Expanding Indications for a Ketogenic Diet as an Adjuvant Therapy in Adult Refractory Status Epilepticus: an Exploratory Study Using Moderation Analysis.

Refractory status epilepticus (RSE) requires multimodal treatment approaches to achieve rapid seizure cessation and neuroprotection. A ketogenic diet (KD) has demonstrated efficacy as a nutritional therapeutic option for adult RSE. However, the group of adult RSE patients who would benefit from adopting a KD needs to be determined to appropriately select the patients indicated for a KD. Therefore, we conducted a nonrandomized retrospective cohort study to explore the therapeutic efficacy of a KD by investigating the moderation effect of a KD on the association between the clinical characteristics of RSE patients and their functional outcomes. This study investigated 140 RSE patients, including 32 patients treated with a KD; among these patients, 28 (81%) achieved seizure cessation. We found that KD moderated the reduction in the modified Rankin scale (mRS) score at discharge among patients who were older, had higher seizure severity scores, were under continuous intravenous anesthetic therapy (CIVAD), and had super-RSE. Age and seizure severity scores, but not CIVAD or super-RSE, were associated with a KD-moderated change in mRS score at 3 months. Thus, we consider that our study provides evidence of a neuroprotective effect of KD in the most severe RSE patients with very few remaining therapeutic options, but future randomized controlled trials in these subgroups of KD patients are necessary.

ES-RED (Early Seizure Recurrence in the Emergency Department) Calculator: A Triage Tool for Seizure Patients.

Seizure is a common neurological presentation in patients visiting the emergency department (ED) that requires time for evaluation and observation. Timely decision and disposition standards for seizure patients need to be established to prevent overcrowding in the ED and achieve patients' safety. Here, we conducted a retrospective cohort study to predict early seizure recurrence in the ED (ES-RED). We randomly assigned 688 patients to the derivation and validation cohorts (2:1 ratio). Prediction equations extracted routine clinical and laboratory information from EDs using logistic regression (Model 1) and machine learning (Model 2) methods. The prediction equations showed good predictive performance, the area under the receiver operating characteristics curve showing 0.808 in Model 1 [95% confidential interval (CI): 0.761-0.853] and 0.805 in Model 2 [95% CI: 0.747-0.857] in the derivation cohort. In the external validation, the models showed strong prediction performance of 0.739 [95% CI: 0.640-0.824] in Model 1 and 0.738 [95% CI: 0.645-0.819] in Model 2. Intriguingly, the lowest quartile group showed no ES-RED after 6 h. The ES-RED calculator, our proposed prediction equation, would provide strong evidence for safe and appropriate disposition of adult resolved seizure patients from EDs, reducing overcrowding and delays and improving patient safety.

Usefulness of arterial spin labeling perfusion as an initial evaluation of status epilepticus.

This study aimed to evaluate the sensitivity and prognostic value of arterial spin labeling (ASL) in a large group of status epilepticus (SE) patients and compare them with those of other magnetic resonance (MR) sequences, including dynamic susceptibility contrast (DSC) perfusion imaging. We retrospectively collected data of patients with SE in a tertiary center between September 2016 and March 2020. MR images were visually assessed, and the sensitivity for the detection of SE and prognostication was compared among multi-delay ASL, DSC, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). We included 51 SE patients and 46 patients with self-limiting seizures for comparison. Relevant changes in ASL were observed in 90.2% (46/51) of SE patients, a percentage higher than those for DSC, FLAIR, and DWI. ASL was the most sensitive method for initial differentiation between SE and self-limiting seizures. The sensitivity of ASL for detecting refractory SE (89.5%) or estimating poor outcomes (100%) was higher than those of other MR protocols or electroencephalography and comparable to those of clinical prognostic scores, although the specificity of ASL was very low as 9.4% and 15.6%, respectively. ASL showed a better ability to detect SE and predict the prognosis than other MR sequences, therefore it can be valuable for the initial evaluation of patients with SE.

Pentobarbital coma therapy for super-refractory status epilepticus and in-hospital mortality: an observational study.

