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Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina. [ABSTRACT FROM AUTHOR]

Communication between the nervous system and the immune system has evolved to optimally respond to potentially dangerous stimuli both from within and outside the body. Tumors pose a severe threat to an organism and current therapies are insufficient for tumor regression in the majority of cases. Studies show that tumors are innervated by peripheral nerves from the sensory, parasympathetic and sympathetic nervous systems. Interactions between cancer cells, nerves and immune cells regulate overall tumor progression. Clinical studies have indicated the potential of targeting the peripheral nervous system for promoting anti‐tumor immune responses. This view point provides an opinion on the current evidence and therapeutic potential of manipulating neuro‐immune communications in cancer. [ABSTRACT FROM AUTHOR]

Background: Pediatric-Onset Multiple Sclerosis (POMS) is considered a complex disease entity and several genetic, hormonal, and environmental factors have been associated with disease pathogenesis. Linkage studies in Caucasians have consistently suggested the human leukocyte antigen (HLA) polymorphisms, as the genetic locus most strongly linked to MS, with the HLA-DRB1*15:01 allele, being associated with both adult and pediatric MS patients. Here we aim to investigate the prevalence of the HLA-DRB1 alleles among a Hellenic POMS cohort and any possible associations with clinical and imaging disease features. Materials and methods: 100 POMS patients fulfilling the IPMSSG criteria, 168 Adult-Onset MS (AOMS) patients, and 246 Healthy Controls (HCs) have been enrolled. HLA genotyping was performed with a standard low-resolution sequence-specific oligonucleotide (SSO) technique. Results: POMS patients display a significantly increased HLA-DRB1*03 frequency compared to both HCs [24% vs. 12.6%, OR [95%CI]: 2.19 (1.21-3.97), p=0.016) and AOMS (24% vs. 13.1%, OR [95%CI]: 2.1 (1.1-3.98), p=0.034] respectively. HLA-DRB1*03-carriers display reduced risk for brainstem lesion development (OR [CI 95%]:0.19 (0.06-0.65), p=0.011). A significantly lower frequency of HLA-DRB1*07 (4% vs 13.4%, OR (95% CI): 0.27 (0.09-0.78), p= 0.017) and HLA-DRB1*11 (37% vs 52%, OR [95% CI]: 0.54 (0.34-0.87), p= 0.016) was observed in POMS compared to HCs. Conclusion: The HLA-DRB1*03 allele was associated with a higher risk for POMS, replicating our previous findings, and with a lower risk for brainstem lesion development, a common clinical and neuroimaging feature in POMS, while HLA-DRB1*07 and HLA-DRB1*11 display a protective role. These findings expand the existing knowledge of HLA associations and POMS. [ABSTRACT FROM AUTHOR]

Lymphotoxin α and lymphotoxin β (LTs), TNF superfamily members, are expressed in either soluble (LTα3) or membrane‐bound (LTα1β2 or LTα2β1) forms. In the pathological context, LT‐mediated signaling is known to exacerbate autoimmunity by perpetuating inflammation and promoting the formation of tertiary lymphoid organs. Despite this understanding, the exact roles of LTα and LTβ in the pathogenesis of the murine model of multiple sclerosis, and experimental autoimmune encephalomyelitis (EAE), remain controversial. Here, we employed a panel of gene‐modified mice with cell‐type restricted ablation of LTα (targeting both membrane‐bound and soluble forms of LTs) to unravel the contributions of LTs from various lymphoid cells, namely T cells, type 3 innate lymphoid cells (ILC3) and B cells, in EAE. We found that the effects of LTα deletion were dependent on the cellular source. ILC3‐derived lymphotoxins exerted a protective role in EAE by regulating the accumulation of IFN‐ɣ‐ and GM‐CSF‐producing TH cells in the CNS. In contrast, T‐cell‐derived lymphotoxins promoted IL‐17A‐ and GM‐CSF‐mediated TH responses in the periphery, whereas B‐cell‐derived lymphotoxins were pathogenic only in the autoantibody‐mediated EAE model. Collectively, our findings unveil the multifaceted involvement of lymphotoxins in EAE pathogenesis and challenge the view that lymphotoxins play a solely pathogenic role in neuroinflammation. [ABSTRACT FROM AUTHOR]

