Central Nervous System Impairment Research Articles

Correlation of HIV-Induced Neuroinflammation and Synaptopathy with Impairment of Learning and Memory in Mice with HAND.

Over 38 million people worldwide are living with HIV/AIDS, and more than half of them are affected by HIV-associated neurocognitive disorders (HAND). Such disorders are characterized by chronic neuroinflammation, neurotoxicity, and central nervous system deterioration, which lead to short- or long-term memory loss, cognitive impairment, and motor skill deficits that may show gender disparities. However, the underlying mechanisms remain unclear. Our previous study suggested that HIV-1 infection and viral protein R (Vpr) upregulate the SUR1-TRPM4 channel associated with neuroinflammation, which may contribute to HAND. The present study aimed to explore this relationship in a mouse model of HAND. This study employed the HIV transgenic Tg26 mouse model, comparing Tg26 mice with wildtype mice in various cognitive behavioral and memory tests, including locomotor activity tests, recognition memory tests, and spatial learning and memory tests. The study found that Tg26 mice exhibited impaired cognitive skills and reduced learning abilities compared to wildtype mice, particularly in spatial memory. Interestingly, male Tg26 mice displayed significant differences in spatial memory losses (p < 0.001), while no significant differences were identified in female mice. Consistent with our early results, SUR1-TRPM4 channels were upregulated in Tg26 mice along with glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4), consistent with reactive astrocytosis and neuroinflammation. Corresponding reductions in neurosynaptic responses, as indicated by downregulation of Synapsin-1 (SYN1) and Synaptophysin (SYP), suggested synaptopathy as a possible mechanism underlying cognitive and motor skill deficits. In conclusion, our study suggests a possible relationship between SUR1-TRPM4-mediated neuroinflammation and synaptopathy with impairments of learning and memory in mice with HAND. These findings could help to develop new therapeutic strategies for individuals living with HAND.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

Severe anaphylactic reactions to home doses may occur during food allergy oral immunotherapy (OIT). To study the rate and risk factors for such reactions. We studied all patients aged greater than 3.5 years who completed OIT in a single center between April 2010 and January 2020. All home epinephrine-treated reactions (HETRs) were identified. High-grade HETRs (HG-HETRs) were defined as HETRs involving respiratory (SpO2 of 94% or less), cardiovascular (low blood pressure), or central nervous system impairment (loss of consciousness). We investigated the rate and risk factors for HG-HETRs. A total of 1,637 OIT treatments were studied: milk (880), peanut (346), tree nuts (221), sesame (115), and egg (75). Of 390 identified HETRs, 30 HG-HETRs occurred during 27 treatments (1.65% of all treatments). Nearly all (26 of 30) were during milk OIT in patients with house dust mite (HDM) sensitization and asthma (26 of 30 each). Of the 30 patients with HG-HETRs, 21 recovered with one or two epinephrine treatments, but nine (0.55% of all treatments) did not respond to a second dose of epinephrine and were deemed to have refractory anaphylaxis. Three patients required intensive care unit admission and three received epinephrine drip, but none required ventilatory support. Risk factors for HG-HETRs included milk OIT (P= .031), asthma (P= .02) and HDM sensitization (P= .02). No specific triggers for HG-HETR were identified. Of patients with HG-HETRs, 25.9% were fully desensitized, including the four non-milk treated patients; 22.2% were partially desensitized; and 51.9% failed. High-grade HETRs are uncommon, particularly refractory anaphylactic reactions to home OIT doses. Although milk OIT, asthma, and HDM sensitization are the main risk factors for such reactions, identification of patients who are at risk is challenging.

The GABA system, a new target for medications against cognitive impairment-Associated with neuroactive steroids.

The prevalence of cognitive dysfunction, dementia, and neurodegenerative disorders such as Alzheimer's disease (AD) is increasing in parallel with an aging population. Distinct types of chronic stress are thought to be instrumental in the development of cognitive impairment in central nervous system (CNS) disorders where cognitive impairment is a major unmet medical need. Increased GABAergic tone is a mediator of stress effects but is also a result of other factors in CNS disorders. Positive GABA-A receptor modulating stress and sex steroids (steroid-PAMs) such as allopregnanolone (ALLO) and medroxyprogesterone acetate can provoke impaired cognition. As such, ALLO impairs memory and learning in both animals and humans. In transgenic AD animal studies, continuous exposure to ALLO at physiological levels impairs cognition and increases degenerative AD pathology, whereas intermittent ALLO injections enhance cognition, indicating pleiotropic functions of ALLO. We have shown that GABA-A receptor modulating steroid antagonists (GAMSAs) can block the acute negative cognitive impairment of ALLO on memory in animal studies and in patients with cognitive impairment due to hepatic encephalopathy. Here we describe disorders affected by steroid-PAMs and opportunities to treat these adverse effects of steroid-PAMs with novel GAMSAs.

