Sensory sentinels: Neuroimmune detection and food allergy.

Food allergy is classically characterized by an inappropriate type-2 immune response to allergenic food antigens. However, how allergens are detected and how that detection leads to the initiation of allergic immunity is poorly understood. In addition to the gastrointestinal tract, the barrier epithelium of the skin may also act as a site of food allergen sensitization. These barrier epithelia are densely innervated by sensory neurons, which respond to diverse physical environmental stimuli. Recent findings suggest that sensory neurons can directly detect a broad array of immunogens, including allergens, triggering sensory responses and the release of neuropeptides that influence immune cell function. Reciprocally, immune mediators modulate the activation or responsiveness of sensory neurons, forming neuroimmune feedback loops that may impact allergic immune responses. By utilizing cutaneous allergen exposure as a model, this review explores the pivotal role of sensory neurons in allergen detection and their dynamic bidirectional communication with the immune system, which ultimately orchestrates the type-2 immune response. Furthermore, it sheds light on how peripheral signals are integrated within the central nervous system to coordinate hallmark features of allergic reactions. Drawing from this emerging evidence, we propose that atopy arises from a dysregulated neuroimmune circuit.

The risk factors affecting the persistence of corpus callosum splenium lesions.

BACKGROUND: The most compact portion of the corpus callosum (CC) is the corpus splenium (CS). PURPOSE: To evaluate the connection between clinical and demographic features to determine whether neuroimaging findings will be permanent or temporary in CS patients. MATERIAL AND METHODS: We enrolled 93 patients (age range = 18-86 years) with CS lesions. Demographic and clinical information were recorded. We examined the lesions depending on the location. Group 1 (n = 20) had lesions limited to the CS (egg-shaped or round); group 2 (n = 15) had "boomerang sign" lesions; and group 3 (n = 58) had splenium involvement in conditions affecting the whole brain (Boomerang sign+ plus). RESULTS: Group 1 had a lower mean age, shorter disease duration, and fewer persistent lesions than others (P < 0.01, P < 0.001, and P < 0.001, respectively). The mean disease onset age (in years) in group 1 was higher than that of the other groups (P < 0.045). Group 2 had lower potassium (K) (P < 0.003) and red cell distribution width levels (P < 0.029) than the other groups. Age <41.5 years (P < 0.001), age at illness initiation <48.5 years (P < 0.002), disease duration <5.5 months (P < 0.001), and eosinophil level <0.29 uL (P 0.014) all point to temporary lesions. CONCLUSION: Cases with limited CS lesions have younger onset ages, lower disease onset ages, and shorter disease durations. Age, age of disease onset, disease duration, and eosinophil level are risk variables that affect whether CS lesions are permanent or temporary.

From cytokines to chemokines: Understanding inflammatory signaling in bacterial meningitis.

Bacterial meningitis is a serious central nervous system (CNS) infection, claiming millions of human lives annually around the globe. The deadly infection involves severe inflammation of the protective sheath of the brain, i.e., meninges, and sometimes also consists of the brain tissue, called meningoencephalitis. Several inflammatory pathways involved in the pathogenesis of meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus suis, etc. are mentioned in the scientific literature. Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs), Nucleotide oligomerization domain (NOD)-like receptor-mediated signaling, pneumolysin related signaling, NF-κB signaling and many other pathways that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation. The activation of another protein complex, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, also takes place resulting in the maturation and release of IL-1ß and IL-18, hence potentiating neuroinflammation. This review aims to outline the inflammatory signaling pathways associated with the pathogenesis of bacterial meningitis leading to extensive pathological changes in neurons, astrocytes, oligodendrocytes, and other central nervous system cells.

Clinical Features of Cytokine Storm Syndrome.

