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Aim: To date, there is no reported effective biomarker that can predict which Alzheimer's disease (AD) patients will respond to donepezil and which will not. This study aimed to investigate whether baseline values of Aβ oligomers (AβOs), measured by the Multimer Detection System-Oligomeric Aβ (MDS-OAβ), can be used to predict responders after 6 months of donepezil medication., Methods: The study enrolled 104 patients diagnosed with probable AD. After 6 months of donepezil medication, the response to treatment was evaluated by re-assessing the Korean version of the Mini-Mental State Examination (K-MMSE) and Clinical Dementia Rating scale-Sum of Box (CDR-SB) scales conducted at baseline. The patients were categorized into two groups according to the baseline MDS-OAβ values known as the cut-off for AD diagnosis: a group with values below 0.78 and another group with values equal to or above 0.78., Results: After 6 months of medication, the number of responders was 50 (49.5%). Responders exhibited significantly worse baseline CDR, CDR-SB, K-MMSE, and Barthel index compared with non-responders. There was a significantly higher number of responders among patients with MDS-OAβ values below the cut-off of 0.78 compared with those with values equal to or above this threshold. Furthermore, there was a significant improvement in the K-MMSE and CDR-SB after 6 months of donepezil medication in patients with MDS-OAβ values below 0.78 compared with those with values equal to or above 0.78., Conclusions: Baseline MDS-OAβ values might constitute a novel biochemical marker for the efficacy of 6 months of donepezil treatment in AD. Geriatr Gerontol Int 2024; 24: 918-923., (© 2024 Japan Geriatrics Society.)

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., (© 2022. The American Society for Experimental Neurotherapeutics, Inc.)

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.

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., (© 2021. The Author(s).)

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.

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

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.

Background: We investigated levels of the β-amyloid 1-42 (Aβ42), 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 Aβ42, 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 Aβ42 group and 17 patients were classified into the higher CSF Aβ42 group. There was no difference in the iNPH grading score and its improvement after LP between the two groups. The lower CSF Aβ42 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.

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.

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., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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.

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.

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.

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.

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.

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., (2008 S. Karger AG, Basel.)

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.

Beta-site APP cleaving enzyme 1 (BACE1) is an essential enzyme for the production of beta amyloid. Since we found that injection of interferon-gamma (IFN-gamma) into young mouse brains increased BACE1 expression in astrocytes, we investigated molecular mechanisms underlying this process by cloning a putative BACE1 promoter. BACE1 promoter activity was differentially regulated by IFN-gamma in a region specific manner and down-regulated by an inhibitor of Janus kinase 2 (JAK2). A dominant negative mutant of signal transducer and activator of transcription 1 (STAT1) expression suppressed BACE1 promoter activity, and this was rescued by transfecting wild type STAT1. Electrophoretic mobility shift assay and promoter activity assays indicated that STAT1 binds directly to the putative STAT1 binding sequence of BACE1 promoter. Because IFN-gamma treatment induced STAT1 phosphorylation, we examined whether the expression of a suppressor of cytokine signaling (SOCS), negative regulator of JAK2, suppresses BACE1 promoter activity. The results show that SOCS1 or SOCS3 expression suppressed BACE1 promoter by blocking phosphorylation of Tyr701 residue in STAT1. Also, because IFN-gamma treatment specifically potentiated extracellular signal regulated MAP kinase (ERK) 1/2 activation, pretreatment of mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, PD98059, significantly attenuated IFN-gamma-induced BACE1 promoter activity and protein expression through blocking phosphorylation of Ser727 residue in STAT1, suggesting that ERK1/2 is associated with IFN-gamma-induced STAT1 signaling cascade. Taken together, our results suggest that IFN-gamma activates JAK2 and ERK1/2 and then phosphorylated STAT1 binds to the putative STAT1 binding sequences in BACE1 promoter region to modulate BACE1 protein expression in astrocytes., (Copyright 2006 Wiley-Liss, Inc.)

