Symptomatic Migraine with Prolonged Visual Aura and Unruptured Occipital Arteriovenous Malformation.

A 35 year-old woman had a two-year history of recurrent headache with clinical presentations of visual aura in her left visual field followed by right-sided throbbing headache. The patient suffered from a similar attack but her visual aura-like symptoms persisted for over 48 hours. The concurrent electroencephalogram demonstrated focal non-epileptiform rhythmic slow waves in the right occipital region. The magnetic resonance images showed prominent parenchymal edema in the right occipital area. The cerebral angiographic study proved a small cerebral arteriovenous malformation. This illustrated case showed that cerebral arteriovenous malformation produces headaches mimicking migraine with visual aura. The acute vascular flow change and the parenchymal edema trigger a prolonged visual aura with coinstantaneous evidence of cortical depression shown on the electroencephalogram. Keywords: Symptomatic migraine; Prolonged visual aura; Unruptured arteriovenous malformation.

Methylpiperidinopyrazole Attenuates Estrogen-Induced Mitochondrial Energy Production and Subsequent Osteoblast Maturation via an Estrogen Receptor Alpha-Dependent Mechanism.

An estrogen deficiency is the main cause of osteoporosis in postmenopausal women. In bone remodeling, estrogen receptors (ERs) can mediate estrogen-transducing signals. Methylpiperidinopyrazole (MPP) is a highly specific antagonist of ER-alpha (ERα). This study was designed to evaluate the effects of MPP on estrogen-induced energy production, subsequent osteoblast maturation, and the possible mechanisms. Exposure of primary osteoblasts isolated from neonatal rat calvarias to MPP did not affect cell morphology or survival. Estradiol can induce translocation of ERα into mitochondria from the cytoplasm. Interestingly, pretreatment of rat calvarial osteoblasts with MPP lowered estrogen-induced ERα translocation. Sequentially, estrogen-triggered expressions of mitochondrial energy production-linked cytochrome c oxidase (COX) I and COX II messenger (m)RNAs were inhibited following pretreatment with MPP. Consequently, MPP caused decreases in estrogen-triggered augmentation of the activities of mitochondrial respiratory complex enzymes and levels of cellular adenosine phosphate (ATP). During progression of osteoblast maturation, estrogen induced bone morphogenetic protein (BMP)-6 and type I collagen mRNA expressions, but MPP treatment inhibited such induction. Consequently, estrogen-induced osteoblast activation and mineralization were attenuated after exposure to MPP. Taken together, MPP suppressed estrogen-induced osteoblast maturation through decreasing chromosomal osteogenesis-related BMP-6 and type I collagen mRNA expressions and mitochondrial ATP synthesis due to inhibiting energy production-linked COX I and II mRNA expressions. MPP can appropriately be applied to evaluate estrogen-involved bioenergetics and osteoblast maturation.

The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and Epileptic Seizures.

BACKGROUND/AIMS: Immunological mechanisms can be triggered as a response to central nervous system insults and can lead to seizures. In this study an investigation was made to determine if glatiramer acetate (GA), an immunomodulator currently used in the treatment of multiple sclerosis, could protect rats from pilocarpine-induced seizures and chronic epilepsy. METHODS: Two groups of adult male Sprague-Dawley rats, experimental (GA) and control, were used in the study. The systemic IL-1α and IL-1ß levels at baseline were checked as well as status epilepticus (SE), and the spontaneous recurrent seizure (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150 µg/kg, ip) and the control group was given a saline injection prior to pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were evaluated, using Racine seizure classification and hippocampal damage was evaluated by Nissl staining. The GA group received GA (150 µg/kg/day, ip) daily after SE, and the chronic spontaneous seizures were evaluated by long-term video recording, and mossy fiber sprouting was evaluated by Timm staining. The IL-1α and IL-1ß levels were correlated with seizure activities. The TNF-α level in the hippocampus was determined at the SRS stage by immunohistochemistry. The effect of GA on ionic currents and action potentials (APs) in NG108-15 differentiated neurons was investigated using patch-clamp technology. RESULTS: It was found that latency to severe seizures was significantly longer in the GA (p < 0.01) group, which also had SE of shorter duration and less frequent SRS (p < 0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL-1α, but not with IL-1ß or TNF-α levels. Mechanistically, GA reduced the peak amplitude of voltage-gated Na+ current (INa), with a negative shift in the inactivation curve of INa and reduced the amplitude of APs along with decreased firing of APs. CONCLUSION: GA might serve as a neuroexcitability modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity. Sodium channel attenuation was partially independent of the immunomodulatory effect.

