of Health Stroke Scale (NIHSS).Of all participants screened, 167 reported pain and 69 had novel pain. The pain group had significantly lower physical component summary (PCS) scores after adjusting for sex, education, DSM-IV depression and BI, GDS, HADSA, and FSS scores. The FPS score was negatively correlated with a lower PCS score in patients with pain and with novel pain.The presence and intensity of pain have significant negative effects on HRQoL in stroke survivors. Interventions for pain could make a valuable contribution to improving HRQoL in stroke survivors.

Insomnia is a common complaint in stroke survivors. Insomnia after stroke is correlated with physical disability, dementia, anxiety, depression, and fatigue. However, the influence of insomnia following stroke on health-related quality of life (HRQoL) has not been investigated.The current study aimed to examine the effect of insomnia on HRQoL in stroke survivors 3 months after their index stroke over and above confounding variables.Three hundred and thirty-six patients were recruited from the acute stroke unit in a regional hospital in Hong Kong. Insomnia was ascertained by a single item on a locally validated, seven-item insomnia questionnaire. HRQoL was measured by the total score and the 12 domain scores of the Stroke Specific Quality of Life (SSQoL) scale. Demographic and clinical characteristics were obtained using the following scales: National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS).Forty-four percent of stroke survivors reported experiencing insomnia in the past month; they were more likely to be female and to have a higher GDS score. The insomnia group had significantly lower overall SSQoL, energy and thinking scores after adjusting for sex, BI, and GDS scores.The findings show that stroke survivors who experienced insomnia had a reduced overall HRQoL and were impaired in the energy and thinking domains of HRQoL. Early screening for sleep disturbance would be beneficial to prevent later development of post-stroke insomnia. Pharmacological and non-pharmacological interventions are suggested to improve HRQoL in stroke patients with insomnia.

We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions.Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted.In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods.Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies.

Although the Virchow's triad on thrombosis includes reduced blood flow as a factor, there has been relatively little data on the importance of total cerebral blood flow on the risk of subsequent stroke. In the current study, we investigate whether total cerebral blood flow helps predict stroke recurrence. Extracranial arterial blood flow volume estimated by color velocity imaging quantification ultrasound (CVIQ) is an index of cerebral blood flow measurement. We performed a cohort study of 210 consecutive acute stroke patients. Patients were studied with transcranial Doppler and duplex ultrasound for intra- and extracranial large artery disease within 3 days of symptom onset. The association between the risk of recurrent stroke and CVIQ was analyzed with Cox proportional hazards model. Thirty-nine patients (17.7%) developed an ischemic stroke during a mean follow-up of 47.5 months. The mean extracranial blood flow volume was significantly lower for patients who had a recurrent stroke than those without (594.4 ± 130.3 versus 683.8 ± 176.9mL/min; P = 0.003). In a Cox proportional hazards model adjusting for potential confounding variables, extracranial blood flow volume (hazard ratio (HR) for lowest tertile, 4.1; 95% confidence interval (CI), 1.5 to 11.0) along with male sex (HR, 2.5; 95% CI, 1.3 to 5.1), diabetes (HR, 2.5; 95% CI, 1.2 to 5.0) and large artery stenosis (HR, 2.2; 95% CI, 1.1 to 4.4) were independent predictors for stroke recurrence. Our data indicated that patient with low amount of blood flow to the brain is at risk of recurrent stroke.

Background and Purpose. Small subcortical infarcts (SSI, maximum lesion diameter ≤2.0 cm) are usually considered as infarcts caused by small vessel disease. However, SSI can also be associated with large artery occlusive disease such as middle cerebral artery (MCA) stenosis. We performed a prospective study to investigate the relationship between MCA stenosis and SSI distribution and further to investigate the mechanism of SSI caused by MCA stenosis. Methods. Magnetic resonance angiography (MRA) and diffusion-weighed MRI (DWI) of consecutive acute ischemic stroke patients with recent SSI were studied. The distribution of acute infarcts on DWI was categorized as cortical infarct (CI), border zone infarct (BI), or perforating artery infarct (PAI). Results. Totally, 93 cases were recruited, among which 12 had single SSI with MCA stenosis (group 1) and 26 patients had multiple SSI with MCA stenosis (group 2), while 55 patients without MCA stenosis had single SSI (group 3). For patients with single SSI and MCA stenosis, 6 had BI and 6 had PAI; for patients with multiple SSI and MCA stenosis, 25 had BI, 4 had PAI and 9 had CI (compared with group1: P= .001); for patients with single SSI but without MCA stenosis, 20 had BI and 35 had PAI (compared with group1: P= .58). Conclusion. Multiple acute infarcts along the border zone are the commonest pattern in small infarcts with MCA stenosis, especially among those with multiple acute infarcts. Our data suggest that hemodynamic compromise and artery-to-artery embolism may be both important factors for infarcts in patients with MCA stenosis.