Cytokine storm syndrome (CSS) is a severe life-threatening condition characterized by a clinical phenotype of overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multiple organ failure (MOF), and, if untreated, it can potentially lead to death. The hallmark of CSS is an uncontrolled and dysfunctional immune response involving the continual activation and expansion of lymphocytes and macrophages, which secrete large amounts of cytokines, causing a cytokine storm. Many clinical features of CSS can be explained by the effects of pro-inflammatory cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and IL-18 [1-7]. These cytokines are elevated in most patients with CSS as well as in animal models of CSS [8, 9]. A constellation of symptoms, signs, and laboratory abnormalities occurs that depends on the severity of the syndrome, the underlying predisposing conditions, and the triggering agent.

Unveiling the biological effects of radio-frequency and extremely-low frequency electromagnetic fields on the central nervous system performance.

Introduction: Radiofrequency electromagnetic radiation (RF-EMR) and extremely low-frequency electromagnetic fields (ELF-EMF) have emerged as noteworthy sources of environmental pollution in the contemporary era. The potential biological impacts of RF-EMR and ELF-EMF exposure on human organs, particularly the central nervous system (CNS), have garnered considerable attention in numerous research studies. Methods: This article presents a comprehensive yet summarized review of the research on the explicit/implicit effects of RF-EMR and ELF-EMF exposure on CNS performance. Results: Exposure to RF-EMR can potentially exert adverse effects on the performance of CNS by inducing changes in the permeability of the blood-brain barrier (BBB), neurotransmitter levels, calcium channel regulation, myelin protein structure, the antioxidant defense system, and metabolic processes. However, it is noteworthy that certain reports have suggested that RF-EMR exposure may confer cognitive benefits for various conditions and disorders. ELF-EMF exposure has been associated with the enhancement of CNS performance, marked by improved memory retention, enhanced learning ability, and potential mitigation of neurodegenerative diseases. Nevertheless, it is essential to acknowledge that ELF-EMF exposure has also been linked to the induction of anxiety states, oxidative stress, and alterations in hormonal regulation. Moreover, ELF-EMR exposure alters hippocampal function, notch signaling pathways, the antioxidant defense system, and synaptic activities. Conclusion: The RF-EMR and ELF-EMF exposures exhibit both beneficial and adverse effects. Nevertheless, the precise conditions and circumstances under which detrimental or beneficial effects manifest (either individually or simultaneously) remain uncertain.

Chronic inflammatory demyelinating polyneuropathy. A case description.

Patients affected by chronic inflammatory demyelinating polyradiculoneuropathy require close follow up due to the neuronal demyelination along with axonal degeneration associated with the disease process, giving the opportunity to the medical team of adequating therapeutics and other medical interventions, according to the evolution of the symptoms, to prevent irreversible axonal degeneration.

Unveiling the Veiled: Enteroviral Meningitis Mimicking Idiopathic Intracranial Hypertension.

Meningitis is a significant health concern globally, with enterovirus (EV) being the most common cause of viral meningitis in adults. We discuss the case of a 57-year-old female patient with enteroviral meningitis manifesting as pseudotumor cerebri, posing significant clinical challenges. She presented with symptoms, signs, and radiological evidence suggesting idiopathic intracranial hypertension. The CSF analysis showed pleocytosis, which led to further investigations that unveiled a positive case of EV by real-time reverse transcription polymerase chain reaction analysis. This case highlights the fact that not all cases of raised intracranial pressure are detrimental or recalcitrant. It accentuates the need for thorough diagnostic evaluation and emphasizes the potential for favorable outcomes with conservative management.

Hematopoietic stem cell transplantation leads to biochemical and functional correction in two mouse models of acid ceramidase deficiency.

Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare lysosomal storage disorders caused by deficient acid ceramidase (ACDase) activity. Although both conditions are caused by mutations in the ASAH1 gene, clinical presentations differ considerably. FD patients usually die in childhood while SMA-PME patients can live until adulthood. There is no treatment for FD or SMA-PME. Hematopoietic stem cell transplantation (HSCT) and gene therapy strategies for the treatment of ACDase deficiency are being investigated. We have previously generated and characterized mouse models of both FD and SMA-PME that recapitulate the symptoms described in patients. Here, we show that HSCT improves lifespan, behavior, hematopoietic system anomalies, plasma cytokine levels, and significantly reduces histiocytic infiltration and ceramide accumulation throughout the tissues investigated, including the CNS, in both models of ACDase deficient mice. HSCT was also successful in preventing lesion development and significant demyelination of the spinal cord seen in SMA-PME mice. Importantly, we note that only early and generally pre-symptomatic treatment was effective and kidney impairment was not improved in either model.

