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Background: The natural history of vertebrobasilar artery (VBA) stenosis or occlusion remains understudied. Methods: Patients with diagnosis of ischemic stroke or transient ischemic attack (TIA) who were noted to have VBA stenosis based on computed tomography or magnetic resonance imaging or catheter-based angiogram were selected from Taiwan Stroke Registry. Cox proportional hazards model was used to determine the hazards ratio (HR) of recurrent stroke and death within 1 year of index event in various groups based on severity of VBA stenosis (none to mild: 0–49%; moderate to severe: 50–99%: occlusion: 100%) after adjusting for differences in demographic and clinical characteristics between groups at baseline evaluation. Results: None to mild or moderate to severe VBA stenosis was diagnosed in 6972 (66%) and 3,137 (29.8%) among 10,515 patients, respectively, and occlusion was identified in 406 (3.8%) patients. Comparing with patients who showed none to mild stenosis of VBA, there was a significantly higher risk of recurrent stroke (HR 1.21, 95% CI 1.01–1.45) among patients with moderate to severe VBA stenosis. There was a nonsignificantly higher risk of recurrent stroke (HR 1.49, 95% CI 0.99–2.22) and significantly higher risk of death (HR 2.21, 95% CI 1.72–2.83), among patients with VBA occlusion after adjustment of potential confounders. Conclusions: VBA stenosis or occlusion was relatively prevalent among patients with TIA or ischemic stroke and associated with higher risk of recurrent stroke and death in patients with ischemic stroke or TIA who had large artery atherosclerosis.

Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise.

Objectives The ankle–brachial index is a noninvasive modality to evaluate atherosclerosis and is a predictive role for future cardiovascular events and mortality. However, few studies have evaluated its relation to long-term future ischemic stroke in hemodialysis patients. Therefore, we examined the relationship between ankle–brachial index and ischemic stroke events among hemodialysis patients in a seven-year follow-up. Methods A total of 84 patients were enrolled. Ankle–brachial index was assessed in January 2009. Primary outcomes included ischemic stroke. An ankle–brachial index Results Mean values for ankle–brachial index were 0.98 ± 0.21at study entrance. In addition, 28 patients encountered ischemic stroke in the seven-year follow-up. In univariate Cox regression analysis, old age (hazard ratio (HR): 1.065, 95% confidence interval (CI): 1.030–1.102, p Conclusions These findings suggest that ankle–brachial index is an impressive predictor of future ischemic stroke among hemodialysis patients.

Hemodialysis patients have a high incidence of anti-platelet factor 4/heparin antibody (PF4-H Ab) and are at a high risk of cardiovascular disease. This study determines the association between PF4-H Ab and cardiovascular events including coronary artery disease (CAD), ischemic stroke (IS), and native arteriovenous fistula thrombosis (AVFT), in a longitudinal 7-year follow-up. 84 hemodialysis patients were enrolled. Data collection included chart reviews and assessments of laboratory records. PF4-H Ab was evaluated by ELISA and a titer ≥ 0.4 was defined to have PF4-H Ab. 30 patients were PF4-H Ab positive, 30 patients had CAD, 29 patients had IS, and 43 patients had AVFT. In Cox proportional hazard regression analysis, PF4-H Ab (HR 2.72, p = 0.01) was a significant risk factor for CAD. Age (HR 1.06, p = 0.003), PF4-H Ab (HR 4.53, p

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Introduction Nonketotic hyperglycemia-related seizures are not uncommonly encountered in clinical practice. Their presentation varies, and they may cause serious consequences if they remain unnoticed. Case We report a case of nonketotic hyperglycemia-related seizures of unique left parieto-occipital origin and semiology, presenting as focal aware (simple partial) and impaired awareness (complex partial) seizures, including contralateral limb convulsion and apraxialike behavior. Discussion Nonketotic hyperglycemia-related seizures can present with a relatively unique semiology. Careful education to the patients and family regarding attention to the paroxysmal symptoms and an effort to maintain good glycemic control are mandatory in clinical practice.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), an unusual pattern in electroencephalography, have been described in critically-ill encephalopathic patients in response to alerting stimuli. The phenomenon may be seen in patients with a broad range of aetiologies, including cerebral infarct, haemorrhage, anoxia, and degenerative diseases. Here, we report a unique case of status epilepticus presenting with SIRPIDs during funduscopic examination-induced focal to bilateral tonic-clonic seizures.

