Neuron Signs Research Articles

Characterization of Pseudorabies Virus Associated with Severe Respiratory and Neuronal Signs in Old Pigs

Pseudorabies virus (PRV) represents a leading threat to the global pig industry. Generally, pigs exhibit a pronounced age resistance against PRV, and the virus generally does not cause severe clinical signs and even death in old pigs. However, we characterized two PRV strains (HeN21 and HuB20) associated with severe respiratory and neuronal signs in old pigs. Among these two strains, HeN21 was isolated from the tonsil of a 24-week-old pig that died from severe neuronal and respiratory signs in a PRV-outbreak farm where a commercial PRV attenuated vaccine developed based on a PRV variant was used; while, HuB20 was isolated from the lung and lymph node of a 20-week-old with symptoms in another farm where Bartha-K61 vaccine was used. In vitro evaluations in different cell models demonstrated that HeN21 and HuB20 led to similar cytotoxic effects to those caused by PRV variants on PK-15, Vero, and SK-N-SH cells after 30 hours of inoculation. However, HeN21 possessed a higher titer than the other PRV variants from the first to the fifth passage on PK-15 cells and induced plaques with larger size. In vivo assessments in mouse and fattening pig models showed that inoculations of HeN21 and HuB20 caused higher morbidity and mortality and severe pathological damages in tested animals. In particular, challenge of HeN21 led to severe respiratory and neuronal signs in 90-day-old pigs. These two strains displayed higher virus loads on the main organs of challenged mice and pigs. Phylogenetic analysis revealed that HeN21 and HuB20 belonged to genotype II. In addition, recombinant events were identified in the genomes of HeN21 and HuB20, and several events were located within genes associated with PRV virulence. Our data herein may suggest the emergence of novel PRV strains in China.

P80-F The spectrum of involuntary movements in patients with motor neuron disease – A cross-sectional study

Background We have commonly observed involuntary jerks and tremor in patients with otherwise typical motor neuron disease (MND). We conducted prospective clinical study to explore their prevalence and phenomenology. Materials and methods Seventy-four consecutive patients were clinically examined by movement disorders specialists. Based on regularity and distribution, movements observed at rest were classified as minipolymioclonus (MPMC) or rest thumb tremor (RTT) and movements present during action as action MPMC or action tremor. Results Involuntary movements (IMs) were present in 54 patients (73%). Rest MPMC was present in 26 (35%), RTT in 22 (31%), action MPMC in 22 (30%) and action tremor in 20 patients (27%), with some overlap. Sixteen patients (22%) reported negative impact of IMs on their ability to use hands. Regression model showed that lower distal muscle power and less prominent upper motor neuron (UMN) signs significantly increased the probability of I. Conclusions IMs are common yet largely overlooked feature of MND and may have negative impact on patient’s functional abilities. Lower distal muscle power increased the probability of IMs of fingers and wrist, suggesting that generation of IMs in MND patients is associated with muscle weakness. The presence of UMN signs decreased the probability of IMs, possibly by increasing muscle and joint stiffness. Overall, our findings suggest IMs in MND patients are of peripheral origin. We propose that IMs are caused by activation of enlarged motor units without sufficient previous recruitment of smaller units to smooth their contraction during action and by their spontaneous firing at rest.

Neuroinvasive influenza virus A(H5N8) in fattening ducks, Hungary, 2015

Highly pathogenic avian influenza (HPAI) A virus H5N8 was detected in far east Asian countries during 2014 and emerged in late 2014 in European countries. Hungary reported a HPAI A(H5N8) outbreak during late winter of 2015 at a Pekin duck fattening facility. Epidemiologic monitoring was extended to holdings in neighboring areas and nearby habitats used by wild birds but failed to identify the source of infection. In addition to respiratory symptoms, the affected birds showed lethargy and neuronal signs, including torticollis. Consistent with this finding, influenza A virus antigen was detected in large quantity in the brain. Molecular analysis of the identified strain showed very close genetic relationship (and >99% nucleotide sequence identity) with co-circulating HPAI A(H5N8) strains. A number of unique or rarely detected amino acid changes was detected in the HA (T220I, R512G), the M2 (I39M), the NA (T211I), the NS1 (P85T), and the PB2 (I261V) proteins of the Hungarian strain. Further studies are needed to demonstrate whether any of these mutations can be linked to neuroinvasiveness and neurovirulence in ducks.

