Regiodivergent Ring-Expansion of Oxindoles to Quinolinones.

The development of divergent methods to expedite structure-activity relationship studies is crucial to streamline discovery processes. We developed a rare example of regiodivergent ring expansion to access two regioisomers from a common starting material. To enable this regiodivergence, we identified two distinct reaction conditions for transforming oxindoles into quinolinone isomers. The presented methods proved to be compatible with a variety of functional groups, which enabled the late-stage diversification of bioactive oxindoles as well as facilitated the synthesis of quinolinone drugs and their derivatives.

Acute ischemic stroke in Tsutsugamushi: understanding the underlying mechanisms and risk factors.

BACKGROUND: Tsutsugamushi (scrub typhus) is an acute infectious febrile disease common in the Asia-Pacific region. Common symptoms of tsutsugamushi include lymphadenopathy, fever, and myalgia, and it rarely causes acute ischemic stroke (AIS). However, we hypothesized that tsutsugamushi infection could trigger AIS. METHOD: We retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over a 15-year period. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group and those (of similar age and sex) who did not develop AIS as the control group. The case and control groups consisted of 22 and 66 participants, respectively. When a scattered pattern was observed or lesions were found in two or more vascular territories on diffusion-weighted imaging, the pattern was defined as embolic. Other patterns were defined as nonembolic. RESULTS: Among the 19 patients, excluding three with transient ischemic stroke, 15 (78.9%) showed an embolic pattern. Although fever was common in the control group, it was less common in the case group. A higher D-dimer level at the time of hospitalization was associated with the development of AIS in patients with tsutsugamushi. CONCLUSIONS: AIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. It was more likely to occur in patients with risk factors for stroke. Tsutsugamushi patients with AIS were likely to have no fever or high D-dimer levels. We hypothesized that D-dimers play an important role in the pathophysiology, where tsutsugamushi infection increases the likelihood of AIS.

Long Sleep Duration and Dissatisfaction with Sleep Quality Are Associated with Ischemic Stroke in Young Patients.

INTRODUCTION: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients. METHODS: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (<45 years) ischemic stroke patients in 8 tertiary hospitals in Korea. A total of 225 patients and 225 age- and sex-matched controls were enrolled in the same period. Detailed information about patients' demographics, socioeconomic state, and traditional and nontraditional risk factors including sleep-related factors were obtained using structured questionnaires. Risk of ischemic stroke was estimated using conditional logistic regression analysis. RESULTS: Although average sleep duration was similar in patients and controls, patients were more likely to have long (≥9 h) or extremely short (<5 h) sleep durations. In addition, the proportion of subjects with dissatisfaction with sleep quality was higher in patients than controls (66.2 vs. 49.3%, p < 0.001). In multivariable conditional logistic regression analysis, long sleep duration (OR: 11.076, 95% CI: 1.819-67.446, p = 0.009) and dissatisfaction with sleep quality (OR: 2.116, 95% CI: 1.168-3.833, p = 0.013) were independently associated with risk of ischemic stroke. CONCLUSIONS: Long sleep duration and dissatisfaction with sleep quality may be associated with increased risk of ischemic stroke in young adults. Improving sleep habit or quality could be important for reducing the risk of ischemic stroke.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports.

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Headaches during pregnancy and the risk of subsequent stroke.

BACKGROUND: Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women. METHODS: Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes. RESULTS: Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30-1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12-2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23-2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19-2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke. CONCLUSIONS: We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Longitudinal intravital imaging of cerebral microinfarction reveals a dynamic astrocyte reaction leading to glial scar formation.