Umbilical mesenchymal stem cell-derived exosomes promote spinal cord functional recovery through the miR-146b/TLR4 -mediated NF-κB p65 signaling pathway in rats

Spinal cord injury (SCI) is an incurable central nervous system impairment that lack of efficient treatment. Exosomes derived from mesenchymal stem cells (MSCs) are widely applied in disease treatment. This work aimed to determine the promising therapeutic effects of MSC-derived exosomal miRNA146b on SCI. A rat spinal cord injury (SCI) model and lipopolysaccharide (LPS)-induced PC12 cell model were established. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs). The identification of exosomes was performed by using transmission electronic microscope (TEM) and nanoparticle tracking analysis (NTA). Hematoxylin and eosin (HE) staining and TUNEL assay were performed to assess tissue damage and apoptosis, respectively. ELISA was performed to detect levels of inflammatory cytokines. Cell viability was checked by cell counting kit 8 (CCK-8). Gene expression and protein levels were detected by qPCR and western blotting assay. The interaction between miR-146 b and Toll-like receptor 4 (TLR4) was assessed by luciferase reporter gene assay. The hUCMSC-derived exosomes could notably alleviate the spinal cord injury and cell apoptosis. The exosomal miR-146 b treatment suppressed the release of IL-1 β, IL-6, and TNFα. The miR-146 b suppressed the expression of TLR4, directly interact with the 3′-untranslated region (3′UTR) of TLR4, and inactivated the nuclear factor κB (NF-κB) signaling. The hUCMSCs-derived exosomal miR-146 b protects neurons from spinal cord injury through targeting the TLR4 and inactivating the NF-κB signaling. Our findings supported the application of hUCMSCs-derived exosomal miR-146 b for the protection of SCI.

Evaluating 3D human face reconstruction from a frontal 2D image, focusing on facial regions associated with foetal alcohol syndrome

Foetal alcohol syndrome (FAS) is a preventable condition caused by maternal alcohol consumption during pregnancy. The FAS facial phenotype is an important factor for diagnosis, alongside central nervous system impairments and growth abnormalities. Current methods for analysing the FAS facial phenotype rely on 3D facial image data, obtained from costly and complex surface scanning devices. An alternative is to use 2D images, which are easy to acquire with a digital camera or smart phone. However, 2D images lack the geometric accuracy required for accurate facial shape analysis. Our research offers a solution through the reconstruction of 3D human faces from single or multiple 2D images. We have developed a framework for evaluating 3D human face reconstruction from a single-input 2D image using a 3D face model for potential use in FAS assessment. We first built a generative morphable model of the face from a database of registered 3D face scans with diverse skin tones. Then we applied this model to reconstruct 3D face surfaces from single frontal images using a model-driven sampling algorithm. The accuracy of the predicted 3D face shapes was evaluated in terms of surface reconstruction error and the accuracy of FAS-relevant landmark locations and distances. Results show an average root mean square error of 2.62 mm. Our framework has the potential to estimate 3D landmark positions for parts of the face associated with the FAS facial phenotype. Future work aims to improve on the accuracy and adapt the approach for use in clinical settings. Significance: Our study presents a framework for constructing and evaluating a 3D face model from 2D face scans and evaluating the accuracy of 3D face shape predictions from single images. The results indicate low generalisation error and comparability to other studies. The reconstructions also provide insight into specific regions of the face relevant to FAS diagnosis. The proposed approach presents a potential cost-effective and easily accessible imaging tool for FAS screening, yet its clinical application needs further research.

Two Cases of Acute Focal Bacterial Nephritis With Central Nervous System Manifestations in Children and Literature Review.

