Genomic Context of SARS-CoV-2 Outbreaks in Farmed Mink in Spain during Pandemic: Unveiling Host Adaptation Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects various mammalian species, with farmed minks experiencing the highest number of outbreaks. In Spain, we analyzed 67 whole genome sequences and eight spike sequences from 18 outbreaks, identifying four distinct lineages: B.1, B.1.177, B.1.1.7, and AY.98.1. The potential risk of transmission to humans raises crucial questions about mutation accumulation and its impact on viral fitness. Sequencing revealed numerous not-lineage-defining mutations, suggesting a cumulative mutation process during the outbreaks. We observed that the outbreaks were predominantly associated with different groups of mutations rather than specific lineages. This clustering pattern by the outbreaks could be attributed to the rapid accumulation of mutations, particularly in the ORF1a polyprotein and in the spike protein. Notably, the mutations G37E in NSP9, a potential host marker, and S486L in NSP13 were detected. Spike protein mutations may enhance SARS-CoV-2 adaptability by influencing trimer stability and binding to mink receptors. These findings provide valuable insights into mink coronavirus genetics, highlighting both host markers and viral transmission dynamics within communities.

Genomic characterisation of respiratory syncytial virus: a novel system for whole genome sequencing and full-length G and F gene sequences.

To advance our understanding of respiratory syncytial virus (RSV) impact through genomic surveillance, we describe two PCR-based sequencing systems, (i) RSVAB-WGS for generic whole-genome sequencing and (ii) RSVAB-GF, which targets major viral antigens, G and F, and is used as a complement for challenging cases with low viral load. These methods monitor RSV genetic diversity to inform molecular epidemiology, vaccine effectiveness and treatment strategies, contributing also to the standardisation of surveillance in a new era of vaccines.

Antibiotic Utilization in Hospitalized Children with Bronchiolitis: A Prospective Study Investigating Clinical and Epidemiological Characteristics at a Secondary Hospital in Madrid (2004-2022).

Bronchiolitis is a viral respiratory infection, with respiratory syncytial virus (RSV) being the most frequent agent, requiring hospitalization in 1% of affected children. However, there continues to be a noteworthy incidence of antibiotic prescription in this setting, further exacerbating the global issue of antibiotic resistance. This study, conducted at Severo Ochoa Hospital in Madrid, Spain, focused on antibiotic usage in children under 2 years of age who were hospitalized for bronchiolitis between 2004 and 2022. In that time, 5438 children were admitted with acute respiratory infection, and 1715 infants (31.5%) with acute bronchiolitis were included. In total, 1470 (87%) had a positive viral identification (66% RSV, 32% HRV). Initially, antibiotics were prescribed to 13.4% of infants, but this percentage decreased to 7% during the COVID-19 pandemic thanks to adherence to guidelines and the implementation of rapid and precise viral diagnostic methods in the hospital. HBoV- and HAdV-infected children and those with viral coinfections were more likely to receive antibiotics in the univariate analysis. A multivariate logistic regression analysis revealed a statistically independent association between antibiotic prescription and fever > 38 °C (p < 0.001), abnormal chest-X ray (p < 0.001), ICU admission (p = 0.015), and serum CRP (p < 0.001). In conclusion, following guidelines and the availability of rapid and reliable viral diagnostic methods dramatically reduces the unnecessary use of antibiotics in infants with severe bronchiolitis.

Surveillance of Viral Respiratory Infections in the Neonatal Intensive Care Unit-Evolution in the Last 5 Years.

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks' gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants' birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.

Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome.

