Myeong Kyu Kim

Single nucleotide polymorphisms in the multidrug resistance 1 gene in Korean epileptics.

PURPOSE P-glycoprotein 170 encoded by the multidrug resistance 1 (MDR1) gene exports various antiepileptic drugs out of the CNS, which leads to multidrug resistance. This study was performed to elucidate the relationship between single nucleotide polymorphisms (SNPs) in the MDR1 gene and drug resistance in Koreans with epilepsy. SUBJECTS AND METHODS Three SNPs at nucleotide position 1236 in exon 12, 2677 in exon 21 and 3435 in exon 26 of the MDR1 gene were genotyped in 207 Korean epileptics. Subjects were classified according to whether they had drug-resistant (RS group; N=99) or drug-responsive epilepsy (RP group; N=108). The frequencies of genotype and haplotype were compared between the RS and RP groups. RESULTS The frequencies of genotype and haplotype in the RS group were not statistically different from those in the RP group. CONCLUSIONS In Korean epileptics, there was no significant relationship between three known SNPs in MDR1 and drug resistance. And there was no association of MDR1 haplotype based on above three sites with pharmacoresistance.

Cyp1a reporter zebrafish reveals target tissues for dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

Familiarity with, understanding of, and attitudes toward epilepsy among people with epilepsy and healthy controls in South Korea

This study identifies differences between people with epilepsy (PWE) and healthy controls in South Korea with respect to their familiarity with, understanding of, and attitudes toward epilepsy. PWE and controls older than 18 years of age were recruited from outpatient clinics and health promotion centers, respectively, associated with five university hospitals located throughout the country. Structured questionnaires consisting of 18 items were administered in face-to-face interviews. The sample consisted of 1924 participants (PWE: 384, controls: 1540). The groups did not differ with respect to age, sex, and place of residence. However, the groups did differ significantly in educational, marital, and occupational status (P=0.000). Familiarity with seizures and epilepsy (two items) did not differ significantly between the groups. Questions pertaining to understanding seizures and epilepsy (seven items) showed that controls had significantly greater misunderstanding of the etiology and long-term prognosis of epilepsy compared with PWE. Attitudes expressed toward PWE were significantly different in response to six of seven questions. Control subjects expressed more negative attitudes toward PWE than did PWE themselves, particularly concerning potential relationships with their children (e.g., friendships, marriage). In conclusion, we found significant differences between PWE and controls, particularly with respect to understanding of and attitudes toward epilepsy. We recommend the development of different strategies for PWE and controls to improve understanding of and attitudes toward epilepsy and to reduce the knowledge gap between these groups. Nationwide educational programs conducted by associated organizations and the government may provide the solution to this problem.

Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome

Objective: To electrophysiologically characterize the Nav1.4 mutant N440K found in a Korean family with a syndrome combining symptoms of paramyotonia congenita, hyperkalemic periodic paralysis, and potassium-aggravated myotonia. Methods: We characterized transiently expressed wild-type and mutant Nav1.4 using whole-cell voltage-clamp analysis. Results: N440K produced a significant depolarizing shift in the voltage dependence of fast inactivation and increased persistent current and acceleration in fast inactivation recovery, which gave rise to a 2-fold elevation in the dynamic availability of the mutant channels. In addition, the mutant channels required substantially longer and stronger depolarization to enter the slow-inactivated state. Conclusions: N440K causes a gain of function consistent with skeletal muscle hyperexcitability as observed in individuals with the mutation. How the same mutation results in distinct phenotypes in the 2 kindreds remains to be determined.

Association of restless legs syndrome variants in Korean patients with restless legs syndrome.

STUDY OBJECTIVES Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis. The study objectives were to evaluate whether the associations of RLS with all loci determined in previous GWAS for Caucasians can be replicated significantly for the Korean population and to elucidate whether an epistasis plays a role in the pathogenesis of RLS. DESIGN SETTING AND PARTICIPANTS DNA from 320 patients with RLS and 320 age- and sex-matched controls were genotyped for variants in the RLS loci. MEASUREMENTS AND RESULTS A significant association was found for rs3923809 and rs9296249 in BTBD9 (P < 0.0001 and P = 0.001, respectively); the odds ratio (OR) for rs3923809 was 1.61 (P < 0.0001) to 1.88 (P < 0.0001) and the OR for rs9296249 was 1.44 (P = 0.001) to 1.73 (P = 0.002), according to the model of inheritance. The OR for the interaction between rs3923809 in BTBD9 and rs4626664 in PTPRD was 2.05 (P < 0.0001) in the additive model, 1.80 (P = 0.002) in the dominant model and 2.47 (P = 0.004) in the recessive model. There was no significant association between genotypes of all tested single nucleotide polymorphisms and the mean value of serum iron parameters. CONCLUSIONS Our results suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the role of epistasis in the genetic architecture of restless legs syndrome.