Cerebral microinfarct increases the risk of dementia. But how microscopic cerebrovascular disruption affects the brain tissue in cellular-level are mostly unknown. Herein, with a longitudinal intravital imaging, we serially visualized in vivo dynamic cellular-level changes in astrocyte, pericyte and neuron as well as microvascular integrity after the induction of cerebral microinfarction for 1 month in mice. At day 2-3, it revealed a localized edema with acute astrocyte loss, neuronal death, impaired pericyte-vessel coverage and extravascular leakage of 3 kDa dextran (but not 2 MDa dextran) indicating microinfarction-related blood-brain barrier (BBB) dysfunction for small molecules. At day 5, the local edema disappeared with the partial restoration of microcirculation and recovery of pericyte-vessel coverage and BBB integrity. But brain tissue continued to shrink with persisted loss of astrocyte and neuron in microinfarct until 30 days, resulting in a collagen-rich fibrous scar surrounding the microinfarct. Notably, reactive astrocytes expressing glial fibrillary acidic protein (GFAP) appeared at the peri-infarct area early at day 2 and thereafter accumulated in the peri-infarct until 30 days, inducing glial scar formation in cerebral cortex. Our longitudinal intravital imaging of serial microscopic neurovascular pathophysiology in cerebral microinfarction newly revealed that astrocytes are critically susceptible to the acute microinfarction and their reactive response leads to the fibrous glial scar formation.

Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection.

BACKGROUND: The definition of sudden sensorineural hearing loss (SSNHL) is broadly accepted as acute sensorineural hearing loss of more than 30 dB over at least three consecutive frequencies in a pure-tone audiogram (PTA). Acute audiovestibular loss is common with ischaemic stroke in the territory of the anterior inferior cerebellar artery (AICA). However, cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction. CASE PRESENTATION: A 51-year-old man suddenly developed acute hearing loss (AHL) in his left ear and vertigo. On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had apogeotropic nystagmus during head turns to either side. The head impulse test (HIT) was normal. PTA showed mild unilateral SSNHL in the left ear. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed territorial perfusion deficits in the left posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) without infarction. Two months later, the patient had no vertigo but still had hearing impairment in his left ear. A follow-up PTA documented persistent unilateral SSNHL in the left ear. Additionally, perfusion computed tomography (CT) showed that perfusion deficits remained in the left cerebellum along the PICA and AICA territories. CONCLUSIONS: Our case highlights a case of AHL and vertigo presented by isolated cerebellar hypoperfusion without infarction. It is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm this possibility through brain magnetic resonance imaging (MRI), including PWI, and magnetic resonance angiography (MRA).

Variation in Knowledge of Stroke Warning Signs by Age and Presence of Conventional Risk Factors: A Community Health Survey in Korea.

BACKGROUND: It is important to recognize stroke in the general public. OBJECTIVES: The purpose of this study was to investigate factors affecting knowledge of stroke warning signs (SWSs) according to age group in the Korean population. METHODS: This study is a cross-sectional study. Using data from the Korean Community Health Survey conducted in Korea in 2017, 198 403 subjects were analyzed. Knowledge about SWSs was assessed by face-to-face interviews using structured close-ended questionnaires with 5 items about stroke symptoms (sudden unilateral weakness of face, arm or leg; sudden difficulty in speaking, or trouble understanding speech; sudden visual impairment in 1 eye, or double vision; sudden dizziness or loss of balance; and sudden severe headache). RESULTS: The overall percentage of subjects with good knowledge of SWSs (>4 correct answers to the SWS questionnaire) was 66.5%. It was highest in the middle-aged subjects (72.6%), followed by the young subjects (63.5%) and the older subjects (61.5%). The youngest of the young subjects and the oldest of the older subjects had the least knowledge. Subjects with conventional risk factors generally had more knowledge about SWSs, except for those with diabetes mellitus. However, in the young subjects, knowledge about SWSs was not increased by the presence of conventional risk factors such as hypertension and dyslipidemia. CONCLUSION: Stoke risk factors are increasing among young people; they still have poor knowledge about SWSs. More education is needed to increase appropriate treatment, especially in young people with stroke-related risk factors.

Homocysteinemia is Associated with the Presence of Microbleeds in Cognitively Impaired Patients.

