Long-standing neuromyelitis optica with leukodystrophy-like asymptomatic MRI changes.

Patients with neuromyelitis optica (NMO) are unlikely to develop clinically silent lesions on brain magnetic resonance imaging (MRI), unlike patients with multiple sclerosis (MS). We encountered a patient with NMO who showed radiological progression and leukodystrophy-like changes on MRI during a long-standing, clinically asymptomatic period.

MRI-negative myelitis associated with MOG-IgG antibody: A case report and literature reviews.

According to few case reports, myelin oligodendrocyte glycoprotein-associated disease (MOGAD) could present as myelitis subtype with normal spine MRI, though it is rare. Herein, we report a case of clinically myelitis but MRI was normal, with strongly positive anti-MOG-IgG antibody in the sera. The patient showed a rapid improvement following a high dose methylprednisolone treatment.

Translocator Protein (18 kDa) Polymorphism (rs6971) in the Korean Population.

Background and Purpose: The expression of the 18-kDA mitochondrial translocator protein (TSPO) in the brain is an attractive target to study neuroinflammation. However, the binding properties of TSPO ligands are reportedly dependent on genetic polymorphism of the TSPO gene (rs6971). The objective of this study is to investigate the rs6971 gene polymorphism in the Korean population. Methods: We performed genetic testing on 109 subjects including patients with mild cognitive impairment, Alzheimer's disease (AD) dementia, non-AD dementia, and cognitively unimpaired participants. Magnetic resonance imaging scans and detailed neuropsychological tests were also performed, and 29 participants underwent 18F-DPA714 PET scans. Exon 4 of the TSPO gene containing the polymorphism rs6971 (Ala or Thr at position 147) was polymerase chain reaction amplified and sequenced using the Sanger method. The identified rs6971 genotype codes (C/C, C/T, or T/T) of the TSPO protein generated high-, mixed-, or low-affinity binding phenotypes (HABs, MABs, and LABs), respectively. Results: We found that 96.3% of the study subjects were HAB (105 out of 109 subjects), and 3.7% of the subjects were MAB (4 out of 109 subjects). 18F-DPA-714 PET scans showed nonspecific binding to the thalamus and brainstem, and increased tracer uptake throughout the cortex in cognitively impaired patients. The participant with the MAB polymorphism had a higher DPA714 signal throughout the cortex. Conclusions: The majority of Koreans are HAB (aprox. 96%). Therefore, the polymorphism of the rs6971 gene would have a smaller impact on the availability of second-generation TSPO PET tracers.

Factors associated with functional disability in patients with acute stroke excluded from alteplase administration due to minor non-disabling neurological deficits.

Background: Although the PRISMS study did not demonstrate the benefit of intravenous alteplase administration in patients with mild stroke within 3 h, about 30% of patients presenting with mild symptoms showed unfavorable functional outcomes. We investigated the factors predictive of functional disability at 90 days in patients who were excluded from alteplase administration due to the National Institutes of Health Stroke Scale (NIHSS) scores of 0-5 and a score between 0 and 2 for each NIHSS score item. Methods: All patients were diagnosed with acute ischemic stroke or transient ischemic attack within 4.5 h of admission to a tertiary hospital and did not receive alteplase due to a minor stroke between January 2013 and December 2020. Radiological data and clinical information were collected, including baseline and discharge NIHSS scores and modified Rankin Scale (mRS) scores at 90 days. Early neurological deterioration (END) was defined as an increase of two or more NIHSS scores. We defined moderate motor weakness as a NIHSS limb motor score of more than 3 and defined a favorable outcome as a mRS score at 90 days that was 0 or 1. Results: During the investigation period, 400 patients did not receive alteplase. END occurred significantly more frequently in patients with large artery disease (LAD) than in those with other TOAST classifications. In the multivariate regression analysis, NIHSS per 1-point increase, presenting as moderate motor weakness, and LAD were independent predictors of poor functional outcome (OR, 1.811 NIHSS per 1-point increase; 95% confidence interval [CI], 1.503-2.182; P < 0.0001; OR, 2.173 moderate motor weakness; 95% CI 1.028-4.595; P = 0.042; OR, 2.033 LAD; 95% CI 1.099-3.762; P = 0.024, respectively). Conclusion: Moderate motor weakness presentation and LAD may be important factors associated with poor functional outcomes in patients with acute stroke excluded from alteplase administration due to mild symptoms.