Treatment of super-refractory status epilepticus (SRSE) is associated with various complications of anaesthetic coma therapy. This study aimed to describe the factors affecting the prognosis, especially in-hospital mortality, of patients receiving pentobarbital coma therapy for the treatment of SRSE. This was a retrospective cohort study conducted in a single tertiary referral centre with patients who received pentobarbital coma therapy for the treatment of SRSE from 2006 to 2018. Exploratory analyses were performed for clinical, laboratory, electrographic, and radiological factors for the entire cohort and were compared between the mortality and survivor groups. In total, 19 patients were enrolled, and five (26.3%) patients died in the hospital. The maximal pentobarbital infusion dose was higher in the mortality group than in the survivor group (4.4±1.0 mg/kg/h vs. 2.9±1.4 mg/kg/h, respectively; p=0.025). The high-dose pentobarbital infusion group (>3.75 mg/kg/h) underwent longer mechanical ventilation (24 [20-36.75] vs. 41 [28-70], p=0.025) and blood culture results were more frequently positive, suggestive of septicaemia (8.3% vs. 57.1%, p=0.038). The group of SRSE patients treated with pentobarbital coma therapy who died in the hospital received a higher pentobarbital infusion dose compared to survivors; a complication of high-dose pentobarbital infusion was septicaemia. Considering the high rate of septicaemia observed, systematic treatment strategies focusing on infectious complications should be established and implemented. The association between maximal pentobarbital infusion dose and in-hospital mortality needs to be further validated.

Prognostic significance of subsequent extra-temporal involvement in cryptogenic new onset refractory status epilepticus (NORSE) initially diagnosed with limbic encephalitis.

INTRODUCTION: New-onset refractory status epilepticus (NORSE) is defined as refractory SE in patients without active epilepsy or relevant neurological disorder with no clear active causes. Diverse types and etiologies of NORSE are reported in various groups. Limbic encephalitis (LE) is reported as one of etiologies of NORSE. In this study, we investigated whether there were any intersections between NORSE and limbic encephalitis, as well as the presence of prognostic factors in intersection patients. METHODS: We retrospectively analyzed patients who met both the definition of NORSE and diagnostic criteria of LE at the initial presentation from our database. Clinical characteristics and blood test, cerebrospinal fluid, electroencephalography, and magnetic resonance imaging results were reviewed. Prognosis was recorded as ICU admission stay, total length of hospitalization, and modified Rankin Scale at discharge. In particular, we determined which factors were associated with patients' prognosis. RESULTS: Thirteen patients were selected. Nine of the 13 patients had myalgia and 8 patients had fever in the prodromal period. Twelve of the 13 patients had acute memory impairment or confusion before SE development. In addition, 46.2% of the patients showed leukopenia or thrombocytopenia. Median body temperature at hospital arrival was 37.6 °C. Nine patients showed generalized tonic-clonic SE. All patients were treated with immunotherapy and 11 of the 13 patients achieved burst suppression through induced coma therapy. Ten patients showed lesion extension on follow-up imaging. The most common extension site was the claustrum. Patients with more lesion extension showed poorer outcomes than those without lesion extension. CONCLUSION: Subsequent extratemporal lesion extension was closely associated with poor prognosis in NORSE-LE patients. This study explores a new subtype of NORSE and suggests a possible common underlying pathomechanism between NORSE and LE.

Uric acid is a useful marker to differentiate between responsive and refractory status epilepticus.