BACKGROUND & OBJECTIVE: Homocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function. METHODS: A total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds. RESULTS: One hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores. CONCLUSIONS: Elevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype.

Cycle-consistent deep learning approach to coherent noise reduction in optical diffraction tomography.

We present a deep neural network to reduce coherent noise in three-dimensional quantitative phase imaging. Inspired by the cycle generative adversarial network, the denoising network was trained to learn a transform between two image domains: clean and noisy refractive index tomograms. The unique feature of this network, distinct from previous machine learning approaches employed in the optical imaging problem, is that it uses unpaired images. The learned network quantitatively demonstrated its performance and generalization capability through denoising experiments of various samples. We concluded by applying our technique to reduce the temporally changing noise emerging from focal drift in time-lapse imaging of biological cells. This reduction cannot be performed using other optical methods for denoising.

Distal versus Proximal Middle Cerebral Artery Occlusion: Different Mechanisms.

BACKGROUND: Clinical and radiological characteristics of middle cerebral artery (MCA) infarction may differ according to the location of occlusion. OBJECTIVES: We investigated the difference between proximal and distal symptomatic MCA occlusion (MCAO) in patients with ischemic stroke. The factors associated with the imaging characteristics were also analyzed. METHODS: Patients with ischemic stroke due to MCAO were consecutively enrolled. The location of MCAO was determined by the ratio of the length of the ipsilesional MCA to that of the contralateral MCA and dichotomized to proximal and distal MCAO. Clinical and radiological characteristics were compared between patients with proximal and distal MCAO. Factors associated with the basal ganglia (BG) involvement, hemorrhagic transformation (HT), and neurological change during admission were investigated. RESULTS: Among 181 included patients, MCAO location showed a bimodal peak (at the proximal [n = 99] and distal MCA [n = 82]). Proximal MCAO was more frequently associated with hyperlipidemia and large artery atherosclerosis, whereas distal MCAO was more frequently associated with hypertension, atrial fibrillation, and cardioembolic stroke. BG involvement was similar between the 2 groups (48 vs. 39%; p = 0.21), whereas HT was more frequent in distal MCAO (10 vs. 23%; p = 0.02). Among patients with proximal MCAO, hyperintense vessel sign was less frequently observed in those with a BG involvement than those without (38 vs. 60%; p = 0.03). Among those without BG involvement, the presence of HT was very low and similar between patients with proximal and distal MCAOs (1.9 vs. 2.0%). However, in patients with BG involvement, HT was more frequently observed in those with distal MCAO than in those with proximal MCAO (54.8 vs. 15.7%; p < 0.001). The presence of hyperintense vessel sign (OR 0.172, 95% CI 0.051-0.586; p = 0.005) and distal MCAO (OR 0.200, 95% CI 0.059-0.683; p = 0.011) was independently associated with improvement during admission. CONCLUSION: Proximal MCAO is more frequently associated with atherosclerosis, whereas distal MCAO is more frequently associated with cardioembolism. In proximal MCAO, the status of collateral flow presented by hyperintense vessel sign may affect the involvement of BG. In distal MCAO, distal migration of the embolus, which first impacted at the proximal MCA causing BG ischemia, may explain the high rate of HT by reperfusion injury. Hyperintense vessel sign and distal MCAO were independently associated with neurological improvement during admission.

Relationship between cerebral microbleeds and white matter MR hyperintensities in systemic lupus erythematosus: a retrospective observational study.