Acute focal bacterial nephritis (AFBN) is a kidney disease characterized by a localized bacterial infection that manifests as an inflammatory mass. Most children with AFBN have nonspecific symptoms including fever, vomiting, and abdominal discomfort, and some develop neurological symptoms such as meningeal irritation, unconsciousness, and seizures as their condition worsens. This was 2 cases of AFBN with central nervous system manifestations in children, and we analyzed its possible mechanisms of the clinical and radiographic features. We experience 2 very unusual cases of AFBN which were linked to central nervous system abnormalities. A 6-year-old boy with AFBN and clinically moderate ncephalitis/encephalopathy with a reversible splenial lesion (MERS) presented with neurological symptoms, including unconsciousness and convulsions. The second case involved an 8-year-old child with AFBN-associated acute encephalopathy who exhibited neurological symptoms, including unconsciousness. According to previous research, AFBN is linked to central nervous system impairment. As a result, when a clinician meets a patient with an inexplicable fever caused by a neurological condition, he should pay attention to this diagnosis of AFBN and follow it in the abdominal graph.

NEFL-Related Charcot-Marie Tooth Disease due to P440L Mutation in Two Italian Families: Expanding the Phenotype and Defining Modulating Factors

Introduction: Mutations in the neurofilament polypeptide light chain (NEFL) gene account for <1% of all forms of Charcot-Marie-Tooth (CMT) diseases and present with different phenotypes, including demyelinating, axonal and intermediate neuropathies, and with diverse pattern of transmission, with dominant and recessive inheritance being described. Methods: Here, we present clinical and molecular data in two new unrelated Italian families, affected with CMT. Results: We studied fifteen subjects (11 women, 4 men), age range 23–62 year. Onset of symptoms was mainly in childhood, with running/walking difficulties; some patients were pauci-asymptomatic; almost all shared variably distributed features of absent/reduced deep tendon reflexes, impaired gait, reduced sensation, and distal weakness in the legs. Skeletal deformities were seldom documented and were of mild degree. Additional features included sensorineural hearing loss in 3 patients, underactive bladder in 2 patients, and cardiac conduction abnormalities, requiring pacemaker implantation, in one child. Central nervous system (CNS) impairment was not documented in any subject. Neurophysiological investigation disclosed feature suggestive of demyelinating sensory-motor polyneuropathy in one family and resembling an intermediate form in the other. Multigene panel analysis of all known CMT genes revealed two heterozygous variants in NEFL: p.E488K and p.P440L. While the latter change segregated with the phenotype, the p.E488K variant appeared to act as a modifier factor being associated with axonal nerve damage. Conclusions: CMT related to P440L mutation in NEFL is associated with a mild, childhood-onset phenotype, showing prevalently sensory distal limbs involving and with motor impairment predominantly involving anterolateral leg muscles, in the absence of CNS involvement. Additional findings, never reported so far in patients with NEFL mutation, are cardiological and urinary dysfunctions. Our study expands the array of clinical features associated with NEFL-related CMT.

Magnetic Resonance Imaging Scan of the Brain After Mild COVID-19 Infection.

There have been several reports of central nervous system impairments associated with severe coronavirus disease 2019 (COVID-19) infection on head magnetic resonance imaging and angiography (MRI/A). However, head MRI/A is rarely performed in mild cases, and there have been few reports on intracranial changes after COVID-19 infection in these cases. Here, we report a comparative examination of the findings seen in common head MRI/A sequences in mild cases of COVID-19. Of the 15,376 patients who underwent head MRI/A examination called "Brain Dock"between June 2020 and June 2021, 746 patients who received a COVID-19 antibody test were evaluated. Positive and negative patients were comparatively examined for head MRI/A findings such as cerebral white matter lesions, ischemic changes, cerebral microbleeds, cerebral aneurysms, arterial stenosis, sinusitis, and other abnormal findings. Overall, 31 (4.2%) patients were COVID-19 positive, and all of them had mild infections not requiring hospitalization. There was no significant difference in patient characteristics and head MRI/A findings between positive and negative patients. All positive patients showed no particular abnormalities in the nasal findings such as olfactory bulb atrophy or thickening of the olfactory mucosa. Intracranial lesions in mild patients do not show a clear difference from those in negative patients. This indicates that findings seen in common MRI/A sequences of severe patients are not likely in mild patients, supporting that there is relatively no damage to the central nervous system in mild patients.

Continuous Glucose Monitoring in Enterally Fed Children with Severe Central Nervous System Impairment.