Pioglitazone (PIO), a thiazolidinedone, was reported to stimulate peroxisome proliferator-activated receptor-γ (PPAR-γ) with anti-inflammatory, anti-proliferative, anti-diabetic, and antidepressive activities. However, whether this compound exerts any perturbations on Ca2+-activated K+ and M-type K+ currents in central neurons remains largely unresolved. In this study, we investigated the effects of PIO on these potassium currents in hippocampal neurons (mHippoE-14). In whole-cell current recordings, the presence of PIO (10 μM) increased the amplitude of Ca2+-activated K+ current [IK(Ca)] in mHippoE-14 cells. PIO-induced stimulation of IK(Ca) observed in these cells was reversed by subsequent addition of paxilline, yet not by TRAM-39 or apamin. In inside-out current recordings, PIO applied to the bath concentration-dependently increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels with an EC50 value of 7.6 μM. Its activation of BKCa channels in mHippoE-14 cells was voltage-dependent and accompanied by both a lengthening in mean open time and a shortening in slow component of mean closed time. The activation curve of BKCa channels after addition of PIO was shifted to less depolarized potential without any change in the gating charge. PIO also suppressed the amplitude of M-type K+ currents inherently in mHippoE-14 neurons. Taken together, in addition to its agonistic action on PPAR-γ, PIO-induced perturbation of these potassium channels may be responsible for its widely pharmacological actions on hippocampal neurons.

Hemodialysis patients have a high incidence of ischemic stroke. However, the association between serum phosphate levels and ischemic stroke is controversial among hemodialysis patients. The present study is used to evaluate whether serum phosphate levels are associated with ischemic stroke among patients undergoing hemodialysis. A total of 84 hemodialysis patients were followed up for 8 years. Data collection included chart reviews and assessments of laboratory records. The ischemic stroke diagnosis was made on the basis of history, physical examination and neuroimaging (computed tomography and/or magnetic resonance imaging) by neurologists. Cox proportional hazard regression models were used to analyze the data. During the follow-up period, 29 patients experienced ischemic stroke. According to Cox proportional hazard regression analysis, the risk of ischemic stroke decreased by 45.5% for each 1-mg/dL increase in averaged serum phosphate (HR 0.545, p = 0.011). The risk of ischemic stroke increased by 4.3% for each 1-year increase in age (HR 1.043, p = 0.018). The risk of ischemic stroke increased by 1.1% increase for each 103/μL increase in averaged blood platelet (HR 1.011, p = 0.009). The risk of ischemic stroke in patients with averaged serum phosphate

Background: The risk of recurrent stroke in patients with ischemic stroke with vertebral/basilar artery stenosis remains to be systematically studied. Methods: We analyzed data from Taiwan Stroke Registry (TSR), with stroke registries provided by 59 hospitals. Patients who had diagnosis of ischemic stroke and were categorized into the “large artery atherosclerosis” group by TOAST who underwent CTA, MRA, or catheter- based angiography were identified for the present study. The patients were divided into 3 groups based on the extent of vertebral (VA) and/or basilar artery (BA) stenosis as follows: 0-49%, 50-99%, and 100% (total occlusion). Cox proportional hazards model was used to determine the hazard ratios (HRs) of recurrent stroke within 1 year of index event after adjusting for all relevant risk factors by univariable Cox model. Results: In the TSR data base, 84,831patients were in the ischemic stroke group. Based on TOAST, 20,220 patients were in the large-artery atherosclerosis group. Among these patients, a total of 10,515 were of age 18 or greater who had CTA, MRA or angiographic studies that included VA/BA. There were 6,972 subjects with VA/BA stenosis in the 0-49%, 3,137 in the 50-99% and 406 in the 100% (total occlusion) groups respectively. With VA/BA stenosis in the 0-49% range as the reference, HRs of recurrent stroke in one year by multivariable modeling with adjustment of all relevant risk factors by univariable Cox model was 1. 29 (95% CI, 1.05 - 1.58, p Conclusions: Vertebral or basilar artery stenosis or occlusion was relatively prevalent among patients with ischemic stroke categorized in the large artery artherosclerosis group by TOAST with greater extent of VA/BA stenosis carrying greater risk of recurrent stroke within 1 year after stroke.