Phosphatidylserine: A comprehensive overview of synthesis, metabolism, and nutrition.

Phosphatidylserine (PtdS) is classified as a glycerophospholipid and a primary anionic phospholipid and is particularly abundant in the inner leaflet of the plasma membrane in neural tissues. It is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by PtdS synthase-1 and PtdS synthase-2 located in the endoplasmic reticulum. PtdS exposure on the outside surface of the cell is essential for eliminating apoptotic cells and initiating the blood clotting cascade. It is also a precursor of phosphatidylethanolamine, produced by PtdS decarboxylase in bacteria, yeast, and mammalian cells. Furthermore, PtdS acts as a cofactor for several necessary enzymes that participate in signaling pathways. Beyond these functions, several studies indicate that PtdS plays a role in various cerebral functions, including activating membrane signaling pathways, neuroinflammation, neurotransmission, and synaptic refinement associated with the central nervous system (CNS). This review discusses the occurrence of PtdS in nature and biosynthesis via enzymes and genes in plants, yeast, prokaryotes, mammalian cells, and the brain, and enzymatic synthesis through phospholipase D (PLD). Furthermore, we discuss metabolism, its role in the CNS, the fortification of foods, and supplementation for improving some memory functions, the results of which remain unclear. PtdS can be a potentially beneficial addition to foods for kids, seniors, athletes, and others, especially with the rising consumer trend favoring functional foods over conventional pills and capsules. Clinical studies have shown that PtdS is safe and well tolerated by patients.

Diagnostic uncertainty of steroid-modified Marburg's variant of multiple sclerosis even at autopsy: A case suggesting lymphoma and related myelin loss.

MS (multiple sclerosis) has specific criteria to avoid misdiagnosis. However, the Marburg variant of MS is so fulminant that initial axonal damage and other atypical observations have been allowed in past reports. We present a 74-year-old autopsy case with a vanishing tumor after steroids and radiation therapy, which was pathologically diagnosed as a Marburg variant with initial axonal loss. The case displayed radiological lymphoma-like observations: mass effects protruding to the lateral ventricle, fused extension from the choroid plexus to white matter with C opening sign, a growing lesion from the skull dura mater, high in diffusion-weighted imaging and low in apparent diffusion coefficient on magnetic resonance imaging (MRI) suggesting high cell density lymphoma. In addition, clinical manifestations were atypical for MS: upper limb monoplegia without ipsilateral lower limb involvement, pleocytosis over 50 cells/µL, and class 3 cytological abnormality in cerebrospinal fluid. However, at autopsy following steroids and radiation therapy, there were no lymphoma-like lesions, such as mass effects, fused extensive lesions, masses on the skull dura mater, or high cell density lesions. Instead, there were only myelin losses corresponding to the MRI lesions, highlighting the potential for contamination by other diseases in steroid-modified Marburg's variant of multiple sclerosis, possibly due to lymphoma, even at autopsy.

Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations.

Viral vectors based on recombinant adeno-associated virus (rAAV) have become the most widely used system for therapeutic gene delivery in the central nervous system (CNS). Despite clinical safety and efficacy in neurological applications, a barrier to adoption of the current generation of vectors lies in their limited efficiency, resulting in limited transduction of CNS target cells. To address this limitation, researchers have bioengineered fit-for-purpose AAVs with improved CNS tropism and tissue penetration. While the preclinical assessment of these novel AAVs is primarily conducted in animal models, human induced pluripotent stem cell (hiPSC)-derived organoids offer a unique opportunity to functionally evaluate novel AAV variants in a human context. In this study, we performed a comprehensive and unbiased evaluation of a large number of wild-type and bioengineered AAV capsids for their transduction efficiency in hiPSC-derived brain organoids. We demonstrate that efficient AAV transduction observed in organoids was recapitulated in vivo in both mouse and non-human primate models after cerebrospinal fluid (CSF) delivery. In summary, our study showcases the use of brain organoid systems for the pre-screening of novel AAV vectors. Additionally, we report data for novel AAV variants that exhibit improved CNS transduction efficiency when delivered via the CSF in in vivo preclinical models.

