Ya-Hui Lin

Periictal magnetic resonance imaging in status epilepticus

PURPOSE To determine the changes of magnetic resonance imaging (MRI) during the periictal phase in status epilepticus (SE). PATIENTS AND METHODS We identified 15 patients diagnosed of status epilepticus with corresponding MRI changes, including 11 patients with generalized convulsive status epilepticus (GCSE), 2 with complex partial status epilepticus (CPSE), and 2 with simple partial status epilepticus (SPSE). All MRI changes, corresponding electroencephalogram, and prognosis were evaluated. RESULTS Regional cortical lesions were observed on MRI, including restricted diffusion in diffusion-weighted images (DWIs) (11 out of 15) and hyperintense signal change in fluid-attenuated inversion recovery (FLAIR) images (12 out of 15) with hypervascularity and parenchymal swelling. The remote lesions included crossed cerebellar diaschisis (3 patients), ipsilateral thalamic lesion (4 patients), and basal ganglia lesions (3 patients). Although the periictal MRI changes were usually reversible, irreversible changes were also found, especially in GCSE, such as focal brain atrophy, cortical laminar necrosis, and mesial temporal sclerosis. GCSE patients with periodic epileptic form discharges had higher possibilities of widespread MRI abnormalities and poor prognosis in the future. CONCLUSIONS In this study, DWIs and FLAIR images were proved useful in determining the extent and severity of early neuronal damage caused by epileptic discharges in SE patients. Seizure-induced long-term injuries were also observed in the follow-up MRI.

Gouty Arthritis in Acute Cerebrovascular Disease

Background: Gouty arthritis is a metabolic disorder associated with several medical diseases and is considered as a high-risk factor of acute myocardial infarction and cardiovascular mortality. Since no study has assessed the frequency of gout attack in acute-stroke patients, a retrospective analysis of gouty arthritis in stroke patients was performed to identify the frequency and characteristics of gouty arthritis in hospitalized stroke patients. Methods: We reviewed the data of 920 patients admitted to the neurology ward of the Chiayi Chang Gung Memorial Hospital between 2002 and 2005 with ischemic stroke. The frequency of gouty arthritis in these patients was evaluated. The severity of the risk factors was compared between the patients with gout and those without. Results: The frequency of gouty arthritis in the stroke patients was 6.5%. Most patients had an attack of gout within 9 days of admission. History of gout, uric acid level and hypercholesterolemia were independent risk factors of gout attack during acute stroke. The duration of acute-ward stay was longer in patients with gout than in those without (17.17 vs. 14.01 days, p = 0.016). Conclusions: Our retrospective study demonstrated that gout attack is not uncommon in acute-stroke patients and may result in longer duration of acute-ward stay.

Gastrointestinal Hemorrhage after Acute Ischemic Stroke and Its Risk Factors in Asians

Background: The aim of this study was to examine the frequency and risk factors of gastrointestinal (GI) hemorrhage in acute ischemic stroke patients in Taiwan. Method: 920 patients admitted for acute ischemic stroke from January 2001 to October 2005 were included in the study. We reviewed the available medical records for any episode of GI hemorrhage, possible precipitating factors and administration of ulcer prophylaxis. Results: Seventy-two patients (7.8%) experienced GI hemorrhage; these patients were of an older age (74.7 vs. 69.0 years, p < 0.001), had a longer acute ward stay (30.4 vs. 12.9 days, p < 0.001) and higher mortality rate (odds ratio 9.61, CI 4.53–20.42) than patients without GI hemorrhage. In multivariate logistic regression analysis, the important risk factors of GI hemorrhage included sepsis, previous history of GI hemorrhage, severe stroke, renal insufficiency and abnormal liver function. Of the 779 patients who had a 0–1 risk factor, 26 (3.3%) experienced GI hemorrhage; of the 27 patients with more than 2 risk factors, 17 (63%) suffered GI hemorrhage. Conclusion: This study of Asians revealed a higher frequency of GI hemorrhage after acute ischemic stroke than that reported in previous studies, and the frequency of GI hemorrhage was positively correlated with the number of risk factors present. We suggest that identifying stroke patients with a high risk of hemorrhage may allow clinicians to set up ulcer prophylactic protocols for the patients most likely to benefit, especially in an Asian population.

ALOX5AP genetic variants and risk of atherothrombotic stroke in the Taiwanese population

We explored the role of variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene as factors for atherothrombotic stroke (ATS). A HapMap-based haplotype-tagging single nucleotide polymorphism (htSNP) association study was conducted in an isolated Taiwanese population. Multivariate logistic regression analyses revealed that patients with the GG/CG genotype of rs4293222 and the AA/AG genotype of rs4360791 had a 1.61-fold (odds ratio [OR]=1.61; 95% confidence interval [CI]=1.02-2.56, p=0.042) and a 1.69-fold (OR=1.69; 95% CI=1.00-2.86, p=0.047) increased risk of ATS, compared with patients with the CC/GG genotype, respectively. The most common haplotype allele, GTA, was used as a reference when analyzing the association between the haplotypes related to rs4293222, rs10507391, rs12429692 and ATS. The combined frequencies of all minor variant alleles of the three selected htSNP were associated with a 44% decreased risk of ATS (OR=0.56; 95% CI=0.37-0.84, p=0.005). This study provides preliminary evidence suggesting that genetic polymorphisms of ALOX5AP are associated with ATS.

