ATN Classification and Clinical Progression of the Amyloid-Negative Group in Alzheimer’s Disease Neuroimaging Initiative Participants / 전남의대학술지

Alzheimer’s disease has recently been classified using three biological markers (amyloid [A], tau [T], and neurodegeneration [N]) to help elucidate its progression. We aimed to investigate whether there were differences between cognitive function and the clinical dementia symptoms over time relative to the ATN classification in the amyloid-negative group. In the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, 310 participants who underwent all the tests required for ATN classification were enrolled. The cognitive function score differences (Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 [ADAS-Cog 13], Clinical Dementia Rating Sum of Boxes [CDR-SOB], and Mini-Mental State Examination [MMSE]) between the groups were analyzed using the analysis of covariance and score changes over time with a linear mixed-effects model. In the cross-sectional analysis, ADAS-Cog 13 scores were higher for A-T-N+ and A-T+N+ than for A-T-N- (p＜0.001) and A-T+N- (p＜0.001). In the longitudinal analysis, CDR-SOB scores for A-T+N+ deteriorated faster than A-T-N- (p＜ 0.001), A-T+N- (p＜0.001) and A-T-N+ (p＜0.001). Hippocampal atrophy progressed faster in A-T-N+ (p＜0.001) and A-T+N+ (p=0.02) than in A-T-N-. Through this study, we discovered that even in individuals classified as amyloid negative, neurodegeneration with tau deposition exacerbates cognitive decline and worsens clinical symptoms, underscoring the need for continuous monitoring and observation.

Effect of Education on Discriminability of Montreal Cognitive Assessment Compared to Mini-Mental State Examination

Background@#and Purpose: The Montreal Cognitive Assessment (MoCA) has been known as a screening test for detecting mild cognitive impairment (MCI) better than Mini-Mental State Examination (MMSE). However, in previous domestic studies, no significant difference was found in the discriminability between MoCA and MMSE. Researchers have suggested that this might be because older Koreans are less educated than older Westerners. This study was conducted to examine the effect of education on the discriminability of MoCA compared to the MMSE. @*Methods@#Participants were 123 cognitively normal elderly, 118 with vascular MCI, 108 with amnestic MCI, 121 with vascular dementia, and 113 with dementia of the Alzheimer’s type.The Korean-MoCA (K-MoCA) and Korean-MMSE (K-MMSE) were administered. Multiple regression analyses and receiver operating characteristic (ROC) curve analyses were performed. @*Results@#In all participants, education significantly affected both K-MoCA and K-MMSE scores along with age. The effect of education was re-examined by subgroup analysis after dividing subjects according to the level of education. Effect of education on K-MoCA and K-MMSE was only shown in the group with <9 years of education. ROC curve analyses revealed that the discriminability of K-MoCA to differentiate between vascular MCI and normal elderly was significantly higher than that of K-MMSE. When re-examining subgroups divided by education level, however, this higher discriminability of K-MoCA disappeared in the group with <9 years of education. @*Conclusions@#These results indicate no difference in discriminating cognitive deficits between K-MoCA and K-MMSE in Korean elderly with <9 years of education.

Validity of the Montreal Cognitive Assessment (MoCA) Index Scores:a Comparison with the Cognitive Domain Scores of the Seoul Neuropsychological Screening Battery (SNSB)