The associations among increased pain sensitivity, obesity, and systemic inflammation have not been described as related to BBB dysfunctions. To analyze the metabolic, behavioral, and inflammatory effects of a high-fat diet (HFD) and ultrastructural modifications in brain regions, we used an in vivo experimental model. Adult male Wistar rats were randomly assigned to one of two conditions, an ad libitum control group or an HFD (60%)-fed group, for eight weeks. At the end of the protocol, glucose and insulin tolerance tests were performed. Additionally, we analyzed the response to a normally innocuous mechanical stimulus and changes in motor coordination. At the end of the protocol, HFD-fed rats presented increased HOMA–IR and metabolic syndrome (MetS) prevalence. HFD-fed rats also developed an increased nociceptive response to mechanical stimuli and neurological injury, resulting in impaired motor function. Hypothalamus and cerebellum neurons from HFD-fed rats presented with nuclear swelling, an absence of nucleoli, and karyolysis. These results reveal that HFD consumption affects vital brain structures such as the cerebellum, hippocampus, and hypothalamus. This, in turn, could be producing neuronal damage, impairing cellular communication, and consequently altering motricity and pain sensitivity. Although direct evidence of a causal link between BBB dysfunction and sensory-motor changes was not observed, understanding the association uncovered in this study could lead to targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Summary: Aicardi‐Goutières syndrome (AGS) is a progressive genetic encephalopathy caused by pathogenic mutations in genes controlling cellular anti‐viral responses and nucleic acid metabolism. The mutations initiate autoinflammatory processes in the brain and systemically that are triggered by chronic overproduction of type I interferon (IFN), including IFN‐alpha. Emerging disease‐directed therapies aim to dampen autoinflammation and block cellular responses to IFN production, creating an urgent and unmet need to understand better which cells, compartments, and mechanisms underlying disease pathogenesis. In this review, we highlight existing pre‐clinical models of AGS and our current understanding of how causative genetic mutations promote disease in AGS, to promote new model development and a continued focus on improving and directing future therapies. [ABSTRACT FROM AUTHOR]

The clonal selection theory (CST) is the centrepiece of the current paradigm used to explain immune recognition and memory. Throughout the past decades, the original CST had been expanded and modified to explain new experimental evidences since its original publication by Burnet. This gave origin to new paradigms that govern experimental immunology nowadays, such as the associative recognition of antigen model and the stranger/danger signal model. However, these new theories also do not fully explain experimental findings such as natural autoimmune immunoglobulins, idiotypic networks, low and high dose tolerance, and dual‐receptor T and B cells. To make sense of these empirical data, some authors have been trying to change the paradigm of immune cognition using a systemic approach, analogies with brain processing and concepts from second‐order cybernetics. In the present paper, we review the CST and some of the theories/hypotheses derived from it, focusing on immune recognition. We point out their main weaknesses and highlight arguments made by their opponents and believers. We conclude that, until now, none of the proposed theories can fully explain the totality of immune phenomena and that a theory of everything is needed in immunology. [ABSTRACT FROM AUTHOR]

Interactions between nociceptors and mammalian immune cells are complex; however, most promote tissue repair and homeostasis, adaptive immune responses, or Type 2 immunity and inflammation. Nociceptors inhibit histotoxic, collateral damage-causing immune responses and promote tissue repair chiefly through the secretion of the calcitonin gene-related peptide (CGRP) neuropeptide. Nociceptors promote adaptive immunity by fine-tuning dendritic cell functions, through innervation of secondary lymphoid organs, and by communicating with B lymphocytes. Nociceptors can regulate Type 2 immunity inflammation by secreting neuropeptides or glutamate. While the primary role of nociceptors is to maintain tissue homeostasis, their actions can promote pathological conditions if unchecked. Nociceptor functions are themselves modulated by immune cell actions, forming numerous feed-forward and feed-back loops. The peripheral nervous system is being increasingly recognized as a regulator of immune responses at steady-state and in response to infections, cancer, tissue injury, and other challenges. In particular, nociceptors, a population of somatosensory neurons that confer the sensation of itch or pain, can exert both pro- and anti-inflammatory effects. Developing a better understanding of nociceptors as conductors of immune responses is at the forefront of neuroimmunology research. Nociceptors have emerged as master regulators of immune responses in both homeostatic and pathologic settings; however, their seemingly contradictory effects on the functions of different immune cell subsets have been a source of confusion. Nevertheless, work by many groups in recent years has begun to identify patterns of the modalities and consequences of nociceptor-immune system communication. Here, we review recent findings of how nociceptors affect immunity and propose an integrated concept whereby nociceptors are neither inherently pro- nor anti-inflammatory. Rather, we propose that nociceptors have the role of a rheostat that, in a context-dependent manner, favors tissue homeostasis and fine-tunes immunity by preventing excessive histotoxic inflammation, promoting tissue repair, and potentiating anticipatory and adaptive immune responses. [ABSTRACT FROM AUTHOR]