In some cases, it is difficult to differentiate essential tremor (ET) from Parkinson's disease (PD), especially in the early stages of the disease. We investigated cardiac sympathetic dysfunction using (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 22 patients with ET, in comparison with early PD and tremor-dominant PD (TDPD). The mean ratio of (123)I-MIBG uptake in the region of interest in the heart to that in the mediastinum (H/M ratio) was significantly greater in patients with ET (1.99 +/- 0.21) than in those with either TDPD (1.28 +/- 0.11) or early PD (1.28 +/- 0.17; each P < 0.001). The H/M ratio in all patients with ET was greater than two standard deviations above the range of the ratio in the patients with early PD or TDPD., ((c) 2006 Movement Disorder Society)

The nature of the association between ischemic stroke and Alzheimer's disease (AD) at the cellular and molecular level is still unknown. We evaluated the effect of ischemic neuronal insults on the regulation of amyloid precursor protein (APP) processing. We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation) to evaluate the effect of ischemic neuronal insults on the amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line and primary cultured cells of transgenic mice which expressed human APP (Tg2576). Ischemic neuronal insults increased the production of Abeta in Tg2576 primary culture cells compared to controls. A disintegrin and metalloprotease 10 (ADAM 10) was markedly increased in early stage of ischemic insults, which was followed by decreased level of ADAM 10 expression in later stage. The protein and mRNA expression of beta-site cleavage enzyme (BACE) and BACE activity was not significantly different between the group of ischemic insults and control. By contrast, the activity of gamma-secretase was significantly increased after 4 h of ischemic insults, as compared to controls. The present study showed that the ischemic neuronal insults increased the production of Abeta by influencing APP metabolism, which may link the role of ischemic insults to the pathogenesis of AD.

Background and Purpose: (123)I cardiac meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used to estimate myocardial sympathetic nerve function. We investigate whether cardiac-MIBG SPECT is clinically applicable in the differentiation of Parkinson's disease (PD) from parkinsonian syndromes., Methods: Cardiac-MIBG scintigraphy was performed in 27 controls, in 40 patients with PD and in 52 patients with other parkinsonian syndromes comprising 23 with multiple system atrophy (MSA), 26 with drug-induced parkinsonism (DIP), and 3 with corticobasal degeneration (CBD). The heart to mediastinum (H/M) uptake ratio was calculated for each subjects. Patients who either had medical conditions that confused the MIBG SPECT results or who took medications that interfere with MIBG accumulation were excluded from the study., Results: Both early and delayed H/M ratios were in patients with PD significantly lower than in controls (early, 1.34+/-0.15 vs 1.79+/-0.19; delayed, 1.29+/-0.15 vs 2.06+/-0.29, p<0.001). In patients with PD, both early and delayed H/M ratios were significantly lower than those in patients with MSA (early, 1.68+/-0.23; delayed, 1.80+/-0.34, p<0.001), DIP (early, 1.83+/-0.24; delayed, 2.07+/-0.4, p<0.001), or CBD (early, 1.85+/-0.01; delayed, 1.99+/-0.19, p<0.001). Two patients with DIP, who were within the range of patients with PD, showed clinically similar courses of PD., Conclusions: This study demonstrates that cardiac-MIBG is a clinically powerful tools to differentiate PD from other parkinsonian syndromes.