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells.

BACKGROUND: Temozolomide (TMZ), an oral alkylator of the imidazotetrazine family, is used to treat glioma. Whether this drug has any ionic effects in glioma cells remains largely unclear. METHODS: With the aid of patch-clamp technology, we investigated the effects of TMZ on the ionic currents in U373 glioma cells. The mRNA expression of KCNN4 (KCa3.1) in U373 glioma cells and TMZ's effect on K+ currents in these KCNN4 siRNA-transfected U373 cells were investigated. RESULTS: In whole-cell recordings, TMZ decreased the amplitude of voltage-dependent K+ currents (IK) in U373 cells. TMZ-induced IK inhibition was reversed by ionomycin or 1-ethyl-2-benzimidazolinone (1-EBIO). In cell-attached configuration, TMZ concentration-dependently reduced the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels with an IC50 value of 9.2 µM. Chlorzoxazone or 1-EBIO counteracted the TMZ-induced inhibition of IKCa channels. Although TMZ was unable to modify single-channel conductance, its inhibition of IKCa channels was weakly voltage-dependent and accompanied by a significant prolongation in the slow component of mean closed time. However, neitherlarge-conductance Ca2+-activated (BKCa) nor inwardly rectifying K+ (Kir) channels were affected by TMZ. In current-clamp mode, TMZ depolarized the cell membrane and 1-EBIO reversed TMZ-induced depolarization. TMZ had no effect on IK in KCNN4 siRNA-transfected U373 cells. CONCLUSION: In addition to the DNA damage it does, its inhibitory effect on IKCa channels accompanied by membrane depolarization could be an important mechanism underlying TMZ-induced antineoplastic actions.

Crebanine, an aporphine alkaloid, induces cancer cell apoptosis through PI3K-Akt pathway in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most prevalent and lethal primary central nervous system malignancies. GBM is notorious for its high rates of recurrence and therapy resistance and the PI3K/Akt pathway plays a pivotal role in its malignant behavior. Crebanine (CB), an alkaloid capable of penetrating the blood-brain barrier (BBB), has been shown to have inhibitory effects on proinflammatory molecules and multiple cancer cell lines via pathways such as PI3K/Akt. This study aims to investigate the efficacy and mechanisms of CB treatment on GBM. It is the first study to elucidate the anti-tumor role of CB in GBM, providing new possibilities for GBM therapy. Through a series of experiments, we demonstrate the significant anti-survival, anti-clonogenicity, and proapoptotic effects of CB treatment on GBM cell lines. Next-generation sequencing (NGS) is also conducted and provides a complete list of significant changes in gene expression after treatment, including genes related to apoptosis, the cell cycle, FoxO, and autophagy. The subsequent protein expressions of the upregulation of apoptosis and downregulation of PI3K/Akt are further proved. The clinical applicability of CB to GBM treatment could be high for its BBB-penetrating feature, significant induction of apoptosis, and blockage of the PI3K/Akt pathway. Future research is needed using in vivo experiments and other therapeutic pathways shown in NGS for further clinical or in vivo studies.

Indwelling urinary catheterization after acute stroke.