Background@#and Purpose: A new approach was proposed to score the Montreal Cognitive Assessment (MoCA) index scores for 6 cognitive domains: orientation (OIS), attention (AIS), language (LIS), visuospatial function (VIS), memory (MIS), and executive function (EIS). This study investigated whether the MoCA index scores represent the functions of each cognitive domain by examining the correlations with the corresponding cognitive domain scores derived from conventional neuropsychological tests included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II). @*Methods@#The participants were 104 amnestic mild cognitive impairment (aMCI), 74 vascular mild cognitive impairment (VaMCI), 73 dementia of the Alzheimer's type (DAT), and 41 vascular dementia (VaD) patients. All participants were administered the Korean-MoCA and SNSB-II. @*Results@#Like the MoCA total score, the MoCA-OIS, MoCA-VIS, and MoCA-MIS showed differences between aMCI and AD groups and between VaMCI and VaD groups. The MoCAAIS, MoCA-LIS, and MoCA-EIS showed significant differences between VaMCI and VaD groups, but no difference between aMCI and DAT groups. In the aMCI and VaMCI groups, all index scores of the MoCA showed significant correlations with the corresponding cognitive domain scores of the SNSB-II. Except for MoCA-MIS, the MoCA-AIS, MoCA-LIS, MoCA-VIS, and MoCA-EIS also showed significant correlations with the corresponding domain scores of the SNSB-II in the DAT and VaD groups. @*Conclusions@#These results indicate that all MoCA index scores, except for MoCA-MIS, which does not reflect the severity of memory impairment in dementia patients, provide highly valid information on the function of each cognitive domain in patients with mild cognitive impairment and dementia.

Validity of the Montreal Cognitive Assessment (MoCA) Index Scores:a Comparison with the Cognitive Domain Scores of the Seoul Neuropsychological Screening Battery (SNSB)

Background@#and Purpose: A new approach was proposed to score the Montreal Cognitive Assessment (MoCA) index scores for 6 cognitive domains: orientation (OIS), attention (AIS), language (LIS), visuospatial function (VIS), memory (MIS), and executive function (EIS). This study investigated whether the MoCA index scores represent the functions of each cognitive domain by examining the correlations with the corresponding cognitive domain scores derived from conventional neuropsychological tests included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II). @*Methods@#The participants were 104 amnestic mild cognitive impairment (aMCI), 74 vascular mild cognitive impairment (VaMCI), 73 dementia of the Alzheimer's type (DAT), and 41 vascular dementia (VaD) patients. All participants were administered the Korean-MoCA and SNSB-II. @*Results@#Like the MoCA total score, the MoCA-OIS, MoCA-VIS, and MoCA-MIS showed differences between aMCI and AD groups and between VaMCI and VaD groups. The MoCAAIS, MoCA-LIS, and MoCA-EIS showed significant differences between VaMCI and VaD groups, but no difference between aMCI and DAT groups. In the aMCI and VaMCI groups, all index scores of the MoCA showed significant correlations with the corresponding cognitive domain scores of the SNSB-II. Except for MoCA-MIS, the MoCA-AIS, MoCA-LIS, MoCA-VIS, and MoCA-EIS also showed significant correlations with the corresponding domain scores of the SNSB-II in the DAT and VaD groups. @*Conclusions@#These results indicate that all MoCA index scores, except for MoCA-MIS, which does not reflect the severity of memory impairment in dementia patients, provide highly valid information on the function of each cognitive domain in patients with mild cognitive impairment and dementia.

MRI-Based Multimodal Approach to the Assessment of Clinical Symptom Severity of Obsessive-Compulsive Disorder

Objective@#This study assessed the associations of the abnormal brain activation and functional connectivity (FC) during memory processing and brain volume alteration in conjunction with psychiatric symptom severity in patients with obsessive-compulsive disorder (OCD). @*Methods@#Twenty-OCD patients and 20-healthy controls (HC) underwent T1-weighted and functional imaging underlying explicit memory task. @*Results@#In memory encoding, OCD patients showed higher activities in right/left (Rt./Lt.) inferior temporal gyrus (ITG), medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), compared with HC. In task-based FC, caudate (Cd) was positively connected with DLPFC and ITG in OCD, while HC showed different connectivities of Cd-ACC and Rt.-Lt. ITG. In memory retrieval, only Cd was activated in OCD patients. Cd was positively connected with DLPFC and vmPFC in OCD, but negatively connected between same brain areas in HC. OCD patients showed increased gray matter (GM) volumes of cerebellum, DLPFC, orbitofrontal cortex (OFC), hippocampus, Cd and ITG, and concurrently, increased white matter volumes of DLPFC. In OCD patients, GM volumes of Cd and OFC were positively correlated with HAMA and Y-BOCS. Functional activity changes of Cd in OCD were positively correlated with Y-BOCS. @*Conclusion@#Our findings support to accessing clinical symptom and its severity linked by brain structural deformation and functional abnormality in OCD patients.