OBJECTIVES: Early recognition of refractory status epilepticus (RSE) is essential to select an appropriate treatment strategy and is closely associated with the outcome. Only few studies of RSE biomarkers exist; hence, we investigated the serum levels of uric acid (UA), albumin, and C-reactive protein (CRP) as potential serologic biomarkers for RSE. PATIENTS AND METHODS: Consecutive status epilepticus (SE) patients who had serial conventional blood tests in a referral hospital over a period of 10 years were retrospectively analyzed. Patients with anoxic encephalopathy, renal failure, acute stroke, and myocardial infarction were excluded. RSE was defined as seizure continuing after the first- and second-line treatments. We also assessed SE severity in all included patients using the Status Epilepticus Severity Score (STESS). General demographics and blood test findings were compared between responsive SE and RSE patients. RESULTS: A total of 141 patients (99 responsive and 42 refractory) were recruited from our SE registry. Compared to responsive patients, patients with RSE showed a higher STESS, lower initial albumin levels, lower initial UA levels, lower follow-up UA levels, and greater reduction of UA levels. The RSE group more frequently had acute symptomatic etiology, showed longer hospitalization, and had poorer functional outcomes compared to the responsive-SE group. All evaluated UA level parameters exhibited significant areas under the curve in receiver operating characteristic analyses, predictive of RSE. Initial UA levels, as well as changes therein, were significantly associated with RSE in multivariate logistic regression analysis. CONCLUSION: UA levels at initial and follow-up evaluations, and changes therein differentiated responsive SE and RSE, demonstrating the feasibility of UA serum levels as a biomarker for RSE.

Cigarette smoking is an independent risk factor for post-stroke delirium.

BACKGROUND: Post-stroke delirium is a common problem in the care of stroke patients, and is associated with longer hospitalization, high short-term mortality, and an increased need for long-term care. Although post-stroke delirium occurs in approximately 10 ~ 30% of patients, little is known about the risk factors for post-stroke delirium in patients who experience acute stroke. METHODS: A total of 576 consecutive patients who experienced ischemic stroke (mean age, 65.2 years; range, 23-93 years) were screened for delirium over a 2-year period in an acute stroke care unit of a tertiary referral hospital. We screened for delirium using the Confusion Assessment Method. Once delirium was suspected, we evaluated the symptoms using the Korean Version of the Delirium Rating Scale-Revised-98. Neurological deficits were assessed using the National Institutes of Health Stroke Scale at admission and discharge, and functional ability was assessed using the Barthel Index and modified Rankin Scale at discharge and 3 months after discharge. RESULTS: Thirty-eight (6.7%) patients with stroke developed delirium during admission to the acute stroke care unit. Patients with delirium were significantly older (70.6 vs. 64.9 years of age, P = .001) and smoked cigarettes more frequently (40% vs. 24%, P = .033) than patients without delirium. In terms of clinical features, the delirium group experienced a significantly higher rate of major hemispheric stroke (55% vs. 26%, P < .001), exhibited poorer functional performance at discharge and 3 months after discharge, and stayed in hospital significantly longer. Independent risk factors for delirium were older age, history of cigarette smoking, and major hemispheric stroke. CONCLUSION: Abrupt cessation of cigarette smoking may be a risk factor for post-stroke delirium in ischemic stroke patients. The development of delirium after stroke is associated with worse outcome and longer hospitalization.

Cerebral arterial calcification is an imaging prognostic marker for revascularization treatment of acute middle cerebral arterial occlusion.

BACKGROUND AND PURPOSE: To study the significance of intracranial artery calcification as a prognostic marker for acute ischemic stroke patients undergoing revascularization treatment after middle cerebral artery (MCA) trunk occlusion. METHODS: Patients with acute MCA trunk occlusion, who underwent intravenous and/or intra-arterial revascularization treatment, were enrolled. Intracranial artery calcification scores were calculated by counting calcified intracranial arteries among major seven arteries on computed tomographic angiography. Patients were divided into high (HCB; score ≥3) or low calcification burden (LCB; score <3) groups. Demographic, imaging, and outcome data were compared, and whether HCB is a prognostic factor was evaluated. Grave prognosis was defined as modified Rankin Scale 5-6 for this study. RESULTS: Of 80 enrolled patients, the HCB group comprised 15 patients, who were older, and more commonly had diabetes than patients in the LCB group. Initial National Institutes of Health Stroke Scale (NIHSS) scores did not differ (HCB 13.3±2.7 vs. LCB 14.6±3.8) between groups. The final good reperfusion after revascularization treatment (thrombolysis in cerebral infarction score 2b-3, HCB 66.7% vs. LCB 69.2%) was similarly achieved in both groups. However, the HCB group had significantly higher NIHSS scores at discharge (16.0±12.3 vs. 7.9±8.3), and more frequent grave outcome at 3 months (57.1% vs. 22.0%) than the LCB group. HCB was proven as an independent predictor for grave outcome at 3 months when several confounding factors were adjusted (odds ratio 4.135, 95% confidence interval, 1.045-16.359, P=0.043). CONCLUSIONS: Intracranial HCB was associated with grave prognosis in patients who have undergone revascularization for acute MCA trunk occlusion.

