Encephalitic syndrome and anosmia in COVID-19: Do these clinical presentations really reflect SARS-CoV-2 neurotropism? A theory based on the review of 25 COVID-19 cases.

Since the discovery of coronavirus disease 2019 (COVID-19), a disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathology showed different faces. There is an increasing number of cases described as (meningo)encephalitis although evidence often lacks. Anosmia, another atypical form of COVID-19, has been considered as testimony of the potential of neuroinvasiveness of SARS-CoV-2, though this hypothesis remains highly speculative. We did a review of the cases reported as brain injury caused by SARS-CoV-2. Over 98 papers found, 21 were analyzed. Only four publications provided evidence of the presence of SARS-CoV-2 within the central nervous system (CNS). When facing acute neurological abnormalities during an infectious episode it is often difficult to disentangle neurological symptoms induced by the brain infection and those due to the impact of host immune response on the CNS. Cytokines release can disturb neural cells functioning and can have in the most severe cases vascular and cytotoxic effects. An inappropriate immune response can lead to the production of auto-antibodies directed toward CNS components. In the case of proven SARS-CoV-2 brain invasion, the main hypothesis found in the literature focus on a neural pathway, especially the direct route via the nasal cavity, although the virus is likely to reach the CNS using other routes. Our ability to come up with hypotheses about the mechanisms by which the virus might interact with the CNS may help to keep in mind that all neurological symptoms observed during COVID-19 do not always rely on CNS viral invasion.

Assessment of transthyretin cut-off values for a better screening of malnutrition: Retrospective determination and prospective validation.

The use of transthyretin (TTR, prealbumin) as a marker of malnutrition and the definition of associated cut-offs are a matter of debate. In order to clarify this issue, we performed a retrospective study and then a prospective validation one. In the first study, data from 23,617 consecutive patients from our University hospital were analysed. Using the 0.11 and 0.05 g/L cut-off values defined by the French Health Authority, only 3.13% and 0.49% appeared malnourished or severely malnourished indicating that these cut-off values are clearly inappropriate. In the prospective study, consecutive patients were stratified for normal (≥0.2 g/L) or low (<0.2 g/L) TTR, and normal (<15 mg/L) or high (≥15 mg/L) C-reactive protein, hence defining 4 groups (n = 50 to 57/group), and data were analysed according to nutritional status estimated from patient files. Receiver operating characteristic (ROC) curve of TTR level associated with malnutrition allowed setting cut-off values at 0.17 and 0.12 g/L for malnutrition and severe malnutrition respectively.

[SARS-CoV-2 infection: do not neglect neurological symptoms!] / Infection par le SARS-CoV-2 : attention aux signes neurologiques !

Covid-19: do not neglect neurological symptoms. Covid-19 is a highly contagious acute viral disease caused by a new coronavirus, SARS-CoV-2. It appeared in December 2019 in China and has spread rapidly affecting more than 2.5 million people with more than 177,000 deaths worldwide to date. Among the diverse symptoms depicted around this pathology neurological ones have been long overlooked. They may be signs of a severe form of Covid-19.

Infection sars-cov-2 : attention aux signes neurologiques ! Le Covid-19 est une maladie aiguë virale très contagieuse due à un nouveau coronavirus, le SARS-CoV-2. Elle est apparue en décembre 2019 en Chine et s'est propagée rapidement, touchant plus de 2,5 millions de personnes, avec plus de 177 000 décès à travers le monde à ce jour. Parmi la diversité des atteintes décrites dans cette pathologie, une a longtemps été ignorée : l'atteinte neurologique. Pourtant, elle pourrait être le signe d'une forme sévère de Covid-19.

New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T).

Mutations at HIV-1 reverse transcriptase (RT) codon 184 such as M184V confer resistance to two nucleos(t)ide RT inhibitors (NRTI), lamivudine (3TC) and emtricitabine (FTC). The prevalence of mutations at HIV-1 RT codon 184 was evaluated using three independent RT sequence databases from treatment-experienced (TE) and treatment-naïve (TN) individuals. Data were collected retrospectively from three centers: one in Italy and two in France between 1997 and 2016. In order to highlight the role of these mutations in conferring drug resistance, structural and thermodynamic analyses were conducted by means of computational approaches. Among 32,440 RT sequences isolated from TE and 12,365 isolated from TN patients, the prevalence of HIV-1 RT codon 184 substitutions in each group was 31.21% and 0.72%, respectively. The mutations M184L and M184T have been observed only in TE patients. In all cases but four, M184L and M184T mutations were present during NRTI treatment. Molecular recognition studies on M184L and M184T structures showed both FTC and 3TC thermodynamic profiles unfavorable in comparison with the wild-type sequence, corroborated by molecular dynamic simulations (MDS). In this study, we highlighted two new resistance mutations in vivo for NRTI resistance. The low frequency of this pathway can be related to high impairment of replicative capacity mediated by these mutations.

Tracking social motivation systems deficits: the affective neuroscience view of autism.

Abnormal functioning of primary brain systems that express and modulate basic emotional drives are increasingly considered to underlie mental disorders including autism spectrum disorders. We hypothesized that ASD are characterized by disruptions in the primary systems involved in the motivation for social bonding. Twenty adults with ASD were compared to 20 neurotypical participants on the basis of self-reports and clinical assessments, including the Social Anhedonia Scale (SAS) and the Affective Neuroscience Personality Scales (ANPS). ASD diagnosis was related to SAS, as well as to positive (PLAYFULNESS) and negative (FEAR) ANPS-traits. In the overall sample, levels of autistic traits (AQ) were related to SAS and PLAYFULNESS. We argue that PLAYFULNESS could be at the root of social bonding impairments in ASD.