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) score is known to be effective in predicting the likelihood of recovery after stroke. However, the baseline NIHSS score predicts long-term outcomes rather crudely because early changes in stroke scores may influence the stroke outcomes. Therefore, a precise prognostic algorithm or a cutoff point for predicting long-term outcomes based on data from serial NIHSS scores is needed., Methods: We serially assessed 437 patients with acute symptomatic ischemic stroke within the middle cerebral artery territory who presented with nonlacunar stroke and were followed-up for at least 6 months after symptom onset. The NIHSS score was serially checked at 0, 1, 3, 7, and 14 days after admission. In all patients, the Barthel index (BI) and the modified Rankin Scale (mRS) score were checked, with a poor outcome defined as any of the following endpoints: death, modified mRS score of >3, or BI of <60., Results: A marked neurological improvement or worsening (i.e., a change in the NIHSS score of at least 4) was seen in 13.5% or 5.5% of the patients, respectively, during the first 7 days after admission. About 25% of the 437 patients had poor long-term outcomes. Analysis of receiver operating characteristic curves showed that the NIHSS score at day 7 after admission was better for predicting poor long-term outcomes than was the baseline score (P=0.003). In addition, we analyzed the cutoff point of the 7th-day NIHSS score for predicting a poor outcome at 6 months after symptom onset. An NIHSS score of at least 6 at day 7 after admission predicted poor long-term outcomes with a sensitivity of 84% [95% confidence interval (CI), 76-90%], a specificity of 92% (95% CI, 88-94%), and positive and negative predictive values of 77% and 95%, respectively. A logistic regression analysis revealed that age, diffusion-weighted imaging lesion volume, stroke history, and 7th-day NIHSS score were independently associated with poor outcome. However, no score used in addition to the 7th-day NIHSS score improved the prediction of a poor outcome., Conclusions: An NIHSS score of at least 6 on day 7 after admission accurately forecasts a poor long-term outcome after stroke. Our data may be helpful in predicting the long-term prognosis as well as in making decisions regarding novel therapeutic applications in subacute-stroke trials.

Background and Purpose: Although gait disturbance is an important feature of idiopathic normal pressure hydrocephalus (NPH), only tentative theories have been offered to explain its pathophysiology. It has been suggested that the mesencephalic locomotor region is the anatomical substrate for the development of the hypokinetic NPH gait. To investigate this possibility, we evaluated the correlation between gait disturbance and midbrain diameter., Methods: We enrolled 21 patients with NPH and 20 age-matched control subjects for the study. The maximal diameter of the midbrain and pons, and the width of the lateral and third ventricles were measured using midsagittal T1-weighted MRI and axial T2-weighted MRI, respectively. Gait disturbance, cognitive dysfunction, and incontinence were semiquantified., Results: The maximal midbrain diameter was significantly smaller in the NPH group than in the controls (14.8 +/- 0.9 vs. 17.1 +/- 0.7 mm, p < 0.001). There were inverse correlations between the midbrain diameter and the widths of the two ventricles (r = -0.562, p = 0.008 for the third ventricle, and r = -0.510, p = 0.018 for the lateral ventricle). The severity of gait disturbance was negatively correlated with the midbrain diameter (r = -0.598, p = 0.004), but the degree of cognitive dysfunction and incontinence showed no significant correlation with midbrain diameter or ventricular width., Conclusions: This study suggests that midbrain atrophy is significantly associated with gait disturbance in NPH.

Background: The role of several cardiogenic risk factors, including patent foramen ovale, in patients with cryptogenic stroke has been extensively studied. However, little attention has been paid to the role of non-cardioembolic causes of cryptogenic stroke. We therefore sought to identify the characteristics of cryptogenic stroke., Methods: We studied 832 patients with acute infarction in the middle cerebral arterial territory. We divided the patients into four subtypes: 402 with large artery atherosclerosis (LAA), 133 with cardioembolism, 182 with small arterial occlusion (SAO), and 115 with cryptogenic stroke. We compared risk factors and lesion patterns observed by diffusion-weighted imaging (DWI) between patients with cryptogenic stroke and those with stroke of other subtypes., Results: Both risk factors and DWI lesion patterns differed between the cryptogenic and cardioembolic groups (P<0.05). Risk factors for cryptogenic stroke were similar to those for the LAA and SAO groups. Similarly, DWI lesion patterns for cryptogenic stroke were similar to LAA patients. Large cortical infarcts on DWI were more common in the cardioembolic group than in the LAA or cryptogenic groups (P<0.001). In contrast, deep, non-lacunar (OR 5.02; 95% CI 2.68~9.40; P<0.001) and superficial perforator infarcts (OR 2.23; 95% CI 1.08~4.59; P=0.029) were independently associated with the cryptogenic group., Conclusions: Our results indicate that non-cardioembolic causes, such as macro- and microangiopathy, are important mechanisms in the pathogenesis of cryptogenic stroke.