AIMS: Prolonged indwelling urinary catheterization (IUC) increases risk of urinary tract infection. We aimed to investigate the incidence and risk factors associated with IUC following acute stroke, and its impact on stroke outcome. METHODS: We prospectively enrolled stroke patients hospitalized within 10 days after onset from August 2006 to December 2008. Kaplan-Meier method was used to estimate the cumulative incidence of IUC, and Cox regression analysis to evaluate the independent predictors. The impact of IUC on poor outcome (modified Rankin Scale >2 or dead) at 3 months was studied by logistic regression. RESULTS: Of 2,803 patients, 697 (25%) received indwelling urinary catheters. Catheterization was carried out mostly within 1-2 days of admission (86%), with estimated cumulative incidence of 13% (95% confidence interval, 11-14%) at 2 days in patients with ischemic stroke (IS), and 57% (53-61%) in patients with intracerebral hemorrhage (ICH). In IS patients, IUC was significantly associated with increasing age, baseline stroke severity, and neurological deterioration. In ICH patients, stroke severity on admission was the only significant predictor after adjustment. We assessed the 3-month outcome in 2,388 patients, after excluding 177 (6%) dead at discharge, 164 (6%) without providing informed consent, and 74 (3%) lost to follow-up. IUC during acute hospitalization was significantly associated with unfavorable 3-month outcome after adjustment. CONCLUSIONS: IUC was common in acute stroke care and associated with unfavorable outcome at 3 months. Whether judicious use of urinary catheters in acute stroke patients would improve outcomes may warrant further studies.

Cytotoxic Lesions beyond the Corpus Callosum Following Acute Meningoencephalitis and Mycoplasma Pneumoniae Infection: A Case Report and Literature Review.

Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with a variety of clinical causes. The presence of a small and reversible lesion in the splenium of corpus callosum with restricted diffusion on cranial magnetic resonance imaging is the defining feature. The clinical-radiological manifestations have been documented as mild and reversible. Severer presentations were scarcely reported. In this report, we described a 25-year-old man with preceding fever, worsening somnolence, and convulsions. He was diagnosed with acute meningoencephalitis and Mycoplasma pneumoniae infection after workups. After medical treatments, he had neurological deterioration and progressing CLOCCs from a small oval lesion in the center of splenium extending to the whole corpus callosum and bilaterally adjacent white matter. The patient received intravenous methylprednisolone and immunoglobulin successively, and his neurological conditions improved. The CLOCCs, not always mild and reversible, could present with severe clinicoradiological features.

[Guideline of neuropathic pain treatment and dilemma from neurological point of view].

Neuropathic pain is a complicated symptomatic disease as migraine in recent years. Not because the pain character differed from the nociceptive inflammatory symptoms but because of its complexity of mechanisms. Though peripheral sensitization, ectopic discharge, central sensitization, central re-organization and loss of inhibition play part of roles in mechanisms, however, based on this mechanistic treatment, the outcome still disappointed physicians and patients, exampled as central post-stroke central pain (CPSP). The pain reduction is far less than the expectation from patients and physician's under-treatment frequently occur due to the fear of adverse effects or off-label use of these anti-neuropathic pain drugs. Therefore, a multidisciplinary procedure including non-pharmacological management, rehabilitation program, careful explanation, stepwise pain reduction, daily diary record, and tailored individual planning for medications are helpful in treating this kind of sufferers. Pharmacological treatment is the mainstream in post-herpetic neuralgia (PHN), diabetic peripheral neuropathic pain (DPNP), central post-stroke pain (CPSP), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), cancer pain, failed back syndrome etc, while polypharmacy is still the major prescriptions facing such kind of miserable patients. The tricyclic antidepressants (TCA), gamma- aminobutyric acid (GABA), voltage-dependent calcium channel blockers, selective non-epinephrine reuptake inhibitor (SNRI), opioid or morphine etc, are still evidence-based medicines (EBM) but with different outcome for individuals. Acupuncture is to some extend effective in Taiwanese people with perceived evidence or placebo. The Taiwan guidance for total pain management and review of EBM in treating neuropathic pain from neurological point of view will be introduced in this manuscript.

Determinants of Prolonged Length of Hospital Stay in Patients with Severe Acute Ischemic Stroke.