Levels of autistic traits in anorexia nervosa: a comparative psychometric study.

BACKGROUND: A number of characteristics associated with Autism Spectrum Disorders (ASD) are over-represented among patients with Anorexia Nervosa (AN) as well as among relatives of these patients. Yet the co-occurrence of autistic traits in AN has not been fully explored and no previous study has directly compared self-reported evaluations of cognitive and socio-affective skills in AN and ASD. METHODS: We aimed to determine the degree of overlap between AN and ASD from scores on questionnaires classically used to measure ASD impairments. Fifteen AN participants, 15 ASD participants and two groups of matched controls completed a battery of self-reports measuring: autistic traits (Autism-Spectrum Quotient), empathy (Empathy Quotient-short and Interpersonal Reactivity Index), systemizing (Systemizing Quotient-short) and alexithymia (Bermond-Vorst Alexithymia Questionnaire-B). Univariate comparisons of mean totalled scores were performed on each measure (patients vs. controls, and AN vs. ASD), and a Principal Component Analysis was used to study subject proximities in a reduced-factor space constructed from AQ, BVAQ-B and IRI subscales. RESULTS: These analyses revealed similarities in a few cognitive domains (Attention Switching, Perspective Taking and Fantasy, lack of emotional introspection) and in some nonspecific affective dimensions (depression and feelings of distress), but also marked dissimilarities in social skills (the ability to communicate emotions to others, empathizing). CONCLUSION: The AN and ASD participants reported similar needs for sameness, and similar difficulties understanding their emotions and taking the perspective of another, but contrasting abilities to feel concerned in interpersonal situations. Our mixed findings encourage further exploration of transdiagnostic similarities and associations between these disorders.

Self-relevance modulates brain responses to angry body expressions.

In a social context, the direction of the body of surrounding agents indicates whether one is the potential target of an impending action or simply an observer, and thus influences the way one processes and reacts to their emotional expressions. The present functional magnetic resonance imaging experiment investigated how self-relevance influences anger processing in the brain by independently manipulating target (oriented to self or to other) and emotion (neutral and anger). The perception of body expression of anger elicits activity in a previously identified network that includes the amygdala, the fusiform gyrus, the superior temporal sulcus and the premotor cortex. Activity within this network is independent of body direction and is parametrically modulated by the intensity of the bodily emotional expression. Moreover, the ventromedial prefrontal cortex and somatosensory cortices responded preferentially to anger expressions oriented to self. We suggest that these brain areas may participate in the selection of specific behavioural strategies when one is the potential target of someone's anger.

Determination of emotional endophenotypes: a validation of the Affective Neuroscience Personality Scales and further perspectives.

The study of endophenotypes, notably with configured self-reports, represents a promising research pathway to overcome the limits of a syndromal approach of psychiatric diseases. The Affective Neuroscience Personality Scales (ANPS) is a self-report questionnaire, based on neuroethological considerations, that could help to assess emotional endophenotypes related to the activity in 6 core cerebral emotional systems (FEAR, ANGER, SADNESS, CARING, PLAYFULNESS, SEEKING). We further investigated its psychometric properties among 830 young adults and showed that they were satisfactory. As participants also completed several other self-reports that shared potential traits with the ANPS, we offer new validity evidence based on relations to other variables. We also provide additional evidence to consider that the ANPS scores can be validly interpreted for the characterization of emotional endophenotypes involved in a variety of psychiatric disorders. On the grounds of present results, of previous clinical studies, as well as some preliminary neuroimaging findings, we discuss new steps in the ANPS validation.

Individual differences in socioaffective skills influence the neural bases of fear processing: the case of alexithymia.

Being exposed to fear signals makes us feel threatened and prompts us to prepare an adaptive response. In our previous studies, we suggested that amygdala (AMG) and premotor cortex (PM) play a role in the preparation of the observers' motor response required by the situation. The present experiment aimed at assessing how interindividual differences in alexithymia--a personality trait associated with deficits in emotional reactivity and regulation--influence the neural network associated with the perception of fear. Using fMRI, we scanned 34 healthy subjects while they were passively observing fearful body expressions. Applying a dimensional approach, we performed correlation analyses between fear-related brain areas and alexithymia scores among all participants. Using a categorical approach, we conducted a between-group comparison (13 high vs. 12 low-alexithymia subjects). Our results were threefold. First, the right AMG activity in response to fearful stimuli was negatively correlated with the level of difficulty to identify emotions. Second, PM activity was linked to reduced subjective emotional reactivity. Third, the between-group comparison revealed greater activity in anterior cingulate cortex (ACC) for high than low-alexithymia scorers. Moreover, the relationship between ACC and PM was in opposite direction in individuals with high (negative link) and low (positive link) alexithymia. Therefore, compared to our previous findings, we hereby further reveal how ACC interacts with PM to sustain self-regulation of one's own emotional state in response to threatening social signals. Moreover, this neural mechanism could account for the description of the "cold-blooded" personality of individuals with alexithymia.