Background: The risk factors for intracranial atherosclerosis are unclear but may differ from those for other stroke subtypes. Here, we investigated whether metabolic syndrome, an emerging risk factor for cardiovascular disease, is associated with intracranial atherosclerotic stroke., Methods: Using the Adults Treatment Panel III criteria, we evaluated the components of metabolic syndrome in 439 patients with ischemic stroke or transient ischemic attacks. The prevalence of metabolic syndrome within each stroke subtype was determined, and the association between intracranial atherosclerosis and metabolic syndrome was evaluated., Results: Metabolic syndrome was observed more frequently in patients with intracranial atherosclerosis than in those with other types of stroke (P=0.003). In a multiple regression analysis, metabolic syndrome, but not conventional risk factors, was independently associated with intracranial atherosclerosis (P=0.016). By contrast, the serum level of C-reactive protein was correlated negatively with the presence of intracranial atherosclerosis. Intracranial atherosclerosis was most prevalent in patients with metabolic syndrome and low levels of C-reactive protein (P=0.024)., Conclusions: Our results indicate that metabolic syndrome is a strong independent risk factor for intracranial atherosclerotic stroke. Therefore, treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerotic stroke.

Repetitive involuntary limbs movements have been mostly reported in patients with extensive brainstem pathologies, but the region responsible is unknown. We describe two patients with progressive basilar artery infarcts who showed automatic stepping and one patient with an osmotic demyelination disorder who showed periodic involuntary leg movements. By subtracting diffusion-weighted images before and after the development of repetitive involuntary leg movements, the brainstem lesion responsible for the involuntary movements was distinctively located in the vicinity of the pontine tegmentum, which is known as the pontine inhibitory region in animal studies.

Purpose: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy., Methods: The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for >or=1 year during the follow-up period., Results: Sixty-six (75%) patients achieved complete seizure freedom for >or=1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction (n=60), and in seven (12%) patients after discontinuation of AEDs (n=38). The seizure recurrence rate was not different between the immediate-and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, nine (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in six of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs. 23%). At the final assessment, 54 (61%) patients had been seizure free >or=1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration., Conclusions: Our results suggest that seizure freedom without aura at >or=1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period.

Estrogen is beneficial to patients with Alzheimer's disease (AD) but has a limited clinical use due to its proliferative and oncogenic effects on non-neuronal cells responsive to estrogen. In an attempt to find an estrogen substitute that retains the beneficial effects of estrogen with minimal side effects, we compared the neuroprotective and proliferative effects of genistein, a selective estrogen receptor (ER) beta-agonist, with those of estrogen. Genistein and 17beta-estradiol showed comparable levels of protection against Abeta-induced deaths of cultured SH-SY5Y human neuroblastoma cells, which were blocked by an estrogen receptor antagonist, ICI 182,780. On the other hand, 17beta-estradiol, but not genistein, induced proliferation of uterine endometrial cells. Our results suggest that genistein is a potential alternative to estrogen in the treatment of Alzheimer's disease.

Charcot-Marie-Tooth disease with deafness is a clinically distinct entity and is associated with mutations or deletions in several genes including PMP22 gene. Here, we report a large family showing characteristic phenotypes of Charcot-Marie-Tooth type 1A along with deafness in an autosomal dominant fashion. We detected a sequence variation (c.68C>G) co-segregating with the disease phenotype and leading to a T23R missense mutation in PMP22.