This prospective, observational study included nineteen patients (median (25-75 pc) age: 12.75 (6.17-15.55) years) with permanent CNS damage (Gross Motor Function Classification System V) receiving long-term tube enteral feeding, recruited from two paediatric university nutritional treatment centres. Patients with acute conditions and diagnosed diabetes were excluded. The nutritional status and nutritional support were analysed in all the inpatients in accordance with a uniform protocol. Using the CGM system (Medtronic iPro2), glycaemic curves were analysed, and in addition, HbA1C levels were determined in fourteen patients. CGM results were analysed using GlyCulator2.0. Statistical analysis was performed using the Statistica version 11 software (StatSoft Inc. Tulsa, OK, USA). More than half (11/19; 58%) of the patients were undernourished (BMI < 3 pc for age and gender), with the stature age being significantly lower than calendar age (5 (4.5-9) vs. 12.75 (6.17-15.55) years; p = 0.0010). The actual caloric intake was 50 (37.7-68.8) kcal/kg (median; 25-75 pc). In patients fed using the bolus method, the number of calories consumed per day was statistically significantly higher than in children subjected to a continuous feeding supply (56.00 (41.00-75.00) vs. 33.40 (26.70-50.00) kcal/kg BW (body weight; p = 0.0159). Decreases in blood glucose levels below the alarm level (<70 mg/dL) were recorded in fifteen patients (78.9%), including two patients with episodes of clinically significant hypoglycaemia (<54 mg/dL). The minimum and maximum glycaemic values recorded in any individual CGM records were 67 mg/dL (median) (minimum: 41 mg/dL; maximum: 77 mg/dL) and 146 (minimum: 114 mg/dL; maximum: 180 g/dL), respectively, for the entire recording. The maximum percentage of glycaemic concentrations > 140 mg/dL (TAR 140) recorded overnight in children with BMI ≥ 3 amounted to 1.6% vs. 0% in undernourished patients (TAR 140: 0.0 (0.00-1.6%) vs. 0% (0.00-0.0%; p = 0.0375); the percentage of glycaemic concentrations <70 mg/dL in the entire recording was comparable (0.77% (0.13-2.2%) vs. 1.8% (0.5-14.4%) vs. p = 0.2629). There was a positive correlation between the mean daily glucose recorded using the CGM method and patients' BMI z-scores (R = 0.48, p = 0.0397). No statistically significant relationship was demonstrated between the occurrence of alarm hypoglycaemia events in the CGM records and undernutrition expressed by BMI z-scores (OR = 1.50 (95%CI: 0.16-13.75), the type of diet (for commercially manufactured OR = 0.36 (95%CI: 0.04-3.52), and the modality of diet delivery (for bolus feeding OR = 2.75 (95%CI: 0.28-26.61). In children with chronic OU damage, enteral feeding is associated with a risk of hypoglycaemia, but further studies involving a larger number of patients are needed, and CGM might be a useful tool to estimate the metabolic adequacy of enteral nutritional support in terms of glucose control.

Nocardia Farcinica Mastoiditis and Epidural Abscess in an Immunocompetent Patient: A Rare Entity.

Nocardia is regarded as an opportunistic pathogen primarily affecting the respiratory system, whereas Nocardia farcinica is the species of the Nocardia family that is most frequently blamed for central nervous system impairment. The authors present the first case of mastoiditis caused by Nocardia farcinica, accompanied by intracranial complications. An immunocompetent 74-year-old woman who reported a three-week left ear discharge and a two-week facial nerve palsy was referred to our department. MRI revealed mastoiditis and epidural abscess. The bacterial cultures obtained during the surgical management of the patient confirmed the presence of Nocardia farcinica. Targeted antibiotic therapy was subsequently administrated, gradually resulting in favourable outcomes. Nocardia species provoke a disseminated infection that emerges not only among the immunosuppressed individuals but can also affect the healthy population. The nonspecific clinical manifestations in addition to the difficulties identifying the pathogen, remain obstacles to a punctual diagnosis. However, the combination of surgical debridement and antibiotic treatment with trimethoprim and sulfamethoxazole is considered the most appropriate management, leading to propitious results.

Balance control impairments in Fabry disease.