The brain-centric view of neurodegenerative diseases has been challenged by new discoveries related to the neuroimmune axis. Recent reports describe signatures of immune dysfunction that may perpetuate symptoms of neurodegeneration. Signatures of neurodegenerative diseases may go hand-in-hand with accelerated aging of the mammalian immune system; indeed, markers of immune exhaustion have been reported to increase with disease progression for certain pathologies. Harnessing the immune system by means of active vaccination, or by targeting inhibitory immune checkpoints might boost the homing of reparative immune cells (monocyte-derived macrophages and regulatory T cells) into the brain to fight disease. The immune system is vital for proper brain function. Neurodegenerative diseases can emerge as a result of prolonged immune dysregulation. Therefore, boosting peripheral immune cell functions might ultimately promote brain repair and help fight neurodegeneration. Reciprocal communication between the brain and the immune system is essential for maintaining lifelong brain function. This interaction is mediated, at least in part, by immune cells recruited from both the circulation and niches at the borders of the brain. Here, we describe how immune exhaustion and senescence, even if not primary causative factors, can accelerate neurodegenerative diseases. We emphasize the role of a compromised peripheral immune system in driving neurodegeneration and discuss strategies for harnessing peripheral immunity to effectively treat neurodegenerative diseases, including the underlying mechanisms and opportunities for clinical translation. Specifically, we highlight the potential of boosting the immune system by blocking inhibitory checkpoint molecules to harness reparative immune cells in helping the brain to fight against neurodegeneration. [ABSTRACT FROM AUTHOR]

This preface introduces the Special Issue on Neuroimmunology in the Journal of Neurochemistry. The basis of neuroimmunology is to understand functional interactions between cells of the immune system and the central nervous system (CNS). These cells communicate across systems because they share signaling molecules and corresponding receptors. Moreover, this cell signaling allows for dynamic bidirectional communication between the immune system and the brain both within the CNS proper as well as across peripheral organs. Because of this, Neuroimmunology intersects with many biological processes including immunity, behavior, endocrinology, metabolism, and pathology. Understanding neuroimmune interactions that influence CNS homeostasis is especially relevant in health and disease. This special issue comprises of 14 articles, representing 9 review articles and 5 original articles, covering the roles of neuroimmunology relevant to CNS injury, CNS & peripheral infections, cancer, Alzheimer's disease, and COVID‐19. Thus, these articles highlight different aspects of neuroimmunology and signaling, and represent progress in understanding the consequences of inflammation on key communication pathways between the immune system and the brains. [ABSTRACT FROM AUTHOR]