Evaluation of coexistence of Alzheimer's disease in idiopathic normal pressure hydrocephalus using ELISA analyses for CSF biomarkers.

BACKGROUND: We investigated levels of the ß-amyloid 1-42 (Aß42), total tau protein (T-tau) and tau phosphorylated at position threonine 181 (P-tau) in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (iNPH) patients and tried to find their clinical implications in the evaluation and treatment of iNPH. METHOD: Twenty-five possible iNPH patients were prospectively enrolled and their CSF was collected to analyze levels of Aß42, T-tau and P-tau using ELISA method. Gait disturbance, urinary incontinence, and cognitive impairment were semi-quantified and detailed neuropsychological (NP) test was performed. RESULT: Eight iNPH patients were classified into the lower CSF Aß42 group and 17 patients were classified into the higher CSF Aß42 group. There was no difference in the iNPH grading score and its improvement after LP between the two groups. The lower CSF Aß42 group showed more deficits in attention, visuospatial function and verbal memory in the baseline NP test and less improvement in phonemic categorical naming and frontal inhibitory function after LP. CONCLUSIONS: Our study suggested that concomitant AD in iNPH patients might contribute to lumbar puncture or shunt unresponsiveness, especially in the field of cognitive dysfunction.

Galantamine administration in chronic post-stroke aphasia.

BACKGROUND: To investigate the influence of galantamine on linguistic function, any associated factors in patients with chronic post-stroke aphasia were analysed. METHODS: 45 patients younger than 75 years with chronic aphasia (≥1 year since onset) were prospectively enrolled in the study. Language testing was performed at weeks 0 and 16. Initial galantamine dose was 8 mg/day for 4 weeks, and 16 mg/day for the following 12 weeks. Efficacy was evaluated by the sum of four domains (spontaneous speech, comprehension, repetition and naming) on the aphasia quotient (AQ) of the Western Aphasia Battery from baseline (AQ1) to endpoint (AQ2). Patients were considered as 'responding' if the increase in AQ was ≥20. RESULTS: Mean age was 60.4 years (22-74) and 14 patients were female. Mean duration of aphasia was 2.2±1.5 years. There was a significant increase in the total AQ score in the galantamine group (n=23, 48.5-57.0 percentile; p=0.007) but not in the control group (n=22, 54.3-54.9 percentile; p=0.308). The AQ2 score was independently associated with AQ1, galantamine administration and Mini-Mental State Examination (MMSE) score in multiple linear regression models. With the galantamine group, the good responders (vs poor responders) had a higher level of education (p=0.048), higher baseline MMSE score (p=0.009) and a subcortical dominant pattern (p=0.030). After adjusting for potential variables, subcortical dominant lesion was the independent determinant for galantamine responsiveness (OR 30.3; 95% CI 1.1 to 805.9, p=0.041). CONCLUSION: Administration of galantamine had a beneficial effect on chronic post-stroke aphasia, and was more prominent in subcortical dominant lesions.

Induced-hypertension in progressing lacunar infarction.

