J-Shaped Relationship of Serum Uric Acid with Unfavorable Short-Term Outcomes among Patients with Acute Ischemic Stroke.

(1) Background: The role of uric acid in stroke outcomes remains inconclusive. (2) Methods: We retrospectively enrolled 3370 patients with acute ischemic stroke. (3) Results: Uric acid level was higher in men than in women. Univariate analyses revealed that the rates of hyperuricemia were higher in all patients and in women for unfavorable outcomes. For death, the hyperuricemia rates were higher in all patients including men and women, and the uric acid levels were also higher in all patients and in women. A J-shaped curve was observed between uric acid and the discharge-modified Rankin Scale score. Patients within Quartiles 1 (<4.1 mg/dL) and 4 (>6.5 mg/dL) of uric acid had higher rates of unfavorable outcomes and death than patients within Quartiles 2 (4.1−5.1 mg/dL) and 3 (5.1−6.2 mg/dL). Multivariable analyses for unfavorable outcomes revealed that Quartile 1 of uric acid was a significant factor in all patients and in men. In men, a significant factor for death was being in Quartile 1 of uric acid. In women, higher levels of uric acid or hyperuricemia (>6.6 mg/dL) were significant factors for death. (4) Conclusions: Lower uric acid levels are a predictor for unfavorable outcomes and death in men, and higher uric acid levels are a predictor for death in women.

Comparison of Clinical Features, Immune-Inflammatory Markers, and Outcomes Between Patients with Acute In-Hospital and Out-of-Hospital Ischemic Stroke.

PURPOSE: We investigated the differences of clinical features, four immune-inflammatory markers, namely neutrophil counts, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as outcomes between patients with in-hospital ischemic stroke (IHIS) and out-of-hospital ischemic stroke (OHIS). PATIENTS AND METHODS: We retrospectively enrolled 72 patients with IHIS and 3330 patients with OHIS. RESULTS: IHIS accounted for 2% of all patients with ischemic stroke and occurred more often in cardiology and orthopedic surgery wards. Infection, cardiac disease, and pulmonary disorder were the most common causes of hospitalization. Compared with those with OHIS, patients with IHIS had higher levels of immune-inflammatory markers, initial National Institute of Health Stroke Scale (NIHSS) scores, longer hospital stays, higher rates of heart disease, large-artery atherosclerosis or cardioembolism, received more intravenous thrombolysis (IVT) or endovascular thrombectomies (EVTs), more complications, unfavorable outcomes, and mortality. Every immune-inflammatory marker exhibited positive correlations with initial NIHSS scores and discharge modified Rankin Scale scores among patients with OHIS. NLR and SII were higher among patients with a fatal outcome in both groups. Among patients receiving IVT, most of treatment time intervals were shorter for those with IHIS than those with OHIS. Significant factors for mortality were NLR >5.5, atrial fibrillation, and complications, with a C-statistic of 0.897 in those with IHIS; in those with OHIS, these factors were an initial NIHSS score of >10, NLR >6.0, atrial fibrillation, prior stroke, cancer history, and complications with a C-statistic of 0.902. The results were similar after replacing the NLR with SII. CONCLUSION: Patients with IHIS had more complicated clinical features, higher levels of immune-inflammatory markers, and higher rates of mortality than patients with OHIS. The most significant predictor for mortality among those with OHIS was NIHSS score >10, and the predictors among patients with IHIS were NLR >5.5 and SII >2120.

Association of a High Neutrophil-to-Lymphocyte Ratio with Hyperdense Artery Sign and Unfavorable Short-Term Outcomes in Patients with Acute Ischemic Stroke.