Residual Shunt after Patent Foramen Ovale Device Closure in Patients With Cryptogenic Stroke: Serial Bubble Contrast Transesophageal Echocardiography Data.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is an alternative option to medical treatment for secondary prevention for cryptogenic stroke (CS). Despite technical success of procedure, residual shunt (RS) which is a presumable cause for recurrent stroke is observed in some patients. We evaluated the RS with serial follow-up bubble contrast transesophageal echocardiography (BCTEE) after PFO closure. METHODS: Among consecutive 47 CS patients who underwent PFO closure, a serial follow-up BCTEE at 3 and 9 months after the index procedure was completed in 38 patients (81%, 46 ± 10 years, 19 men). To evaluate the efficacy of PFO closure, the incidence of any and significant RS (≥ moderate) was assessed. RESULTS: All PFO closure procedures were successful. The Amplatzer PFO Occluder (n = 19) or the Gore Septal Occluder (n = 19) were used. Any RS was observed in 13 (34%) and 10 patients (26%) at 3 and 9 months after the procedure. Significant RS was observed in 6 (16%) and 4 (11%) patients at 3- and 9-month follow-up BCTEE. Patients who were treated with the Gore Septal Occluder have a less incidence of any RS in 3 months, and any/significant RS in 3- and 9-month follow-up BCTEE without statistical significance. CONCLUSIONS: RS grade keeps decreasing after PFO closure, but it remains even after 9 months in some patients. Incomplete sealing of PFO should be taken into consideration in management of CS patients even after technically successful PFO closure.

Molecular characterization of rice arsenic-induced RING finger E3 ligase 2 (OsAIR2) and its heterogeneous overexpression in Arabidopsis thaliana.

Arsenic (As) accumulation adversely affects the growth and productivity of plants and poses a serious threat to human health and food security. In this study, we identified one As-responsive Really Interesting New Gene (RING) E3 ubiquitin ligase gene from rice root tissues during As stress. We named it Oryza sativa As-Induced RING E3 ligase 2 (OsAIR2). Expression of OsAIR2 was induced under various abiotic stress conditions, including heat, salt, drought and As exposure. Results of an in vitro ubiquitination assay showed that OsAIR2 possesses an E3 ligase activity. Within the cell, OsAIR2 was found to be localized to the Golgi apparatus. Using yeast two-hybrid (Y2H) assay, the 3-ketoacyl-CoA thiolase (KAT) protein was identified as an interaction partner. We found that the O. sativa KAT1 (OsKAT1) is localized to the cytosol and peroxisomes. Moreover, in vitro pull-down assay verified the physical interaction between OsAIR2 and OsKAT1. Interestingly, in vitro ubiquitination assay and in vivo proteasomal degradation assay revealed that OsAIR2 ubiquitinates OsKAT1 and promotes the degradation of OsKAT1 via the 26S proteasome degradation pathway. Heterogeneous overexpression of OsAIR2 in Arabidopsis improved the seed germination and increased the root length under arsenate stress conditions. Therefore, these results suggest that OsAIR2 may be associated with the plant response to As stress and acts as a positive regulator of As stress tolerance.

The Impact of Discrepancy between Measured versus Stated Weight on Hemorrhagic Transformation and Clinical Outcomes after Intravenous Alteplase Thrombolysis.

BACKGROUND: An accurate measurement of patient weight is important in determining the dosage for intravenous alteplase thrombolysis. In most emergency rooms, however, weight is not measured. We investigated the difference between stated and measured weight and its effect on hemorrhagic transformation and clinical outcomes. METHODS: We enrolled 128 consecutive patients who had hyperacute stroke and were treated by alteplase. Alteplase dose was calculated using the weight provided by patient or guardian/caregiver, and the actual weight was measured after administration. Patients were classified into 2 groups: overused group (stated weight >measured weight) and underused group (measured weight ≥stated weight). The prevalence of hemorrhagic transformation on follow-up, determined by gradient-recalled echo MRI or non-enhanced CT, was compared between the 2 groups. The predictors for hemorrhage with progression, defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) by a value of 4 or more accompanied by hemorrhage, were determined using multivariable logistic regression analysis and included the overused or underused alteplase and baseline clinical and laboratory findings. RESULTS: Sixty-six (51.6%) of 128 patients were in the underused group and 62 patients (48.4%) in the overused group. The median difference between the stated and measured weights was 1.5 (interquartile range 0.56-3.81) kg, with the largest difference being 25.6 kg. Although there were no significant difference in baseline clinical and laboratory findings between the 2 groups, the overused group showed a significantly higher prevalence of hemorrhagic transformation (p = 0.012) and hemorrhage with progression (p = 0.025). The multivariable logistic regression analysis demonstrated that overused alteplase (OR 7.26; 95% CI 1.24-42.45; p = 0.028), baseline glucose (>144 mg/dL; OR 5.03; 95% CI 1.00-25.26; p = 0.050), and initial NIHSS (OR 1.13 per 1-point NIHSS increase; 95% CI 1.00-1.27; p = 0.047) in model 1 that use alteplase overdose as a categorical variable and overused alteplase (OR 1.67 1-mg increase; 95% CI 1.05-2.66; p = 0.027) in model 2 that use an overused alteplase dose as numerical variable were significant predictors for hemorrhage with progression. CONCLUSION: More alteplase usage than actual weight led to higher hemorrhagic transformation. As one of the predictors for clinical deterioration, it is important to administrate alteplase based on an accurately measured weight.

