Ji Man Hong

A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke.

We previously evaluated the short‐term follow‐up preliminary data of mesenchymal stem cells (MSCs) transplantation in patients with ischemic stroke. The present study was conducted to evaluate the long‐term safety and efficacy of i.v. MSCs transplantation in a larger population. To accomplish this, we performed an open‐label, observer‐blinded clinical trial of 85 patients with severe middle cerebral artery territory infarct. Patients were randomly allocated to one of two groups, those who received i.v. autologous ex vivo cultured MSCs (MSC group) or those who did not (control group), and followed for up to 5 years. Mortality of any cause, long‐term side effects, and new‐onset comorbidities were monitored. Of the 52 patients who were finally included in this study, 16 were the MSC group and 36 were the control group. Four (25%) patients in the MSC group and 21 (58.3%) in the control group died during the follow‐up period, and the cumulative surviving portion at 260 weeks was 0.72 in the MSC group and 0.34 in the control group (log‐rank; p = .058). Significant side effects were not observed following MSC treatment. The occurrence of comorbidities including seizures and recurrent vascular episodes did not differ between groups. When compared with the control group, the follow‐up modified Rankin Scale (mRS) score was decreased, whereas the number of patients with a mRS of 0–3 increased in the MSC group (p = .046). Clinical improvement in the MSC group was associated with serum levels of stromal cell‐derived factor‐1 and the degree of involvement of the subventricular region of the lateral ventricle. Intravenous autologous MSCs transplantation was safe for stroke patients during long‐term follow‐up. This therapy may improve recovery after stroke depending on the specific characteristics of the patients. Stem Cells 2010;28:1099–1106

Ischemic Stroke in Cancer Patients With and Without Conventional Mechanisms. A Multicenter Study in Korea

Background and Methods— To assess the precise mechanisms of stroke in cancer patients, we analyzed the data for cancer patients with acute ischemic stroke registered from 6 centers in South Korea. Clinical features, risk factors, diffusion-weighted imaging lesion patterns, and laboratory findings including d-dimer levels were compared between patients with conventional stroke mechanisms (CSMs) and cryptogenic group. Results— A total of 161 patients were included in this study: 97 (60.2%) patients in the CSM group and 64 (39.8%) in the cryptogenic group. Patients in the CSM group were older and vascular risk factors were more prevalent than in the cryptogenic group. Diffusion-weighted imaging patterns of multiple lesions involving multiple arterial territories were observed more frequently in the cryptogenic group than in the CSM group. In addition, levels of the d-dimer were higher in the cryptogenic group than in the CSM group (11.5±14.6 versus 3.6±10.3 &mgr;g/dL). In multivariate analysis, the diffusion-weighted imaging lesion pattern of multiple vascular territories (odds ratio, 11.2; 95% CI, 3.74 to 33.3), and d-dimer levels of >1.11 &mgr;g/dL (odds ratio, 10.6; 95% CI, 3.29 to 33.8) were associated independently with the cryptogenic group. Conclusions— Stroke outside of CSM occurred in a large number in cancer patients. In stroke patients with cancer, d-dimer levels and diffusion-weighted imaging lesion patterns may be helpful in early identification of non-CSMs (especially coagulopathy associated with cancer) and possibly in guiding preventive strategies for stroke.

Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts

Objectives: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. Methods: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The “dominant” VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. Results: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). Conclusions: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.

Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes

Background Cancer and ischemic stroke are two of the most common causes of death among the elderly, and associations between them have been reported. However, the main pathomechanisms of stroke in cancer patients are not well known, and can only be established based on accurate knowledge of the characteristics of cancer-related strokes. We review herein recent studies concerning the clinical, laboratory, and radiological features of patients with cancer-related stroke. Main Contents This review covers the epidemiology, underlying mechanisms, and acute and preventive treatments for cancer-related stroke. First, the characteristics of stroke (clinical and radiological features) and systemic cancer (type and extent) in patients with cancer-specific stroke are discussed. Second, the role of laboratory tests in the early identification of patients with cancer-specific stroke is discussed. Specifically, serum D-dimer levels (as a marker of a hypercoagulable state) and embolic signals on transcranial Doppler (suggestive of embolic origin) may provide clues regarding changes in the levels of coagulopathy related to cancer and anticoagulation. Finally, strategies for stroke treatment in cancer patients are discussed, emphasizing the importance of preventive strategies (i.e., the use of anticoagulants) over acute revascularization therapy in cancer-related stroke. Conclusion Recent studies have revealed that the characteristics of cancer-related stroke are distinct from those of conventional stroke. Our understanding of the characteristics of cancer-related stroke is essential to the correct management of these patients. The studies presented in this review highlight the importance of a personalized approach in treating stroke patients with cancer.