The main objective of this study was to determine the influence of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) on the outcome of unvaccinated individuals with critical COVID-19 admitted to the ICU. Blood samples from 23 individuals were collected upon admission and then every 2 weeks for 13 weeks until death (Exitus group) (n = 13) or discharge (Survival group) (n = 10). We did not find significant differences between groups in sociodemographic, clinical, or biochemical data that may influence the fatal outcome. However, direct cellular cytotoxicity of PBMCs from individuals of the Exitus group against pseudotyped SARS-CoV-2-infected Vero E6 cells was significantly reduced upon admission (-2.69-fold; p = 0.0234) and after 4 weeks at the ICU (-5.58-fold; p = 0.0290), in comparison with individuals who survived, and it did not improve during hospitalization. In vitro treatment with IL-15 of these cells did not restore an effective cytotoxicity at any time point until the fatal outcome, and an increased expression of immune exhaustion markers was observed in NKT, CD4+, and CD8+ T cells. However, IL-15 treatment of PBMCs from individuals of the Survival group significantly increased cytotoxicity at Week 4 (6.18-fold; p = 0.0303). Consequently, immunomodulatory treatments that may overcome immune exhaustion and induce sustained, efficient cytotoxic activity could be essential for survival during hospitalization due to critical COVID-19.

Viral respiratory infections in very low birthweight infants at neonatal intensive care unit: prospective observational study.

BACKGROUND AND OBJECTIVE: Very low birthweight (VLBW) infants are highly susceptible to respiratory infections. Information about prevalence of viral respiratory infections (VRIs) in neonatal intensive care unit (NICU) is scarce. Recent evidence suggests short-term and long-term impact of VRI in morbidity of VLBW infants. The goal of this study is to conduct a VRI surveillance in VLBW infants during NICU admission to address the prevalence, type of viruses and associated clinical features. METHODS: Prospective observational cohort study on infants below 32 gestational weeks admitted to a tertiary NICU during a 2-year period. Respiratory virus detection (influenza, parainfluenza, rhinovirus (hRV), enterovirus, respiratory syncytial virus, metapneumovirus, coronavirus, bocavirus and adenovirus) was performed by real time multiplex PCR assays in nasopharyngeal aspirates (NPAs), within the first 72 hours after birth and weekly, until discharge. Additional samples were taken if clinically indicated. RESULTS: 147 out of 224 eligible infants were enrolled. At least one positive NPA was found in 38% of the study cohort. Main viruses identified were hRV (58%) and adenovirus (31%). Among the 56 infants with positive NPA, 26 showed non-specific respiratory features in 58% (increased respiratory workload, tachypnoea, apnoea) or typical cold features in 38% (rhinorrhea, cough, fever), at least in one episode. Antibiotics were prescribed in 29% of cases. Positive infants showed higher rates of bronchopulmonary dysplasia (BPD), need for supplemental oxygen and mechanical ventilation, and had longer hospital stay. Cox regression analysis found BPD as an independent risk factor for viral infection (p<0.001) and symptomatic VRI (p<0.04). CONCLUSIONS: Systematic surveillance in VLBW infants reports VRI is frequent, particularly by hRV. Asymptomatic infection is highly prevalent which is critical in the face of establishing appropriate preventive strategies. Infants with BPD are especially vulnerable to such infections.

First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020.

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.

Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia.

BACKGROUND: Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. METHODS: Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV. RESULTS: There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08). CONCLUSIONS: A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.

Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation.

Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients.

PARP1 and Poly(ADP-ribosyl)ation Signaling during Autophagy in Response to Nutrient Deprivation.

Autophagy is considered to be the primary degradative pathway that takes place in all eukaryotic cells. Morphologically, the autophagy pathway refers to a process by which cytoplasmic portions are delivered to double-membrane organelles, called autophagosomes, to fuse with lysosomes for bulk degradation. Autophagy, as a prosurvival mechanism, can be stimulated by different types of cellular stress such as nutrient deprivation, hypoxia, ROS, pH, DNA damage, or ER stress, promoting adaptation of the cell to the changing and hostile environment. The functional relevance of autophagy in many diseases such as cancer or neurodegenerative diseases remains controversial, preserving organelle function and detoxification and promoting cell growth, although in other contexts, autophagy could suppress cell expansion. Poly(ADP-ribosyl)ation (PARylation) is a covalent and reversible posttranslational modification (PTM) of proteins mediated by Poly(ADP-ribose) polymerases (PARPs) with well-described functions in DNA repair, replication, genome integrity, cell cycle, and metabolism. Herein, we review the current state of PARP1 activation and PARylation in starvation-induced autophagy.

New Adenovirus Groups in Western Palaearctic Bats.

In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.

Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy.

BACKGROUND: Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance. METHODS: Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%. RESULTS: Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm2; P < 0.05). CONCLUSION: The accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.

Thymic stromal lymphopoietin, IL-33, and periostin in hospitalized infants with viral bronchiolitis.

Much attention has recently been focused on thymic stromal lymphopoietin (TSLP), IL-33, and periostin in allergic disease, but less is known about their role in viral bronchiolitis.The aim of the study was to investigate whether infants exhibit enhanced nasal airway secretion of TSLP, IL-33, and periostin during natural respiratory viral bronchiolitis compared to healthy controls.In total, 213 infants < 2 years of age, hospitalized with bronchiolitis from October/2013 to April/2016 were enrolled alongside 45 healthy infants. Nasopharyngeal aspirates (NPA) were screened for respiratory viruses by the polymerase chain reaction. TSLP, IL-33, and periostin were measured in NPAs. Clinical data were recorded.At least 1 virus was detected in 186 (87.3%) hospitalized infants: 149 (70%) respiratory syncytial virus (RSV); 42 (19.7%) rhinovirus (HRV); 16 (7.5%) parainfluenza virus (PIV); 9 (4.2%) adenovirus; 10 (4.7%) bocavirus; and 7 (3.3%) metapneumovirus (hMPV). Infants with bronchiolitis had higher levels of TSLP (P = .02), IL-33 (P<.001), and periostin (P = .003) than healthy controls.Detectable levels of TSLP and periostin were more frequent in virus-positive than in virus-negative patients (P = .05). TSLP and IL-33 were also more common in coinfections, mainly RSV and HRV, than in single-infections (P < .05). No patient with bronchiolitis but with negative viral detection had detectable levels of nasal TSLP or IL-33. Infants with hospital stay ≥5 days were more likely to have detectable levels of nasal TSLP and periostin after adjusting by age (P = .01).Bronchiolitis by common respiratory viruses is associated with elevated nasal levels of TSLP, IL-33, and periostin, factors known to be important in the development of Th2-response. Respiratory viruses in early life might shift immune responses toward Th2, involving asthma, and allergic diseases.

Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study.

BACKGROUND: Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. METHODS AND FINDINGS: A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children's mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. CONCLUSIONS: HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections.

Genetic variability of respiratory syncytial virus A in hospitalized children in the last five consecutive winter seasons in Central Spain.

Human respiratory syncytial virus group A (RSV-A) was detected in symptomatic hospital attended children in Central Spain for a continuous time period, September 2010 to April 2015. In order to accurately describe the epidemiology of this virus, the genetic diversity of the complete G gene and the clinical manifestations observed were jointly analyzed. Out of 3,011 respiratory specimens taken from 2,308 children, 640 were positive to RSV (21.3%) and 405 were RSV-A (63.2%). Complete G gene sequences of 166 randomly selected RSV-A virus identified NA1 and ON1 genotypes. In 2011-2012, ON1 emerged sporadically and become dominant in 2012-2013 with 38 cases (70%). In 2014-2015, all the 44 sequences contained the 72-nt duplication (100%). Clinical diagnosis of children with ON1 genotype were bronchiolitis in 55 (62.5%), recurrent wheezing or asthma exacerbations in 22 (25%), laryngotracheobronchitis in 3 (3.4%), and upper respiratory tract infections in eight. Results showed replacement and substitution of circulating NA1 genotype with the new ON1 genotype. Nevertheless, at this stage, none of the RSV-A genotypes identified have resulted in significant clinical differences. The amino acid composition of the complete G gene ON1 sequences demonstrated an accumulation of single changes not related with different clinical presentation. J. Med. Virol. 89:767-774, 2017. © 2016 Wiley Periodicals, Inc.

Identification of Novel Betaherpesviruses in Iberian Bats Reveals Parallel Evolution.