Central nervous injury risk factors after endovascular repair of a thoracic aortic aneurysm with type B aortic dissection.

BACKGROUND: Aortic dissection is the deadliest disease of the cardiovascular system. Type B aortic dissection accounts for 30%-60% of aortic dissections and is mainly treated by endovascular repair of thoracic endovascular aneurysm repair (TEVAR). However, patients are prone to various complications after surgery, with central nervous system injury being the most common, which seriously affects their prognosis and increases the risk of disability and death. Therefore, exploring the risk factors of central nervous system injury after TEVAR can provide a basis for its prevention and control. AIM: To investigate the risk factors for central nervous system injury after the repair of a thoracic endovascular aneurysm with type B aortic dissection. METHODS: We enrolled 306 patients with type B aortic dissection who underwent TEVAR at our hospital between December 2019 and October 2022. The patients were categorized into injury (n = 159) and non-injury (n = 147) groups based on central nervous system injury following surgery. The risk factors for central nervous system injury after TEVAR for type B aortic dissection were screened by comparing the two groups. Multivariate logistic regression analysis was performed. RESULTS: The Association between age, history of hypertension, blood pH value, surgery, mechanical ventilation, intensive care unit stay, postoperative recovery times on the first day after surgery, and arterial partial pressure of oxygen on the first day after surgery differed substantially (P < 0.05). Multivariate logistic regression analysis indicated that age, surgery time, history of hypertension, duration of mechanical ventilation, and intensive care unit stay were independent risk factors for central nervous system injury after TEVAR of type B aortic dissection (P < 0.05). CONCLUSION: For high-risk patients with central nervous system injury after TEVAR of type B aortic dissection, early intervention measures should be implemented to lower the risk of neurological discomfort following surgery in high-risk patients with central nervous system injury after TEVAR for type B aortic dissection.

Translational Research Platform for Malignant Central Nervous System Tumors.

Some central nervous system (CNS) malignancies are highly aggressive and urgently need innovative treatment strategies to improve prognosis. A significant concern for therapeutic development is the time-consuming nature of developing treatments for CNS tumors. Therefore, a rapid and efficient translational approach is needed to address this problem. Translational and reverse translational research aims to bridge the gap between laboratory data and clinical applications and has been developed in the field of neuro-oncology. This study presents our translational platform systems for malignant CNS tumors, which combine an intraoperative integrated diagnostic system and comprehensive in vitro and in vivo assay systems. These laboratory systems may contribute to a better understanding of tumor biology and the development of novel therapeutic strategies for the poor prognosis of CNS tumors.

Integrated transcriptomic and proteomic analyses reveal the effects of chronic benzene exposure on the central nervous system in mice.

Benzene exposure is known to cause serious damage to the human hematopoietic system. However, recent studies have found that chronic benzene exposure may also cause neurological damage, but there were few studies in this issue. The aim of this study was to investigate the mechanism of damage to the central nervous system (CNS) by chronic benzene exposure with a multi-omics analysis. We established a chronic benzene exposure model in C57BL/6J mice by gavage of benzene-corn oil suspension, identified the differentially expressed proteins (DEPs) and differentially expressed genes (DEGs) in mice brain using 4D Label-free proteomic and RNA-seq transcriptomic. We observed that the benzene exposure mice had a significant loss of body weight, reduction in complete blood counts, abnormally high MRI signals in brain white matter, as well as extensive brain edema and neural demyelination. 162 DEPs were identified by the proteome, including 98 up-regulated and 64 down-regulated proteins. KEGG pathway analysis of DEPs showed that they were mainly involved in the neuro-related signaling pathways such as metabolic pathways, pathways of neurodegeneration, chemical carcinogenesis, Alzheimer disease, and autophagy. EPHX1, GSTM1, and LIMK1 were identified as important candidate DEGs/DEPs by integrated proteomic and transcriptomic analyses. We further performed multiple validation of the above DEGs/DEPs using fluorescence quantitative PCR (qPCR), parallel reaction monitoring (PRM), immunohistochemistry, and immunoblotting to confirm the reliability of the multi-omics study. The functions of these DEGs/DEPs were further explored and analyzed, providing a theoretical basis for the mechanism of nerve damage caused by benzene exposure.