Polymorphisms at the LDLR locus may be associated with ischemic cerebrovascular disease independent of lipid profile.

The low-density lipoprotein receptor (LDLR) gene has been reported to be associated with cerebral infarction. This study aimed to explore 2 genetic LDLR variants, rs688 and rs5925, for their potential roles in cerebral infarction. This genetic association study was conducted within an isolated Taiwanese population; 815 ischemic stroke patients (431 with atherothrombotic stroke and 384 with lacunar infarction) and 430 normal controls were enrolled. There was no significant difference in the genetic frequency of rs688 and rs5925 between the control group and overall ischemic stroke, atherothrombotic stroke, or lacunar infarct groups. However, when analyzing the association between the haplotypes related to rs688 and rs5925 and cerebral ischemic stroke, the most common haplotype allele CT was used as the reference allele, and the haplotype TC associated with a 65% increased risk of overall ischemic stroke, 72% increased risk of atherothrombotic stroke, and 70% increased risk of lacunar infarction; this indicated a synergistic effect between these 2 single-nucleotide polymorphisms. The LDLR analysis based on the haplotypes rs688 and rs5925 was conducted in a Taiwanese population and provided preliminary evidence suggesting that genetic polymorphisms of LDLR are associated with cerebral infarction.

Genetic polymorphism of LDLR (rs688) is associated with primary intracerebral hemorrhage.

Intracranial hemorrhage is the third most common cause of cerebrovascular disease. Some polymorphisms that affect clotting factors increase the risk of thrombosis. However, few reports have analyzed the effect of polymorphisms on the hemostatic state in bleeding disorders. The low-density lipoprotein receptor (LDLR) has been shown to contribute to factor VIII (FVIII) homeostasis, which represents a link between LDLR and hemostasis. FVIII plays a pivotal role in the coagulation cascade. Patients with high levels of FVIII are at an increased risk of arterial and venous thrombosis. On the other hand, patients with insufficient FVIII tend to bleed excessively, such as in hemophilia A. In a previous study, analysis of the genetic LDLR variant rs688 provided evidence suggesting that genetic polymorphisms of rs688 are associated with thrombotic cardiovascular diseases. The current study aimed to investigate the potential role of rs688 in primary intracerebral hemorrhage (PICH). This genetic association study was conducted within an isolated Taiwanese population (447 PICH patients and 430 controls). Genotypes C/C and C/T were used as the reference genotypes, and the genotype T/T was found to be associated with a 73% decreased risk of PICH. The preliminary evidence suggests that genetic polymorphisms of LDLR are associated with PICH.

Hemodynamic Factors May Play a Critical Role in Neurological Deterioration Occurring within 72 hrs after Lacunar Stroke

Background Whether a perfusion defect exists in lacunar infarct and whether it is related to early neurological deterioration (END) is still under debate. The aim of this study was to evaluate whether END in lacunar infarct is related to a perfusion defect using diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI) and perfusion MR imaging. Methods One hundred and forty-one consecutive patients had an MRI scan within 30 hours after onset of symptoms and 43 patients with acute lacunar infarct and classic lacunar syndrome were recruited. The MRI sequences included DWI, DTI and cerebral blood flow (CBF) maps to respectively represent the topographic locations of acute infarcts, the corticospinal tract and perfusion defects. The END was defined in reference to the National Institute of Health Stroke Scale (NIHSS) as an increase ≧2 within 72 hours. Cohens Kappa coefficient was used to examine the reliability between the 2 image readers. A multivariate logistic regression model was constructed adjusting for baseline variables. Results Ten out of the 43 patients had END. Patients having END was significantly associated with lower chances of favorable and good outcomes at 3 months (p = 0.01 and p = 0.002, respectively). END was predicted when the non-core hypoperfused area overlapped on the corticospinal tract, which is defined as the expected END profile. Cohens Kappa coefficient between the 2 image readers to define images of expected END profiles was 0.74. In 15 patients with expected END profile, 9 had END clinically, whereas 28 patients had no expected END profile, and only 1 patient had END (p<0.0001). After adjusting for sex, the expected END profile was still associated with END (odds ratio, 42.2; p = 0.002). Conclusion Our study demonstrated that the END in acute lacunar stroke is likely related to the transformation of non-core hypoperfused area into infarction in the anatomy of corticospinal tracts.

