Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Association between Brain-Derived Neurotrophic Factor and Lipid Profiles in Acute Ischemic Stroke Patients.

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55-90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187-3.051) for TG/HDL-C, 1.975 (95% CI: 1.188-3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113-3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003-1.030) and 0.926 (95% CI: 0.876-0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations.

Patient and hospital characteristics associated with do-not-resuscitate/do-not-intubate orders: a cross-sectional study based on the Taiwan stroke registry.

BACKGROUND: Previous studies of do-not-resuscitate (DNR) or do-not-intubate (DNI) orders in stroke patients have primarily been conducted in North America or Europe. However, characteristics associated with DNR/DNI orders in stroke patients in Asia have not been reported. METHODS: Based on the Taiwan Stroke Registry, this nationwide cross-sectional study enrolled hospitalized stroke patients from 64 hospitals between 2006 and 2020. We identified characteristics associated with DNR/DNI orders using a two-level random effects model. RESULTS: Among the 114,825 patients, 5531 (4.82%) had DNR/DNI orders. Patients with acute ischemic stroke (AIS) had the highest likelihood of having DNR/DNI orders (adjusted odds ratio [aOR] 1.76, 95% confidence interval [CI] 1.61-1.93), followed by patients with intracerebral hemorrhage (ICH), and patients with subarachnoid hemorrhage (SAH) had the lowest likelihood (aOR 0.53, 95% CI 0.43-0.66). From 2006 to 2020, DNR/DNI orders increased in all three types of stroke. In patients with AIS, women were significantly more likely to have DNR/DNI orders (aOR 1.23, 95% CI 1.15-1.32), while patients who received intravenous alteplase had a lower likelihood (aOR 0.74, 95% CI 0.65-0.84). Patients with AIS who were cared for by religious hospitals (aOR 0.55, 95% CI 0.35-0.87) and patients with SAH who were cared for by medical centers (aOR 0.40, 95% CI 0.17-0.96) were significantly less likely to have DNR/DNI orders. CONCLUSIONS: In Taiwan, DNR/DNI orders increased in stroke patients between 2006 and 2020. Hospital characteristics were found to play a significant role in the use of DNR/DNI orders.

Brain-Derived Neurotrophic Factor (BDNF) and Translocator Protein (TSPO) as Diagnostic Biomarkers for Acute Ischemic Stroke.

Brain-derived neurotrophic factor (BDNF) interacts with tropomyosin-related kinase B (TrkB) to promote neuronal growth, survival, differentiation, neurotransmitter release, and synaptic plasticity. The translocator protein (TSPO) is known to be found in arterial plaques, which are a symptom of atherosclerosis and a contributory cause of ischemic stroke. This study aims to determine the diagnostic accuracy of plasma BDNF and TSPO levels in discriminating new-onset acute ischemic stroke (AIS) patients from individuals without acute ischemic stroke. A total of 90 AIS patients (61% male, with a mean age of 67.7 ± 12.88) were recruited consecutively in a stroke unit, and each patient was paired with two age- and gender-matched controls. The sensitivity, specificity, and area of the curve between high plasma BDNF and TSPO and having AIS was determined using receiver operating characteristic curves. Furthermore, compared to the controls, AIS patients exhibited significantly higher levels of BDNF and TSPO, blood pressure, HbA1c, and white blood cells, as well as higher creatinine levels. The plasma levels of BDNF and TSPO can significantly discriminate AIS patients from healthy individuals (AUC 0.76 and 0.89, respectively). However, combining the two biomarkers provided little improvement in AUC (0.90). It may be possible to use elevated levels of TSPO as a diagnostic biomarker in patients with acute ischemic stroke upon admission.

Progressive encephalomyelitis with rigidity: A Taiwanese case and review of literature.

INTRODUCTION: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disorder. However, the outcome is still variable with different serological and tumor associations, and the elements to good response with less relapse is yet to be elucidated. METHOD: We present a case and obtain a literature review of patients with PERM and make comparisons based on different serological groups. We also analyze patients with idiopathic PERM that had detailed medical records. RESULTS: 81 patients were collected and analyzed. The largest group were glycine receptor-antibody (GlyR-Ab)-positive (70%), and the seropositive-GlyR-Ab-negative group had better response to immunotherapy. Malignancy can occur up to 2 years from the presentation of PERM. Among the 18 cases with detailed records, the patients who had good outcome initiate immunotherapy within 2 months from presentation. 9 of the 12 patients who experienced no relapse had non-steroid immunotherapy. The maximal interval time of relapse was 24 months. CONCLUSION: We recommend tumor surveillance up to 2 years in patients with PERM and early administration of immunotherapies and maintain with non-steroid immunotherapy with or without oral corticosteroid for a minimum of 2 years to reduce the risk of relapse in GlyR-Ab-positive patients.

Prognostic impact of renal dysfunction on embolic stroke of undetermined source-Role beyond CHA2 DS2 -VASc score: Results from Taiwan Stroke Registry.