The role of phenylephrine in patients with small deep subcortical infarct and progressive weakness.

BACKGROUND AND PURPOSE: Although progression of small deep subcortical infarct (PSDI) comprises 12% to 36% of all small deep subcortical infarcts, the therapy for progression is not clear. This study investigated whether induced-hypertension therapy using phenylephrine is a useful therapy for PSDI. METHODS: A group of 2427 consecutive patients, diagnosed with stroke at a tertiary hospital over a period of 4years was reviewed retrospectively. We analyzed patients with small deep subcortical infarct using clinical, laboratory, and pulse wave velocity (PWV). PSDI is defined as one or more increase in the motor score according to the NIHSS. Good outcome was designated as a modified Rankin scale of 0 to 2 at discharge. RESULTS: Among all 662 patients who had a small deep subcortical infarct, 66 patients experienced motor progression (9.97%). The induced-hypertension therapy group (n=25) received phenylephrine, and the conventional group (n=41) received anticoagulation therapy such as heparin, volume expansion, or both. Although there were no significant differences in baseline clinical and laboratory findings, the PSDI group showed a significantly more frequent decrease in blood pressure at progression (P<0.0001) and higher PWV (P=0.001). The phenylephrine group (vs the conventional group) had a lower NIHSS score (P=0.036) and good outcome at discharge (P=0.004). In multiple regression analysis, PWV (OR, 1.004 per 1-cm/s increase; 95% CI, 1.001-1.008; P=0.018) was an independent predictor of good outcome in the phenylephrine group. A side effect of phenylephrine treatment was dysuria (n=1). CONCLUSIONS: The present study suggests that vascular stiffness can be not only a predictor for PSDI but also a predictor of motor improvement after induced-hypertension therapy using phenylephrine in lacunar stroke.

Vitamin D levels are not predictors of survival in a clinic population of patients with ALS.

OBJECTIVE: This study aimed to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations, bone mineral density (BMD), and the parameters of bone metabolism in amyotrophic lateral sclerosis (ALS) patients, and their correlation with survival. METHODS: We retrospectively analysed data of 100 ALS patients who consecutively visited a single referral ALS clinic between January and December 2011. Sex; age and site of symptom onset; and death were recorded. Serum 25(OH)D concentration was dichotomized as <10ng/ml and ≥10ng/ml. RESULTS: There was absent relationship between serum 25(OH)D and concentration of bone turnover parameters or between 25(OH)D and BMD. According to the results of the Kaplan-Meier analysis with log-rank test, the survival rates of patients without (≥10ng/ml) and of those with severe vitamin D deficiency (< 10ng/ml) were not significantly different. Cox regression analysis showed that a poor prognosis was most correlated with older age at onset and bulbar onset after adjustment for all the clinical factors. CONCLUSIONS: In conclusion, vitamin D levels were not correlated to other bone markers and survival in a clinic population of ALS patients.

Molecular characterization of Oryza sativa arsenic-induced RING E3 ligase 1 (OsAIR1): Expression patterns, localization, functional interaction, and heterogeneous overexpression.

High levels of arsenic (As) in plants are a serious threat to human health, and arsenic accumulation affects plant metabolism and ultimately photosynthesis, growth, and development. We attempted to isolate As-responsive Really Interesting New Gene (RING) E3 ubiquitin ligase genes from rice, and we have designated one such gene Oryza sativa arsenic-induced RING E3 ligase 1 (OsAIR1). OsAIR1 expression was induced under abiotic stress conditions, including drought, salt, heat, and As exposure. Results from an in vitro ubiquitination assay showed that OsAIR1 possesses E3 ligase activity. Within the cell, the expression of this gene was found to be localized to the vacuole. In a network-based analysis, we found significantly enriched gene ontology (GO) functions, which included ribonucleoprotein complexes such as ribosomes, suggesting that the function of OsAIR1 are related to translation. Differences in the proportion of seedlings with expanded cotyledons and root lengths, and the lack of differences in germination rates between OsAIR1-overexpressing lines and control plants under AsV stress, suggest that OsAIR1 may positively regulate post-germination plant growth under stress conditions.