BackgroundFabry disease (FD) is a rare inherited lysosomal storage disorder caused by the deficiency of the enzyme alpha-galactosidase A. This deficiency leads to an accumulation of glycosphingolipids leading to progressive and multisystemic disease, including renal, cardiac, and neurological damages. FD may also have neuro-otological and visual impairments, which can generate postural control alterations, inner ear, and vision being involved in this function. This study aimed to evaluate the impact of FD on postural control.MethodsIn total, fourteen adult patients (8 men/6 women, mean age = 37.6 ± 11.4 years) and two children (mean age = 11 years) with FD and 19 healthy adults (12 men/7 women, mean age = 36.5 ± 16.9 years) and two healthy children (mean age = 10.5 years) took part in this study. Postural control was evaluated by a sensory organization test combining three visual situations (eyes open, eyes closed, and sway referenced visual surround motion) with two platform situations (stable platform and sway referenced platform motion), aiming to calculate a composite equilibrium score (CES), a high score being representative of good postural control. Somatosensory (RSOM), visual (RVIS), and vestibular (RVEST) contributions to postural control were calculated, a low score reflecting a poor use of the indicated sensory input.ResultsThe CES was lower in adult patients with FD compared with the healthy subjects (p < 0.001). RVIS (p = 0.001) and RVEST (p = 0.003) were lower in patients with FD compared with the control group, whereas no difference in RSOM was observed.ConclusionInner ear and visual pathologies associated with the central nervous system impairments are factors of postural control impairments. Physical activities, which can also be rehabilitative, by maintaining or increasing the weight of proprioception, may help diminish dependency on altered sensorial inputs.

In Vivo Parieto-Occipital White Matter Metabolism Is Correlated with Visuospatial Deficits in Adult DM1 Patients.

Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a (CTG) expansion in the DM protein kinase (DMPK) gene, representing the most common adult muscular dystrophy, characterized by a multisystem involvement with predominantly skeletal muscle and brain affection. Neuroimaging studies showed widespread white matter changes and brain atrophy in DM1, but only a few studies investigated the role of white matter metabolism in the pathophysiology of central nervous system impairment. We aim to reveal the relationship between the metabolic profile of parieto-occipital white matter (POWM) as evaluated with proton MR spectroscopy technique, with the visuoperceptual and visuoconstructional dysfunctions in DM1 patients. MR spectroscopy (3 Tesla) and neuropsychological evaluations were performed in 34 DM1 patients (19 F, age: 46.4 ± 12.1 years, disease duration: 18.7 ± 11.6 years). The content of neuro-axonal marker N-acetyl-aspartate, both relative to Creatine (NAA/Cr) and to myo-Inositol (NAA/mI) resulted significantly lower in DM1 patients compared to HC (p-values < 0.0001). NAA/Cr and NAA/mI correlated with the copy of the Rey-Osterrieth complex figure (r = 0.366, p = 0.033; r = 0.401, p = 0.019, respectively) and with Street’s completion tests scores (r = 0.409, p = 0.016; r = 0.341, p = 0.048 respectively). The proportion of white matter hyperintensities within the MR spectroscopy voxel did not correlate with the metabolite content. In this study, POWM metabolic alterations in DM1 patients were not associated with the white matter morphological changes and correlated with specific neuropsychological deficits.

Metabolic Fingerprinting of Fabry Disease: Diagnostic and Prognostic Aspects.

Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype–phenotype correlation. In the early stages, FD could involve the peripheral nervous system (acroparesthesias and dysautonomia) and the ski (angiokeratoma), but later kidney, heart or central nervous system impairment may significantly decrease life expectancy. The advent of omics technologies offers the possibility of a global, integrated and systemic approach well-suited for the exploration of this complex disease. In this narrative review, we will focus on the main metabolomic studies, which have underscored the importance of detecting biomarkers for a diagnostic and prognostic purpose in FD. These investigations are potentially useful to explain the wide clinical, biochemical and molecular heterogeneity found in FD patients. Moreover, the quantitative mass spectrometry methods developed to evaluate concentrations of these biomarkers in urine and plasma will be described. Finally, the complex metabolic biomarker profile depicted in FD patients will be reported, which varies according to gender, types of mutations, and therapeutic treatment.

Inorganic arsenic contamination and the health of children living near an inactive mining site: northern Thailand.