PURPOSE: Immune-inflammatory processes are involved in all the stages of stroke. This study investigated the association of the neutrophil-to-lymphocyte ratio (NLR) with the hyperdense artery sign (HAS) observed on brain computed tomography (CT) and with clinical features in patients with acute ischemic stroke. METHODS: We retrospectively enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data collected included imaging studies, risk factors, laboratory parameters, and clinical features during hospitalization. RESULTS: The HAS was identified in 6% of the 2903 patients and 66% of the 236 patients with acute middle cerebral artery occlusion. Patients with the HAS had a higher NLR. HAS prevalence was higher in men and patients with cardioembolism. The NLR exhibited positive linear correlations with age, glucose and creatinine levels, length of hospital stay, initial National Institutes of Health Stroke Scale (NIHSS) scores, and mRS scores at discharge. The NLR was significantly higher in patients with large-artery atherosclerosis and cardioembolism and was the highest in patients with other determined etiology. Multivariate analysis revealed that an initial NIHSS score of ≥10 and an NLR of >3.5 were significant positive factors, whereas diabetes mellitus and age > 72 years were significant negative factors for the HAS, with a predictive performance of 0.893. An initial NIHSS score of ≥5, positive HAS, age > 75 years, diabetes mellitus, an NLR of >3.5, female sex, a white blood cell count of >8 × 103/mL, and elevated troponin I were significant predictors of unfavorable outcomes, with a predictive performance of 0.886. CONCLUSION: An NLR of >3.5 enabled an efficient prediction of CT HAS. In addition to conventional risk factors and laboratory parameters, both an NLR of >3.5 and CT HAS enabled improved prediction of unfavorable stroke outcomes.

Impact of code stroke on thrombolytic therapy in patients with acute ischemic stroke at a secondary referral hospital in Taiwan.

BACKGROUND: Efficacy of thrombolytic therapy decreases with time elapsed from symptom onset. We sought to identify the impact of code stroke on the thrombolytic therapy. METHODS: Code stroke is activated by the emergency physician when a patient is eligible for thrombolytic therapy. We retrospectively reviewed patients with acute ischemic stroke between January 2011 and December 2014. RESULTS: In total, 1809 patients were enrolled. Code stroke was activated in 233 of 351 patients arriving at the emergency room (ER) within 3 h of symptom onset, and in 21 patients arriving >3 h. The sensitivity, specificity, and positive and negative predictive values of code stroke were 76%, 46%, 72%, and 51%, respectively. Thrombolytic therapy was provided to 58 patients, accounting for 3.4% of all cerebral infarcts. Code stroke was activated in 40 of these patients. The most common reasons for excluding thrombolytic therapy were: National Institute of Health Stroke Scale (NIHSS) < 6, intracranial hemorrhage (ICH), and age >80 years. Mean liaison-to-neurological evaluation time was only 6 min. Code stroke activation significantly reduced all the intervals, except for the onset-to-ER and door-to-order times. During the 4-year study period, there were significant reductions of the door-to-neurology liaison time by 28 min and door-to-laboratory time by 22 min. The proportion of door-to-needle time within 60 min improved from 33% in 2011 to 67% in 2014. Improved NIHSS scores during hospitalization were most prominent in tPA-treated patients. Symptomatic ICH occurred in 3.6% patients arriving within 3 h. Death occurred in 50% of patients received tPA treatment on family's request, and only 13% of those patients had favorable outcome. CONCLUSION: Code stroke is effective in reducing in-hospital delays. The accuracy of code stroke activation has acceptable sensitivity but low specificity. Rapid patient assessment by neurologists increases the number of patients eligible for thrombolytic therapy.

Common Neurological Disorders Involving Inpatient Liaisons at a Secondary Referral Hospital in Taiwan: A Retrospective Cross-Sectional Study.

