Yo-Sik Kim

Endothelial Function in Lacunar Infarction: A Comparison of Lacunar Infarction, Cerebral Atherosclerosis and Control Group

Background: There are conflicting evidences on endothelial function in lacunar infarction. This may be attributed to the effects of risk factors on the vascular smooth muscle. To test endothelial function only in patients with lacunar infarction, we evaluated the endothelium-dependent and -independent vasodilatation of the brachial artery. Methods: We enrolled consecutive patients with lacunar infarction defined by clinical characteristics and MRI findings. The control group included age- and sex-matched patients with hypertension who do not have any history of clinical stroke, coronary artery disease or peripheral vascular disease. Endothelial function was evaluated using flow-mediated dilatation (FMD) and nitrogen-mediated dilatation (NMD) of the brachial artery. FMD and NMD were examined by an experienced vascular sonographer using a high-resolution ultrasound. Intracranial stenosis was defined as flow gap or >50% reduction in vessel diameter on MRA. Results: FMD was 6.6 ± 4.5% in the lacunar infarction group and 12.2 ± 4.6% in the control group (p = 0.000). NMD was 14.3 ± 4.9% in the lacunar infarction group and 13.8 ± 4.9% in the control group (p = 0.37). FMD in patients with lacunar infarction and intracranial arterial stenosis was 6.4 ± 3.9%, and FMD in patients with lacunar infarction was only 6.9 ± 5.5%. In the control group, it was 12.2 ± 4.6%. Conclusion: FMD was low in patients with lacunar infarction. NMD was similar between the lacunar infarction group and the control group. These results are suggestive of pure endothelial dysfunction in lacunar infarction. Endothelial dysfunction was as severe in lacunar infarction as in intracranial arterial stenosis.

Relationship between Flow Diversion on Transcranial Doppler Sonography and Leptomeningeal Collateral Circulation in Patients with Middle Cerebral Artery Occlusive Disorder

Flow diversion (FD) has been considered as indirect evidence of intracranial artery occlusion, and it was associated with early improvement in patients with MCA occlusion. It is not known whether FD can represent leptomeningeal collateral circulation or not in patients with middle cerebral artery (MCA) occlusive disorder.

Marital status of people with epilepsy in Korea

A multicentre face-to-face interview was conducted to identify factors contributing to the marital status of people with epilepsy (PWE) in Korea. The marriage rate of PWEs was only 80% and the divorce rate was more than double that in the general population. Among the single subjects, 34% replied that they were unmarried because of epilepsy, and 76% of divorced PWEs replied that epilepsy was the cause of the divorce. The factors affecting the single and divorced status in PWEs included gender, an earlier onset of seizure and seizure onset before marriage. Not informing the spouse of the disease before marriage for fear of discrimination was not related to disadvantage in marriage negotiation or to divorce. Social stigmatization of epilepsy continues and impacts on the marital status of PWEs in Korea. However, there is no correlation between the perceived and the enacted stigmas of epilepsy.

Correlation Between Insulin Resistance and Intracranial Atherosclerosis in Patients With Ischemic Stroke Without Diabetes

BACKGROUND Insulin resistance (IR) is associated with an increased risk for cardiovascular morbidity and mortality including ischemic stroke. Its final complications are cardiovascular and cerebrovascular disease caused by atherosclerosis. However, few studies on the relationship between IR and intracranial (IC) atherosclerosis have been reported. METHODS We analyzed 110 patients with acute stroke without diabetes who underwent brain magnetic resonance angiography and cerebral angiography. Patients were divided into 3 equal groups according to the tertiles of homeostasis model assessment of IR (HOMA-IR): group I (n = 36; HOMA-IR < 0.92), group II (n = 37; 0.92 <or= HOMA-IR < 1.55), and group III (n = 37; HOMA-IR >or= 1.55). Cerebral artery atherosclerosis was classified as either IC or extracranial (EC). RESULTS Patients with IC or EC atherosclerosis showed higher level of HOMA-IR than those without. When the association was assessed according to the site of atherosclerosis, HOMA-IR showed a significant association with the site of atherosclerosis (IC + EC > IC > EC, P < .01). Multivariate analysis revealed that HOMA-IR was an independent predictor of IC atherosclerosis. CONCLUSIONS Although the association between IR and stroke patterns in patients with atherosclerosis remains uncertain, IR is associated with IC atherosclerosis in patients with acute ischemic stroke without diabetes.

Evidence for epistatic interactions in antiepileptic drug resistance

To investigate the epistatic interactions involved in antiepileptic drug (AED) resistance, 26 coding single-nucleotide polymorphisms (SNPs) were selected from 16 candidate genes. A total of 200 patients with drug-resistant localization-related epilepsy and 200 patients with drug-responsive localization-related epilepsy were genotyped individually for the SNPs. Rather than using the traditional parametric statistical method, a new statistical method, multifactor dimensionality reduction (MDR), was used to determine whether gene–gene interactions increase the risk of AED resistance. The MDR method indicated that a combination of four SNPs (rs12658835 and rs35166395 from GABRA1, rs2228622 from EAAT3 and rs2304725 from GAT3) was the best model for predicting susceptibility to AED resistance with a statistically significant testing accuracy of 0.625 (P<0.001) and cross-validation consistency of 10/10. This best model had an odds ratio of 3.68 with a significant 95% confidence interval of 2.32–5.85 (P<0.0001). Our results may provide meaningful information on the mechanism underlying AED resistance and, to the best of our knowledge, this is the first report of evidence for gene–gene interactions underlying AED resistance.