OBJECTIVE: Long hospitalizations are associated with a high comorbidity and considerable hospital cost. Admissions of severe acute ischemic stroke are prone to longer hospitalizations. We aimed to explore the issue and method for improving the length of stay. METHODS: From the prospective Stroke Registry between January 2019 and June 2020, acute ischemic strokes with an admission National Institutes of Health Stroke Scale ≥ 15 were identified. Prolonged length-of-stay was defined as in-hospital-stay ≥ 30 days. All clinical characteristics were collected, and all do-not-resuscitate documentations were categorized if the order had been written within 7 days of onset. RESULTS: A total of 212 patients were eligible for severe stroke. Of these, 42 (19.8%) had prolonged length-of-stay and 170 had non-prolonged length-of-stay (median 43 vs. 13 days). The prolonged group was younger, mostly men, and was more likely to be in an independent state and more likely to receive reperfusion therapy, and there was a higher frequency of late do-not-resuscitate orders if signed. Although there was a lower in-hospital mortality rate in the prolonged group (12% vs. 23%), there was a higher proportion with a severe functional state (Modified Rankin Scale = 4-5) among the survivors (97% vs. 87%). CONCLUSIONS: Severe acute ischemic stroke patients with a prolonged length-of-stay were younger, mostly male, more likely to receive reperfusion therapy, less likely to have an early do-not-resuscitate order if signed, and more likely to have poor functional status at discharge, although there was a lower rate of in-hospital mortality.

Limb-shaking TIA related to moyamoya disease: diagnosis with magnetic resonance imaging and magnetic resonance angiography.

PURPOSE: In a case with moyamoya disease, we found the magnetic resonance image and magnetic angiographic studies were helpful for the definite diagnosis of the disease. CASE REPORT: A young adult presented limb-shaking transient ischemic attacks caused by moyamoya disease. The magnetic resonance angiography proved the steno-occlusive lesions in the major arteries of circle of Willis, and the magnetic resonance images demonstrated compensatively congested and dilated leptomeningeal vessels and lenticulostriate arteries with exhausted vasomotor elasticity. CONCLUSION: In this case, without the aid of conventional angiography, the noninvasive magnetic resonance studies offered explicit imaging evidence to support the diagnosis and to illuminate the patient's clinical manifestation.

Comparing Mini-Mental State Examination and Attention and Digit Span in elderly exposed to polychlorinated biphenyls and polychlorinated dibenzofurans.

BACKGROUND: Polychlorinated biphenyls (PCB)/polychlorinated dibenzofurans (PCDF) are known to affect central nervous functioning. In recent studies, elderly patients who have been exposed to these have been noted to have psychological deficits. There is little known about which test is sensitive to neurotoxins in cognitive evaluation. The objective of the present study was to compare the significance between selective psychological tests in cognitive assessment in PCB-laden elderly. METHODS: A retrospective PCB/PCDF exposed cohort was observed. Exposed elderly aged ≥ 60 years and registered in Central Health Administration were enrolled, and similar age- and sex-matched subjects served as non-exposed controls. The Mini-Mental State Examination (MMSE) and Attention and Digit Span (ADS) were tested in both groups. Student's t-test, χ(2) -test and linear regression models were used for statistical analysis. RESULTS: A total of 165 exposed patients and 151 controls were analyzed. The exposed group included 49% men, a mean age of 69.3 ± 6.4 years and an education level of 4.0 ± 3.9 years. The controls included 52% men, a mean age of 69.9 ± 5.5 years and an education level of 4.5 ± 3.2 years. There was no statistical difference in MMSE before and after adjusting for the confounding variables of age, sex and education (P= 0.16 vs P= 0.12). However, ADS-forward and ADS-total scores showed a significant decline in the exposed subjects (P= 0.0001 vs P= 0.001). Using a linear regression among stratified PCB and cognitive functioning (≤30 ppb; 31-89; ≥90), a dose effect was found at the medium (31-89 ppb) and high exposure (≧90 ppb) levels. CONCLUSION: Our observations showed attention and short-term memory were impaired in PCB-laden elderly patients. Higher exposure level showed lower cognitive functioning in ADS. The MMSE was insensitive to neurotoxins. The present study shows that the selective test has a decisive role in toxic-related cognitive assessments.

Magnetic-Resonance Diffusion-Tensor Tractography in the Diagnosis of Tumefactive Spinal-Cord Lesions in Neuromyelitis Optica.

Magnetic-resonance (MR) imaging is the modality of choice for the evaluation of spinal-cord lesions. However, challenges persist in discriminating demyelinating processes from neoplastic lesions using conventional MR sequences. Consequently, an invasive spinal-cord biopsy is likely for most patients. MR diffusion-tensor imaging is an emerging noninvasive and powerful method for characterizing changes in tissue microstructure associated with spinal disorders. We currently present the case of a middle-aged woman suffering from neuromyelitis optica, and highlight that MR diffusion-tensor tractography can be helpful in the identification of tumefactive spinal-cord lesions.