A thorough search for bat herpesviruses was carried out in oropharyngeal samples taken from most of the bat species present in the Iberian Peninsula from the Vespertilionidae, Miniopteridae, Molossidae and Rhinolophidae families, in addition to a colony of captive fruit bats from the Pteropodidae family. By using two degenerate consensus PCR methods targeting two conserved genes, distinct and previously unrecognized bat-hosted herpesviruses were identified for the most of the tested species. All together a total of 42 potentially novel bat herpesviruses were partially characterized. Thirty-two of them were tentatively assigned to the Betaherpesvirinae subfamily while the remaining 10 were allocated into the Gammaherpesvirinae subfamily. Significant diversity was observed among the novel sequences when compared with type herpesvirus species of the ICTV-approved genera. The inferred phylogenetic relationships showed that most of the betaherpesviruses sequences fell into a well-supported unique monophyletic clade and support the recognition of a new betaherpesvirus genus. This clade is subdivided into three major clades, corresponding to the families of bats studied. This supports the hypothesis of a species-specific parallel evolution process between the potentially new betaherpesviruses and their bat hosts. Interestingly, two of the betaherpesviruses' sequences detected in rhinolophid bats clustered together apart from the rest, closely related to viruses that belong to the Roseolovirus genus. This suggests a putative third roseolo lineage. On the contrary, no phylogenetic structure was detected among several potentially novel bat-hosted gammaherpesviruses found in the study. Remarkably, all of the possible novel bat herpesviruses described in this study are linked to a unique bat species.

Infections and coinfections by respiratory human bocavirus during eight seasons in hospitalized children.

The human bocavirus (hBoV) has been identified in respiratory infections in children in a large number of studies. Despite this, the pathogenic role of the HBoV is under discussion. The main objectives of the study were: to determine the incidence of HBoV in hospitalized children; to describe the main clinical features of the positive children; and to compare the data with those from other viral infections in the same population. A prospective study was performed between 2005 and 2013 including children up to 14-year old with respiratory infection admitted to the Severo Ochoa Hospital (Spain). Nasopharyngeal aspirates were taken from 3,275 patients and were tested for HBoV and other 15 respiratory viruses by RT-nested PCR. HBoV was detected in 319 patients (9.9%); 80 cases as a single pathogen, and 239 cases (75%) as coinfections with other viruses. The HBoV was the fourth most common virus detected, behind respiratory syncytial virus (39.8%), rhinovirus (30.6%), and adenovirus (15%). The most common clinical diagnosis, in cases that HBoV was detected as a single pathogen was asthma exacerbation followed by pneumonia. A seasonal distribution was shown, with higher positivity rates in December and January. Children affected by HBoV were older than children infected by other viruses. Differences in terms of clinical diagnosis were found, bronchiolitis diagnosis was lower compared with the other viruses, and HBoV was associated with diagnosis of pneumonia, with increased use of antibiotics (41.8%), and radiographic infiltrates (47%). These findings could suggest a pathogenic role of HBoV in respiratory infections in children under 14 years of age. J. Med. Virol. 88:2052-2058, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson's Disease.

Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7% in 70% of the patients.

Limb-Shaking TIA Presenting as Hemichorea-Hemiballismus: TIA Chameleons Diagnostic Challenge in the Emergency Department.

BACKGROUND: demonstrate the importance of considering limb-shaking syndrome in the differential diagnosis of patients who present to the emergency department (ED) with hyperkinetic movements. METHODS: In this article, we describe a diagnostic challenge in the ED in which a patient presents with hyperkinetic movements that are initially diagnosed as hemichorea-hemiballismus (HCHB) but are subsequently found to be limb-shaking syndrome with important therapeutic opportunities. RESULTS: Following a diagnosis of left carotid obstruction, the patient underwent left carotid endarterectomy 5 days after admission. Six months after surgery, the patient had no further symptoms, and an ultrasound scan and magnetic resonance angiography have confirmed no restenosis. CONCLUSION: Limb shaking is an uncommon form of transient ischemic attack that should be recognized and differentiated from conditions such as focal motor seizures. Recognition will almost invariably indicate carotid artery occlusion, and timely treatment may not only abolish the attacks in patients but also reduce their risk of stroke. HCHB represents a spectrum of hyperkinetic movement disorders varying in the severity of choreic and/or ballistic movements. The presented case includes limb-shaking syndrome in the differential diagnosis and prompts for further investigations to complete the assessment.