BACKGROUND AND PURPOSE: The CHA2 DS2 -VASc score has immense prognostic value in patients with embolic stroke of undetermined source (ESUS). We aimed to determine the usefulness of advanced renal dysfunction and its addition to the CHA2 DS2 -VASc score in improving predictive accuracy. METHODS: In total, 3775 ESUS patients were enrolled from a nationwide hospital-based prospective study. Advanced renal dysfunction was defined as estimated glomerular filtration rate <30 ml/min per 1.73 m2 or patients under dialysis. Clinical outcomes included recurrent stroke and 1-year all-cause mortality. Poor functional outcome was defined as a modified Rankin Scale >2 at first-, third-, and sixth-month post-stroke. The renal (R)-CHA2 DS2 -VASc score was derived by including advanced renal dysfunction in the CHA2 DS2 -VASc score. Risk stratification improvement after including advanced renal dysfunction was assessed using C statistic, integrated discrimination improvement (IDI), and category-free net reclassification index (NRI). RESULTS: After adjusting for confounding factors and CHA2 DS2 -VASc score, advanced renal dysfunction showed significant associations with all-cause mortality (HR: 2.88, 95% CI: 1.92-4.34) and poor functional outcome at third- (OR: 2.69, 95% CI: 1.47-4.94) and sixth-month post-stroke (OR: 2.67, 95% CI: 1.47-4.83). IDI and NRI showed that incorporating advanced renal dysfunction significantly improved risk discrimination over the original CHA2 DS2 -VASc score. R-CHA2 DS2 -VASc score ≥2 increased risk by 1.94-fold (95% CI: 1.15-3.27) for all-cause mortality, and ≥4 increased risk by 1.62-fold (95% CI: 1.05-2.50) of poor functional outcome at third-month post-stroke and by 1.81-fold (95% CI: 1.19-2.75) at sixth-month post-stroke. CONCLUSIONS: Advanced renal dysfunction was significantly associated with clinical and functional outcomes in ESUS patients and may improve prognostic impact of the CHA2 DS2 -VASc score.

Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan.

Objective: Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy ( CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. Methods: This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Results: Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1-3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67-12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03-35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26-12.92) were significantly associated with p.R544C. Interpretation: p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.

Plasma Translocator Protein Levels and Outcomes of Acute Ischemic Stroke: A Pilot Study.

Translocator protein 18 kDa (TSPO) has been used as a biomarker of brain injury and inflammation in various neurological diseases. In this study, we measured the level of TSPO in acute ischemic stroke patients and determined its association with the degree of stroke severity and its ability to predict stroke functional outcomes. In total, 38 patients with moderate to severe acute ischemic stroke were enrolled. Demographic information, cerebral risk factors, and stroke severity were examined at the baseline. The National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthal Index were assessed at discharge as measures of poor functional outcomes and severe disability. The baseline fasting plasma TSPO level was assessed within 24 h after the incident stroke and during hospitalization (on days 8-10). The proportion of patients with poor functional outcomes was significantly higher in the higher-TSPO group (compared to the lower group) in terms of clinical worsening (odds ratio (OR) = 11.69, 95% confidence interval (CI) = 2.08-65.6), poor functional outcomes (OR = 10.5, 95% CI = 1.14-96.57), and severe disability (OR = 4.8, 95% CI = 1.20-19.13). Plasma TSPO may be intimately linked with disease progression and worse functional outcomes in acute ischemic stroke patients.

10-Point CT-ASPECTS-based reperfusion therapy for unknown onset stroke.

Under the time-based criteria, patients with unknown onset stroke (UOS) are ineligible for reperfusion therapies. However, previous studies suggest that some patients with UOS may benefit from reperfusion. Several imaging modalities have been suggested to select patients for intervention, but the optimal imaging criteria are still controversial. Herein we present a series of four cases using 10-point CT-ASPECTS to support our decision of reperfusion therapy. We decided based on history, symptoms, and the 10-point CT-ASPECTS alone. Each patient's history suggested that the stroke just took place. All four patients had apparent clinical symptoms, with 10-point CT-ASPECTS. All of them had a reduction in their NIHSS after the reperfusion therapy. 10-point CT-ASPECTS could be used to support the presumption that the stroke just happens in patients with UOS. Further study is warranted to elucidate the value of CT-ASPECTS for UOS patients.

Significant Association Between Low Mitochondrial DNA Content in Peripheral Blood Leukocytes and Ischemic Stroke.