Biomechanical and tomographic differences in the microarchitecture and strength of trabecular and cortical bone in the early stage of male osteoporosis.

Osteoporosis is a continuous process of loss of bone tissue. Compared to women, osteoporosis in men is associated with greater morbidity and mortality. In this study, we conducted tomographic and biomechanical evaluations of trabecular and cortical bone in the early stage of male osteoporosis. Male Wistar rats were subjected to orchiectomy and sham operation. Four weeks after being castrated, decreased levels of testosterone in plasma were found and resulted in concurrent bone loss. Separately, the orchiectomy led to significant tomographic alterations in the trabecular bone number, trabecular separation, and trabecular pattern factor. Data of a mechanistic compression test further showed that the orchiectomy diminished the maximum loading force, displacement at maximum load, energy at maximum load, and ultimate stress. Interestingly, orchiectomy-triggered changes in the maximum loading force and tomographic parameters were highly correlated. In contrast, tomographic and biomechanical analyses showed that 4 weeks after rats were orchiectomized, the thickness, area, maximum loading force, bone stiffness, energy at maximum load, and ultimate stress of the cortical bone were not changed. Taken together, this study showed specific differences in the microarchitecture and strength of trabecular bone in the early stage of male osteoporosis.

Epilepsia Partialis Continua as the First Presenting Symptom in Probable Sporadic Creutzfeldt-Jacob Disease: A Case Report and Literature Review.

We present the case of a middle-aged man suffering from epilepsia partialis continua 3 weeks before the start of cognition decline, visual disturbance, and pyramidal dysfunction. The epilepsia partialis continua was difficult to control, and the underlying cause was uncertain even after thorough surveys for infection, inflammation, autoimmunity, and neoplasm. However, progressive signal intensity changes were noted over the involved cortical gyri, bilateral caudate, and putamen on serial magnetic resonance diffusion-weighted images, which were compatible with sporadic Creutzfeldt-Jacob disease. Therefore, we tested for 14-3-3 protein in the cerebrospinal fluid, and the results were positive. Multifocal myoclonus jerks, severe mental decline, akinetic mutism, and typical periodic sharp wave complexes on electroencephalogram developed late in his disease course. He died under the hospice care, and his total disease duration was approximately 5 months. This case highlights that epilepsia partialis continua can be the first presenting symptoms of sporadic Creutzfeldt-Jacob disease, and that magnetic resonance imaging abnormalities can be helpful to identify the disease.

Differential risks of subsequent vascular events for transient ischaemic attack and minor ischaemic stroke.

Using a prospective hospital-based registry, 146 patients with transient ischaemic attack (TIA) were compared with 376 patients with minor first-ever ischaemic stroke with respect to the 3-month risk of subsequent vascular events, in order to clarify the distinctions between the disease entities. All patients were enrolled within 48 h of onset. The risk factor distribution for the two groups was comparable, except that the TIA patients had more previous TIAs. Large artery atherosclerosis (34%) and small vessel occlusion (32%) were the main aetiologies in the TIA group, whereas small vessel occlusion (49%) was the major cause in the stroke group. The 3-month risk of combined endpoints of stroke, myocardial infarction, and vascular death for TIA patients was higher than that for the minor stroke group (15.1% vs. 3.2%; hazard ratio 4.6, 95% confidence interval 2.3-9.3 in multivariate analysis). Large artery atherosclerosis and male sex were the other significant predictors. TIA may demand more urgent management than minor stroke. The fact that aetiology is a predictor, highlights the need for rapid diagnostic tests to establish pathogenesis.

Honokiol induces autophagy of neuroblastoma cells through activating the PI3K/Akt/mTOR and endoplasmic reticular stress/ERK1/2 signaling pathways and suppressing cell migration.