The Brain Donation Program in South Korea

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Proposal Guidelines for Standardized Operating Procedures of Brain Autopsy: Brain Bank in South Korea

To obtain an in-depth understanding of brain diseases, including neurodegenerative diseases, psychiatric illnesses, and neoplasms, scientific approach and verification using postmortem human brain tissue with or without disease are essential. Compared to other countries that have run brain banks for decades, South Korea has limited experience with brain banking; nationwide brain banks started only recently. The goal of this study is to provide provisional guidelines for brain autopsy for hospitals and institutes that have not accumulated sufficient expertise. We hope that these provisional guidelines will serve as a useful reference for pathologists and clinicians who are involved and interested in the brain bank system. Also, we anticipate updating the provisional guidelines in the future based on collected data and further experience with the practice of brain autopsy in South Korea.

Prognostic Factors for Recurrence of Seizure After Antiepileptic Drug Withdrawal

BACKGROUND: Discontinuation of antiepileptic drug (AED) is valuable in patients of epilepsy who have been seizure free for a considerable time. However, there are few established methods to successfully stop AED. The purpose of study was to find the prognostic factors and the method of desirable AED withdrawal. METHODS: Seventy-eight patients who were seizure free for more than 18 months were enrolled in this retrospective study. The patients were followed for more than 2 years after starting withdrawal, or until seizure recurrence within 2 years. To clarify the prognostic factors affecting the seizure recurrence related to the withdrawal, statistical analyses were done about AED types, EEG before withdrawal, sex, age, onset age of seizure, febrile convulsion, family history, brain CT/MRI, trauma history, loss of consciousness history, seizure nature, and duration of seizure free. Furthermore, survival analysis between groups over the duration of withdrawal period and AED decrement rate was done to elucidate the most successful methods of AED withdrawal. RESULTS: Fifty-seven patients (73%) experienced seizure recurrence after starting withdrawal within 2 years. Over 12 months of withdrawal duration (p=0.037) and under 20 percent per month of the decrement rate of carbamazepine (p=0.019) were related to reduce the seizure recurrence. These were also confirmed via survival curve analysis. CONCLUSIONS: This study is a new attempt to apply reduction rate in withdrawal. AED withdrawal duration and decrement rate are important factor to prognostic factors of desirable AED withdrawal and minimize the recurrence after withdrawal.

Multiple Cerebral Arterial Stenosis Associated with Hepatitis B Virus Infection

BACKGROUND: There are conflicting findings regarding the association between hepatitis B (HB) virus (HBV) infection and atherosclerosis. CASE REPORT: A 34-year-old man was admitted for transient dysarthria and facial palsy. Ten years previously he had been diagnosed with HBV infection and treated with lamivudine (100 mg/day). Reactivation of HBV was detected 6 months before this recent admission. Serologic tests revealed that he was positive for HB early antigen, HB surface antigen, and anti-HB core. Brain magnetic resonance images were normal, but magnetic resonance angiograms revealed severe stenosis of the right middle cerebral artery, both external carotid arteries, and the basilar artery. CONCLUSIONS: This case report reveals that a young patient with reactivated HBV developed multiple arterial stenoses even though he had no risk factors for this disease.