Background/PurposeExplaining the risks and benefits of recombinant tissue-plasminogen activator (rtPA) to eligible patients with acute ischemic stroke (AIS) within a few minutes is important but difficult. We examined whether a new thrombolysis program can decrease the door-to-needle (DTN) time when treating patients with AIS.MethodsA new rtPA thrombolysis program with video assistance was adapted for patients with AIS and their families. We retrospectively compared outcome quality before (2009–2011) and after (2012) the program began. Outcomes included DTN time, the percentage of rtPA thrombolysis within 3 hours of onset in all hospitalized patients with AIS who presented within 2 hours of onset (2hr%) and the percentage of rtPA thrombolysis in all hospitalized patients with AIS (AIS%).ResultsWe recruited patients with AIS who had undergone thrombolytic therapy before (n = 18) and after (n = 14) the initiation of the new program. DTN time decreased (93 ± 24 minutes to 57 ± 14 minutes, p

Neuropathic pain is a complicated disorder. This complexity arises not because the characteristics of the pain differ from nociceptive inflammatory symptoms, but because of its complex mechanism. Peripheral transduction, ectopic impulse, central sensitization, low threshold A-beta fiber mediated pain, and loss of inhibitory control all play a role in the mechanism. Nevertheless, the outcomes are still unsatisfactory for physicians and patients with regards to treatment. For example, certain disorders such as central post-stroke pain are extremely difficult to treat, not only because of the intolerable side effects of the medications but also because of the unknown effectiveness of pain reduction, especially in the elderly. Under-treatment frequently occurs in the absence of attention to the pain characteristics, and because physicians are concerned of adverse effects or inappropriate up-titration of neuropathic drugs such as anti-epileptic medicines. Multidisciplinary approaches including non-pharmacological management, rehabilitation, biofeedback, acupuncture, education on stepwise pain reduction, and keeping a diary are somewhat helpful in clinical practice but not easily implemented without the cooperation of multidisciplinary teams. Physicians prescribe opioids to alleviate the symptoms, however this carries the risk of addiction. Therefore, it is important that clinicians are made aware of common neuropathic disorders in order to establish strategies to manage such types of pain.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with 200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC 15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI)

A 78-year-old woman presented with slowly progressive weakness of her hands and numbness in her feet when she stood up or walked. A neurological examination showed generally brisk deep tendon reflexes. Her ability to feel vibrations was reduced, particularly in her lower limbs. She is not a vegetarian and has no history of gastric surgery. Laboratory blood analyses disclosed macrocytic anemia (Hemoglobin [Hb]: 6.4 g/dl; mean corpuscular volume [MCV]: 137 fl), and low serum vitamin B12 (110 pg/ml). After a blood transfusion, her Hb rose to 11 g/dl and her MCV to 112.5 fl. A sagittal cervical spinal magnetic resonance image (MRI) reveals a linear high-intensity T2-weighted lesion in the posterior cord from the C2 to the C5 level (Figure 1: left side, arrows). An axial view shows a high signal intensity T2-weighted linear lesion with an inverted V shape in the posterior column (Figure: right side, arrowheads).