Neurological manifestations in dogs with acute leukemia.

Canine acute leukemia is a rare hematopoietic neoplasm. Neurological abnormalities have been frequently reported in dogs with acute leukemia (AL). However, the description of the presentation and findings are limited. This study aimed to describe the clinical findings in dogs with acute leukemia presenting with neurological signs as their primary complaint. The database of a private referral hospital was searched for cases that presented to the neurological department with neurological deficits and were subsequently diagnosed with acute leukemia. Six cases were included; all had neurological clinical signs and an abnormal neurological examination. All cases had a focal neuroanatomical localisation on neurological examination (brain n = 4; spinal = 2). Out of the four dogs with a complete magnetic resonance imaging (MRI) study, there was an ill-defined infiltrative pattern with abnormal signal intensity in the central nervous system (CNS) in three dogs and the loss of grey and white matter differentiation in the brain (n = 2) and/or spinal cord (n = 2). Other MRI findings included abnormal meningeal enhancement (n = 3), changes affecting spinal nerves and epaxial muscles (n = 2), and lymphadenopathy in the field of view (n = 2). The bone marrow assessment on MRI showed evidence of signal change (n = 3), characterized by a loss of normal fat opacity and an abnormal degree of contrast enhancement. The cerebrospinal fluid (CSF) analysis of the four dogs showed an increased protein level with non-specific pleocytosis and without evidence of malignant cells. Treatment with cytotoxic medication was implemented in two dogs. The dogs diagnosed with acute leukemia had focal neuroanatomical localisation, an infiltrative CNS pattern, and bone marrow remodulation on MRI with an increase in CSF protein and negative cytology analysis.

Ocular fundus changes and association with systemic conditions in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and systems. Ocular involvement is estimated to manifest in one-third of individuals with SLE, of which lupus retinopathy and choroidopathy represent the severe subtype accompanied by vision impairment. Advancements in multimodal ophthalmic imaging have allowed ophthalmologists to reveal subclinical microvascular and structural changes in fundus of patients with SLE without ocular manifestations. Both ocular manifestations and subclinical fundus damage have been shown to correlate with SLE disease activity and, in some patients, even precede other systemic injuries as the first presentation of SLE. Moreover, ocular fundus might serve as a window into the state of systemic vasculitis in patients with SLE. Given the similarities of the anatomy, physiological and pathological processes shared among ocular fundus, and other vital organ damage in SLE, such as kidney and brain, it is assumed that ocular fundus involvement has implications in the diagnosis and evaluation of other systemic impairments. Therefore, evaluating the fundus characteristics of patients with SLE not only contributes to the early diagnosis and intervention of potential vision damage, but also holds considerate significance for the evaluation of SLE vasculitis state and prediction of other systemic injuries.

Assessing Health-Related Quality of Life in Children With Spina Bifida in Lithuania.