Cefepime-Induced Non-Convulsive Status Epilepticus in a Patient with Normal Renal Function.

Cefepime-induced encephalopathy including nonconvulsive status epilepticus has been known to develop in the patients with renal impairment. However, we report a 74-year-old woman with normal renal function who developed stuporous mental status during cefepime administration. Electroencephalogram (EEG) revealed 2 Hz rhythmic sharp-and-waves continuously, which suggested nonconvulsive status epilepticus (NCSE). After cefepime discontinuation, clinical symptoms recovered gradually and EEG findings showed only background slowing without epileptiform discharges. Cefepime-induced NCSE could be developed even in the patients with normal renal function, when they are elderly. Therefore, clinicians should be aware of the possibility of cefepime-induced NCSE when prescribing cefepime even to the patients with normal renal function.

Identification of altered metabolic pathways of γ-irradiated rice mutant via network-based transcriptome analysis.

In order to develop rice mutants for crop improvement, we applied γ-irradiation mutagenesis and selected a rice seed color mutant (MT) in the M14 targeting-induced local lesions in genome lines. This mutant exhibited differences in germination rate, plant height, and root length in seedlings compared to the wild-type plants. We found 1645 different expressed probes of MT by microarray hybridization. To identify the modified metabolic pathways, we conducted integrated genomic analysis such as weighted correlation network analysis with a module detection method of differentially expressed genes (DEGs) in MT on the basis of large-scale microarray transcriptional profiling. These modules are largely divided into three subnetworks and mainly exhibit overrepresented gene ontology functions such as oxidation-related function, ion-binding, and kinase activity (phosphorylation), and the expressional coherences of module genes mainly exhibited in vegetative and maturation stages. Through a metabolic pathway analysis, we detected the significant DEGs involved in the major carbohydrate metabolism (starch degradation), protein degradation (aspartate protease), and signaling in sugars and nutrients. Furthermore, the accumulation of amino acids (asparagine and glutamic acid), sucrose, and starch in MT were affected by gamma rays. Our results provide an effective approach for identification of metabolic pathways associated with useful agronomic traits in mutation breeding.

A patient with atonic seizures mimicking transient ischemic attacks.

A focal atonic seizure is a partial seizure in which the ictal manifestation consists of paresis of the extremities or muscles on one side of the body, and this phenomenon can easily be misdiagnosed as a transient ischemic attack. An 86-year-old woman visited our hospital complaining of transient right upper extremity weakness lasting for 10 min following an unusual sensation in her chest accompanied by palpitations. On the third hospital day, she again complained of right arm weakness, which progressed to jerky movements of her right extremity accompanied by facial twitching and then generalized into a tonic-clonic seizure. The EEG displayed several interictal spikes in the contralateral temporal area, and the ictal SPECT, analyzed using the SISCOM system, showed an increased signal in both the contralateral superior parietal area and the mesial frontal area. In this case, the patient was diagnosed with focal atonic seizures as the cause of the monolimb weakness, which had been initially misdiagnosed aas transient ischemic attacks. In cases in which a patient presents with monolimb paresis, physicians should consider the possibility of an atonic seizure as the cause.

Molecular characterization of the cold- and heat-induced Arabidopsis PXL1 gene and its potential role in transduction pathways under temperature fluctuations.

LRR-RLK (Leucine-Rich Repeat Receptor-Like Kinase) proteins are believed to play essential roles in cell-to-cell communication during various cellular processes including development, hormone perception, and abiotic stress responses. We isolated an LRR-RLK gene previously named Arabidopsis PHLOEM INTERCALATED WITH XYLEM-LIKE 1 (AtPXL1) and examined its expression patterns. AtPXL1 was highly induced by cold and heat stress, but not by drought. The fluorescence signal of 35S::AtPXL1-EGFP was closely localized to the plasma membrane. A yeast two-hybrid and bimolecular fluorescence complementation assay exhibited that AtPXL1 interacts with both proteins, A. thaliana histidine-rich dehydrin1 (AtHIRD1) and A. thaliana light-harvesting protein complex I (AtLHCA1). We found that AtPXL1 possesses autophosphorylation activity and phosphorylates AtHIRD1 and AtLHCA1 in an in vitro assay. Subsequently, we found that the knockout line (atpxl1) showed hypersensitive phenotypes when subjected to cold and heat during the germination stage, while the AtPXL1 overexpressing line as well as wild type plants showed high germination rates compared to the knockout plants. These results provide an insight into the molecular function of AtPXL1 in the regulation of signal transduction pathways under temperature fluctuations.