PURPOSE: White matter hyperintensities (WMH) and cerebral microbleeds (CMBs) are known to be associated with small vessel diseases (SVD) and neuroinflammation. The purpose was to investigate the relationship between CMBs and WMH in patients with systemic lupus erythematosus (SLE). METHODS: Thirty-one SLE patients with WMH and 27 SLE patients with normal brain MRI were compared. The presence, location, and grading of CMBs were assessed using susceptibility-weighted images. WMH volume was quantitatively measured. Clinical characteristics and serologic markers were compared. We also performed two separate subgroup analyses after (1) dividing WMH into inflammatory lesion vs. SVD subgroups and (2) dividing WMH into those with vs. without CMB subgroups. RESULTS: The WMH group showed more frequent CMBs than the normal MR group (p < 0.001). The WMH group showed higher SLE disease activity index, longer disease duration, and a higher incidence of antiphospholipid syndrome than the normal MR group (p = 0.02, 0.04, and 0.04, respectively). There was a moderate correlation between WMH volume and CMB grading (r = 0.49, p = 0.006). Within the WMH group, the inflammatory lesion subgroup showed more frequent CMBs and larger WMH volume than the SVD subgroup (p < 0.001 and 0.02, respectively). The WMH with CMB subgroup had larger WMH volume than the WMH without CMB subgroup (p = 0.004). CONCLUSION: In patients with SLE, CMBs could be related to large-volume WMH and inflammatory lesions. CMBs along with severe WMH could be used as an imaging biomarker of vasculitis in patients with SLE.

Combining Three-Dimensional Quantitative Phase Imaging and Fluorescence Microscopy for the Study of Cell Pathophysiology.

Quantitative phase imaging (QPI) has emerged as one of the powerful imaging tools for the study of live cells in a non-invasive manner. In particular, multimodal approaches combining QPI and fluorescence microscopic techniques have been recently developed for superior spatiotemporal resolution as well as high molecular specificity. In this review, we briefly summarize recent advances in three-dimensional QPI combined with fluorescence techniques for the correlative study of cell pathophysiology. Through this review, biologists and clinicians can be provided with insights on this rapidly growing field of research and may find broader applications to investigate unrevealed nature in cell physiology and related diseases.

Quantitative susceptibility mapping of the motor cortex: a comparison of susceptibility among patients with amyotrophic lateral sclerosis, cerebrovascular disease, and healthy controls.

PURPOSE: The purpose of this study was to investigate the differences in motor cortex susceptibility among patients with amyotrophic lateral sclerosis (ALS), cerebrovascular disease (CVD), and healthy controls using quantitative susceptibility mapping (QSM). METHODS: We retrospectively reviewed 78 QSM images from 26 patients with ALS, 26 age- and sex-matched patients with CVD, and 26 healthy controls. A region of interest was drawn in the hand lobule of both the motor cortexes and subcortical white matter. The relative susceptibility (RS) of the motor cortex was obtained by subtracting the susceptibility of the subcortical white matter from that of the motor cortex. We compared the cortexmean, cortexmax, subcortical white mattermean, RSmean, and RSmax values among the three groups using analysis of variance and Tukey's post hoc test. Receiver operating characteristic (ROC) curve analysis was also performed. RESULTS: There were significant differences in the cortexmean, cortexmax, RSmean, and RSmax among the three groups, with higher values in patients with ALS (p = 0.01, p = 0.004, p < 0.001, and p < 0.001, respectively). Subcortical white mattermean was significantly lower in patients with ALS compared with patients with CVD and healthy controls (p = 0.04). ROC curve analysis showed that the area under the curve of RSmean was 0.70, the highest among the measured parameters. CONCLUSION: Quantitative measurements of susceptibility of the motor cortex with QSM demonstrate its potential as an imaging biomarker in ALS patients.

Noninfectious Meningitis Caused by Systemic Lupus Erythematosus: A Case Series of 4 Patients.

We report magnetic resonance imaging findings of 4 patients with systemic lupus erythematosus who presented with noninfectious meningitis by lupus itself. Magnetic resonance imaging of the brain demonstrated diffuse or localized high-signal intensity in subarachnoid spaces on fluid-attenuated inversion recovery (FLAIR) or postcontrast fluid-attenuated inversion recovery. Cerebrospinal fluid study revealed no abnormalities other than increased level of proteins. Our report is the first description of magnetic resonance findings in context of leptomeningeal involvement in non-infectious meningitis of patients with systemic lupus erythematosus.