BACKGROUND AND PURPOSE: The requirement for neurology liaison is increasing in accordance with the growing health care demands associated with aging populations. The aim of this study was to characterize the nature of neurological inpatient liaisons (NILs) to help plan for the appropriate use of neurology resources. METHODS: This was a retrospective cross-sectional study of NILs in a secondary referral hospital over a 12-month period. RESULTS: There were 853 neurological consultations with a liaison rate of 3% per admission case. Chest medicine, gastroenterology, and infectious disease were the three most frequent specialties requesting liaison, and altered consciousness, seizure, and stroke were the three most frequent disorders for which a NIL was requested. Infection was the most common cause of altered consciousness. Epilepsy, infection, and previous stroke were common causes of seizure disorders. Acute stroke accounted for 44% of all stroke disorders. Electroencephalography was the most recommended study, and was also the most frequently performed. Ninety-five percent of emergency consultations were completed within 2 hours, and 85% of regular consultations were completed within 24 hours. The consult-to-visit times for emergency and regular consultations were 44±47 minutes (mean±standard deviation) and 730±768 minutes, respectively, and were shorter for regular consultations at intensive care units (p=0.0151) and for seizure and stroke disorders (p=0.0032). CONCLUSIONS: Altered consciousness, seizure, and stroke were the most common reasons for NILs. Half of the patients had acute neurological diseases warranting immediate diagnosis and treatment by the consulting neurologists. Balancing increasing neurologist workloads and appropriate health-care resources remains a challenge.

Infectious Mononucleosis Complicated with Acute Cerebral Infarction: A Case Report.

PURPOSE: Infectious mononucleosis (IM) complicated with a neurological manifestation, including acute cerebellar ataxia, Guillain-Barre syndrome, meningitis, encephalitis, cranial nerve palsies, optic neuritis or transverse myelitis, has been rarely reported; however, IM complicated with acute cerebral infarction has never been reported in the literature. CASE REPORT: A 49-year-old man with diabetic mellitus suffered from IM with fever, pharyngitis, parotiditis with lymphadenopathies, thrombocytopenia and splenomegaly. After two weeks of conservative treatment, left upper limb paresis and left hemihypesthesia occurred. Neuroimaging demonstrated acute ischemic stroke involving the right frontal lobe. In view of the underlying infection, immediate intravenous rt-PA was not recommended; hence, oral aspirin 100 mg daily was prescribed and he received regular rehabilitation in the subsequent follow up. CONCLUSION: Although IM is known to be self-limited, it could contribute to acute cerebral infarction, which is a rare IM neurological complication.

Neurological complications of acute intermittent porphyria.

BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder of heme biosynthesis, the clinical manifestations of which are incompletely understood. In this report, we describe 12 cases of AIP, focusing on the neurological manifestations. METHODS: Twelve patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogen deaminase (PBGD) activity, and molecular genetics. Central and peripheral nervous system manifestations were noted, and electrophysiological and radiological studies performed. Potential precipitating factors were recorded. RESULTS: Eleven PBGD gene mutations were identified in 12 patients. Nine patients experienced neurological symptoms involving the central nervous system (consciousness disturbance, n = 8; convulsion/seizure, n = 4; behavior change, n = 1), while 7 patients experienced peripheral neuropathies (motor paresis, n = 7; impairment of bulbar or respiratory function, n = 4). The electrophysiological and electroencephalographic findings were consistent with the neurological symptoms of AIP. Urinary PBG and δ-aminolevulinic acid levels were elevated in all patients. PBGD enzyme activity levels were below normal in all patients. Eight patients had documented exposure to porphyrogenic agents. CONCLUSIONS: Our detailed description of a relatively large number of cases of AIP may help clinicians to recognize this often difficult-to-diagnose disorder.

New 3beta,5alpha,6beta-trihydroxysteroids from the octocorals Bebryce sp. (Plexauridae) and Carijoa sp. (Clavulariidae).

A new 3beta,5alpha,6beta-trihydroxysteroid, bebryceoid A (1), has been isolated from an octocoral Bebryce sp. In addition, an octocoral Carijoa sp. yielded two new 3beta,5alpha,6beta-trihydroxysteroids, carijoids A (2) and B (3). The structures of steroids 1-3 were elucidated by spectroscopic methods and by comparison of the spectral data with those of known steroid analogues.