BACKGROUND: Although an early neurological deterioration after lacunar infarction is not rare, its therapeutic options are still undetermined. We investigated the effect of induced-hypertension in lacunar infarction with motor progression. METHODS: We reviewed 82 lacunar infarction patients who experienced motor progression [≥ 1-point increase of NIH stroke scale (NIHSS) during hospitalization]. Induced-hypertension using phenylephrine was applied to 52 patients and the others received conventional treatment. Target blood pressure (BP) was defined as a 20% increase of initial systolic BP and motor stabilization time as a period from motor progression to motor stabilization. Good outcome was designated as a modified Rankin disability scale 0-2 at discharge in phenylephrine group. RESULTS: Phenylephrine group (vs. conventional group) had a lower NIHSS motor score after each treatment (p=0.022), a shorter motor stabilization time (p<0.001) and hospitalization period (p=0.047), although there were not significantly different from baseline clinical and laboratory findings (ie. age, sex, risk factors for stroke, initial BPs, and NIHSS motor score) in two groups. In multiple regression analysis, a history of hypertension (odds ratio, OR 7.11, 95% CI 1.43-35.31, p=0.016), achievement of target BP (OR 8.13, 95% CI 1.49-44.45, p=0.016) and motor stabilization time (OR 0.51 per 1-day increase, 95% CI 0.29-0.87, p=0.015) were independent predictors for good outcome in the phenyephrine group. Side effects of phenylephrine treatment were transient chest tightness (n=3) and dysuria (n=2). CONCLUSION: The present study suggests that phenylephrine induced-hypertension can result in early motor restoration without serious side effects in progressing lacunar infarction.

The missing button sign as a tool for detecting proximal internal carotid artery occlusion.

The aim of this study was to develop a simple and reliable sign for detecting proximal internal carotid artery occlusion (ICAO) using conventional CT scanning. The missing button sign (MBS) is defined as the absence of the ICA at the level of the foramen magnum on contrast-enhanced CT (CECT) scans. Two raters independently reviewed random CECT samples from consecutive patients with acute ischaemic stroke. A total of 399 patients with 798 carotid arteries were analysed. Rater A identified the MBS in 41 (5%) of the carotid arteries, and did not identify the MBS in 735 (92%) carotid arteries. Rater B identified the MBS in 45 (6%) of the arteries, and lack of the MBS in 731 (91%) arteries. The kappa value for agreement was 0.90 (95% CI 0.84-0.95). Compared with CT angiography, Rater A's sensitivity, specificity, positive predictive value, and negative predictive value for detecting proximal ICAO were 85%, 100%, 100%, and 99%, respectively, while Rater B's values were 87%, 99%, 93%, and 99%, respectively. This study indicated that the MBS on CECT scanning is both a consistent and specific tool for the early identification of proximal ICAO.

Simultaneous vasomotor reactivity testing in the middle cerebral and basilar artery with suboccipital probe fixation device.

BACKGROUND: We assess the feasibility of using the newly designed suboccipital probe fixation device (SPFD) as a convenient and reliable tool for simultaneous measurement of vasomotor reactivity (VMR) in the middle cerebral artery (MCA) and basilar artery (BA). METHODS: We analyzed 30 healthy volunteers' VMR values by using both SPFD and conventional handheld method. The VMR values were measured as percentage increase of the mean flow velocity on transcranial Doppler (TCD) in response to hypercapnia induced by the rebreathing method. The VMR tests were performed three times: (1) for both MCAs, (2) for the index MCA (the better signal window) and the BA by using the SPFD, and (3) for the index MCA and the BA by using the handheld technique. RESULTS: The VMR values of the right and left MCAs were similar (P > .05). Although the VMR values of the index MCA and the BA obtained by SPFD application and the handheld technique were similar (P > .05), the correlation coefficient of VMR values obtained by using the SPFD was higher (r= .827, P < .001 vs. r= .568, P= .001). CONCLUSION: The SPFD is a convenient and reliable tool for the evaluation of relative VMR between the MCA and BA during TCD monitoring.

Frequency and clinical significance of acute bilateral cerebellar infarcts.