Predictors of Hemorrhage Volume after Intravenous Thrombolysis.

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) is one of the most feared complications after administration of intravenous recombinant tissue plasminogen activator (IV rtPA). The aim of this study was to determine correlations between hemorrhage volume (HV) after IV rtPA treatment and risk factors for sICH. METHODS: We analyzed 318 patients from the stroke registries of 4 hospitals in Korea. We confirmed hemorrhage by computed tomography (CT) or magnetic resonance imaging within 36 hours. Patient groups were classified by HV (0, 0-10, 10-25, and greater than 25 mL). Based on the HV, we evaluated the following: (1) predictors for hemorrhage; (2) rates of sICH according to various sICH definitions; and (3) 3-month functional outcomes after IV rtPA treatment. RESULTS: Among the 318 patients, hemorrhage occurred in 72 patients. HV was significantly correlated with atrial fibrillation (OR = 3.38, 95% CI = 1.87-6.09), early CT changes (OR = 3.17, 95% CI = 1.69-5.93), and dense artery sign (OR = 1.90, 95% CI = 1.07-3.39). Compared with the groups with HV less than 25 mL, patients with an HV of greater than 25 mL were more likely to have higher mortality rates (33.3% versus 11.8%) and worse outcomes at 3 months (good: 8.3% versus 50.3%; excellent: 0% versus 33.7%). CONCLUSIONS: HV after IV rtPA is an important predictor of clinical outcomes. Atrial fibrillation, early CT changes, and dense artery sign were significantly associated with large HVs; therefore, these patient factors might be considered before and after thrombolytic treatment.

Protocol of the Stroke in Korean Young Adults Study: A Multicenter Case-Control Study and Prospective Cohort Study.

BACKGROUND: The incidence of ischemic stroke in young adults has been rising over recent decades, but there is still limited information on its risk factors, etiologies, and outcomes. Because these patients generally participate in social life, risk factors associated with lifestyle may have a great impact and need to be identified. METHODS: The SKY (Stroke in Korean Young Adults) study is a multicenter case-control study and a prospective cohort study in 8 tertiary medical centers in the Republic of Korea. The case subjects are patients aged 18-44 years with first-ever ischemic stroke occurring within 1 month of stroke onset, and the control subjects are age- and gender-matched community controls. Our aim is to include 470 cases and 470 controls. The main objective of our study is to determine the risk factors and the causes of ischemic stroke in Korean young adults. Both well-documented risk factors and little-known lifestyle-related risk factors such as lifestyle habits and psychological distress including job strain will be evaluated by comparing cases and controls using a structured questionnaire. Secondary objectives are to determine the risks of mortality, recurrent vascular events, and poststroke epilepsy in these patients. Conditional logistic regression analysis will be used to estimate odds ratios and 95% confidence intervals. CONCLUSIONS: The SKY study is designed to obtain more insights into relatively little-known risk factors in young Korean adults with ischemic stroke. The results may also help identify the frequencies of uncommon etiologies and outcomes in these patients.

Effect of seasonal and monthly variation in weather and air pollution factors on stroke incidence in Seoul, Korea.