Carijoside A, a bioactive sterol glycoside from an octocoral Carijoa sp. (Clavulariidae).

A new bioactive sterol glycoside, 3beta-O-(3',4'-di-O-acetyl-beta-D-arabinopyranosyl)-25xi-cholestane-3beta,5alpha,6beta,26-tetrol-26-acetate) (carijoside A, 1), was isolated from an octocoral identified as Carijoa sp. The structure of glycoside 1 was established by spectroscopic methods and by comparison with spectral data for the other known glycosides. Carijoside A (1) displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils and this compound exhibited moderate cytotoxicity toward DLD-1, P388D1, HL-60, and CCRF-CEM tumor cells.

VKORC1 haplotypes in five East-Asian populations and Indians.

AIMS: Warfarin, a widely prescribed oral anticoagulant, is used for the prevention of thromboembolism. Several polymorphisms in VKORC1 have been shown to be associated with warfarin dose requirements. The frequencies of these VKORC1 polymorphisms display population differences; however, this has not been examined in many populations. In this study, we examined VKORC1 polymorphisms in five East-Asian populations (Han Chinese, Indonesian, Filipino, Thai and Vietnamese) and Indians. MATERIALS & METHODS: A total of six SNPs in the VKORC1 gene (-1639G>A, 497T>G, 1173C>T, 1542T>G, 2255C>T and 3730G>A) were genotyped. Frequencies, linkage disequilibrium and haplotype structures of these six VKORC1 SNPs were analyzed. RESULTS: Our data showed that 497T>G is only polymorphic in the Indian population. The 497G allele is very rare in the East-Asian populations (frequency < 1%). The remaining SNPs demonstrated high linkage disequilibrium and had similar frequencies and haplotype structures in all but the Indian population. The Indian population is mostly made up of the H7 haplotype (76%) while the rest of the recruited populations consisted of the H1 haplotype (> 80%).

Toluene disrupts synaptogenesis in cultured hippocampal neurons.

Prenatal toluene exposure may lead to significant developmental neurotoxicity known as fetal solvent syndrome. Emerging evidence suggests that toluene embryopathy may arise from an elusive deviation of the neurogenesis process. One key event during neural development is synaptogenesis, which is essential for the progression of neuronal differentiation and the establishment of neuronal network. We therefore aim to test the hypothesis that toluene may interfere with synaptogenesis by applying toluene to cultured hippocampal neurons dissected from embryonic rat brains. In the presence of toluene, hippocampal neurons displayed a significant loss of the immunostaining of synapsin and densin-180 punctas. Notably, a dramatic reduction was also discerned for the colocalization of the two synaptic markers. Moreover, Western blotting analyses revealed that toluene exposure resulted in considerable down-regulation of the expression of synapse-specific proteins. None of the preceding observations can be attributed to toluene-induced cell death effects, since toluene treatments failed to affect the viability of hippocampal neurons. Overall, our data are consistent with the idea that toluene may alter the expression and localization of essential synaptic proteins, thereby leading to a disruption of synapse formation and maintenance.

Extramedullary plasmacytoma masquerading as Tolosa-Hunt syndrome: a case report.

Painful ophthalmoplegia due to extramedullary plasmacytoma is a rare initial manifestation of multiple myeloma. The present report describes a 48-year-old man who suffered an acute onset of retro-orbital pain, left abducens palsy and left facial hypoesthesia. In addition, he exhibited an elevated erythrocyte sedimentation rate and partial responsiveness to corticosteroid treatment, all of which resemble the features of Tolosa-Hunt syndrome. Imaging studies revealed a multilobulated tumour invading the left sphenoid bone and sphenoid sinus, later confirmed as a plasmacytoma at pathology. Multiple myeloma was also diagnosed by bone marrow examination. After completion of chemotherapy and radiotherapy, the patient has been free of symptoms for 10 months. Although cranial neuropathies with any combination of oculomotor, abducens, trochlear, ophthalmic and maxillary nerves may indicate a cavernous sinus lesion, neuropathies exclusive to the abducens and maxillary nerves may raise the possibility of extracavernous sinus origin. Cranial imaging is crucial in diagnosing painful ophthalmoplegia with additional minimal cranial nerve signs.