Intra-Arterial Thrombolysis after Full-Dose Intravenous tPA via the "Drip and Ship" Approach in Patients with Acute Ischemic Stroke: Preliminary Report / 전남의대학술지

According to the "drip and ship" concept, patients who are not responsive to intravenous tissue plasminogen activator (IV-tPA) at a community hospital may be candidates for subsequent intra-arterial (IA) thrombolysis at a comprehensive stroke center. We elucidated the efficacy and safety of combined IV/IA thrombolysis via the drip and ship approach. We retrospectively reviewed patients with acute ischemic stroke who underwent combined IV/IA thrombolysis between March 2006 and June 2009. The patients were divided into two groups (inside hospital IV-tPA vs. outside hospital IV-tPA). We compared the short- and long-term clinical outcome, recanalization rate, intracranial hemorrhage after the procedure, and onset to treatment time between the two groups. A total of 23 patients with inside hospital IV-tPA and 10 patients with outside hospital IV-tPA were included. The mean pre-treatment National Institutes of Health Stroke Scale (NIHSS) scores were 15.8 and 17.5, respectively. Baseline characteristics were not significantly different between the two groups. The NIHSS score at 1 week and favorable outcome rate (modified Rankin Scale < or =2) 3 months after the procedure were not significantly different (p=0.730 and p=0.141, respectively). The rate of recanalization and intracranial hemorrhage were not significantly different (p=0.560 and p=0.730, respectively). The onset to IA thrombolysis time was also not significantly different (222.7 vs. 239.3 minutes, p=0.455). Our results suggest that initiation of IV-tPA in a community hospital with rapid transfer to a comprehensive stroke center for subsequent IA thrombolysis can be a safe and feasible therapeutic option in acute stroke management.

Intra-Arterial Thrombolysis after Full-Dose Intravenous tPA via the "Drip and Ship" Approach in Patients with Acute Ischemic Stroke: Preliminary Report / 전남의대학술지

According to the "drip and ship" concept, patients who are not responsive to intravenous tissue plasminogen activator (IV-tPA) at a community hospital may be candidates for subsequent intra-arterial (IA) thrombolysis at a comprehensive stroke center. We elucidated the efficacy and safety of combined IV/IA thrombolysis via the drip and ship approach. We retrospectively reviewed patients with acute ischemic stroke who underwent combined IV/IA thrombolysis between March 2006 and June 2009. The patients were divided into two groups (inside hospital IV-tPA vs. outside hospital IV-tPA). We compared the short- and long-term clinical outcome, recanalization rate, intracranial hemorrhage after the procedure, and onset to treatment time between the two groups. A total of 23 patients with inside hospital IV-tPA and 10 patients with outside hospital IV-tPA were included. The mean pre-treatment National Institutes of Health Stroke Scale (NIHSS) scores were 15.8 and 17.5, respectively. Baseline characteristics were not significantly different between the two groups. The NIHSS score at 1 week and favorable outcome rate (modified Rankin Scale < or =2) 3 months after the procedure were not significantly different (p=0.730 and p=0.141, respectively). The rate of recanalization and intracranial hemorrhage were not significantly different (p=0.560 and p=0.730, respectively). The onset to IA thrombolysis time was also not significantly different (222.7 vs. 239.3 minutes, p=0.455). Our results suggest that initiation of IV-tPA in a community hospital with rapid transfer to a comprehensive stroke center for subsequent IA thrombolysis can be a safe and feasible therapeutic option in acute stroke management.

Myasthenia Gravis Aggravated by Steroid-Induced Isolated Mediastinal Tuberculous Lymphadenitis

BACKGROUND: Myasthenia gravis (MG) is occasionally aggravated by chronic infection, of which there are many kinds. CASE REPORT: We report herein the case of a 56-year-old woman with MG aggravated by the activation of isolated mediastinal tuberculous lymphadenitis (MTL) during corticosteroid administration. The possibility of MTL had been disregarded in the differential diagnosis of aggravation of MG weakness, because MTL without pulmonary manifestations is uncommon even in areas where tuberculosis is endemic. CONCLUSIONS: This case suggests that chronic infections such as tuberculosis should be considered in myasthenic patients with progressive exacerbation if definite evidence for aggravating factors of MG is not obtained.