Cerebral embolism of iodized oil (lipiodol) after transcatheter arterial chemoembolization for hepatocellular carcinoma.

Cerebral lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). Its pathological mechanism remains ambiguous despite several investigations. In Case 1, a 67‐year‐old man with hepatocellular carcinoma (HCC) experienced neurological deficits soon after undergoing a fourth session of TACE. Computed tomography (CT) scan showed multiple hyperdense lesions along the gyrus of frontal lobes and in the subcortical white matter. Transcranial Doppler (TCD) and transesophageal echocardiogram performed during the intravenous injection of agitated saline documented the presence of a right‐to‐left shunt (RLS) by demonstrating microbubbles in the left middle cerebral artery and left atrium. In Case 2, a 63‐year‐old woman underwent a third TACE due to a large HCC. After the procedure, her mental status deteriorated. Brain CT showed multiple hyperdense lesions on the cerebral and cerebellar cortex. TCD with agitated saline showed multiple microembolic signals shortly after the injection of agitated saline. The risk of cerebral lipiodol embolism may increase with recurrence and progression of HCC in patients who have a pre‐existing RLS in the heart or lung. A test for the detection of an RLS may be necessary to identify patients with a heightened risk of cerebral embolism when multiple TACE procedures are required. TACE for HCC can cause pulmonary embolism or infarction. 1,2 However, cerebral lipiodol embolism is rare after TACE. There have been several reports of cerebral embolism after TACE, but their exact mechanism has not yet been fully elucidated. We report herein 2 patients who developed cerebral lipiodol embolism after undergoing multiple TACE procedures for remnant HCC through a pre‐existing RLS.

Modulation of neuronal activity by EGCG.

This study aims to investigate whether (-)-epigallocatechin-3-gallate (EGCG) affects neuronal activity of acutely isolated rat medial vestibular nuclear neurons in whole-cell configuration patch-clamp experiments. EGCG (0.5 and 1 muM) lowered the spontaneous firing rate and hyperpolarized the membrane potential of medial vestibular nuclear neurons. However, it did not change the amplitude of afterhyperpolarization or the spike width of the action potential. A second application of EGCG with the same concentration elicited lesser responses. These results suggest that EGCG decreases neuronal activity by affecting potassium currents which are responsible for membrane potentials.

Genetic susceptibility to ischemic cerebrovascular disease in Koreans

Ischemic cerebrovascular disease (ICVD) is a multifactorial disease caused by the interactions of several genetic and environmental factors. Tobacco smoke is a major cause of both cancer and vascular disease. Although its carcinogenic role via induction of DNA damage and mutation is well established, the mechanisms involved in vascular disease remain unclear. One possibility is that DNA damage causes smooth muscle cell proliferation in the intima of arteries, thereby contributing to atherothrombotic processes. The binding of chemicals to DNA is modulated by detoxification enzymes, including glutathione S-transferase (GST). We examined whether polymorphisms in this gene, as well as the angiotensin-converting enzyme (ACE) gene influence the risk of ICVD on smoking status. DNA was analyzed for deletions in the GST M1, T1, and ACE genes by polymerase chain reaction (PCR). No significant association was observed between GST null genotype and ICVD, even in smokers. However, a significant association between ACE and ICVD was observed only in smokers (X2=0.023, p<0.05). We conclude that GST polymorphism is not a risk factor for the development of ICVD through smoking and suggest a high probability that ACE polymorphism may contribute to the odds of ICVD in smokers.

Gene-to-gene interaction between sodium channel-related genes in determining the risk of antiepileptic drug resistance.

The pathogenesis of antiepileptic drug (AED) resistance is multifactorial. However, most candidate gene association studies typically assess the effects of candidate genes independently of each other, which is partly because of the limitations of the parametric-statistical methods for detecting the gene-to-gene interactions. A total of 200 patients with drug-resistant epilepsy and 200 patients with drug-responsive epilepsy were genotyped for 3 representative the single nucleotide polymorphisms (SNPs) of the voltage-gated sodium channel genes (SCN1A, SCN1B, and SCN2A) by polymerase chain reaction and direct sequencing analysis. Besides the typical parametric statistical method, a new statistical method (multifactor dimensionality reduction [MDR]) was used to determine whether gene-to-gene interactions increase the risk of AED resistance. None of the individual genotypes or alleles tested in the present study showed a significant association with AED resistance, regardless of their theoretical functional value. With the MDR method, of three possible 2-locus genotype combinations, the combination of SCN2A-PM with SCN1B-PM was the best model for predicting susceptibility to AED resistance, with a p value of 0.0547. MDR, as an analysis paradigm for investigating multi-locus effects in complex disorders, may be a useful statistical method for determining the role of gene-to-gene interactions in the pathogenesis of AED resistance.

A Novel Nonsense Mutation of the GTP Cyclohydrolase I Gene in a Family with Dopa-Responsive Dystonia

We report a new nonsense mutation in the GTP cyclohydrolase I (GCH1) gene in a family with dopa-responsive dystonia. Two sisters and three children of the sisters are affected. The exons of the GCH1 gene were amplified by PCR and sequenced. The substitution of thymine for cytosine at nucleotide position 142 causing a nonsense mutation (Q48X) in exon 1 was identified in all of the five affected patients. There were three asymptomatic carriers of the mutation in the family.