Posterior communicating artery hypoplasia as a risk factor for acute ischemic stroke in the absence of carotid artery occlusion.

Posterior communicating artery (PCoA) hypoplasia is a fetal variant of the Circle of Willis. According to angiograms and autopsy reports, this congenital variation is found in 6-21% of the general population. PCoA hypoplasia only becomes a risk factor for ischemic stroke in the presence of ipsilateral internal carotid artery (ICA) occlusion. The aim of our study was to determine the role of PCoA hypoplasia in acute ischemic stroke in the absence of ICA occlusion. We examined 310 acute ischemic stroke patients (mean age+/-standard deviation; 68.9+/-15.6 years). Cerebral magnetic resonance angiography was performed within 72 hours of ischemic stroke onset. For comparison, a risk factor-matched control group was recruited. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to estimate the independent effect of potential risk factors. The overall incidence of PCoA hypoplasia in our experimental group was 19.35% (n=60), which was significantly higher than in the control group (8.20%, n=22, p=0.036, OR, 3.21; 95% CI, 1.43-9.62). The most common ischemic event was ipsilateral thalamic lacunar infarctions with or without occipital lobe involvement. Based on our results, PCoA hypoplasia appears to be a contributor to the risk of ischemic stroke, even in the absence of ICA occlusion. This risk is especially pronounced for strokes involving arteries that penetrate the thalamus.

Intragenic microdeletion of RUNX2 is a novel mechanism for cleidocranial dysplasia.

Cleidocranial dysplasia (CCD; MIM 119600) is a rare autosomal dominant disorder characterized by facial, dental, and skeletal malformations. To date, rearrangement and mutations involving RUNX2, which encodes a transcription factor required for osteoblast differentiation on 6p21, has been the only known molecular etiology for CCD. However, only 70% patients were found to have point mutations, 13% large/contiguous deletion but the rest of 17% remains unknown. We ascertained a family consisted of eight affected individuals with CCD phenotypes. Direct sequencing analysis revealed no mutations in the RUNX2. Real time quantitative PCR were performed which revealed an exon 2 to exon 6 intragenic deletion in RUNX2. Our patients not only demonstrated a unique gene change as a novel mechanism for CCD, but also highlight the importance of considering "deletion" and "duplication" in suspected familial cases before extensive effort of gene hunting be carried.

Toward a further elucidation: role of vertebral artery hypoplasia in migraine with aura.

A higher frequency of hypoplastic vertebral artery (VA) in patients with migraine with aura than in normal controls has been documented. However, the role of a hypoplastic VA in a migraine attack remains unclear. The aim of our work was to measure the net VA flow volume and related spectral parameters in patients with migraine with aura and a hypoplastic VA. From January 2005 to October 2005 we reviewed the records of 250 migraine outpatients (108 men and 142 women; mean age = 30.8 +/- 14.0 years, range = 25-55). Ninety-two patients with migraine with aura were selected. Among these patients, 26 had a hypoplastic VA that was delineated by cervical magnetic resonance angiography. We performed a case-control study that included these 26 migrainous patients. Duplex color-coded ultrasonography was utilized to calculate the spectral parameters during attacks and headache-free periods. The net VA flow volume did not decrease during attacks. A reduction in the resistance index of the hypoplastic VA was noted during attacks in subjects who had migraine with aura. Our observation of VA vasomotor alteration during migraine attacks extends the understanding of the role of a hypoplastic VA. Vasomotor regulation of the VA could be neurogenic in origin. We hypothesize that VA hypoplasia contributes to migraine through complex neurovascular pathways rather than through its low flow volume.

