Yeu-Jhy Chang

Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles.

We investigated the feasibility and efficacy of target thrombolysis with recombinant tissue plasminogen activator (rtPA) covalently bound to magnetic nanoparticle (MNP) and retained to the target site in vivo by an external magnet. Polyacrylic acid-coated magnetite (PAA-MNP, 246 nm) was synthesized and characterized; rtPA was immobilized to PAA-MNP through carbodiimide-mediated amide bond formation. The enzyme activities of the bound rtPA, as measured by a chromogenic substrate assay and (125)I-fibrinolysis assay, were 87+/-1% and 86+/-3% of that of free rtPA. Under guidance with the magnet moving back and forth along the iliac artery, the thrombolytic activity of PAA-MNP-rtPA with rtPA equivalent to 0.2mg/kg was determined by flowmetry in a rat embolic model. Intra-arterial administration of PAA-MNP-rtPA restored the iliac blood flow within 75 min to 82% of that before the clot lodging, whereas equivalent amount of PAA-MNP or free rtPA exerted no improvement on hemodynamics. At the end of 2-h period, PAA-MNP-rtPA did not alter levels of hemoglobin, hematocrit, or blood cell count. In conclusion, immobilization of rtPA to PAA-MNP with covalent binding resulted in a stable rtPA preparation and predictable amount of rtPA around the target site under magnetic guidance; this approach may achieve reproducible and effective target thrombolysis with <20% of a regular dose of rtPA.

Spinal Cord Infarction in Chinese Patients

Background: The clinical presentations, MRI findings and outcomes for spinal cord infarction (SCI) are well documented in the West but scarce in the East. We investigated the clinical characteristics of SCI patients and further analyzed etiologies and prognostic factors in Chinese subjects. Methods: We reviewed all SCI patients from March 1993 to March 2007. Clinical symptoms, laboratory and imaging findings as well as outcomes were retrospectively analyzed. Results: Twenty-two patients (12 female) were identified; their mean age was 57.6 years. Nine patients (40.9%) had probable etiologies, while 13 were cryptogenic (59.1%). The primary etiologies were aortic diseases. Hypertension was the most common vascular risk factor (50%). Most patients (10/22 = 45.5%) had thoracolumbar lesions (mainly at T9–L1), while cervical lesions (9/22 = 40.9%) were the second most common (mainly at C4–C7). ‘Owl’s eyes’ signs were common with the anterior spinal artery (93.8%) and central cord infarctions (50%) but not in the posterior spinal artery or transverse spinal infarctions. After a mean follow-up of 18 months, only 10 patients (10/22 = 45%) had good outcomes (independent walking or walking with 1 aid). Conclusion: Most SCI patients had acute, monophasic symptoms, reaching nadir in <24 h. The subjects frequently had acute pain near their lesions before SCI signs/symptoms (16/22 = 72.7%). Initial severe weakness (Medical Research Council score ≤2) and a young age at onset (55 years old) are correlated with poor recovery of motor functions.

Predictors of carotid artery stenosis after radiotherapy for head and neck cancers

OBJECTIVE To study the prevalence of and risk factors associated with carotid artery stenosis (CAS) after radiotherapy (RT) for head and neck cancer. METHODS DESIGN OF STUDY Prospective, cross-sectional study. SETTING Patients recruited from a hospital Radiation-Oncology department. SUBJECTS From March 2002 to August 2006, 290 consecutive head and neck cancer patients were enrolled in this study. One hundred ninety-two of these patients had previously undergone RT (RT group) and 98 had no RT (control group). INTERVENTION After detecting CAS by carotid duplex sonography, the severity of CAS was evaluated by a bilateral plaque scoring system. MAIN OUTCOME MEASURE CAS score. RESULTS There were no differences in age or gender between the two groups. The RT group had a significantly higher plaque score than the non-irradiated group (P < .05). Multiple regression analysis of the 290 head and neck cancer patients revealed that bilateral plaque score was significantly correlated with age, hyperlipidemia, and RT. Multiple regression analysis was performed in the RT group alone with patients 41-50 years old serving as the reference group. This analysis showed that in RT patients > 50 years old, age was inversely correlated with plaque score; however, in RT patients <or= 41 years old, age was positively correlated with plaque score. CONCLUSION In head and neck cancer, the high post-treatment incidence of radiation-induced CAS indicates the importance of regular examination of the carotid duplex and early antiplatelet prophylaxis. Different age groups may require different irradiation strategies to prevent radiation-induced CAS.

Dose Titration to Reduce Dipyridamole-Related Headache

Background: Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance. Methods: This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1–28), reduced dose (placebo on days 1–4, ASA+MR-DP once daily before bed during days 5–14, and b.i.d. on days 15–28), and regular dose (placebo on days 1–4, and ASA+MR-DP b.i.d. on days 5–28). Using Chinese diary card, headache was assessed as mean cumulated headache (Σ frequency × intensity/occurrence days × study days) over the study period, and was graded 0–4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0. Results: Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5–14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant. Conclusions: Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache.