Arsenic toxicity is a global health problem affecting millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water, and may also be caused by mining and other industrial processes. Acute arsenic poisoning is associated with nausea, vomiting, abdominal pain, and severe diarrhea. Chronic arsenic toxicity results in multisystemic diseases leading to central nervous system (CNS) impairments such as cognitive or intellectual deficits in children. Over the past ten years, arsenic contamination has been reported in northern Thailand. The Ministry of Public Health; Thailand, Forensic Science Institute Thammasat University, and the Research Center to Promote Safety and Prevent Injuries in Children at the Ramathibodi Hospital compiled a report on the health impact of the population within a 10 kilometer radius around a mine tailing in the Phichit, Phitsanulok, and Phetchabun Provinces of Thailand. It showed that more than 30 % of children (aged 8-13 years) had higher than normal arsenic contamination levels based on the Agency for Toxic Substances and Disease Registry (ATSDR). After the publication of that report, the mine was temporarily closed in 2016. Based on this data, this research aimed to follow arsenic contamination after the mining operation had stopped operation for three years. The study showed that 4.5 % of school aged children had levels of inorganic arsenic in their urine, higher than the normal range (ATSDR), showing clearly that inorganic arsenic contamination is still above the normal range in children living near an inactive mining site. Therefore, monitoring heavy metal contamination in Thailand and the health effects on vulnerable children who live near mines during regular operation or after being temporarily suspended can prevent and mitigate possible health impacts.

Cell activation, PD-1 expression and in vitro cytokine production in patients with juvenile systemic lupus erythematosus.

Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease. To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls. Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin. jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls (p = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls (p = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (p=0.080) and higher concentrations of IL-23 (p = 0.063) than controls. jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.

Potential mechanism of SARS-CoV-2-associated central and peripheral nervous system impairment.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is more than merely a respiratory disease, as it also presents with various neurological symptoms. SARS‐CoV‐2 may infect the central nervous system (CNS) and thus is neurotropic. However, the pathophysiological mechanism of coronavirus disease 2019 (COVID‐19)‐associated neuropathy remains unclear. Many studies have reported that SARS‐CoV‐2 enters the CNS through the hematogenous and neuronal routes, as well as through the main host neurological immune responses and cells involved in these responses. The neurological immune responses to COVID‐19 and potential mechanisms of the extensive neuroinflammation induced by SARS‐CoV‐2 have been investigated. Although CNS infection with SARS‐CoV‐2 was shown to lead to neuronal impairment, certain aspects of this mechanism remain controversial and require further analysis. In this review, we discussed the pathway and mechanisms of SARS‐CoV‐2 invasion in the CNS, and associated clinical manifestations, such as anosmia, headache, and hyposmia. Moreover, the mechanism of neurological damage caused by SARS‐CoV‐2 may provide potential treatment methods for patients presenting with SARS‐CoV‐2‐associated neuropathy.

Aldicarb-related suicide attempt cases in North of France (2012-2021).

Aldicarb, a carbamate pesticide banned in France since 2008, represents a persistent risk of human poisoning. There is no up-to-date picture of aldicarb intentional poisonings associated to detailed diagnosis and clinical management of cases to evaluate the effect of its ban on intoxication risk reduction, including suicide. This retrospective epidemiological study describes cases of suicidal intoxication from the Hauts-de-France region between 2012 and 2021 and illustrates this situation through one analytically documented case. 60 cases were collected, mostly presenting a pathognomonic symptomatology. Thirty-five victims presented a muscarinic syndrome (58.3%), 14 a nicotinic syndrome (23.3%), and 37 a central nervous system impairment (61.7%). Hospitalization was necessary for 44 cases (73.3%), with 2 fatal evolutions. Diagnosis was based on the blood cholinesterase activities. Among the 25 cases with toxicology results, 45.8% presented a moderate decrease of acetylcholinesterase activity, whereas 87.5% presented a strong decrease of butyrylcholinesterase activity. Blood or urine detection of aldicarb and its metabolites may be considered in therapeutic management, although their quantification is unlikely to change the emergency medical care. Our study updates epidemiology of aldicarb poisoning at a regional level, highlighting a persisting health threatening situation with banned pesticides. More than 65% of national cases occurred in this agricultural area, aldicarb remaining available from storage of previously purchased products. Robust evidence is presented that acute poisoning is an ongoing major global public health challenge. There is a need for continued international efforts in risk reduction, knowledge, and information strategies.