Targeted assessment of lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis

Estimating survival in amyotrophic lateral sclerosis (ALS) is challenging due to heterogeneity in clinical features of disease and a lack of suitable markers that predict survival. Our aim was to determine whether scoring of upper or lower motor neuron weakness is associated with survival.With this objective, 161 ALS subjects were recruited from two tertiary referral centres. Scoring of upper (UMN) and lower motor neuron (LMN) signs was performed, in addition to a brief questionnaire. Subjects were then followed until the censorship date. Univariate analysis was performed to identify variables associated with survival to either non-invasive ventilation (NIV) or death, which were then further characterized using Cox regression. Results showed that factors associated with reduced survival included older age, bulbar and respiratory involvement and shorter diagnostic delay (all p < 0.05). Whole body LMN score was strongly associated with time to NIV or death (p ≤0.001) whereas UMN scores were poorly associated with survival. In conclusion, our results suggest that, early in disease assessment and in the context of other factors (age, bulbar, respiratory status), the burden of LMN weakness provides an accurate estimate of outcome. Such a scoring system could predict prognosis, and thereby aid in selection of patients for clinical trials.

Effects of chronic exposure to electromagnetic waves on the auditory system

Conclusion: The results support that chronic electromagnetic field exposure may cause damage by leading to neuronal degeneration of the auditory system. Objectives: Numerous researches have been done about the risks of exposure to the electromagnetic fields that occur during the use of these devices, especially the effects on hearing. The aim of this study is to evaluate the effects of the electromagnetic waves emitted by the mobile phones through the electrophysiological and histological methods. Methods: Twelve adult Wistar albino rats were included in the study. The rats were divided into two groups of six rats. The study group was exposed to the electromagnetic waves over a period of 30 days. The control group was not given any exposure to the electromagnetic fields. After the completion of the electromagnetic wave application, the auditory brainstem responses of both groups were recorded under anesthesia. The degeneration of cochlear nuclei was graded by two different histologists, both of whom were blinded to group information. Results: The histopathologic and immunohistochemical analysis showed neuronal degeneration signs, such as increased vacuolization in the cochlear nucleus, pyknotic cell appearance, and edema in the group exposed to the electromagnetic fields compared to the control group. The average latency of wave in the ABR was similar in both groups (p > 0.05).

Neural injury after use of vasopressin and adrenaline during porcine cardiopulmonary resuscitation

Background. Our aim was to investigate cerebral and cardiac tissue injury subsequent to use of vasopressin and adrenaline in combination compared with vasopressin alone during cardiopulmonary resuscitation (CPR).Methods. In a randomized, prospective, laboratory animal study 28 anesthetized piglets were subject to a 12-min untreated cardiac arrest and subsequent CPR. After 1 min of CPR, 10 of the piglets received 0.4 U/kg of arg8-vasopressin (V group), and 10 piglets received 0.4 U/kg of arg8-vasopressin, 1 min later followed by 20 µg/kg body weight of adrenaline, and another 1 min later continuous administration (10 µg/kg/min) of adrenaline (VA group). After 8 min of CPR, the piglets were defibrillated and monitored for another 3 h. Then they were killed and the brain immediately removed pending histological analysis.Results. During CPR, the VA group had higher mean blood pressure and cerebral cortical blood flow (CCBF) but similar coronary perfusion pressure. After restoration of spontaneous circulation there was no difference in the pressure variables, but CCBF tended to be (36% ± 16%) higher in the V group. Neuronal injury and signs of a disrupted blood–brain barrier (BBB) were greater, 20% ± 4% and 21% ± 4%, respectively, in the VA group. In a background study of repeated single doses of adrenaline every third minute after 5 min arrest but otherwise the same protocol, histological measurements showed even worse neural injury and disruption of the BBB.Conclusion. Combined use of vasopressin and adrenaline caused greater signs of cerebral and cardiac injury than use of vasopressin alone during experimental cardiopulmonary resuscitation.

White Matter Changes: New Perspectives on Imaging, Clinical Aspects, and Intervention