Cognitive deficits are a common comorbidity with neurological disorders and normal aging. Inflammation is associated with multiple diseases including classical neurodegenerative dementias such as Alzheimer's disease (AD) and autoimmune disorders such as multiple sclerosis (MS), in which over half of all patients experience some form of cognitive deficits. Other degenerative diseases of the central nervous system (CNS) including frontotemporal lobe dementia (FTLD), and Parkinson's disease (PD) as well as traumatic brain injury (TBI) and psychological disorders like major depressive disorder (MDD), and even normal aging all have cytokine‐associated reductions in cognitive function. Thus, there is likely commonality between these secondary cognitive deficits and inflammation. Neurological disorders are increasingly associated with substantial neuroinflammation, in which CNS‐resident cells secrete cytokines and chemokines such as tumor necrosis factor (TNF)α and interleukins (ILs) including IL‐1β and IL‐6. CNS‐resident cells also respond to a wide variety of cytokines and chemokines, which can have both direct effects on neurons by changing the expression of ion channels and perturbing electrical properties, as well as indirect effects through glia–glia and immune‐glia cross‐talk. There is significant overlap in these cytokine and chemokine expression profiles across diseases, with TNFα and IL‐6 strongly associated with cognitive deficits in multiple disorders. Here, we review the involvement of various cytokines and chemokines in AD, MS, FTLD, PD, TBI, MDD, and normal aging in the absence of dementia. We propose that the neuropsychiatric phenotypes observed in these disorders may be at least partially attributable to a dysregulation of immunity resulting in pathological cytokine and chemokine expression from both CNS‐resident and non‐resident cells. [ABSTRACT FROM AUTHOR]

Background: There are established associations between viral and autoimmune encephalitis as well as between autoimmune encephalitis and demyelinating central nervous system (CNS) diseases. Here, we report the evolution from varicella zoster virus (VZV) encephalitis to limbic autoimmune encephalitis (AIE) to multiple sclerosis (MS) in one patient. Case report: A woman in her mid-thirties presented with headache, aphasia, and a generalized tonic–clonic seizure. Cerebrospinal fluid (CSF) VZV polymerase chain reaction was positive and treatment with acyclovir was administered for VZV encephalitis. Five months later, the patient presented with cognitive deficits and MRI showed new bilateral hippocampal T2-hyperintensities. CSF analyses revealed pleocytosis and neuropil antibodies in tissue-staining. A diagnosis of limbic AIE was established and treatment with IV steroids and IV immunoglobulins initiated. One year later, the patient developed paresthesia of both legs and magnetic resonance imaging studies now showed new supratentorial and spinal demyelinating lesions. The patient was diagnosed with MS and treatment was changed to rituximab. Conclusions: This unique case report links three important neuroimmunological entities in characterizing the evolution from infectious to autoimmune encephalitis to multiple sclerosis in one patient. Identification of such rare clinical constellations is critical for correct treatment choice and provides important novel insights into the pathophysiology of neuroimmunological disorders including viral triggers and overlap manifestations of autoimmune CNS diseases. [ABSTRACT FROM AUTHOR]

Progressive inflammation of one hemisphere characterises Rasmussen's encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and 2018 at a tertiary centre (Centre 1) and reviewed all available EEG datasets. The temporal occurrence of preoperative contralesional epileptiform activity (interictal/ictal) was evaluated using mixed-effects logistic regression. Cases with/without contralesional epileptiform activity were compared for cognition, inflammation (ipsilesional brain biopsies), and MRI (cortical and fixel-based morphometry). EEG findings were validated in a second cohort treated at another tertiary centre (Centre 2) between 1995 and 2020. We included 127 people with RE and 687 EEG samples. Preoperatively, contralesional epileptiform activity was seen in 30/68 (44%, Centre 1) and 8/59 (14%, Centre 2). In both cohorts, this activity was associated with younger onset age (OR = 0.9; 95% CI 0.83–0.97; P = 0.006). At centre 1, contralesional epileptiform activity was associated with contralesional MRI alterations, lower intelligence (OR = 5.19; 95% CI 1.28–21.08; P = 0.021), and impaired verbal memory (OR = 10.29; 95% CI 1.97–53.85; P = 0.006). After hemispherotomy, 11/17 (65%, Centre 1) and 28/37 (76%, Centre 2) were seizure-free. Contralesional epileptiform activity was persistent postoperatively in 6/12 (50%, Centre 1) and 2/34 (6%, Centre 2). Preoperative contralesional epileptiform activity reduced the chance of postoperative seizure freedom in both cohorts (OR = 0.69; 95% CI 0.50–0.95; P = 0.029). Our findings question the concept of strict unilaterality of RE and provide the evidence of contralesional epileptiform activity as a possible EEG predictor for persisting postoperative seizures. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a complex brain problem that causes significant morbidity and mortality among people of all age groups. The complex pathophysiology, varied symptoms, and inadequate treatment further precipitate the problem. Further, TBI produces several psychiatric problems and other related complications in post-TBI survival patients, which are often treated symptomatically or inadequately. Several approaches, including neuroprotective agents targeting several pathways of oxidative stress, neuroinflammation, cytokines, immune system GABA, glutamatergic, microglia, and astrocytes, are being tried by researchers to develop effective treatments or magic bullets to manage the condition effectively. The problem of TBI is therefore treated as a challenge among pharmaceutical scientists or researchers to develop drugs for the effective management of this problem. The goal of the present comprehensive review is to provide an overview of the several pharmacological targets, processes, and cellular pathways that researchers are focusing on, along with an update on their current state. [ABSTRACT FROM AUTHOR]