The objective of this study was to examine the prevalence and clinical correlates of poststroke cognitive impairment in Chinese stroke patients in Hong Kong. One hundred seventy-nine stroke patients were interviewed by a psychiatrist 3 months after their stroke. Cognitive impairment was determined according to the Mini-Mental State Examination score. Thirty-nine participants (21.8%) had cognitive impairment. Univariate analysis found that cognitive impairment was associated with age, female sex, level of education, previous stroke, prestroke Rankin score, National Institutes of Health Stroke Scale dysarthria and total scores, urinary incontinence, and cerebral atrophy index. Multivariate logistic regression suggested that female sex, education, National Institutes of Health Stroke Scale dysarthria score, urinary incontinence, and atrial fibrillation were independent risk factors of poststroke cognitive impairment. After removal of 54 patients with previous stroke from the sample, the frequency of cognitive impairment decreased to 18.4%. It was concluded that cognitive impairment is common among nondemented Chinese stroke patients in Hong Kong.

Background and Purpose. The relationships between cerebral vasomotor reactivity (CVR) and white matter lesions (WMLs) were investigated mainly in patients with carotid stenosis. We aimed to study the relationship in asymptomatic elderly subjects without large artery occlusive disease. Methods. A total of 33 elderly individuals (mean age was 76.2 years) who were free from neurological deficit or cognitive impairment were studied. Bilateral mean blood flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler (TCD) system together with intravenous administration of acetazolamide as vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR) sequence of MRI were classified into two categories: subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The lesions in each category were then divided into three grades (grade 0-I, grade II, grade III) according to the Fazekas scale. Results. CVR was inversely associated with the extent of SDWMH and PVH. The differences in CVR were statistically significant among different severity of WMLs: for SDWMH (70%± 10% in grade 0-I, 60%± 10% in grade II, and 40%± 10% in grade III, P < .001); for PVH (80%± 10% in grade 0-I, 60%± 10% in grade II, and 40%± 10% in grade III, P < .001). Conclusions. Impaired CVR is related to the extent of WMLs in asymptomatic elderly individuals without large artery stenosis. The findings in our study suggest that dysfunction of cerebral vascular autoregulation might be an important factor in the development of WMLs in the asymptomatic elderly without large artery occlusive disease.

Intracranial atherosclerosis is a common cause of stroke, accounting for about 50% of ischaemic stroke in Asia and 8% in North America. Many prospective studies have confirmed that intracranial stenosis is an independent predictor for poor outcomes such as recurrent vascular event and death, despite the use of antiplatelet agents. The annual event rate is about 15% per year. The dismal outcome prompts the study of more aggressive treatment strategies, including warfarin and endovascular intervention. We have reviewed the published literature for the treatment of symptomatic intracranial stenosis. The Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial and Warfarin–Aspirin Recurrent Stroke Study (WARSS) studies failed to show that oral anticoagulation was better than aspirin in IAS. Initial encouraging results were found in the use of dual antiplatelet therapy in arresting the progression of stenosis. The results of the endovascular studies are mixed: there are more encouraging results with recent advances of technology in stent design, but a randomized controlled study is still lacking. Although there is still no established therapy for IAS, the results of ongoing randomized clinical trials to study dual antiplatelet agents and the use of endovascular intervention may soon provide clinicians with more evidence to better manage patients with this condition.

Background: Intracranial artery calcification is common but the prevalence and determinants are not well established. We aim to describe the prevalence and location of calcification in intracranial arteries according to brain multi-detector-row computed tomography (MDCT) images, and to investigate its correlation with potential risk factors. Methods: We studied consecutive men and women referred for brain CT in December 2004. All patients received a questionnaire regarding their medical history related to atherosclerosis, including traditional risk factors of atherosclerosis, serum chemistry values and inflammatory markers. All CT examinations were done with a 16-slice MDCT and the severity of intracranial artery calcification was categorized. Results: Four hundred and ninety patients aged 1.4–101 years (62.92 ± 19.04; mean ± SD) were included in our study. There were 340 patients (69.4%) who had intracranial artery calcification. The highest prevalence of intracranial artery calcification was seen in the internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Patients with calcification were significantly older than those without calcification (p < 0.001). A significantly higher prevalence of calcification was present among patients with hypertension (p < 0.001), diabetes (p < 0.001), renal failure (p < 0.05), atrial fibrillation (p < 0.05), smoking (p < 0.05), hyperlipidemia (p < 0.001), ischemic heart disease (p < 0.05) and ischemic stroke (p < 0.001). Mean values of serum phosphate, serum urea and CRP level were also significantly higher in patients with intracranial artery calcification (p < 0.05, respectively), and there was a trend that patients with intracranial calcification had a higher white blood cell count (p = 0.070). Stepwise multiple logistic regression showed age (RR = 2.795 per 10 years), a history of ischemic stroke (RR = 3.915), and white blood cell count (RR = 1.107) to be independently associated with intracranial artery calcification. Conclusions: Calcification of the intracranial arteries is associated with age, history of ischemic stroke and white blood cell count. Further prospective studies to investigate the clinical significance of intracranial artery calcification are needed.