In the last three decades, the development of more sensitive techniques used in the assessment of in vivo brain functioning, such as computed tomography (CT) scan and magnetic resonance imaging (MRI), has contributed to identify cerebral changes that are either associated with clinical features (dementia and cognitive impairment) or described in normal subjects [1]. The presence of age-related white matter changes (ARWMCs) is described with the increasing age and the presence of vascular risk factors as the major determinants for these findings [2–4], but also in subjects over 50 years old [5]. The research of the clinical significance of ARWMC has clearly demonstrated the association between the presence of white matter changes and cognitive impairment, behavioural changes, urinary disturbances, and gait difficulties. However, and despite the increasing interest in this field, the interpretation of the data and explanation of these mechanisms are still under discussion. The aim of the current special issue was to explore the heterogeneity of the areas of impact of the ARWMC, by including different and less frequent approaches that allow for a more comprehensive picture. Focused in this general goal, we included a variety of papers ranging from an overview of the pathophysiology, assessment, and clinical manifestations of ARWMC, as well as a complete revision of proposed treatments—illustrated by the review of Y. Y. Xiong and V. Mok—to the proposal of a mouse model of chronic cerebral hypoperfusion as a possible tool on the explanation of the molecular pathology of white matter lesions—presented by M. Ihara and H. Tomimoto. With the same perspective, we included the paper of C. Sierra et al. that presents a nice review about the relation between hypertension and long-standing effect in the cerebral white matter. L. Yang reviewed issues related to brain plasticity and its possible relation to age-related white matter changes, a topic of novel interest. Also of interest is the work of A. Xekardaki et al. that explores the use of diffusion tensor imaging in bipolar disorder. Besides the review papers, 8 original articles were included in this special issue and are grouped in three blocks. The first one tried to focus on the anatomical correlations and clinical features that are related with the presence and progression of white matter changes—cognitive changes (memory), motor dysfunction, late-onset depression, and health-related quality of life. E. T. Schulze et al. provided us with an innovative approach by using multifaceted imaging techniques on the evaluation of brain functional changes during working memory tasks. In a less addressed field of research, M. Viana-Baptista et al. reflected on the importance of frontal white matter lesions for the compromise of motor performance. J. A. Brommelhoff et al. also pointed out that late-onset depression could be a process different from neurodegenerative changes and describe no differences in frontal lobe deep or subcortical white matter between Alzheimer's patients with or without late-onset depression. A. M. Grool et al. discussed the relation between progression of WMC volume and health-related quality as part of the large SMART Study adding data to the existing body of literature on the role of progression of white matter lesions on decline in mental functioning in patients with symptomatic vascular disease. A very interesting paper by V. Rajagopalan et al. reports innovative imaging data in amyotrophic lateral sclerosis (ALS) patients with predominant upper motor neuron (UMN) signs. A second section, mainly addressed to MRI analysis and measurement of white matter changes, is represented in the paper by S. D. Smart et al., who present the validation of automated WMH segmentation. These authors showed that automated segmentation of the brain provides good to very good estimates of the volume of the affected white matter, which will enable further research into the role of ARWMC in various diseases. Finally, the last block of papers refers to different basic sciences, reflected both on the interesting paper of H. Chen et al. that evidences reductions in fiber tract volumes and loss of axonal neurofilaments, and on the paper by B. D. James et al., that brought surprising findings on genetic precursors of dementia and led us into an open discussion for possible future directions. Sofia Madureira Ana Verdelho Leonardo Pantoni Philip Scheltens

Tethered Cord Syndrome in Occult Spinal Dysraphism. Timing and Outcome of Surgical Release

Objective To investigate the influence of neurosurgical intervention on the appearance of upper motor neuron (UMN) signs in newborns diagnosed with occult spinal dysraphism and tethered cord (TC) during the first month of life. Methods A prospective study (1990 to 1996) of 22 consecutive newborns with occult spinal dysraphism monitored for the appearance of UMN signs. Untethering was performed when neurologic or urodynamic investigation indicated the presence of UMN dysfunction. Results Of 22 patients, 10 remained free of UMN symptoms during follow-up (mean, 67 ± 22 months). Untethering was performed in 12 of 22 patients because of the presence of UMN symptoms. In 7 of these 12 patients, there was a documented asymptomatic period of 13 ± 11 months before the onset of UMN symptoms. Untethering at a mean age of 18 ± 17 months restored normal neurologic and urinary function in all patients (mean postoperative follow-up, 25 ± 16 months). Of the 12 children, 5 presented with UMN signs at birth. In these children, untethering was performed at a mean age of 9 ± 5 months. In two of these five patients, UMN symptoms did not resolve after surgery, and ongoing conservative bladder treatment was required (mean follow-up, 37 ± 14 months). In none of the 12 operated children did signs of retethering occur. Conclusions A significant number (10/22) of children born with occult spinal dysraphism and TC did not develop UMN symptoms during follow-up; neurosurgical correction after the appearance of an UMN sign restored normal neurologic and urinary function in all children; and untethering in children presenting at birth with UMN symptoms resulted in poorer outcome.