BACKGROUND AND PURPOSE: The purpose of the present study was to determine whether seasonal and monthly variations in stroke incidence exist and whether they are related to meteorologic and air pollution parameters under similar weather and environmental conditions in selected areas of Seongdong district, Seoul, South Korea. METHODS: From January 1, 2004, to December 31, 2013, 3001 consecutive stroke events were registered in residents of selected areas of Seongdong district, Seoul, South Korea. The authors calculated the stroke attack rate per 100,000 people per month and the relative risk of stroke incidence associated with meteorologic and air pollution parameters. We also analyzed odds ratios with a 95% confidence interval for seasonal and monthly stroke incidence. RESULTS: The incidence of stroke in September was significantly higher (odds ratio, 1.233; 95% confidence interval, 1.042-1.468) compared with January. The seasonal ischemic stroke incidence in summer (odds ratio, 1.183; 95% confidence interval, 1.056-1.345) was significantly higher than in winter, whereas the seasonal incidence of intracerebral hemorrhage relative to winter was not significant. The mean temperature was positively correlated with ischemic stroke (relative risk, 1.006; P=0.003), and nitrogen dioxide (relative risk, 1.262; P=0.001) showed a strong positive correlation with intracerebral hemorrhage incidence among the older age group. CONCLUSIONS: We demonstrated distinct patterns of seasonal and monthly variation in the incidence of stroke and its subtypes through consideration of the meteorologic and air pollution parameters. We therefore expect that these findings may enhance our understanding of the relationships between stroke and weather and pollutants.

Activation of the phosphatidylinositol 3-kinase pathway plays important roles in reduction of cerebral infarction by cilnidipine.

Cerebral infarction causes permanent neuronal loss inducing severe morbidity and mortality. Because hypertension is the main risk factor for cerebral infarction and most patients with hypertension take antihypertensive drugs daily, the neuroprotective effects and mechanisms of anti-hypertensive drugs need to be investigated. Cilnidipine, a long-acting, new generation 1,4-dihydropyridine inhibitor of both L- and N-type calcium channels, was reported to reduce oxidative stress. In this study, we investigated whether cilnidipine has therapeutic effects in an animal model of cerebral infarction. After determination of the most effective dose of cilnidipine, a total of 128 rats were subjected to middle cerebral artery occlusion. Neurobehavioral function test and brain MRI were performed, and rats with similar sized infarcts were randomized to either the cilnidipine group or the control group. Cilnidipine treatment was performed with reperfusion after 2-h occlusion. Western blots and immunohistochemistry were also performed after 24-h occlusion. Initial infarct volume on diffusion-weighted MRI was not different between the cilnidipine group and the control group; however, fluid-attenuated inversion recovery MRI at 24 h showed significantly reduced infarct volume in the cilnidipine group compared with the control group. Cilnidipine treatment significantly decreased the number of triphosphate nick end labeling-positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3ß, and Bcl-2 and decreased expression of Bax and cleaved caspase-3. These results suggest that cilnidipine, which is used for the treatment of hypertension, has neuroprotective effects in the ischemic brain through activation of the PI3K pathway. We investigated whether cilnidipine has neuroprotective effects on ischemic stroke in an animal model. We have demonstrated that the neuroprotective effect of cilnidipine is associated with the activation of the PI3K pathway. Considering the daily use of antihypertensive drugs for patients with hypertension, cilnidipine could be beneficial for patients with ischemic stroke.

Chronic inflammatory demyelinating polyneuropathy-like neuropathy as an initial presentation of Crohn's disease.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare complication of Crohn's disease (CD), and it is uncertain whether it is associated with CD itself or with its treatment. We describe a case of CIDP-like neuropathy as an initial symptom of CD. The neurologic symptoms of the patient which responded partially to intravenous immunoglobulin (IVIG) recovered after resection of the appendiceal CD. CASE PRESENTATION: A 17-year-old male had experienced three separate attacks of motor weakness and paresthesia of all four extremities over a period of 7 months. The electrophysiologic findings revealed a demyelinating sensory-motor polyneuropathy which was compatible with CIDP. However, repeated intravenous IVIG (2 g/kg) treatment gave only a partial response. Four days after the last discharge, he was diagnosed as appendiceal CD after surgical resection of a periappendiceal abscess. His neurologic symptoms and electrophysiologic findings recovered without any maintenance therapy. CONCLUSIONS: CIDP-like neuropathy can be an initial presentation of CD, and recovery of the CIDP symptoms may result from resection of the CD. Clinicians should be aware of the possibility of CD in patients with intractable CIDP symptoms.