Focused Update of Guidelines for Antithrombotic Management of Patients with Atrial Fibrillation and Ischemic Stroke or Transient Ischemic Attack

Cardioembolic stroke related to atrial fibrillation is problematic due to high recurrence, mortality, and morbidity rates. The optimal anticoagulant therapy therefore needs to be applied to prevent the occurrence of a second stroke in patients with nonvalvular atrial fibrillation. The oral anticoagulant warfarin has traditionally been used, but it is limited by its narrow efficacy window, complex pharmacokinetics, and multiple drug interactions, thus requiring frequent blood monitoring. New oral anticoagulants have recently been developed that target a specific coagulation component. Dabigatran (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (inhibitors of factor Xa) have advantages of rapid action time, short half-life, stable plasma concentration, and few drug interactions. Large randomized clinical trials and meta-analyses have recently been published on the efficacy and safety of these new oral anticoagulants. Based on the results obtained in recent clinical trials, we have revised the recommendations for selecting optimal anticoagulant therapy in patients with nonvalvular atrial fibrillation.

Analysis of 10,811 Cases with Acute Ischemic Stroke from Korean Stroke Registry: Hospital-Based Multicenter Prospective Registration Study

BACKGROUND: Although several hospital-based stroke studies were published, there has not been any reliable data representing the clinical characteristics of stroke in Korea. We analyzed the clinical characteristics of patients with ischemic stroke registered in the Korean Stroke Registry (KSR), which is the largest prospective hospital-based nation-wide stroke registry in Korea. METHODS: The KSR provided standardized protocols for collecting data, which includes the data of demographics, subtypes of stroke, risk factors, and neurological outcome at discharge. The brain imaging studies, including CT or MRI, were performed in all cases. RESULTS: KSR registered 10,811 patients of acute ischemic stroke between Nov. 2002 and Jun. 2004. The large-artery atherosclerosis was the most common subtype (37.3%), followed by small vessel occlusion (30.8%). Hypertension (65.4%) was the most common risk factor, followed by smoking (34.5%) and diabetes (28.3%). Although most of the hypertensive and diabetic patients had been diagnosed before the stroke, less than 45.4% and 32.5% of them were under regular control. The steno-occlusive lesion of extracranial carotid artery was only 29.3% and the ratio of intra- to extracranial artery disease was more than 2 in KSR. Only 20.5% of patients were admitted within 3 hours after stroke onset and 2.1% were treated with intravenous thrombolysis. In-hospital case-fatality was 5.2%, which is relatively comparable to those of previous studies. CONCLUSIONS: The KSR provided informative data in understanding the clinical characteristics of ischemic stroke in Korea. Further analysis of KSR will facilitate clinical trials and development of guidelines for the management of stroke patients.

Methylenetetrahydrofolate Reductase Gene Polymorphism in Korean Patients with Migraine or Ischemic Stroke

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been implicated in both migraine and ischemic stroke. The homozygous C677T mutation in the MTHFR gene was more frequent in the Japanese and Turkish migraineurs than in the control group. Positive associations have also been found in ischemic stroke. The purpose of this study is to investigate the role of MTHFR C677T polymorphism in Korean patients with migraine or ischemic stroke. METHODS: We analyzed the allele frequencies and genotype of MTHFR C677T polymorphism in 115 patients with migraine, 213 with cerebral infarction, and 73 controls. RESULTS: There was no significantly increased frequency of homozygosity for the T677 allele in both of the diagnostic groups, compared to the controls. CONCLUSIONS: Our results suggest that MTHFR gene C677T polymorphism is unlikely to play a major role in the pathogenesis of migraine or ischemic stroke in Korean patients.

The Effectiveness of Physical Therapy for the Horizontal Canal Cupulolithiasis

BACKGROUND & OBJECTIVES: Recently many reports suggest the horizontal canal benign paroxysmal positional vertigo (h-BPPV) is not rare. However there have been few reports on physical therapy for horizontal canal cupulolithiasis, while horizontal canal canalithiasis has a relatively well defined and effective therapy. To evaluate the efficacy of different methods of treating horizontal canal cupulolithiasis, we conducted prospective study. METHODS: We enrolled 104 consecutive patients who were diagnosed with h-BPPV. During that period, patients with posterior canal BPPV numbered 112. Patients with h-BPPV were diagnosed when lateral head rotation in the supine position resulted in geotropic or apogeotropic bilateral horizontal nystagmus. In patients presenting with apogeotropic variant (n=40), following maneuvers was performed sequentially. First of all, we performed head shaking and applied vibrator to the mastoid bone to detach otolith from cupula. If they failed to detach otolith from cupula, we performed barbecue rotation and forced prolonged position (FPP). The treatment outcome was considered as responsive when, immediately after each physical therapy, nystagmus shifted from apogeotropic to geotropic or no nystagmus was elicited by provocation test and symptoms of positional vertigo abated. RESULTS: There were 27 women and 13 men from ages 30 to 80 (mean 55) years. The average duration of symptoms before intervention was 0 to 12 (mean 0.6) days. In 4 cases, symptoms resolved spontaneously after provocation test. Of the 36 patients treated with headshaking, 6 were responsive. Of the 30 patients treated with vibrator after failure of head shaking, only 1 were responsive. In the barbecue rotation, none obtained relief after barbecue rotation. Of the 9 patients treated with FPP after failure of the barbecue rotation, 4 were symptom free after FPP. Twenty five patients, including 5 non-responders with FPP, underwent no more rehabilitation maneuver. In most of cases (n=24), horizontal canal cupulolithiasis resolved spontaneously within a week. CONCLUSIONS: The direct effectiveness of physical therapy for horizontal canal cupulolithiasis is largely unsatisfactory. However, in many cases, horizontal canal cupulolithiasis resolved spontaneously in a few days.