A Computerized In-Hospital Alert System for Thrombolysis in Acute Stroke

Background and Purpose— An effective stroke code system that can expedite rapid thrombolytic treatment requires effective notification/communication and an organized team approach. We developed a stroke code program based on the computerized physician order entry (CPOE) system and investigated whether implementation of this CPOE-based program is useful for reducing the time from arrival at emergency departments (ED) to evaluation steps and the initiation of thrombolytic treatment in various hospital settings. Methods— The CPOE-based program was implemented by 10 hospitals. Time intervals from arrival at the ED to blood tests, computed tomography scanning, and thrombolytic treatment during the 1-year period before and the 1-year period after the program implementation were compared. Results— Time intervals from ED arrival to evaluation steps were significantly reduced after implementation of the CPOE-based program. Times from ED arrival to CT scan, complete blood counts, and prothrombin time testing were reduced by 7.7 minutes, 5.6 minutes, and 26.8 minutes, respectively (P<0.001). The time from ED arrival to intravenous thrombolysis was reduced from 71.7±33.6 minutes to 56.6±26.9 minutes (P<0.001). The number of patients who were treated with thrombolysis increased from 3.4% (199/5798 patients) before the CPOE-based program to 5.8% (312/5405 patients) afterward (P<0.001). The CPOE implementation also improved the inverse relationship between onset-to-door time and door-to-needle time. Conclusions— The CPOE-based stroke code could be successfully implemented to reduce in-hospital time delay in thrombolytic therapy in various hospital settings. CPOE may be used as an efficient tool to facilitate in-hospital notification/communication and an organized team approach.

Chronic cerebral hypoperfusion in a mouse model of Alzheimer's disease: an additional contributing factor of cognitive impairment.

The purpose of the present study was to evaluate whether chronic cerebral hypoperfusion would affect cognitive status in an Alzheimer mouse model. Behavioral tests and histological evaluations were performed using female Tg2576 mice eight weeks after right common carotid artery occlusion (rCCAO), which is known to induce a type of vascular dementia without neuronal necrosis in nontransgenic mice. Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was utilized to evaluate metabolic status in the rCCAO-operated brain of nontransgenic mice. Escape latency from the Morris water maze test was not significantly different between rCCAO- and sham-operated mice. However, the learning curve was impaired in rCCAO-operated transgenic mice while it was preserved in sham-operated transgenic or rCCAO-operated nontransgenic mice. Histological examination revealed no evidence of cell death in the rCCAO-operated brains, and the extent of amyloid deposition was not different in rCCAO- and sham-operated mice. The brain of rCCAO-operated mice showed metabolic deficits in the ipsilateral parietal cortex through FDG-PET. In conclusion, further cognitive decline which is more comparable to typical Alzheimers disease was induced by chronic cerebral hypoperfusion in an Alzheimer mouse model. This aggravation might be associated with hypometabolism via chronic cerebral hypoperfusion.

Olfactory function and neuropsychological profile to differentiate dementia with Lewy bodies from Alzheimer's disease in patients with mild cognitive impairment: A 5-year follow-up study

BACKGROUND Mild cognitive impairment (MCI) is a well-known precursor of Alzheimers disease (AD) but often also precedes dementia with Lewy bodies (DLB). The early differentiation of DLB from AD is important to delay disease progression. Olfactory dysfunction is a well-known early sign of both AD and Lewy body disorders, including Parkinsons disease (PD) and DLB. Thus, the aim of the present study was to determine whether olfactory and neuropsychological tests can aid in the differentiation of DLB from AD at the MCI stage. METHODS The present study included 122 MCI patients who were monitored until they developed dementia or until their condition stabilized; the follow-up period averaged 4.9 years (range: 3.9-6.2 years). Baseline olfactory function as measured with the Cross-Cultural Smell Identification (CCSI) test and neuropsychological data were compared. RESULTS During the follow-up period, 32 subjects developed probable AD (MCI-AD), 18 had probable DLB (MCI-DLB), 45 did not convert to dementia (MCI-stable), and eight developed a non-AD/DLB dementia. The mean CCSI score (95% confidence interval [CI]) in patients with MCI-DLB (4.6; 95% CI: 4.0-5.3) was significantly lower than that of MCI-AD patients (6.4; 95% CI: 6.0-6.7, p<0.001) and MCI-stable patients (7.3; 95% CI: 6.9-7.8, p<0.001). The area under the curve of the receiver operating characteristic to discriminate MCI-DLB from MCI-AD using CCSI scores was (0.84; 95% CI: 0.72-0.97). Frontal-executive function and visuospatial ability was worse in patients with MCI-DLB, while verbal recognition memory impairment was greater in those with MCI-AD. CONCLUSION Olfactory and neuropsychological tests can help predict conversion to DLB or AD in patients with MCI.

Conventional enhancement CT: a valuable tool for evaluating pial collateral flow in acute ischemic stroke.

