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Pei-Ya Chen,1,2 Guei-Chiuan Chen,1,2 Cheng-Lun Hsiao,1 Po-Jen Hsu,1 Fu-Yi Yang,1 Chih-Yang Liu,1 Adam Tsou,1 Wan-Ling Chang,1 Hsiu-Hsun Liu,1 Shinn-Kuang Lin1,2 1Stroke Center and Department of Neurology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, TaiwanCorrespondence: Shinn-Kuang Lin, Tel +886-2-66289779 ext 3129, Fax +886-2-66289009, Email stuartlin0428@gmail.com; sk2022@tzuchi.com.twPurpose: 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.Keywords: immune-inflammatory markers, in-hospital ischemic stroke, intrahospital delay, neutrophil-to-lymphocyte ratio, out-of-hospital ischemic stroke, systemic immune-inflammation index

Shinn-Kuang Lin,1,2 Pei-Ya Chen,1,2 Guei-Chiuan Chen,1 Po-Jen Hsu,1 Cheng-Lun Hsiao,1 Fu-Yi Yang,1 Chih-Yang Liu,1 Adam Tsou1 1Stroke Center and Department of Neurology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, TaiwanCorrespondence: Shinn-Kuang LinStroke Center and Department of Neurology, Taipei Tzu Chi Hospital, No. 289, Jian Guo Road, 231, Sindian District, New Taipei City, TaiwanTel +886-2-66289779 ext 3129Fax +886-2-66289009Email stuartlin0428@gmail.comPurpose: 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.Keywords: acute ischemic stroke, hyperdense artery sign, neutrophil-to-lymphocyte ratio, NIHSS, unfavorable outcome

Background Atherosclerosis is a chronic inflammatory process that occurs in the arterial wall. This immuno-inflammatory process plays a role throughout all stages of stroke. Neutrophils, lymphocytes, and platelets are crucial blood cells for innate and adaptive immunity. This study investigated the associations of four types of immuno-inflammatory markers, namely the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil count (NC), with clinical outcomes in patients with acute ischemic stroke. Methods In this retrospective study, we enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data included risk factors, laboratory parameters, and clinical features during hospitalization. The National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) were used to assess stroke severity and outcomes. Results All four immuno-inflammatory markers exhibited positive linear correlations with age, glucose, creatinine, length of hospital stay, NIHSS score on admission, and mRS score at discharge. The levels of the four immuno-inflammatory markers were significantly higher in patients with large-artery atherosclerosis and cardioembolism and were highest in patients with other determined etiology. Patients with levels of immuno-inflammatory markers higher than their cutoff values for unfavorable outcomes also exhibited higher rates of cancer history (except for SII and NC), uremia (except for NC), elevated troponin I, and in-hospital complications. Multivariate analysis including SII revealed that admission NIHSS score ≥ 5, age > 75 years, SII > 724, diabetes mellitus, female sex, elevated troponin I, heart disease, and prior stroke were significant predictors for unfavorable outcomes. These significant predictors were retained after replacing SII > 724 with NLR > 143, PLR > 3.5, or NC > 6 × 10 3 /mL, except for prior stroke. For a basic model comprising seven significant predictors of unfavorable outcomes, the C-statistic was 0.860. The addition of SII, NLR, and PLR to the basic model resulted in a significant improvement in the prediction performance to 0.864, 0.863, and 0.863, respectively. Conclusions Immuno-inflammatory markers provide more useful information than conventional risk factors and other laboratory parameters for the prediction of stroke outcomes. SII > 724 is the most appropriate marker when combined with other predictors.

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) 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. Keywords: Acute stroke, Brain infarction, Code stroke, In-hospital delays, Thrombolytic therapy

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.

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.

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.

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.

Electrical stimulation may produce excitation or inhibition of the motor neurons, as represented the blink reflex and masseter silent period in response to trigeminal nerve stimulation. Clinically, a light touch on the palm may evoke a mentalis muscle response (MMR), i.e. a palmomental reflex. In this study, we attempted to characterize the MMR to median nerve stimulation. Electrical stimulation was applied at the median nerve with recordings at the mentalis muscles. An inhibition study was done with continuous stimuli during muscle contraction (I1 and I2 of MMRaverage). Excitation was done with a single shot during muscle relaxation (MMRsingle) or by continuous stimuli during muscle contraction (E1 and E2 of MMRaverage). The characteristic differences between MMRaverage and MMRsingle were as follows: earlier onset latencies of MMRaverage (MMRaverage45 ms; MMRsingle60 ms), and a lower amplitude of MMRaverage (MMRaverage50 microV; MMRsingle150 microV). The receptive field of MMRsingle was widespread over the body surface and that of MMRaverage was limited to the trigeminal, median and index digital nerves. Series of stimuli usually significantly decreased the amplitude of MMRsingle, as a phenomenon of habituation. On the other hand, it was difficult to evoke the earlier response (i.e. MMRaverage) without continuous stimuli and an average technique. MMRaverage had the components of both excitation (E) and inhibition (I); for example, E1-I1-E2-I2 or I1-E2-I2. E2 was the most consistent component. In patients with dorsal column dysfunction, median nerve stimulation could successfully elicit MMRsingle, but not MMRaverage. Contrarily, in patients with pain sensory loss, it was more difficult to reproduce MMRsingle than MMRaverage. It seemed that MMRaverage and MMRsingle did not have equivalents across the different modalities of stimulation.