Min-Yu Lan

Level and Value of Circulating Endothelial Progenitor Cells in Patients After Acute Ischemic Stroke

Background and Purpose— Endothelial progenitor cells (EPCs) migrate from bone marrow to systemic circulation in response to tissue ischemia where they differentiate into mature endothelial cells for angiogenesis in situ. This study tested the hypothesis that the level of circulating EPCs is substantially increased and predictive of prognostic outcomes after acute ischemic stroke (IS). Methods— The level of circulating EPCs (staining markers: CD31/CD34 [E1], CD62E/CD34 [E2], and KDR/CD34 [E3]) were examined using flow cytometry at 48 hours after acute IS in 138 consecutive patients. The EPC level was also evaluated once in 20 healthy volunteers and in 40 at-risk control subjects. Results— Level of circulating EPCs (E1–3) was significantly higher in patients with IS than in at-risk control subjects (P<0.05). Additionally, EPC (E1–3) level was significantly lower in patients with severe neurological impairment (defined as a score ≥12 on the National Institutes of Health Stroke Scale) than in patients with less severe impairment (National Institutes of Health Stroke Scale < score 12) at 48 hours after IS (P<0.0001). Moreover, the EPC (E3) level was strongly correlated with improved National Institutes of Health Stroke Scale ≥4 on day 21 after IS (P=0.0004). Furthermore, low circulating EPC level was independently predictive of severe neurological impairment (National Institutes of Health Stroke Scale ≥12) at 48 hours (E1–3) and combined major adverse clinical outcomes (defined as recurrent IS, any cause of death, or National Institutes of Health Stroke Scale of ≥12) on day 90 (E1) after IS (P<0.001). Conclusions— Level of circulating EPCs is independently predictive of prognosis after IS.

Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke

IntroductionErythropoietin (EPO) enhances the circulating level of endothelial progenitor cells (EPCs), which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. The aim of this study was to evaluate the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.MethodsIn total, 167 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or serve as placebo (group 2). The circulating level of EPCs (double-stained markers: CD31/CD34 (E1), CD62E/CD34 (E2) and KDR/CD34 (E3)) was determined using flow cytometry at 48 h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.ResultsCirculating EPC (E1 to E3) level at 48 h after IS was remarkably higher in patients than in control subjects (P < 0.02). At 48 h and on Day 7 after IS, EPC (E1 to E3) level did not differ between groups 1 and 2 (all P > 0.1). However, by Day 21, EPC (E1 to E3) level was significantly higher in group 1 than in group 2 (all P < 0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (P = 0.022). Multivariate analysis demonstrated that EPO therapy (95% confidence interval (CI), 0.153 to 0.730; P = 0.006) and EPC (E3) (95% CI, 0.341 to 0.997; P = 0.049) levels were significantly and independently predictive of a reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale ≥8, or death).ConclusionsEPO therapy significantly improved circulating EPC level and 90-day MANE.Trial registration numberISRCTN: ISRCTN96340690

Serial Changes in Platelet Activation in Patients After Ischemic Stroke Role of Pharmacodynamic Modulation

Background and Purpose— Enhanced platelet activity has previously been reported in the acute phase after ischemic stroke. We tested the hypothesis that activated platelets (expressed by CD62p) are substantially increased in the acute stage after a stroke and decrease thereafter, and that antiplatelet therapies can suppress CD62p expression. Methods— We serially examined platelet CD62p expression using flow cytometry after acute ischemic stroke in 87 consecutive patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33 at-risk control subjects. Results— CD62p expression was significantly higher in the acute phase after ischemic stroke than in normal and at-risk control subjects (both P < 0.0001). CD62p expression decreased to a significantly lower level on day 21, and to a substantially lower level on day 90. CD62p expression was not significantly suppressed by warfarin. However, CD62p expression was significantly suppressed by aspirin treatment (P = 0.024) and more substantially suppressed by clopidogrel (P < 0.0001) on day 90. Furthermore, only clopidogrel treatment (P = 0.0016) was significantly independently associated with decreased CD62p expression on day 90. Conclusions— Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy

Lan M‐Y, Fu M‐H, Liu Y‐F, Huang C‐C, Chang Y‐Y, Liu J‐S, Peng C‐H, Chen S‐S. High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy.

Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients.

BACKGROUND Homocysteine (Hcy) has been recognized as a risk factor for atherosclerosis. White matter hyperintensity (WMH) on MRI has been regarded as a hallmark for cerebral small vascular disease. The study is to investigate the relationship between plasma Hcy level and WMH on a hospital-based cohort of Taiwanese stroke patients. METHODS AND RESULTS A total of 352 consecutive stroke patients (64.7+/-11.2 years) were included. Severity of WMH was semi-quantitatively evaluated with a scoring system. The top WMH score tertile was defined as severe white matter change (sv-WMH). Associations between Hcy tertile levels and sv-WMH were examined, adjusting for demographics and atherosclerosis risk factors. Subjects in the top Hcy tertile (>10.25 micromol/L) had higher WMH scores and prevalence of sv-WMH than those in the middle and in the bottom tertile. The adjusted odds ratio of having sv-WMH was 2.04 (95% confidence interval 1.20-3.47, p=0.008) for the top Hcy level tertile than for the lower two tertiles combined. CONCLUSION Hcy is a risk factor for cerebral white matter lesion in stroke patients. Even mild hyperhomocysteinemia can significantly increase severity of cerebral microangiopathy.