Argatroban Treatment in Acute Ischemic Stroke: Multicenter, Randomized, Aspirin-Controlled Study

BACKGROUND: Argatroban, a direct thrombin inhibitor, has been suggested to be beneficial in acute ischemic stroke by preventing microthrombi formation. The aim of this multicenter, aspirin-controlled, randomized trial is to determine the safety and the efficacy of argatroban compared with aspirin in acute ischemic stroke. METHODS: The patients within 48 hours of noncardioembolic ischemic stroke were recruited from 8 centers. Argatroban was infused continuously at 2.5 mg/hr for the first 48 h, and then 10mg of argatroban was infused over 3 h twice a day on days 3-7. Control group received aspirin 300 mg/day for 7 days. The primary outcome was the NIHSS at 30 days and the secondary outcome was Barthel index (BI) and modified Rankin scale (mRS) at 90 days. The safety was evaluated by the incidence of bleeding complication. RESULTS: A total of 236 patients (123 for argatroban and 113 for aspirin) were included. NIHSS at 30 days, BI at 90 days and mRS at 90 days did not show significant difference between the argatroban and the aspirin group (3.1 +/- 3.1 vs 3.5 +/- 3.0, 88.9 +/- 22.5 vs 86.2 +/- 23.8, 1.4 +/- 1.1 vs 1.6 +/- 1.3, p>0.3, respectively). Post hoc analysis revealed that as for the patients who were treated within 24 hours after onset, numbers of patients with NIHSS=1 at 30 days were larger in the argatroban group (23 of 49) than in the aspirin group (10 of 40) (p=0.03). Bleeding complication was not different between the two groups (2 of 123 vs 0 of 113: p>0.4). CONCLUSIONS: Argatroban treatment is relatively safe in acute ischemic stroke. The efficacy of argatroban is not superior to aspirin. However, argatroban may be more beneficial in some subgroup of stroke patients than aspirin.

Treatment outcome of two different methods of canalith repositioning maneuver

BACKGROUND AND OBJECTIVES: Canalith repositioning procedure described by Epley is an effective treatment of benign paroxysmal positional vertigo (BPPV) based on the theory of canalithiasis. Although there are many modifications of Epley's maneuver, they have much similarity and are usually composed of 4 steps. However there is considerable variation of pause at each position from 6 seconds to 4 minutes. The purpose of this study is to determine treatment outcome of short and long pause at each position. MATERIALS AND METHODS: This is a randomized prospective study of patients with posterior canal type BPPV. One hundred patients were randomized to one of two groups at their first clinic visit between March 1999 and September 2000. The diagnosis was based on typical findings of vertigo and nystagmus by Dix-Hallpike maneuver and head turning in supine position. The authors treated patients with two different methods of the canalith repositioning procedure. One group maintained each position until the nystagmus stopped. If no nystagmus was observed, the position was maintained for 5 to 10 seconds. The other group maintained each position for 3 minutes. We assessed treatment outcomes of two methods. RESULTS: We can not find the difference of a success rate between two groups. CONCLUSION: It takes less than one minute with rapid head position changing method, so this method is more feasible in out-patients clinics.

Significance of Multifocal Hypointense Cerebral Lesions on Gradient-echo MRI in Patients with Hypertension or Hypertensive Intracerebral Hemorrhage

BACKGROUND: Multifocal hypointense cerebral lesions (MHCLs) manifesting as minute round signal loss on T2*-weighted gradient echo MR imaging (GE-MRI), are known to be frequently detected in chronic hypertensive patients. The purpose of this study was to elucidate the correlation among hypertension (HTN), intracerebral hemorrhage (ICH), and MHCLs. METHODS: We prospectively examined GE-MRI in 104 patients with HTN (40 ICH and 64 non-ICH patients) and 72 age and sex matched controls. MHCLs on GE-MRI were counted by two neurologists separately and determined as abnormal by consensus, and the number of MHCLs in each subject was graded as 0 (the number of MHCLs: 0), 1 (1-5), and 2 (>5). RESULTS: MHCLs were found in 71 of 104 patients with HTN (68.3%) and in 11 of 72 controls (15.3%). The grade of MHCLs was significantly correlated with HTN (p<0.001). In addition, MHCLs were discovered in 34 of 40 hypertensive patients with ICH (85%) and in 37 of 64 hypertensive patients without ICH (57.8%). The degree of MHCLs was more severe in the former than that in the latter with statistical significance (p<0.005). Multivariate analysis revealed that only HTN and the presence of ICH were the independent risk factors. CONCLUSIONS: Microaneurysm or microbleeding, which has been known as one of the characteristic findings of hyper-tensive microangiopathy, may be shown as MHCLs on GE-MRI. In this study, the positive correlation between MHCLs and HTN was clear. Moreover, we also found that in hypertensive patients with ICH, MHCLs are more fre-quently seen than in patients without ICH. These suggest the causal relationship between MHCLs and ICH. Further cohort study would be necessary in order to confirm this suggestion.