Mononeuropathy Multiplex in a Patient with Chronic Active Hepatitis B

BACKGROUND: Mononeuropathy multiplex is a rare complication during the course of chronic he-patitis 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.

A Case of Recurrent Neuro-Behcet's Disease after Tooth Extraction

We report a 39-yr-old man with neuro-Behcet's disease (NBD) in remission who developed left-sided ataxia with a sensory deficit about 10 days after tooth extraction. Several years ago, he experienced a similar episode of relapse after tooth extraction. Brain magnetic resonance imaging showed a newly developed right thalamic lesion. In cerebrospinal fluid, lymphocyte-dominant pleocytosis and mild elevation of IgG were found. Immunologic factors may be important in the pathogenesis of NBD because of the time delay between tooth extraction and relapse. Careful observation and prevention are needed before dental procedures in patients with NBD.

Analysis of Posterior Circulation Vascularity in Vestibular Neuritis

BACKGROUND: Vestibular neuritis (VN) is one of the most common causes of acute vertigo. Viral infection is regarded to be the most common etiology of VN, but other various causes including labyrinthine ischemia have not yet been fully elucidated. We assumed that labyrinthine ischemia can develop from various disorders in the posterior circulation including vertebral artery hypoplasia and vertebrobasilar dolichoectasia. METHODS: Fifty-six patients with acute VN and 56 healthy controls were enrolled. Two neurologists independently used magnetic resonance angiography (MRA) to retrospectively investigate the posterior circulation in VN patients. The relation between the presence of VN and abnormalities of posterior circulation vascularity was analyzed. RESULTS: MRA findings of vertebral artery hypoplasia and vertebrobasilar dolichoectasia were present in 15 (27%) and 14 (25%) of the VN patients. However, the frequencies of these findings did not differ significantly from those in the healthy controls (p=0.16). CONCLUSIONS: The frequencies of vertebral artery hypoplasia and vertebrobasilar dolichoectasia did not differ significantly between VN patients and healthy subjects. We suggest that brain MRI and MRA are not essential in acute VN patients without central signs. Large prospective studies are needed to characterize the vascular etiology of vestibular neuritis.

Publicly Available Single Nucleotide Polymorphisms in Genes Possibly Susceptible to Antiepileptic Drug Resistance in Healthy Koreans

BACKGROUND: The completion of the human genome project means that a high-quality reference sequence of the gene-rich portion of the human genome is now available. However, the strong influence of ethnic, geographical, and other characteristics of study populations on the frequencies of different single-nucleotide polymorphisms (SNPs) makes it questionable whether foreign SNP data should be used in domestic studies. METHODS: Twenty-seven possible candidate genes of antiepileptic drug (AED) resistance were resequenced in a DNA pool from 200 healthy Koreans to identify SNPs and calculate their minor allele frequencies (MAFs). RESULTS: A total of 98 SNPs were present in 22 of the 27 genes: 28 were in the coding regions, 34 were in introns, 23 were in 5' near genes, 10 were in 5' untranslated regions, and 3 were in 3' near genes. CONCLUSIONS: The comparative analysis using the pooled DNA adopted in the present study was highly reliable in estimating MAFs and was compatible with the common disease/common variant hypothesis. The reported data on 98 publicly available SNPs of genes possibly associated with AED resistance that be useful to researchers with limited availability of domestic SNP data.