Serum level and prognostic value of neopterin in patients after ischemic stroke.

BACKGROUND We hypothesized that serum level of neopterin is significantly predictive of prognostic outcome in patients after acute ischemic stroke (IS). METHODS Between November 2008 and May 2010, serum levels of neopterin were prospectively collected at 48 h after acute IS in 157 patients. RESULTS Serum neopterin levels were substantially higher in patients with severe neurological impairment [National institutes of Health Stroke Scale (NIHSS) score ≥12] than in those with NIHSS <12 (p<0.008). Furthermore, Spearmans test showed a strongly positive correlation between neopterin level and NIHSS (p=0.003). Multiple logistic regression analysis demonstrated that serum neopterin level was strongly and independently predictive of NIHSS ≥12 (p=0.002) at 48 h after acute IS and 90-day major adverse clinical outcome (defined as NIHSS≥12, recurrent stroke or death) (p=0.003). CONCLUSION Serum level of neopterin was notably increased after acute IS. This biomarker was strongly and independently predictive of 90-day unfavorable clinical outcome in patients after acute IS.

Botulinum toxin type A treatment for Parkinsonian patients with moderate to severe sialorrhea.

PURPOSE To investigate the effect of botulinum toxin type A (BTX-A; Botox) in reducing saliva in patients with Parkinsonism. METHODS Fifteen patients with clinical diagnosis of idiopathic Parkinsons disease, dementia with Lewy bodies, or multiple system atrophy were enrolled in this open clinical trial. A total of 40-unit dose of Botox was injected into the bilateral parotid and submandibular glands. Objective measuring of saliva production with dental rods, subjective Drooling Score, personal impression of clinical improvement, and the duration of response were used for the global assessment of sialorrhea after BTX-A treatment. RESULTS All patients showed objective reduction in saliva production following BTX-A treatment and the mean production was reduced at a significant level. The severity of sialorrhea assessed by Drooling Score was 5.87 +/- 0.92 (range: 5-8) and 3.60 +/- 1.18 (range: 2-6) respectively (p<0.001) before and after BTX-A injection. The mean duration of BTX-A response extended for 16.3 +/- 5.7 weeks (range: 5-24). No severe adverse effect nor worsening of existing dysphagia was observed in all Parkinsonian patients. CONCLUSIONS Parkinsonian drooling may undermine patients health and daily activity. BTX-A local injection is a safe and effective measure in counteracting sialorrhea, even in patients associated with moderate dysphagia.

Association between MIF gene polymorphisms and carotid artery atherosclerosis

Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA.

Association between cerebral microbleeds and prior primary intracerebral hemorrhage in ischemic stroke patients.

OBJECTIVE To investigate association between cerebral microbleeds (CMB) and prior intracerebral hemorrhage (ICH) on MRI and topographic correlation of the two types of lesions. PATIENTS AND METHODS Two hundred and sixty consecutive patients (67.0+/-11.1 years) with ischemic stroke were included. CMB and prior ICH were assessed on T2-gradient-echo MRI. The presence and number of CMB as predictors for prior ICH were examined. Topographic correlations between CMB and ICH lesions in patients with prior ICH in the infratentorial, basal ganglionic/thalamic and cortico-subcortical regions were tested. RESULTS CMB were observed in 113 (43.5%) patients and a total of 50 prior primary ICH lesions were observed in 39 (15.0%) patients. Among the ICH lesions, 39 (78%) were asymptomatic. Presence of CMB (odds ratio 2.53, p=0.015) and number of CMB (odds ratio 1.11, p<0.001) were independent determinants for prior ICH. Topographic correlation between CMB and ICH was significant in the basal ganglionic/thalamic region (p=0.017), but not in the infratentorial (p=0.548) or cortico-subcortical regions (p=0.389). CONCLUSION CMB were associated with prior ICH on MRI of patients with ischemic stroke. CMB in the basal ganglion or thalamus was associated with prior ICH in the same region.

Tetrodotoxin intoxication in a uraemic patient

Tetrodotoxin intoxication results from ingesting puffer fish or other animals containing the toxin. Clinical presentation is mainly acute motor weakness and respiratory paralysis. Death is common in the worst affected victims. Although the severity of the symptoms generally depends on the amount of toxin ingested, it may be influenced by the victim’s medical condition, as described in this report. The patient was a 52 year old uraemic woman. The uraemia was of undefined aetiology. Over the past 3 years she has received regular haemodialysis. One day both she and her husband, a healthy 55 year old man, ate a fish soup. About 4 hours after the meal she developed a headache and a lingual and circumoral tingling sensation and numbness at the distal parts of all four limbs. She was dizzy and unsteady, had difficulty in swallowing, and became very weak. She was taken to the emergency service and was placed on machine assisted ventilation as respiratory distress and cyanosis developed. Her husband remained asymptomatic throughout this time. Changes in the symptoms of poisoning in relation to each course of haemodialysis. Scales in the vertical axis represent the arbitrary measurements of severity of each …