Background: The significance of occlusive lesions of the parent artery in patients with lacunar syndrome (LS) and small deep infarcts (SDIs) on diffusion-weighted imaging remains unclear., Objective: To compare the recurrence of stroke in patients with LS and SDIs between those with vs without a parent arterial lesion., Design: Analysis of data from a prospective acute stroke registry., Setting: University hospital., Patients: Using clinical syndrome, diffusion-weighted imaging, and vascular studies, we divided 173 patients into 3 groups: (1) parent arterial disease occluding deep perforators (PAD), LS with SDIs, and a parent arterial lesion (n = 32); (2) small artery disease (SAD) (n = 70); and (3) large artery disease (LAD) (n = 71)., Main Outcome Measures: Recurrent strokes and the prognosis were registered for 1 year, and the outcome of the PAD group was compared with that of the SAD and LAD groups., Results: During follow-up, there were 9 deaths (6 vascular) and 18 recurrent strokes. The recurrence rate in the PAD group (16%) was significantly higher than that in the SAD group (1%) (P =.01) but similar to that in the LAD group (17%) (P =.87). The presence of the parent arterial lesion was the only independent predictor of stroke recurrence in patients with LS and SDIs (odds ratio, 13.8; 95% confidence interval, 1.5-123.9; P =.02)., Conclusions: Although LS on examination, SDIs on diffusion-weighted imaging, and a stable hospital course suggest lacunar stroke of benign course, our results indicate that the PAD group represents an intracranial type of LAD.

Background: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome. This study localized the lesion and examined the pathogenic mechanism in Korean patients with GAWH, and investigated whether areas of extensive hypoperfusion existed outside the diffusion-weighted imaging (DWI) lesions seen in these patients., Material and Methods: Eleven patients were diagnosed with aphasia using the Western Aphasia Battery. To identify decreased perfusion, which might be functionally relevant to aphasia but not detected by DWI, single photon emission tomography (SPECT) was performed in five patients. To uncover the possible pathogenic mechanisms of ischemic stroke, vascular and cardiologic work-ups were performed in all of the patients., Results: The lesions seen on DWI varied, and included both inferior frontal and superior temporal (three), isolated inferior frontal (four) or superior temporal (one), subcortical (two), and even parieto-occipital (one) lesions. Brain SPECT did not reveal an extensive lesion of the peri-sylvian area outside the DWI lesion in any of the patients, except one with the subcortical lesions., Conclusion: Our results indicate that a single lesion in different locations may be sufficient to produce GAWH, and the lesion profile and stroke mechanism in GAWH are heterogeneous, suggesting that lesions to an area of complex functional anatomy result in aphasia.

The precise anatomical location and pathophysiology of gait ignition failure (GIF) is poorly understood. We investigated the cerebral perfusion patterns using subtraction brain single photon emission computed tomography (SPECT) in a patient with GIF. Subtraction brain SPECT imaging revealed an increased activity in the region of right ventrolateral midbrain and ventral medulla., (Copyright 2003 Movement Disorder Society)

Background: Comparative studies of clinical and magnetic resonance imaging findings in patients with spinocerebellar ataxias (SCAs) have been seldom reported., Objective: To investigate clinical, genetic, and neuroradiological characteristics of SCAs in Korean kindreds., Setting: University hospital., Patients and Methods: Molecular analysis of SCA types 1, 2, 3, 6, and 7 and dentatorubral pallidoluysian atrophy and magnetic resonance imaging were performed in 67 patients with ataxia., Results: The overall prevalence of 6 types of SCAs was 54% (36 of 67 patients), irrespective of patients' family histories. The most frequent type was SCA7 (11 patients, 16%), followed by SCA3 and SCA6 (10 patients, 15% for both). Certain clinical features suggested specific gene defects, although overlap among the 6 SCA subtypes was broad: visual disturbance was noted in patients with SCA3 and SCA6, dystonia in 1 patient with SCA6, and sporadic ataxia without pigmentary retinopathy in 1 patient with SCA7. Compared with the control subjects, patients with SCAs and multisystem atrophy had a significant enlargement of the fourth ventricle and atrophy of the cerebellum (P<.01). An inverse correlation between the pontine area and the degree of cerebellar atrophy was found in patients with multisystem atrophy (r = -0.73) but not in patients with SCAs. Magnetic resonance imaging revealed significant differences in pattern of morphological alterations among patients with different SCA gene mutations. A similar finding was observed in SCA patients with atypical phenotype., Conclusion: The clinical and neuroradiological characteristics of Korean patients with SCAs might be helpful in detecting underlying gene mutations.