BACKGROUND: Unlike acute unilateral cerebellar infarct (UCI), acute bilateral cerebellar infarcts (BCI) have attracted little attention. To evaluate the clinical significance of BCI, we compared UCI and BCI and analyzed potentially prognostic factors. METHODS: Patients who were consecutively admitted at a university hospital over a 4-year period with acute cerebellar infarcts, proven by diffusion-weighted imaging, were studied. Cerebellar infarcts were topographically classified, and divided into 2 groups: UCI and BCI. The demographics, involved territories, concomitant lesions outside the cerebellum (CLOC), bilateral involvement, infarct volume, hospital courses, and mechanisms were analyzed. We performed multiple regression analysis to predict the poor outcome at discharge [> or =3 on the modified Rankin Scale (mRS)]. RESULTS: Among 162 patients with acute cerebellar infarcts, 31% (n = 50) were BCI. Territorial infarcts were 74% (n = 120) and non-territorial infarcts 26% (n = 42) of the total. Posterior inferior cerebellar artery infarcts were the most common, and combined-territorial infarcts were the rarest. Baseline demographics were not significantly different between UCI and BCI, except for initial stroke severity (modified NIH Stroke Scale and infarct volume) and diabetes. Large-artery atherosclerosis was significantly higher in BCI, whereas undetermined causes were higher in UCI (p = 0.028). By multiple regression analysis, BCI was the only independent radiological factor for poor prognosis (odds ratio, 6.96; 95% CI, 1.80-26.92), and represented a significantly more unstable hospital course, longer hospital stay, worse mRS at discharge, and higher mortality. CONCLUSIONS: In acute cerebellar infarcts, bilateral involvement is common and appears to be a superior determinant for early prognosis rather than territories involved or CLOC.

Disrupted intracellular calcium regulates BACE1 gene expression via nuclear factor of activated T cells 1 (NFAT 1) signaling.

Beta-site APP-cleaving enzyme 1 (BACE1) expression is elevated in the brains of Alzheimer's disease (AD) patients and in aged-animal models. Because both AD and aging are associated with disrupted calcium homeostasis, we investigated the role of nuclear factor of activated T cells (NFAT) - a transcription factor regulated by the calcium- and calmodulin-dependent phosphatase calcineurin - in BACE1 expression. BACE1 expression was stimulated by a calcium ionophore in primary cortical cultures, and by SH-SY5Y neuroblastoma cells, which was both blocked by pretreatment with either cyclosporin A, an inhibitor of calcineurin, or ethyleneglycotetraacetic acid, a calcium chelator. Gel shift assays revealed direct binding of NFAT1 to specific DNA sequences within the BACE1 gene promoter region. Treatment with amyloid beta (Abeta), one of the major factors in AD pathogenesis, stimulated activation and nuclear translocation of NFAT1 following up-regulation of BACE1 expression. In addition, primary cortical cultures from Tg2576 mouse brains generated more Abeta by ionophore stimulation, which was reversed by cyclosporin A treatment. Furthermore, NFAT1 activation was observed in Tg2576 mouse brains. These results suggest that calcium ionophore- or Abeta-induced increases in intracellular calcium concentration stimulate BACE1 expression, resulting in accelerated Abeta generation, and that this process is mediated through the calcineurin-NFAT1 signaling pathway. This process may play a significant role in the pathogenesis of AD and aging.

Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing.

Although ex vivo culture expansion is necessary to use autologous mesenchymal stem cells (MSCs) in treating stroke patients, and several researchers have utilized culture-expanded cells in their studies, the effects of culture expansion on neurogenesis and trophic support are unknown. Thus, we evaluated the impact of the passage of MSCs on their effects in a rat stroke model. The i.v. application of ex vivo-cultured human MSCs, earlier (passage 2) or later passage (passage 6), was performed in a rat stroke model. Behavioral tests, immunohistochemical studies, and quantitative analysis using the CAST-grid system were performed to evaluate the degree of neurogenesis. We also evaluated the levels of trophic factors in both control and MSC-treated rat brain extract. Compared to rats that received later-passage human MSCs, behavioral recovery and neurogenesis as revealed by bromodeoxyuridine staining were more pronounced in rats that received earlier-passage human MSCs (p < 0.01 in both cases). Double staining showed that most of the endogenous neuronal progenitor cells, but few human MSCs, expressed neuronal and glial phenotypes. Tissue levels of trophic factors, including glial cell line-derived neurotrophic factor, nerve growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were higher in earlier-passage MSC-treated brains than in control or later-passage MSC-treated brains (p < 0.01 in all cases). Our results indicate that ischemia-induced neurogenesis was enhanced by the i.v. administration of human MSCs. The effects were more pronounced with earlier-passage than with later-passage human MSCs, which may be related to the differential capacity in trophic support, depending on their passage.