BACKGROUND: Cumulative evidence has shown that low mitochondrial DNA (mtDNA) content is related to elevated oxidative stress and atherosclerosis, which play important roles in ischemic stroke. The objective of this study was to explore the association between mtDNA content in peripheral blood leukocytes and ischemic stroke. METHODS AND RESULTS: A total of 350 patients with first-ever ischemic stroke and 350 healthy controls were recruited in this case-control study. The mtDNA content in peripheral blood leukocytes was determined by quantitative real-time polymerase chain reaction. The levels of oxidized glutathione, reduced glutathione, and 8-hydroxy-2'-deoxyguanosine were measured by ELISA kits. Multivariate logistic regression models were used to analyze the relationship between mtDNA content in peripheral blood leukocytes and ischemic stroke. Our results show that mtDNA content of patients with ischemic stroke was notably lower compared with controls. A significant association was found between low mtDNA content and ischemic stroke. Furthermore, significant interactions were identified between low mtDNA and proven risk factors in patients with ischemic stroke. The levels of oxidized glutathione and 8-hydroxy-2'-deoxyguanosine were significantly greater in patients with ischemic stroke compared with controls. CONCLUSIONS: Our results demonstrate that low mtDNA content in peripheral blood leukocytes is associated with ischemic stroke. The relationship of low mtDNA content and ischemic stroke was particularly notable in individuals who had low mtDNA content combined with diabetes mellitus, metabolic syndrome, or cigarette smoking. Oxidative stress may be one of the contributory factors to decreased mtDNA content in patients with ischemic stroke.

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients.

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Beneficial effects of prolonged blood pressure control after carotid artery stenting.

OBJECTIVES: The main purpose of this study was to investigate whether carotid artery stenting (CAS) plus medicine in patients with severe carotid artery stenosis provide a better long-term blood pressure (BP) control compared to other medical treatments alone. The other aim was to explore the correlation between post-CAS hypotension within 6 h and long-term BP reductions after CAS. MATERIALS AND METHODS: Patients with severe carotid stenosis were recruited either in the CAS group or in the medication group. BPs and the number of classes of antihypertensive agents were recorded at baseline, 6, and 12 months. Extra BP information was collected at 6 h, 3 days, and 1 month after CAS. Univariate and multivariate linear regressions were performed to test the relationship of BP changes among CAS and medication groups after 6 and 12 months of follow-up. Univariate linear regressions were also used to determine the correlations between the mean or maximal systolic BP (SBP) reductions at 6 h and 1 year post-CAS. RESULTS: In total, 72 members in the CAS group and 82 members in the medication group were recruited. Compared with the medication group, patients in the CAS group had greater BP reductions at 6 and 12 months of follow-up after adjusting for confounding factors (13.56 mmHg at 6 months, P=0.0002; 16.98 mmHg at 12 months, P<0.0001). This study also shows significant positive correlations between the mean or maximal SBP reductions 6 h post-CAS and SBP reductions 1 year post-CAS (ß =0.20±0.07, P=0.0067 and ß =0.47±0.10, P<0.0001, respectively). CONCLUSION: As compared to medical treatment alone, CAS may provide significant beneficial effect on long-term BP control 1 year post-CAS. Furthermore, SBP reductions 6 h post-CAS may predict the SBP reductions 1 year post-CAS.

Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS.

Hypoperfusion on single-photon emission computed tomography (SPECT) of the stroke-like lesion (SLL) at the hyperacute stage of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) is considered to be a supportive evidence of the mitochondrial angiopathy theory. Our objectives were to examine whether other neuroimages, especially transcranial color-coded sonography (TCCS), done at the hyperacute stage of stroke-like episode (SLE) is consistent with hypoperfusion of the SLL. We reviewed the magnetic resonance imaging (MRI), SPECT, cerebral angiography, and TCCS of a patient with MELAS syndrome, all of which were performed at the hyperacute stage of one SLE. MRI on the 1st day post SLE showed right temporoparietal lesion with vasogenic edema. SPECT on the 2nd day showed focal decreased uptake of technetium-99m hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) in the same region, but cerebral angiography and TCCS on the 3rd day showed increased regional cerebral blood flow (rCBF) and distal arteriole dilation in the same region. TCCS can delineate increased rCBF of the SLL at the hyperacute stage of SLE. We propose that the discrepancy between the decreased (99m)Tc-HMPAO uptake and increased rCBF might be caused by mitochondrial dysfunction. The phenomenon of "hypoperfusion" on SPECT might be caused by cell dysfunction but not decreased rCBF. We suggest that SPECT can be complemented by angiography and TCCS in future studies to delineate the perfusion status of SLLs.

Isolated orbito-cerebral mucormycosis.

Rhino-orbito-cerebral mucormycosis is a fatal infection in immunocompromised hosts. Prompt recognition of this clinical condition is essential for early diagnosis to avoid a delay of treatment. The presence of black eschar, usually in the nasal cavity, is the most alerting sign to the diagnosis. We present a patient with extremely fulminant ROCM in which the disease might be acquired via an orbital infection without nasal or paranasal involvement. With black eschars appearing at the bilateral canthi as the first alarm to extensive vascular involvement, the lethal infection rapidly evolved to occlusion of the bilateral ophthalmic arteries and eventually major intracranial arteries.