Background and Purpose: Because of difficulty in distinguishing between superficial perforator (SP) and internal border-zone (IB) infarcts, some studies lumped SP and IB infarcts together as so-called subcortical white matter infarcts, which might complicate the classification of infarct type and its pathogenesis. Using diffusion-weighted MRI (DWI), we made comparative analyses of clinical and neuroradiological characteristics between IB and SP infarcts to clarify the difference in underlying pathogenesis., Methods: We selected SP and IB infarcts on DWI using templates for the identification of subcortical vascular territories. Sex, age, neurological symptoms, clinical course, risk factors, concomitant cortical spotty lesions, and degree and location of arterial occlusive disease were compared between the 2 groups., Results: Among the 720 consecutive patients, 54 and 29 patients met the criteria for SP and IB infarcts, respectively. The SP group had lower initial National Institutes of Health Stroke Scale scores (2.4+/-2.1 versus 4.4+/-3.1; P=0.001), favorable clinical outcomes (P=0.001), and more frequent potential cardioembolic sources (14.8% versus 0%; P=0.046) than the IB group. Cortical spotty lesions were more frequently accompanied by SP than IB infarcts (72.2% versus 24.1%; P<0.001). IB infarcts were larger (24.2+/-10.2 versus 11.4+/-8.5 mm; P<0.001), appeared in a chainlike fashion (72.4% versus 33.3%; P=0.001), and had a higher degree of stenosis or occlusion (86.2% versus 46.3%; P=0.001) compared with SP infarcts., Conclusions: Our present study suggests that embolic pathogenesis makes a greater contribution to SP infarcts than IB infarcts. This finding may explain the difference in clinical and neuroradiological characteristics between the 2 groups.

The purpose of this study was to better understand the frequency and mechanisms of stroke recurrence after the stroke with no determined cause (NC). We prospectively studied consecutive patients with acute cerebral infarcts. We divided the patients into five groups (large artery disease [LAD], cardioembolism [CE], small artery disease [SAD], two or more causes [TMC], and NC) and registered recurrent strokes and prognosis for 1 year. Those in the NC group were compared with other subtypes. A total of 204 patients were included; 56 LAD, 22 CE, 62 SAD, 27 TMC, and 37 NC. During follow-up, there were 7 deaths and 31 first recurrent strokes. Patients of the NC group showed a significantly higher rate (30%) of recurrent stroke than those of other subtypes (LAD 16%; CE 14%; SAD 2%), and it was associated with the existence of mild stenosis (

To evaluate the differential diagnostic role of apolipoprotein E (apoE) genotype in dementia, we carried out a meta- analysis of 78 case-control series, including our own new data. The dementia subjects were grouped into Alzheimer's disease (AD) and non-AD. AD patients were subgrouped according to their subtypes, and non-AD patients into vascular dementia (VD), mixed dementia (MD), and non-AD non-VD dementia (NAVD). The apoE allele frequencies and apoE genotype-specific odds ratio (OR) of each group were estimated. The (4 allele frequency was higher in all of the dementia subgroups than in the elderly controls, and the associations with (4 allele were lower in the non-AD (OR 1.8) patients than in the AD (OR 4.2) patients. However, the apoE-related risk alsovaried as a function of the subgroup, in both the AD and non-AD groups; for AD, it was dependent on the subtype of AD (OR 2.3 - 11.3), and higher in late- onset and familial cases than in early-onset and sporadic cases, respectively; among non-AD patients, it was higher in MD (OR 2.6) than in VD (OR 1.3), and intermediate in NAVD (OR 1.9), in which a significant difference was also found between Lewy body dementia (LBD) type (OR 5.1) and non-LBD type (OR 1.3). In conclusion, variability in the apoE-related risk was found in both the AD and non-AD cases, depending on the subgroup. Therefore, precise subgrouping of both AD and non-AD patients should be performed, and this information should taken into consideration when interpreting the results of apoE genotyping.