Polymorphisms in the Voltage-gated Sodium Channel Genes and Antiepileptic Efficacy of Carbamazepine

BACKGROUND: Voltage-gated sodium channels are responsible for the initial-depolarization component of action potentials in brain neurons, and hence they are the target for widely used antiepileptic drugs such as carbamazepine (CBZ). With the working hypothesis that genetic defect in voltage-gated sodium channels can alter the response to CBZ, this study was performed to elucidate the relationship between single-nucleotide polymorphisms (SNPs) of the SCN1A, SCN1B, and SCN2A genes and CBZ resistance in Korean epileptics. METHODS: Candidate SNPs of SCN1A, SCN1B, and SCN2A were developed using the pooled DNA from healthy controls (n=200), of which representative SNPs of each of SCN1A, SCN1B, and SCN2A were determined based on theoretical functional values. Each representative SNP was genotyped for a CBZ-resistant group (CRE, n=168) and a CBZ- responsive group (CSE, n=154), and the frequencies of alleles and genotypes of each SNP were compared between the two groups. RESULTS: Eighteen SNPs were developed in SCN1A, SCN1B, and SCN2A. SCN1A-PM in exon 16 of SCN1A, SCN1B-PM in exon 3 of a splicing variant of SCN1B, and SCN2A-PM in the 7th intronic sequence of SCN2A were selected as the representative SNPs for these genes. The distributions of alleles and genotypes of each representative SNP did not differ between the CRE and CSE groups. CONCLUSIONS: In Korean epileptics, there appears to be no significant relationship between representative SNPs of SCN1A, SCN1B, and SCN2A and CBZ resistance.

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.

Long-Term Durability of Percutaneous Transluminal Angioplasty in Patients with Symptomatic Middle Cerebral Artery Stenosis

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty (PTA) is being increasingly used in the treatment of symptomatic middle cerebral artery (MCA) stenosis. We evaluated the long-term durability after PTA for symptomatic MCA stenosis. METHODS: We analyzed consecutive patients included in our stroke database who were treated with angioplasty alone. The subjects without major periprocedural complications were followed up for at least 42 months. Recurrent ischemic symptoms were defined as newly developed episodes of transient ischemic attack or ischemic stroke in the territory of the treated vessel. Stroke was defined as ischemic stroke in any vessel. RESULTS: PTA was technically successful in 37 of the 40 included patients. Thirty-two of the 37 patients were followed up at regular intervals of 1 to 6 months in the outpatient clinic of our institution for at least 42 months. Restenosis occurred in 3 of the 32 patients (9.4%) within 2 years of PTA, and no restenosis was identified thereafter. Two of the three patients with restenosis had asymptomatic complications such as dissection and vasospasm during the intervention. The ischemic area was in the treated vessel in 1 of the 32 patients and in other vessels in 3 of the 32 patients (9.4%). CONCLUSIONS: Successful PTA can result in a low rate of recurrent ischemic symptoms, and restenosis during a long-term follow-up appears to be more frequent in the early period.

beta-Fibrinogen Gene -455 G/A Polymorphism in Korean Ischemic Stroke Patients

Background and Purpose: We investigated the relationship between the beta-fibrinogen gene (FGB) -455 G/A polymorphism and plasma fibrinogen levels in Korean ischemic stroke patients. We also determined whether the frequency of the -455 G/A polymorphism differed between two subtypes of noncardioembolic stroke: large-artery atherosclerosis (LAA) and small-vessel occlusion (SVO). Methods: A total of 267 patients with noncardioembolic stroke were enrolled. Plasma fibrinogen and other risk factors for stroke were evaluated. FGB -455 G/A genotypes were determined by polymerase chain reaction with restrictive enzyme Hae III and automatic DNA sequencing. Results: The FGB -455 G/A polymorphism was significantly associated with an elevated plasma fibrinogen level (p<0.001). The frequency of the A allele in Korean stroke patients was 16.7%. However, the frequency of the -455 G/A polymorphism did not differ between LAA and SVO. Conclusions: The plasma fibrinogen level might be affected by the -455 G/A polymorphism in noncardioembolic stroke patients. However, the LAA and SVO subtypes of ischemic stroke were not affected by the -455 G/A polymorphism.