In children, neuroblastomas are the most common and deadly solid tumor. Our previous study showed that honokiol, a small-molecule polyphenol, can traverse the blood-brain barrier and kill neuroblastoma cells. In this study, we further investigated the mechanisms of honokiol-induced insults to neuroblastoma cells. Treatment of neuroblastoma neuro-2a cells with honokiol elevated the levels of microtubule-associated protein light chain 3 (LC3)-II and induced cell autophagy in time- and concentration-dependent manners. Interestingly, pretreatment with 3-methyladenine (3-MA), an inhibitor of autophagy, led to the simultaneous attenuation of honokiol-induced cell autophagy and apoptosis but did not influence cell necrosis. As to the mechanisms, exposure of neuro-2a cells to honokiol time-dependently decreased the amount of phosphatidylinositol 3-kinase (PI3K). Sequentially, honokiol downregulated phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in neuro-2a cells. Furthermore, honokiol elevated the levels of glucose-regulated protein (GpR)78, an endoplasmic reticular stress (ERS)-associated protein, and amounts of intracellular reactive oxygen species (ROS). In contrast, reducing production of intracellular ROS using N-acetylcysteine, a scavenger of ROS, concurrently suppressed honokiol-induced cellular autophagy. Consequently, honokiol stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2. However, pretreatment of neuro-2a cells with PD98059, an inhibitor of ERK1/2, lowered honokiol-induced autophagy. The effects of honokiol on inducing autophagy and apoptosis of neuroblastoma cells were further confirmed using mouse neuroblastoma NB41A3 cells as our experimental model. Fascinatingly, treatment of neuroblastoma neuro-2a and NB41A3 cells with honokiol for 12 h did not affect cell autophagy or apoptosis but caused significant suppression of cell migration. Taken together, this study showed that honokiol can induce autophagy of neuroblastoma cells and consequent apoptosis through activating the PI3K/Akt/mTOR and ERS/ROS/ERK1/2 signaling pathways and suppressing cell migration. Thus, honokiol has potential for treating neuroblastomas.

Neuron-derived orphan receptor 1 transduces survival signals in neuronal cells in response to hypoxia-induced apoptotic insults.

OBJECT Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults. METHODS Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, cas-pase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding (CREB), and cellular inhibitor of apoptosis protein 2 (cIAP2) genes. Translations of these gene expressions were knocked down using RNA interference. Mice subjected to traumatic brain injury (TBI) and NOR-1 was immunodetected. RESULTS Exposure of neuro-2a cells to OGD decreased cell viability in a time-dependent manner. Additionally, OGD led to cell shrinkage, DNA fragmentation, and cell apoptosis. In parallel, treatment of neuro-2a cells with OGD time dependently increased cellular NOR-1 mRNA and protein expressions. Interestingly, administration of TBI also augmented NOR-1 levels in the impacted regions of mice. As to the mechanism, exposure to OGD increased nuclear levels of the transcription factor CREB protein. Downregulating CREB expression using RNA interference simultaneously inhibited OGD-induced NOR-1 mRNA expression. Also, levels of cIAP2 mRNA and protein in neuro-2a cells were augmented by OGD. After reducing cIAP2 translation, OGD-induced cell death was reduced. Sequentially, application of NOR-1 small interfering RNA to neuro-2a cells significantly inhibited OGD-induced cIAP2 mRNA expression and concurrently alleviated hypoxia-induced alterations in cell viability, caspase-3 activation, DNA damage, and cell apoptosis. CONCLUSIONS This study shows that NOR-1 can transduce survival signals in neuronal cells responsible for hypoxiainduced apoptotic insults through activation of a CREB/cIAP2-dependent mechanism.

Prognosis of young ischemic stroke in Taiwan: impact of prothrombotic genetic polymorphisms.