Effect of sacral neuromodulation on the spinal nociceptive reflex of patients with idiopathic overactive bladder.

Objectives. Sacral root stimulation (SRS) is a technique to restore the idiopathic overactive bladder (IOB). However, its mechanism of action is yet to be elucidated. Hence, we studied whether SRS restored IOB through the mechanism of spinal neuromodulation. Materials and Methods. Six IOB patients and 10 healthy volunteers were included in the study. The spinal nociceptive reflex was used as the index of spinal excitability and was evoked by electrical stimulation at the foot, with recording at the ipsilateral tibialis anterior. Results. IOB patients had increased spinal excitability to somatic nociceptive stimuli of the lower limbs. This spinal excitability decreased and bladder function improved after SRS, an effect that outlasted actual stimulation by at least 30 min. Conclusions. Our results showed that spinal excitability was increased in response to somatic nociceptive afferents in IOB patients. SRS restored bladder function, at least, in part, through spinal neuromodulation.

Brainstem excitability is increased in subjects with palmomental reflex.

BACKGROUND/PURPOSE: The palmomental reflex (PMR) is a brief contraction of the mentalis muscles caused by a scratch over the thenar eminence, i.e. a brainstem reflex to afferents of upper limb. Using electrophysiologic methods, we studied the characteristics of brainstem excitability in PMR subjects. METHODS: Ten healthy PMR subjects were included in the study. Brainstem excitability was assessed with electrical stimulation at the trigeminal nerve, median nerve, ulnar nerve, and sural nerve with recordings at the mentalis muscles. A comparison was made by the probability between the mechanical scratch and the electrical stimulation to evoke the visible muscle contraction of mentalis. RESULTS: An electrical stimulus was able to elicit mentalis muscle responses (MMR(electrical)) in all the subjects if the stimulus was of sufficient strength. Using electrical stimulation, the median nerve at the wrist was the best site to evoke MMR(electrical). However, in PMR subjects, the probability of MMR(electrical) to median nerve stimulation was less than that of MMR(scratch), i.e. the clinical findings of PMR. Significantly lower thresholds and higher amplitudes were noted in PMR subjects only when the median nerve was stimulated. The onset latency did not show any difference between the two groups despite the stimulation sites. CONCLUSION: The facial motor neurons to median nerve stimulation are more sensitive in PMR subjects. In healthy PMR subjects, this indicates that the excitability increases only in the specific neuronal circuits between the lower cervical spinal cord and the facial motor nucleus in the rostral medulla. MMR(electrical) is a physiologic phenomenon, and PMR is a sign of increased brainstem excitability.

Pharmacoeconomics of therapy for Guillain-Barré syndrome: plasma exchange and intravenous immunoglobulin.

Guillain-Barré syndrome (GBS) is an acute neuropathy and a clinical syndrome that includes a number of pathological and electrophysiological subtypes. Intravenous immunoglobulin (IVIG) and plasma exchange (PE) are both equally efficacious for the treatment of GBS; however, the cost of IVIG may be lower for both the patient and the healthcare system. To compare the pharmacoeconomics of PE and IVIG in GBS, a retrospective study was done from 1999 to 2004, which included a total of 24 patients with GBS who were admitted to Taipei Veterans General Hospital. This showed that except for the costs of the drugs used in IVIG, treatment of GBS with IVIG was more cost-effective (p=0.057) than that with PE in total length of hospitalization and the cost of procedures and hospitalization. The study also showed that the total costs were higher for patients on ventilators than those not requiring ventilators (p=0.008, t-test) and the length of hospitalization showed a very strong linear relationship to total costs (Pearson correlation coefficient=0.907). The regression analysis showed that each additional day of hospitalization increased the hospitalization costs by an average of 5599 New Taiwan Dollars (NT) (US$1.00=NT$33.50 in 2005).