Introduction: Although meningiomas are the most common primary brain tumor, there are limited treatment options for recurrent or aggressive lesions. Compared to other brain tumors, meningiomas may be uniquely amenable to immunotherapy by virtue of their location outside the blood–brain barrier. Areas covered: This review describes our current understanding of the immunology of the meninges, as well as immune cell infiltration and immune signaling in meningioma. Current literature on meningioma immunology and immunotherapy was comprehensively reviewed and summarized by a comprehensive search of MEDLINE (1/1/1990-6/1/2024). Further, we describe the current state of immunotherapeutic approaches, as well as potential future targets. Potential immunotherapeutic approaches include immune checkpoint inhibition, CAR-T approaches, tumor vaccine therapy, and immunogenic molecular markers. Expert opinion: Meningioma immunotherapy is in early stages, as no immunotherapies are currently included in treatment guidelines. There is substantial heterogeneity in immune cell infiltration, immunogenicity, and immune escape across tumors, even within tumor grade. Furthering our understanding of meningioma immunology and tumor classification will allow for careful selection of tumors and patient populations that may benefit from primary or adjunctive immunotherapy for meningioma. [ABSTRACT FROM AUTHOR]

Background: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. Case presentation: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. Conclusions: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents. [ABSTRACT FROM AUTHOR]

SUMMARY: Across medicine, key scientific advances in the past couple of decades have deepened knowledge of fundamental mechanisms of disease, leading to new treatments and the possibility of increased personalisation of care. Some of the most important developments in fields as diverse as immunology, the microbiome, genetics, stem cells and artificial intelligence are summarised in this article to raise awareness among psychiatrists and to help understand the opportunities and challenges they may present for mental healthcare in the future. [ABSTRACT FROM AUTHOR]

The neurovascular unit, composed of vascular endothelium, vascular smooth muscle, extracellular matrix components, pericytes, astrocytes, microglia, and neurons, allows the highly regulated exchange of molecules and the limited trafficking of cells to the brain through coordinated signaling activity. The passage of peripheral immune cells to the brain parenchyma is observed when there is clear damage to the barriers of this neurovascular unit, as occurs in traumatic brain injury. The possibility of leukocyte infiltration to the brain in neurodegenerative conditions has been proposed. In this review, we focus on describing the evidence for peripheral immune cell infiltration to the brain in the two most frequent neurodegenerative diseases: Alzheimer's and Parkinson's diseases. In particular, we address the mechanisms that promote the passage of these cells into the brain under such pathological conditions. We also discuss the relevance of the resulting cellular interactions, which provide evidence that the presence of peripheral immune cells in the brain is a key point in these neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

The research in neuroimmunomodulation aims to shed light on the complex relationships that exist between the immune and neurological systems and how they affect the human body. This multidisciplinary field focuses on the way immune responses are influenced by brain activity and how neural function is impacted by immunological signaling. This provides important insights into a range of medical disorders. Targeting both brain and immunological pathways, neuroimmunomodulatory approaches are used in clinical pain management to address chronic pain. Pharmacological therapies aim to modulate neuroimmune interactions and reduce inflammation. Furthermore, bioelectronic techniques like vagus nerve stimulation offer non-invasive control of these systems, while neuromodulation techniques like transcranial magnetic stimulation modify immunological and neuronal responses to reduce pain. Within the context of aging, neuroimmunomodulation analyzes the ways in which immunological and neurological alterations brought on by aging contribute to cognitive decline and neurodegenerative illnesses. Restoring neuroimmune homeostasis through strategies shows promise in reducing age-related cognitive decline. Research into mood disorders focuses on how immunological dysregulation relates to illnesses including anxiety and depression. Immune system fluctuations are increasingly recognized for their impact on brain function, leading to novel treatments that target these interactions. This review emphasizes how interdisciplinary cooperation and continuous research are necessary to better understand the complex relationship between the neurological and immune systems. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. Methods: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. Results: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. Conclusion: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm. [ABSTRACT FROM AUTHOR]