We investigated the effects of genetic factors on the prognosis of cerebral infarction in young adults in Taiwan. Because ischemic stroke with arterial occlusion or undetermined etiology is more likely to be related to a genetic prothrombotic state, 231 patients younger than 50 years (mean age 44.6 years, range 25 to 49 years) with acute ischemic stroke due to large artery atherosclerosis (n=90), small artery occlusion (n=114) or undetermined cause (n=27) were recruited and prospectively followed up for pre-determined outcome. On each patient, we screened the PlA1/PlA2 polymorphism of the platelet glycoprotein IIIa gene, 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene, G10976A polymorphism of the factor VII gene, C677T polymorphism of the methylenetetrahydrofolate reductase gene, and 27 base-pair repeat polymorphism of the endothelial nitric oxide synthase gene. End points were the composite outcome events of stroke, myocardial infarction, and death from all causes. During a mean duration follow-up of 29 months, composite outcome events occurred in 33 patients. There was a higher annual incidence rate of composite outcome events during the first year (9.1%, 95% CI 5.9-13.9%) than in the subsequent 2 years (2.6%, 95% CI 1.2-5.6%, p=0.038). None of the genetic polymorphism was associated with the composite outcome events. Past history of coronary artery disease or cerebrovascular disease was the only independent predictor of the composite outcome events (HR 3.71, 95% CI 1.69-8.14, p=0.001) at the Cox regression analysis. Our data indicate that the prothrombotic genetic polymorphisms do not have a significant influence on the prognosis in young ischemic stroke due to arterial occlusion or undetermined causes in Taiwan.

Cerebrovascular complications in patients with malignancy: report of three cases and review of the literature.

A cerebrovascular thromboembolic event may precede the identification of cancer, and be the first clinical evidence of an underlying malignancy. The malignancy can cause either nonbacterial thrombotic endocarditis or hypercoagulable state, both of which may have clinical manifestions such as thrombotic or embolic occlusion of multiple major cerebral vessels. We present three cases with unusual cerebrovascular events. The first case is a 62-year-old woman who was admitted due to acute left limbs weakness and consciousness disturbance. Brain computed tomographic (CT) scan showed right middle cerebral artery (MCA) and posterior cerebral artery (PCA) infarctions with uncal herniation. The second case is a 44-year-old woman who was hospitalized due to acute bilateral limb weakness and consciousness disturbance. Bilateral MCA, left PCA, anterior cerebral artery (ACA) infarctions and deep vein thrombosis in the left leg were diagnosed. The third case is a 63-year-old man who developed sudden onset of right hemiplegia and consciousness disturbance. Brain CT scan showed bilateral MCA and left ACA infarction. The results of a series of examinations including biochemistry, lipid profile, carotid duplex, and transthoracic and transesophageal echocardiography were unremarkable. All patients had positive disseminated intravascular coagulation (DIC) tests with elevated D-dimers and fibrinogen degradation products (FDP). Further systemic evaluation for malignancy revealed ovarian cancer in the first patient, endometrial carcinoma in the second patient, and adenocarcinoma of lung in the third patient. They all died of the underlying malignancy. Because the hemostatic system can be altered by malignancy, intravascular coagulation abnormalities of these malignancy-related strokes may be disclosed by laboratory assays of hemostasis.

Automated segmentation and quantification of white matter hyperintensities in acute ischemic stroke patients with cerebral infarction.

White matter hyperintensities (WMHs) of presumed vascular origin are common in ageing population, especially in patients with acute cerebral infarction and the volume has been reported to be associated with mental impairment and the risk of hemorrhage from antithrombotic agents. WMHs delineation can be computerized to minimize human bias. However, the presence of cerebral infarcts greatly degrades the accuracy of WMHs detection and thus limits the application of computerized delineation to patients with acute cerebral infarction. We propose a computer-assisted segmentation method to depict WMHs in the presence of cerebral infarcts in combined T1-weighted, fluid attenuation inversion recovery, and diffusion-weighted magnetic resonance imaging (MRI). The proposed method detects WMHs by empirical threshold and atlas information, with subtraction of white matter voxels affected by acute infarction. The method was derived using MRI from 25 hemispheres with WMHs only and 13 hemispheres with both WMHs and cerebral infarcts. Similarity index (SI) and correlation were utilized to assess the agreement between the new automated method and a gold standard visually guided semi-automated method done by an expert rater. The proposed WMHs segmentation approach produced average SI, sensitivity and specificity of 83.142±11.742, 84.154±16.086 and 99.988±0.029% with WMHs only and of 68.826±14.036, 74.381±18.473 and 99.956±0.054% with both WMHs and cerebral infarcts in the derivation cohort. The performance of the proposed method with an external validation cohort was also highly consistent with that of the experienced rater.