Predicting stroke outcome using clinical- versus imaging-based scoring system.

BACKGROUND: Several models to predict outcome in ischemic stroke patients receiving intravenous (i.v.) alteplase can be divided into clinical-based and imaging-based systems. Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) and Dense cerebral artery sign/early infarct signs on admission CT scan, prestroke modified Rankin Scale (mRS) score, Age, Glucose level at baseline, Onset-to-treatment time, and baseline National Institutes of Health Stroke Scale score (DRAGON) are typical imaging- and clinical-based scoring systems, respectively. Therefore, we compared predictability of stroke outcome of clinical (DRAGON)- and imaging (ASPECTS)-based scoring systems. METHODS: We analyzed patients who were diagnosed with middle cerebral artery territory stroke and treated with i.v. alteplase at Gachon University Gil Hospital over 5 years and compared performance of 2 scoring systems for prediction of good functional outcome (mRS, 0-2) with Pearson correlation and area under the curve-receiver operating characteristic (AUC-ROC). In addition, we analyzed predicting power of several clinical factors and 2 scoring systems by multiple regression analysis. RESULTS: Study population (N = 120) had mean age of 66.2 ± 13.2 years. ASPECTS (r = -.841, P < .0001) and DRAGON (r = .657, P < .0001) were significantly correlated with good functional outcome. In addition, statistical comparisons suggested that ASPECTS (AUC-ROC, .972; 95% confidence interval [CI], .947-.996) is significantly superior to DRAGON (AUC-ROC, .854; 95% CI, .786-.922) in predicting functional outcome (difference between areas, .118 ± .0332; 95% CI, .0559-.180, P = .0002). Multiple regression analysis revealed that ASPECTS was the independent predictor of good prognosis (OR, 6.59 per 1-point increase; 95% CI, 2.35-18.49; P < .0001 and OR, 77.67 for ASPECTS ≥ 8; 95% CI, 14.30-421.79; P < .0001). CONCLUSIONS: ASPECTS is superior method for predicting functional outcome in acute ischemic stroke patients receiving i.v. alteplase compared with DRAGON and integration of ASPECTS score into clinical care pathway as decision-making tool can be reasonable.

Sleep problems associated with behavioral and psychological symptoms as well as cognitive functions in Alzheimer's disease.

BACKGROUND AND PURPOSE: It has been shown that sleep problems in Alzheimer's disease (AD) are associated with cognitive impairment and behavioral problems. In fact, most of studies have founded that daytime sleepiness is significantly correlated with cognitive decline in AD. However, a few studies have also shown that nighttime sleep problems are associated with cognitive function and behavioral symptoms in AD. Accordingly, the aim of this study was to evaluate the effects of nighttime sleep on cognition and behavioral and psychological symptoms of dementia (BPSD) in AD. METHODS: The study population comprised 117 subjects: 63 AD patients and 54 age- and sex-matched non-demented elderly subjects. Detailed cognitive functions and behavioral symptoms were measured using the Seoul Neuropsychological Screening Battery (SNSB) and the Korean version of the Neuropsychiatric Inventory (NPI-K). Sleep characteristics were evaluated using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K). The correlations between PSQI-K and SNSB scores and between PSQI-K and NPI-K scores were analyzed. RESULTS: In AD patients, sleep latency was found to be negatively correlated with praxis (p=0.041), Rey-Osterrieth Complex Figure Test (RCFT) immediate recall (p=0.041), and RCFT recognition (p=0.008) after controlling for age and education, while sleep duration and sleep efficiency were positively correlated with praxis (p=0.034 and p=0.025, respectively). Although no significant correlation was found between PSQI-K and NPI-K scores, sleep disturbance and total PSQI-K scores were found to be significantly associated with apathy/indifference in AD. CONCLUSIONS: Sleep problems such as prolonged sleep duration, sleep latency, and poor sleep efficiency in AD patients were correlated with cognitive dysfunction, and especially frontal executive and visuospatial functions, and BPSD. These findings suggest that treatment of nighttime sleep problems might improve cognition and behavioral symptoms in AD patients.