Introduction In recent years, more emphasis has been placed on improving the health-related quality of life (HRQOL) in children with spina bifida (SB). Chronic disability is understood to impact various aspects of the person's life, family, and social functioning, in addition to the specific needs of the disease. The HRQOL is done to assess the patient's quality of life (QOL) in various domains including physical and mental. Back in the 1900s, few children survived SB, whereas today, they almost have normal life expectancy. By understanding the contributing factors to the quality of life (QOL), more targeted interventions can be put in place in order to maximize the psychological and social well-being of these patients. Aim The aim of this study is to estimate the health-related quality of life (HRQOL) in Lithuanian children with spina bifida (SB) in relation to comorbidities, level of lesions, and mobility. Objectives The objectives of this study are to investigate the HRQOL of Lithuanian children with SB born between 1999 and 2012; to analyze the relation between the HRQOL and its comorbidities, including hydrocephalus, Chiari II malformation, incontinence, and epilepsy; and to determine the relationship of health variables, the level of lesions, and mobility to the HRQOL. Methods This was a quantitative cross-sectional study on children with spina bifida across Lithuania to assess the HRQOL. Subjects were chosen and interviewed from various cities including Kaunas, Vilnius, Marijampole, Gargzdai, Birzai, Panevezys, Palanga, and Alytus. A questionnaire was used as an instrument to measure the HRQOL. The level of lesions, comorbidities, and other health variables were obtained from the medical files and directly from the patient's history. Results Regarding the HRQOL, our study population showed the highest scores in the emotional, medical, intellectual, and social domains. The lowest sub-scores were in recreational, vocational, environmental, and then physical domains. We also found that certain comorbidities including hydrocephalus, epilepsy, and incontinence negatively affected the QOL. In our study group, we also found that the ambulatory group scored significantly higher in the overall QOL. However, when comparing the level of lesions to the HRQOL, we found no statistically significant difference. Conclusion Positive results were obtained regarding the medical, emotional, intellectual, and social aspects of patients with SB in Lithuania as they scored high in this domain. However, the environmental and vocational domains scored low, suggesting that further examination needs to be carried in these domains. We concluded that having various comorbidities including hydrocephalus and incontinence has negative impacts on the QOL. Patients who suffered from epilepsy had a statistically significant lower QOL. No significant difference was found in the association between the level of lesion and the QOL in our study.

Primary CNS Burkitt Lymphoma Presenting as Sudden Bilateral Blindness in a Patient With Underlying Kabuki Syndrome: A Case Report.

Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma (NHL). Primary CNS lymphoma (PCNSL) is a rare disease, and the subtype of Burkitt lymphoma presenting as a sole CNS lesion is an even rarer diagnosis. Acute sudden blindness is a rare presenting symptom of PCNSL or NHL in general. We present an interesting case of a four-year-old boy with dysmorphic features whose visual examination showed a sudden bilateral loss of vision. There was bilateral eye proptosis and complete ptosis. Extraocular muscles were fixed straight. The pupils were fixed and mid dilated bilaterally and there was grade 3/4 papilledema in both eyes. Neuroimaging showed a mass in the base of the skull, extending to orbits and sinuses. A cervical biopsy of the enlarged lymph nodes was taken and a histopathological diagnosis of Burkitt lymphoma was made. Genetic analysis showed a GNB1 mutation, and the patient was diagnosed with Kabuki syndrome by a pediatrician, based on characteristic dysmorphic features. Treatment with steroids and chemotherapy was initiated.

Cryptococcal endophthalmitis and meningitis in an immunocompetent middle-aged woman: A case report.

Cryptococcus neoformans is a global invasive mycosis that is known to cause significant morbidity and mortality. It is commonly observed that individuals with compromised immune systems are more prone to developing cryptococcal meningitis. Although ocular involvement is rare, previous studies have indicated that ocular lesions precede symptomatic meningitis in only 27 % of patients with central nervous system involvement. Intraocular infections typically manifest as chorioretinopathy and vitreous inflammation, often leading to severe vision loss. In this case, we present the clinical details of a 57-year-old immunocompetent woman who visited the ophthalmology department of West China Hospital of Sichuan University with a progressive loss of vision in her right eye. After a thorough evaluation, she was diagnosed with fungal endophthalmitis, and subsequently initiated on appropriate induction anti-fungal therapy for cryptococcal meningoencephalitis. This case highlights the importance of early recognition and treatment, which can potentially improve the prognosis for patients.