Clinical Trial in a Dish for Space Radiation Countermeasure Discovery

NASA aims to return humans to the moon within the next five years and to land humans on Mars in a few decades. Space radiation exposure represents a major challenge to astronauts’ health during long-duration missions, as it is linked to increased risks of cancer, cardiovascular dysfunctions, central nervous system (CNS) impairment, and other negative outcomes. Characterization of radiation health effects and developing corresponding countermeasures are high priorities for the preparation of long duration space travel. Due to limitations of animal and cell models, the development of novel physiologically relevant radiation models is needed to better predict these individual risks and bridge gaps between preclinical testing and clinical trials in drug development. “Clinical Trial in a Dish” (CTiD) is now possible with the use of human induced pluripotent stem cells (hiPSCs), offering a powerful tool for drug safety or efficacy testing using patient-specific cell models. Here we review the development and applications of CTiD for space radiation biology and countermeasure studies, focusing on progress made in the past decade.

AB1144 COGNITIVE AND PSYCHOSOCIAL OUTCOME IN CHILDREN WITH MULTISYSTEM INFLAMMATORY SYNDROME FOLLOWING SARS-CoV-2 INFECTION

BackgroundDespite the low rate of neurological deficits following the SARS-COV-2 infection in the pediatric population, children and adolescents who develop multisystem inflammatory syndrome (MIS-C) after being infected with SARS-COV-2 are at a higher risk for neurological abnormalities and brain injury, increasing the risk of adverse cognitive and psychiatric outcome.ObjectivesGiven the increased risk of central nervous system impairment we chose to conduct a prospective study looking at the cognitive and psychosocial outcome of patients with MIS-C.MethodsOur study included 27 of the 29 patients between 2 to 18 years of age (M = 11.1, SD = 4.4) who were treated for MIS-C from the onset of the SARS-COV-2 pandemic until the beginning of May 2021 at the only tertiary care pediatric immunology center in Slovenia. We assessed these patients 6 months after diagnosis using the age-appropriate Wechsler intelligence scales and a battery of neuropsychological test measuring attention, executive function, memory and fine motor skills. We also asked parents to report on patients’ psychosocial outcome using the Achenbach Child Behavior Checklist.ResultsBy using Bayesian statistics to take into account parental education and any potential pre-morbid learning difficulties we found no evidence of impairment on measures of intelligence. However, the posterior distribution of scores on neuropsychological measures indicated that a significant proportion of patients scored 1SD bellow expected levels on measures of attention (31%), executive function (28%) and visual memory (35%). Increased symptoms of depression, anxiety and attention difficulties were also reported by parents, although their extent did not rise to a clinically significant level.ConclusionThe findings from our cohort suggest that the cognitive and psychosocial outcome of patients with MIS-C is generally favorable, although up to 35% may experience specific neuropsychological deficits more than 6 months after diagnosis. The most commonly impaired cognitive domains seem to be attention, executive function and visual memory.AcknowledgementsFunding for this work was provided by the Slovenian Research Agency grant J3-3061 and University Medical Centre grant 20210069. Support was also provided by Dušica Boben and the publisher Center za psihodiagnostična sredstva by providing the local adaptations of psychological assessment tools.Disclosure of InterestsDavid Gosar Speakers bureau: Biogen, Novartis, Mojca Zajc Avramovič: None declared, Nina Emersic: None declared, Mateja Šušterič: None declared, Maja Maša Šömen: None declared, Damjan Osredkar: None declared, Tadej Avcin: None declared

Central Nervous System Complications in Cystinosis: The Role of Neuroimaging.

Despite improvement in the specific treatment, clinical and anatomo-functional central nervous system (CNS) abnormalities of various severities are still observed in cystinosis patients. Patients who develop CNS complications today have a worse compliance to cysteamine treatment. Radiological studies have shown that cortical or central (ventriculomegaly) atrophy is observed in more than two thirds of cystinosis patients’ magnetic resonance imaging (MRI) and correlates with the intelligence quotient score. Half of cystinosis patients have marked aspecific white matter hyperintensities. The development of advanced neuroimaging techniques provides new tools to further investigate CNS complications. A recent neuroimaging study using a voxel-based morphometry approach showed that cystinosis patients present a decreased grey matter volume in the left middle frontal gyrus. Diffusion tensor imaging studies have shown white matter microstructure abnormalities in children and adults with cystinosis, respectively in areas of the dorsal visual pathway and within the corpus callosum’s body. Finally, leucocyte cystine levels are associated with decreased resting cerebral blood flow, measured by arterial spin labelling, in the frontal cortex, which could be associated with the neurocognitive deficits described in these patients. These results reinforce the relevance of neuroimaging studies to further understand the mechanisms that underline CNS impairments.