Patients with optic neuritis (ON) are at an increased risk of developing multiple sclerosis (MS), an illness that may result in physical dysfunction and short life expectancy. Information on the conversion rate to MS of patients with ON is essential in determining the impact of ON on the incidence of MS. Previous Taiwanese studies on the risk of MS in patients with ON were all hospital based, thereby limiting the generalizability of the findings. We aimed to estimate the risk of MS in patients with ON using a nationally representative sample. A cohort of 2,741 patients who sought outpatient care for ON in 2000 was identified from Taiwan's National Health Insurance claims. The control group consisted of 27,330 age- and sex-matched subjects randomly selected from all beneficiaries in 2000. The person-year approach with Poisson assumption was used to estimate the incidence rate of MS from 2000 to 2008. The relative risk of outpatient visit or hospitalization for MS was estimated using the Cox proportional hazard model. The incidence rates of MS in the ON and control groups were 25.6 and 0.4, respectively, per 10,000 person-years; these values represent a relative risk estimate of 30.84 (95% confidence interval: 14.48 to 65.73) after the potential confounders were considered. Female or younger patients with ON were associated with a significantly elevated risk of developing MS. This study found that Taiwanese patients with ON are at a substantially high relative risk of developing MS. In addition to patients with ON, female and younger people should also receive intensive neurological care to further reduce their risk of developing MS.

The effect of reactive oxygen species (ROS) and blocking integrin–extracellular matrix (ECM) interaction on apoptosis in podocytes, and the related signal transduction pathways remain unclear. Primary cultured rat podocytes were exposed to ROS. Integrin–ECM interaction was inhibited with anti- β1-integrin monoclonal antibody (mAb) or RGDS (Arg–Gly–Asp–Ser). Extracellular signal-regulated kinase (ERK) activation was evaluated with Western blotting. U0126 was used to inhibit ERK activation. Terminal deoxynucleotidyl transferase-mediated dUTP-peroxidase nick end-labeling of DNA (TUNEL) was used to evaluate apoptosis. We found that ROS-treated podocytes exhibited increased apoptosis, and both anti- β1-integrin mAb and RGDS induce apoptosis. Addition of ROS to either anti- β1-integrin mAb or RGDS enhanced apoptosis in both conditions. ERK activation was increased by either ROS or blocking integrin–ECM interaction. Preincubation with U0126 decreased apoptosis induced by ROS, anti- β1-integrin mAb or RGDS, respectively. Our study demonstrated that ROS and blocking integrin–ECM interaction induce podocyte apoptosis, which is mediated by ERK activation.

Background and Purpose: Cancer and stroke are the first and third leading cause of death in Taiwan respectively. Cancer has been considered to be a stroke risk factor. Ovarian cancer as a cause of stroke has appeared in the literature as case reports featuring increase in systemic thromboembolic tendency, frequently associated with non-bacterial endocarditis. To the best of our knowledge, no systemic assessment of ovarian cancer as a stroke risk factor has been made. Based on the Taiwan National Health Insurance claim files covering 1997 - 2008, we explored ovarian cancer as a stroke risk factor. Methods: There were a total of 8,728 patients with diagnosis of ovarian cancer from 1997 to 2007. A cohort of 34,912 age- and gender-matched patients without cancer served as the control group. Both groups were followed until the end of 2008. The ovarian cancer and control cohorts were further divided into 2 subgroups with and without key stroke risk factors (hypertension, diabetes, or both). Cox proportional hazard regression analysis was used to estimate the stroke risk in patients with ovarian cancer to derive hazard ratios (HRs) and 95% confidence intervals (CIs) Results: In the ovarian cancer cohort without hypertension or diabetes, the incidence rate was 4.89 per 1000 person-years in comparison with 4.70 in the control group without comorbidity. The hazard ratio (HR) is 1.44 (95% CI 1.22-1.77). For the ovarian cancer cohort with hypertension, diabetes or both, the incidence rate of stroke was 12.05 per 1000 person-years as compared to 30.67 in the control cohort with hypertension, diabetes or both. The HR is 0.44 (95% CI 0.29-0.68). Conclusion: Ovarian cancer increased the risk of stroke by 44% in patients without hypertension, diabetes or both in comparison with the age- and gender-matched control without the same comorbidity. However, patients with ovarian cancer who had hypertension, diabetes or both had signnificantly lower stroke risk than the control group with the same comorbidity. The mechanism for the apparent paradox associated with comorbidity (hypertension, diabetes or both) known to increase the stroke risk in patients with ovarian cancer remains to be determined.