Hyperhomocysteinemia is associated with cerebral small vessel disease (SVD). We examined the relationship between homocysteine and 1) volumetric measure of white matter change (WMC), 2) silent brain infarcts, 3) cerebral atrophy on MRI and 4) cognition on a consecutive cohort of patients with stroke associated with SVD.Fifty-seven patients consecutively admitted to the Acute Stroke Unit in a university hospital due to stroke associated with SVD were recruited and assessed three months after the stroke. Non-fasting homocysteine was obtained. Using MRI, the number of infarcts, volume of WMC and cerebral atrophy were measured. General cognitive functions were assessed using the Mini Mental State Examination and Alzheimer's disease Assessment Scale. Mattis Dementia Rating Scale - Initiation/Perseveration subset was used to assess executive cognitive functions.Hyperhomocysteinemia (or = 14.88 micromol/L) significantly accounted for the volume of WMC on MRI in a multivariate stepwise regression model (adjusted R(2)=0.058, p0.05) after adjustment for age and folate level. Patients in the highest quartile of WMC volume had significantly higher levels of homocysteine than those in lowest quartile (p0.001). No significant relationship was found between homocysteine and silent brain infarcts, cerebral atrophy and performance on psychometric tests.Hyperhomocysteinemia is associated with volumetric measure of WMC among patients with SVD. The role of homocysteine in the development of silent brain infarcts and cerebral atrophy as previously reported cannot be ascertained in this study. No direct relationship was found between homocysteine and cognitive functions.

Background and Purpose. Controversies still exist as to the neuroimaging determinants of cognitive impairment in cerebral small vessel disease (SVD). The authors studied the neuroimaging correlates of cognitive performances among patients with stroke associated with SVD. Methods. The authors per formed cerebral computed tomography, magnetic resonance imaging, and diffusion-weighted imaging among 74 consecu tive patients admitted to the acute stroke unit because of stroke associated with SVD. They examined the association between cognitive performances and the following neuroimaging features: volume of white matter changes (WMC), multiplicity of lacunae, location of lacunae, total cerebral atrophy, and frontal and medial temporal lobe atrophy. Results. Apart from age and education, univariate linear regression analyses revealed that WMC volume, presence of thalamic lacunae, cerebral atrophy, and left frontal lobe atrophy predicted performance on the Mini-Mental State Examination while WMC volume, presence of thalamic infarcts, cerebral atrophy, and frontal lobe atrophy of both sides predicted performance on the Mattis Dementia Rat ing Scale-Initiation/Preservation subscale. In the multivariate analyses, education (R2= 0.22, P < .001), left frontal lobe atrophy (R2= 0.10, P= .004), and presence of thalamic lacunae (R2= 0.04, P= .049) were found to predict performance on the Mini-Mental State Examination while age (R2= 0.23, P < .001) and presence of thalamic lacunae (R2= 0.08, P= .011) were found to predict performance on the Mattis Dementia Rating Scale-Initiation/Preservation. Conclusions. Among patients with stroke associated with SVD, thalamic lacunae and frontal lobe atrophy are key determinants of cognitive performances.

There have been no data on the performance of the Initiation-Perseveration subtest of the Mattis Dementia Rating Scale (MDRS-IP) in screening poststroke dementia (PSDE). Three months after the index stroke, a research assistant administered the MDRS-IP and Mini-Mental State Examination (MMSE) to 83 Chinese stroke patients with lacunar infarcts who were consecutively admitted to the stroke unit of a general hospital. A psychiatrist, who was blind to the MDRS-IP and MMSE scores, interviewed all 83 patients and made a Diagnostic and Statistical Manual of Mental Disorders (4th edition) diagnosis of dementia, which served as the benchmark for judging the performance of MDRSIP. The optimal cutoff point of MDRS-IP was 22/23. The sensitivity, specificity, and positive and negative predictive values of MDRS-IP, and the area under the receiver operating characteristic curve were 82%, 90%, 0.41, 0.98, and 0.91, respectively. The overall performance of the MDRS-IP was comparable to the MMSE. ( J Geriatr Psychiatry Neurol 2005;18:3-7)

Understanding the determinants of prestroke cognitive impairment (PCI) in stroke associated with small vessel disease (SVD) may shed light on how to prevent further cognitive deterioration after stroke. We administered the Informant Questionnaire on Cognitive Decline (IQCODE) to close informants of 78 consecutive stroke patients who had SVD. PCI, as defined by an average score of IQCODE ≧3.4 was found in 19 (24%) patients. Regression analyses were performed on the following risk factors for PCI: age, years of education, gender, previous stroke, volume of white matter changes, measures of silent lacunes, cerebral atrophy index, medial temporal lobe atrophy and frontal lobe atrophy. Multivariate regression analyses revealed that only cerebral atrophy index (OR 1.5, CI 1.2–1.9, p < 0.001) predicted PCI among patients with SVD.