Carotid Artery Stenosis in Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation

Purpose: To study the prevalence, severity and clinical relevance of carotid atherosclerosis in ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). Material and Methods: We reviewed carotid duplex sonography, computed tomography (CT) and clinical features in 103 consecutive ischemic stroke patients with NVAF. Both sonography and CT were performed within 3–7 days after stroke. There were 64 men and 39 women with a mean age at stroke onset of 69 years. Results: High-grade (≧50%) stenosis of the extracranial carotid artery was detected in 25 patients (24.3%), including 11 patients (10.6%) with internal carotid artery (ICA) occlusion. In 15 (66.7%) of the patients who had high-grade carotid stenosis, the lesion was ipsilateral to the infarct, including 8 ICA occlusions. Patients with high-grade stenosis smoked more cigarettes (p < 0.05) and had more peripheral vascular diseases (p < 0.05). Besides NVAF, all patients had more than one vascular risk factor. The clinical presentations (transient ischemic attacks, minor or major strokes) showed no significant difference between the groups of <50% and ≧50% stenosis. Clinical outcome was worse (dead and totally dependent in daily activities) in the group of high-grade stenosis (p < 0.05). Patients with high-grade carotid stenosis showed more cortical infarcts on cerebral CT (p < 0.01). Six out of 7 patients with a hemorrhagic transformation on the initial cerebral CT were in the low-grade carotid stenosis group, though this was statistically insignificant. Conclusions: Ischemic stroke with NVAF is not always cardiogenic. High-grade stenosis of the extracranial carotid artery is found in one fourth of ischemic stroke patients with NVAF and is related to more cortical infarction and worse clinical outcome. We speculate that ischemic stroke patients with NVAF who have high-grade carotid stenosis are less likely to develop hemorrhagic infarct. The pathogenesis of cerebral infarction and the therapeutic strategy in this clinical condition are complicated by the coexistence of carotid arterial lesions and cardiac disease.

Recommendations for the Management of Intracranial Haemorrhage – Part I: Spontaneous Intracerebral Haemorrhage

This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European s

Amyloid deposition after cerebral hypoperfusion: Evidenced on [18F]AV-45 positron emission tomography

Animal studies have shown that cerebral hypoperfusion may be associated with amyloid plaque accumulation. Amyloid plaque is known to be associated with dementia and [(18)F]AV-45 is a positron emission tomography (PET) ligand that binds to extracelluar plaques. We hypothesized that demented patients with cerebral hypoperfusion may have increased [(18)F]AV-45 uptake. Five demented patients with cerebral hypoperfusion due to unilateral carotid artery stenosis (CAS) were examined with [(18)F]AV-45 PET, and the results were compared with six elderly controls. The standard uptake value ratio (SUVR) of each region of interest (ROI) was created using whole cerebellum as the reference region. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. Patients with dementia and unilateral CAS had a higher global [(18)F]AV-45 SUVR (1.34 ± 0.06) as compared with controls (1.10 ± 0.04, p=0.0043), especially over the frontal, temporal, precuneus, anterior cingulate and occipital regions. The statistical distribution maps revealed a significantly increased [(18)F]AV-45 SUVR in the medial frontal, caudate, thalamus, posterior cingulate, occipital and middle and superior temporal regions ipsilateral to the side of CAS (p<0.01). The present study found that cerebral [(18)F]AV-45 binding is increased in demented patients with CAS, and its distribution is lateralized to the CAS side, suggesting that amyloid-related dementia may occur under cerebral hypoperfusion.

Rapid progression and brain atrophy in anti-AMPA receptor encephalitis

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is an anti-neuronal surface antigen autoimmune encephalitis that is rarely reported. Our study evaluated the first known patient who developed anti-AMPA receptor encephalitis during pregnancy. Initial brain MRI revealed bilateral limbic encephalitis. However, rapid brain atrophy on MRI with extensive hypometabolism of cerebral cortices, caudate nuclei and brain stem hypoperfusion on (18)F-FDG PET developed when clinically progressed. IgG index of serial CSF studies reflected the clinical improvements after plasmapheresis and plasma exchange. The clinical spectrum of anti-AMPA receptor encephalitis may be expanded from limited limbic involvement to extended central nervous system.

Establishment of Electronic Chart-based Stroke Registry System in a Medical System in Taiwan

To establish a prospective, real-time, self-sustainable stroke registry system, we incorporated a registry with an electronic chart to create an electronic chart-based stroke registry system in November 2006. The International Classification of Diseases Ninth Revision code (430-437) was used to auto-enroll stroke patients admitted to neurology departments. Clinical information was written by doctors, nursing information was recorded by nurses, and basic patient information was entered by administrative departments. Numerical data and the date and time of any studies were auto-downloaded from the hospital computer. In total, 212 items were auto-downloaded, including basic patient information, laboratory blood test and examination results, and the date and time of imaging and special intervention. The stroke scales (121 items, National Institutes of Health Stroke Scale, Barthel index, and modified Rankin scale) were designed to be auto-adjusted to reduce incompatibility. The 95 items with pull-down options were used to specify the contents. This registry system can be time-, labor- and money-saving with secured data accuracy.

Carotid floating plaques associated with multiple cerebral embolic strokes. Case reports.

The authors describe 2 patients with multiple cerebral infarcts and hemorrhagic trans formation caused by artery-to-artery emboli. Ulcerated plaques with free-floating thrombus adherent to the plaque were detected at the carotid bifurcation by duplex sonography. No other embolic source could be found. One patient developed an occipital infarction due to carotid emboli passing through a fetal-type posterior communicating artery. Both patients recovered well without recurrence of stroke or transient ischemic attack with antiplatelet treatment only. Follow-up carotid duplex sonography showed disappearance of floating thrombus in 1 patient and consolidation of the lesion in the other.