Moyamoya disease associated with Behcet's disease

A 32-year-old woman with Behcets disease suffered repeated transient ischemic attacks (TIA) consisting of left hemiparesis. Cerebral angiography revealed the typical findings of moyamoya disease, with occlusion of the supraclinoid portion of both internal carotid arteries, coupled with abnormal collateral vessels. She underwent right superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalomyosynangiosis, due to decreased reserve capacity demonstrated on acetazolamide single positron emission computed tomography (SPECT). Postoperatively, the TIA symptoms subsided. This is the first report of moyamoya disease associated with Behcets disease, and moyamoya disease should be considered in the differential diagnosis of cerebrovascular events in patients with Behcets disease. Revascularization surgery is recommended for the prevention of ischemic insults resulting in permanent deficits.

Opsoclonus associated with scrub typhus

A 64-year-old woman and a 40-year-old man (video on the Neurology ® Web site at www.neurology.org) diagnosed with scrub typhus presented opsoclonus. Drowsiness and mild nuchal …

Acute inflammatory demyelinating polyradiculoneuropathy in a patient receiving oxaliplatin-based chemotherapy.

We report a case of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) that developed in a patient with cholangiocarcinoma after receiving oxaliplatin‐based chemotherapy. A 62‐year‐old man had multiple hypodense lesions with delayed enhancement in the both lobes of the liver on abdominal computed tomography. He was treated with 5‐fluorouracil, leucovorin and oxaliplatin (100 mg/m2). After eight cycles of treatment and a cumulative oxaliplatin dose of 780 mg/m2, he developed an unsteady gait, dysphagia, weakness of both the upper and lower limbs and impairment of all sensory modalities. Nerve conduction studies confirmed the diagnosis of AIDP. Immunoglobulin G i.v. was administered for 5 days but the neurological deficits of both his upper and lower limbs did not improve. This case highlights unusual peripheral nervous system manifestations in a patient who received chemotherapy with oxaliplatin.

Mononeuropathy Multiplex in a Patient with Chronic Active Hepatitis B

Background Mononeuropathy multiplex is a rare complication during the course of chronic hepatitis B, despite various neuropathies following acute hepatitis B having been reported previously. Case Report A 30-year-old man presented with sensorimotor symptoms in multiple peripheral nerves. The serological tests for hepatitis were consistent with chronic active hepatitis B. After treatment with oral prednisone combined with an antiviral agent, the sensory and motor symptoms improved and hepatitis B virus replication was reduced. Conclusions We suggest that chronic immune-mediated neuropathy associated with hepatitis B virus infection should be considered in the differential diagnosis of patients with hepatitis B.

Recurrent Transient Monocular Blindness with Ophthalmic Artery Stenosis

his medical record did not show any atherosclerotic vascular disease. Physical examination at admission did not reveal any bruits over either of the carotid arteries. No neurological deficits were detected. His blood pressure was 125/82 mm Hg, and his pulse rate was 72 beats/min and regular. Coagulation parameters, including antithrombin III, proDear Sir, Transient monocular blindness (TMB) or amaurosis fugax (AF) is defined as a monocular, transient visual loss lasting a few minutes, which is caused by an abrupt temporary reduction in blood flow to one eye. From increased blood viscosity to vasospasm or multiple occlusions of extracranial arteries, various mechanisms are involved in causing TMB. One of the most clearly demonstrated mechanisms is atherothrombotic embolism from the carotid artery to the ophthalmic artery. However, TMB caused by isolated ipsilateral ophthalmic artery stenosis is very rare. We experienced a patient with recurrent TMB associated with isolated proximal ophthalmic artery stenosis.