Background: To establish an easy and rapid method for evaluating pial collateral flow, we compared the Alberta Stroke Program Early CT Score (ASPECTS) on nonenhanced CT (NECT), conventional contrast-enhanced CT (CECT), and CT angiography source images (CTA-SI) in patients with acute ischemic stroke. Methods: We reviewed 55 consecutive patients with acute ischemic stroke involving the anterior circulation who underwent thrombolysis within 6 h of referral to the stroke center. We evaluated axial images using NECT, CECT and CTA-SI. Pial collateral formation was graded as fair (1–2 points) or bad (3–5 points) based on 4-vessel angiography. The outcomes were dichotomized into good (modified Rankin Scale, mRS 0–2) or poor (mRS 3–6) using a 90-day mRS. Results: Demographics (age, sex, initial National Institutes of Health Stroke Scale score, time to CT acquisition and stroke subtypes) did not significantly differ between patients with fair or bad collateral formation. ASPECTS on CECT (r = –0.788, p < 0.0001) was more inversely correlated with pial collateral formation than ASPECTS on NECT (r = –0.557, p < 0.0001) or ASPECTS on CTA-SI (r = –0.662, p < 0.0001). Furthermore, ASPECTS on CECT demonstrated a high discriminative capability, with an area under the receiver operating characteristic curve of 0.885 for fair collateral circulation, compared to 0.790 for ASPECTS on NECT and 0.794 for ASPECTS on CTA-SI. Multiple regression analysis revealed that ASPECTS on CECT (≧8) was an independent predictor for fair collateral circulation (odds ratio = 23.00, p < 0.001) and a good prognosis (odds ratio = 17.81, p < 0.001). Conclusion: ASPECTS on CECT is a feasible method for predicting pial collateral flow and overall outcomes in acute ischemic stroke.

Influence of Recanalization on Uric Acid Patterns in Acute Ischemic Stroke

Background: Most epidemiological studies have reported a significant association between elevated serum levels of uric acid (UA) and increased cardiovascular disease. On the other hand, UA is the most abundant antioxidant in the human body. We hypothesized that UA levels would change noticeably in association with the degree of oxidative stress in acute ischemic stroke. Methods: We analyzed consecutive patients with acute ischemic stroke in the anterior circulation system within 24 h of symptom onset, confirmed by diffusion-weighted imaging (DWI), and with a modified NIH Stroke Scale (mNIHSS) score of 5 or greater. Baseline demographics, serial clinical scores, serial UA and allantoin (a nonenzymatic metabolite of UA) levels, UA change (baseline UA – UA at 48 h), and DWI lesion volumes were compared between 45 patients with recanalized vessels (RV) and 43 patients with nonrecanalized vessels (NV) in follow-up imaging. Results: The RV (vs. NV) patients were more likely to receive thrombolytic treatment (p = 0.005), achieve a reduction in day-14-mNIHSS scores (p = 0.001), and greater changes in UA (p = 0.024) and allantoin levels (p = 0.003). The UA levels dropped at 48 h and gradually increased in a U-shaped pattern. UA change (r = 0.360; p = 0.001) rather than baseline UA (r = 0.044; p = 0.681) was significantly correlated with infarct volume. In the RV (vs. NV) patients, there was a stronger association between infarct volume and UA change (r = 0.483; p = 0.001) or allantoin levels (r = 0.466; p = 0.017). Conclusion: Our results suggest that UA might be a consumptive and reproducible antioxidant in acute ischemic stroke, and this pattern appears to be influenced by recanalization success and infarct volume size.

Primary Stent Retrieval for Acute Intracranial Large Artery Occlusion Due to Atherosclerotic Disease

Background and Purpose The goal of stent retriever–based thrombectomy is removal of embolic clots in patients with intracranial large artery occlusion. However, outcomes of stent retrieval may differ between acute arterial occlusions due to intracranial atherosclerotic disease (IAD) and those due to embolism. This case series describes the outcomes of stent retriever–based thrombectomy and rescue treatments in 9 patients with IAD-related occlusion. Methods Among patients who underwent endovascular treatment for acute intracranial large artery occlusion, those in whom stent retrieval was attempted as first-line treatment were included in this review. IAD was defined as significant fixed focal stenosis at the occlusion site, which was evident on final angiographic assessment or observed during endovascular treatment. Results Median number of stent retriever passes was 2 (range, 1-3), and temporary bypass was seen in all patients. Immediate partial recanalization (arterial occlusive lesion grade 2-3) was observed in 7 patients. Immediate modified thrombolysis in cerebral infarction grade 2b-3 was seen in 6 patients, but the lesions often required rescue treatment due to reocclusion or flow insufficiency. In terms of rescue treatments, angioplasty and intra-arterial tirofiban infusion seemed to be effective. Conclusions Our findings suggest that stent retrieval can effectively remove thrombi from stenotic lesions and achieve partial recanalization despite the tendency toward reocclusion in most patients with IAD-related occlusion. Further research into the use of rescue treatments, such as tirofiban infusion and angioplasty, is warranted.