Factor VIII Levels are Associated with Ischemic Stroke, Stroke Subtypes and Neurological Worsening

The role played by hemostasis in the pathogenesis of ischemic stroke is still controversial. In the present study, we looked for a possible association of ischemic stroke with the high clotting activity of factor VIII (FVIII). The study population consisted of 116 patients with acute ischemic stroke who had been admitted between September 2013 and September 2014 to the Department of Neurology, Chiayi Chang Gung Memorial Hospital, and 76 control subjects with no history of stroke. FVIII levels were higher in stroke patients as compared to controls (127.5 ± 52.5 vs. 108.4 ± 49.0 IU/dL; P = 0.012). In a univariate risk analysis, FVIII at levels above 150 IU/dL was associated with an odds ratio (OR) for ischemic stroke of up to 2.55 (95% CI, 1.20-5.42, P = 0.013). In a multivariate analysis using a logistic regression model including age, hypertension, low density lipoprotein cholesterol level, estimated glomerular filtration rate, and high FVIII (< 150 IU/dL), high FVIII was still found to significantly add to the risk of ischemic stroke (OR = 3.26 with 95% CI, 1.38-7.68, P = 0.007). As for the stroke subtypes, mean FVIII level was significantly higher in patients with cardioembolic stroke than patients with noncardioembolic stroke (156.0 ± 51.5 IU/dL vs. 124.3 ± 51.9 IU/dL). High levels of FVIII were also associated significantly with neurological worsening (OR = 3.66 with 95% CI, 1.24-10.82, P = 0.019). A high plasma level of FVIII is a prevalent and independent risk factor for ischemic stroke and neurological worsening after acute stroke.

Genetic polymorphisms of low density lipoprotein receptor can modify stroke presentation.

Abstract Low density lipoprotein is transcytosed across the blood–brain barrier mediated by low density lipoprotein receptor (LDLR). LDLR in the brain is mainly expressed on capillary endothelial cells and is therefore considered to be an important susceptibility gene in modifying the stroke presentation. A HapMap-based haplotype-tagging single nucleotide polymorphism association study was conducted in an isolated Taiwanese population. Two hundred and ninety-two unrelated patients with cerebral infarction, 76 patients with small vessel occlusion (SVO) disorder and 216 with non-SVO disorder were enrolled. For rs2738446, under the dominant model, the odds ratios (ORs) associated with the CC genotype were computed, with GG + CG carriers considered as the reference group. Homozygote CC carriers had a two-fold increased risk of SVO disorder [OR=2·0, 95% confidence interval (CI)=1·08–3.70, p=0·025). For rs2738450, under the dominant model, the ORs associated with the CC genotype were computed, with AA + AC carriers considered as the reference group. Homozygote CC carriers had a 1·85-fold increased risk of SVO disorder (OR=1·85, 95% CI=1·01–3.33, p=0·04). When analysing the association between the haplotype related to rs2738446 and rs2738450 and SVO disorder, the most common haplotype allele CC was used as the reference, and the GA haplotype allele was associated with a 48% decreased risk of SVO disorder (OR=0·52; 95% CI=0·29–0.93, p=0·029). Haplotype-based analysis of LDLR in Taiwanese patients with cerebral infarction provided preliminary evidence suggesting that genetic polymorphisms of LDLR can modify the stroke presentation.

Association of Renal Biomarkers with 3-Month and 1-Year Outcomes among Critically Ill Acute Stroke Patients

Background The comparative relationships of widely recognized biomarkers of renal injury with short-term and long-term outcomes among critically ill acute stroke patients are unknown. We evaluated the impact of baseline albuminuria [urine albumin-creatinine ratio (UACR)≥30 mg/g] or low estimated glomerular filtration rate (eGFR<60 ml/min per 1.73 m2) on stroke patients admitted to the intensive care unit (ICU). Methods We reviewed data on consecutive stroke patients admitted to a hospital ICU in Taiwan from September 2007 to August 2010 and followed-up for 1 year. Baseline UACR was categorized into <30 mg/g (normal), 30–299 mg/g (microalbuminuria), and ≥300 mg/g (macroalbuminuria), while eGFR was divided into ≥60, 45–59, and <45 ml/min per 1.73 m2. The outcome measure was death or disability at 3-month and 1-year after stroke onset, assessed by dichotomizing the modified Rankin Scale at 3–6 versus 0–2. Results Of 184 consecutive patients, 153 (83%) met study entry criteria. Mean age was 67.9 years and median admission NIHSS score was 16. Among the renal biomarkers, only macroalbuminuria was associated with poorer 3-month outcome (OR 8.44, 95% CI 1.38 to 51.74, P = 0.021) and 1-year outcome (OR 18.06, 95% CI 2.59 to 125.94, P = 0.003) after adjustment of relevant covariates. When ischemic and hemorrhagic stroke were analyzed separately, macroalbuminuria was associated with poorer 1-year outcome among ischemic (OR 17.10, 95% CI 1.04 to 280.07, P = 0.047) and hemorrhagic stroke patients (OR 1951.57, 95% CI 1.07 to 3561662.85, P = 0.048), respectively, after adjustment of relevant covariates and hematoma volume. Conclusions Presence of macroalbuminuria indicates poor 3-month and 1-year outcomes among critically ill acute stroke patients.