Serial magnetic resonance imagings of multiple brain abscesses in a patient with pneumococcal meningoencephalitis.

We report a 43-yr-old man manifesting bacterial meningoencephalitis and multiple abscesses by Streptococcus pneumoniae. Serial magnetic resonance (MR) imagings and MR spectroscopy showed the evolution of multiple brain abscesses over 4 weeks: the enhanced rings became thicker and the dimension of whole lesions larger despite shrinkage of the ring-enhanced regions. These findings may be evidence of active inflammation working to sequestrate the lesion and protect the surrounding normal brain parenchyma from additional damage, even in the final stage of the brain abscess.

Can aspirin resistance be clinically predicted in stroke patients?

OBJECTIVES: Aspirin resistance is one of several possible explanations for limited efficacy or treatment failure of aspirin. However, the predictors of aspirin resistance are not well known. We therefore conducted a study of laboratory-defined aspirin resistance in Korean patients with ischemic stroke and considered a wide range of factors as possible predictors. PATIENTS AND METHODS: A total of 88 patients taking aspirin daily for the secondary prevention of stroke were included. Platelet function was assessed using the Rapid Platelet Function Assay-Aspirin (RPFA-ASA) system and the level of urinary thromboxane B2 (TX-B2). The result of the RPFA-ASA system was expressed as an aspirin reaction unit (ARU). We analyzed a wide range of factors including demographic data, stroke risk factors, and laboratory findings to identify the clinical predictors of aspirin resistance. RESULTS: Eleven (12%) patients were identified as aspirin resistant by the ARU criteria. Univariate analysis showed that an older age, lower LDL cholesterol levels, and concurrent use of angiotensin converting enzyme inhibitors or receptor blockers were related to aspirin resistance by ARU criteria. Aspirin resistance by urinary TX-B2 criteria was observed in 18 (25%) patients and associated with an older age, metabolic syndrome, diabetes, cigarette smoking, and the use of angiotensin-converting enzyme inhibitors or receptor blockers. In multivariate analysis, this association lost significance by ARU criteria, and only lower fibrinogen levels were associated with increased risk by TX-B2 criteria. In addition, the stroke subtypes and the degree of atherosclerosis were not associated with aspirin resistance. The correlation between the two criteria was poor (r=-0.115, p=0.34). CONCLUSION: Despite the comprehensive analysis of this study, we failed to identify independent predictors for laboratory-defined aspirin resistance. Additionally, little overlap was found between the two criteria with which to assess aspirin resistance.

Efficacy and safety of levetiracetam as adjunctive treatment of refractory partial seizures in a multicentre open-label single-arm trial in Korean patients.

This prospective, open-label study evaluated the efficacy and safety of adjunctive levetiracetam (LEV) in Korean adults with uncontrolled partial epilepsy. Study patients had to have an average of at least 1 and not more than 14 partial seizures per month (averaged over a 3-month historical baseline) despite the use of one or two AEDs. Patients initially received LEV 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of LEV could be increased or decreased once if seizure control was insufficient or tolerability warranted, respectively. Seizure count and adverse events (AEs) were recorded by patients. Global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated. A total of 100 patients were enrolled and 92 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 43.2%. The >or=50% and >or=75% responder rates were 45.4% and 36.1%, respectively. Seizure freedom throughout the 16-week treatment period was observed in 17 patients. On investigator's GES, 81 patients were considered improved, with 41 patients showing marked improvement. Most QOLIE-31 scales improved significantly. Treatment-emergent AEs were reported in 59 patients. Three most common AEs were somnolence (36%), dizziness (12%), and headache (8%). Adjunctive LEV therapy was effective and well-tolerated in Korean adults with refractory partial epilepsy.