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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

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 [≥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. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 22 patients with ET, in comparison with early PD and tremor-dominant PD (TDPD). The mean ratio of 123I-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. © 2006 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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≥1 year during the follow-up period.Results:Sixty-six (75%) patients achieved complete seizure freedom for≥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≥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≥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. [ABSTRACT FROM AUTHOR]

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) β-agonist, with those of estrogen. Genistein and 17β-estradiol showed comparable levels of protection against Aβ-induced deaths of cultured SH-SY5Y human neuroblastoma cells, which were blocked by an estrogen receptor antagonist, ICI 182,780. On the other hand, 17β-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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: Peripheral neuropathy following cisplatin treatment is a major limiting factor in cisplatin chemotherapy of cancer patients. We investigated the pathomechanism underlying cisplatin neuropathy using a mouse dorsal root ganglion neuron-neuroblastoma hybrid cell line (N18D3) developed in our laboratory. DNA fragmentation, a characteristic feature of apoptosis, was induced in hybrid neurons following treatment with cisplatin. Accumulation of p53, Fas, and Fas ligand (Fas-L) was also demonstrated in these neurons. Preincubation with N-acetylcysteine (NAC), a precursor of glutathione, blocked cisplatin-induced apoptosis completely, whereas Trolox, a vitamin E analogue, blocked it partially. Cisplatin-induced p53 accumulation was suppressed by NAC treatment, whereas p53 accumulation was retarded by Trolox treatment. In contrast, neither NAC nor Trolox showed any inhibitory effect on cisplatin-induced Fas/Fas-L accumulation. These results suggest that the neuroprotective effects of antioxidants against cisplatin-induced neurotoxicity in hybrid neurons are mediated mainly through the inhibition of p53 accumulation but not of Fas/Fas-L accumulation by these antioxidants. [ABSTRACT FROM AUTHOR]

• There are intersectional patients who fulfilled the definition of NORSE and criteria of LE. • About half of NORSE-LE patients showed leukopenia or thrombocytopenia on initial evaluation. • Three-fourths of patients showed lesion extension to extra-temporal areas, specifically claustrum. • Subsequent extra-temporal involvement was closely associated with poor prognosis. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]