Purpose: We evaluated the accuracy of transcranial Doppler (TCD) criteria in detecting middle cerebral artery (MCA) stenoses other than solitary severe stenoses., Methods: Three TCD criteria were evaluated in patients with acute MCA territory infarction who also underwent angiography: abnormalities in mean velocity (MV), focal areas of spectral waveform abnormalities, and compensatory increase in MV in collateral vessels., Results: Among 102 patients studied, angiography revealed MCA lesions in 48: 16 had uncomplicated lesions (single stenosis of moderate to severe degree), 19 had mildly complicated lesions (single MCA stenosis of other than moderate to severe degree, or moderate to severe MCA stenosis with a concomitant lesion outside the MCA), and 13 had severely complicated lesions (MCA stenosis of other than moderate to severe degree with a concomitant lesion outside the MCA). The sensitivity of abnormalities in MV in uncomplicated MCA lesions was 81%, whereas it was 53% in mildly complicated MCA lesions and 38% in severely complicated MCA lesions. However, a compensatory increase in MV in collaterals was more frequently found in complicated MCA lesions, and focal areas of spectral waveform abnormalities were observed fairly consistently in all groups., Conclusions: TCD findings of focal areas of spectral waveform abnormalities and compensatory collateral flow were common in complicated MCA lesions and may improve the specificity of TCD in the diagnosis of MCA stenosis., (Copyright 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:142-151, 2003)

Background and Purpose: The transcranial Doppler (TCD) findings in symptomatic small deep infarction are not well known. The aim of this study was to evaluate the role of TCD in striatocapsular small deep infarctions (SSDIs)., Methods: The cerebral angiography and TCD findings were analyzed on 100 patients with symptomatic cerebral infarcts on the middle cerebral artery (MCA) territory. The sensitivity, specificity, and accuracy of TCD in detecting the MCA lesions were compared between lacunar group (the patients with lacunar syndrome and SSDIs on magnetic resonance image) and nonlacunar group., Results: Thirty-eight patients were classified as the lacunar group, whereas 62 patients as the nonlacunar group. On angiography, occlusive lesion of MCA was found in 18 of the lacunar group and 24 patients of the nonlacunar group. The degree of MCA stenosis was higher in the nonlacunar group (80.8% +/- 21.2%) than the lacunar group (60.4% +/- 21.6%). The accuracy of TCD for the detection of MCA stenosis was not different between the groups. However, the sensitivity of TCD in the lacunar group was lower (72%) than in the nonlacunar group (88%), and it might have been due to the difference in the degree of MCA stenosis among the groups., Conclusion: Occlusive lesions of the MCA should be considered as a potential cause of SSDIs. In this respect, TCD may be used for screening candidates for conventional angiography in those patients. High rate of mild-degree stenosis of MCA in patients with SSDIs, however, caused a risk for missing such stenosis on TCD.

Background: The significance of the stenotic lesions of the middle cerebral artery (MCA) in Asian patients with striatocapsular small, deep infarctions (SSDIs) remains undetermined., Objectives: To investigate the frequency of stenotic lesions of the MCA in patients with SSDIs and to evaluate clinical and radiological features in those same patients., Setting: Acute stroke registry of a university hospital., Patients and Methods: One hundred two Korean patients with acute symptomatic SSDIs underwent cerebral angiography or magnetic resonance angiography and echocardiography. We divided these patients into 2 groups-patients with and without MCA occlusive lesions. The clinical and magnetic resonance image features were compared between these 2 groups., Results: Thirty-seven patients (36%) had an ipsilateral proximal MCA lesion, whereas 65 patients (64%) showed no MCA abnormality on cerebral angiography or magnetic resonance angiography. Among 65 patients without an MCA lesion, 18 had an embolic source; the remaining 37 patients had no demonstrable embolic source. There were significant differences in the temporal profile and magnetic resonance imaging findings between the groups. Although the type of lacunar syndrome and the volume of infarcts did not differ between the groups, the unstable temporal profile and magnetic resonance imaging findings of multiple small infarcts in the symptomatic hemisphere were frequently observed in patients with MCA lesions., Conclusions: The proximal MCA lesion was a common cause of SSDIs in Korean patients. Depending on the existence of an MCA lesion, the clinical course and magnetic resonance imaging feature of the patients with SSDIs were different.