Narcolepsy with cataplexy (NT1) is a rare hypothalamic disorder that presents with a dysregulation of the sleep–wake cycle (i.e., excessive daytime sleepiness and sleep and cataplectic attacks) and other motor, cognitive, psychiatric, metabolic, and autonomic disturbances, with putative autoimmune pathogenesis. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder that presents with acute-onset obsessive–compulsive symptoms and/or a severe eating restriction, with concomitant cognitive, behavioral, or affective symptoms caused by infections and other environmental triggers provoking an inflammatory brain response, which evolves into a chronic or progressive neuroimmune disorder. In this study, we present the case of a 13-year-old boy with vocal tics and syncopal-like episodes, eventually diagnosed as NT1 and PANS, and from this we discuss the hypothesis that both NT1 and PANS might belong to the same immunological spectrum, resulting in comparable imbalances in key neurotransmitter axes (i.e., orexinergic and dopaminergic), with conceptual and operational implications, especially with regards to the pharmacological tretament • Highlights (3-5). • Pediatric acute-onset neuropsychiatric syndrome (PANS) and Narcolepsy type 1 (NT1) are two distinctive neurological diseases that begin during developmental age. • PANS and NT1 have a neuroimmune pathogenesis involving different neurotransmitter axes. • NT1 and PANS may belong to the same immunological spectrum, resulting in involvement of different neurotransmitter axes, respectively orexinergic and dopaminergic. [ABSTRACT FROM AUTHOR]

Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use. The autoimmune response affecting the basal ganglia, notably against dopamine, underlies the pathophysiology. Clinical management necessitates an integrated approach, potentially involving immunomodulatory therapies. To address discrepancies in SC management, a survey was conducted across Italy, targeting specialists in neurology, pediatrics, child neuropsychiatry, and rheumatology. Of the 51 responding physicians, consensus favored hospitalization for suspected SC, with broad support for laboratory tests and brain MRI. Treatment preferences showed agreement on oral prednisone and IVIG, while opinions varied on duration and plasmapheresis. Haloperidol emerged as the preferred symptomatic therapy. Post-SC penicillin prophylaxis and steroid therapy gained strong support, although opinions differed on duration. Follow-up recommendations included neuropsychological and cardiological assessments. Despite offering valuable insights, broader and more studies are needed in order to guide treatment decisions in this well-known yet challenging complication of acute rheumatic fever, which continues to warrant scientific attention and concerted clinical efforts. • Sydenham's Chorea is a major concern, especially in children from developing countries, with long-term neuropsychiatric challenges. • We surveyed 51 clinicians via an online questionnaire, revealing current diagnostic and therapeutic practices for SC. • Physicians agreed on hospitalization and prefer MRI as the primary neuroimaging technique for diagnosing SC in children. • Treatment preferences varied, influenced by side effects and disease severity, showing differing clinical judgments. • Findings highlight the need for standardized treatment guidelines to enhance SC management, especially in Italy. [ABSTRACT FROM AUTHOR]

Abstract: People living with HIV (PLWH) may present atypical neurological complications. Recently, autoimmune manifestations of the central nervous system (CNS) have been described. We retrospectively described the features of PLWH presenting with acute neurological symptoms with positive anti-CNS antibodies. We analyzed relevant CSF characteristics. Twelve patients were identified, with demyelinating, inflammatory, or no MRI lesions. We observed CSF inflammatory features. Aspecific CSF anti-CNS antibodies were found in all subjects and a specific antibody (second-level blotting panel) was found in one. The cases presented a slow resolution of symptoms with sequelae. More studies are needed to better describe the spectrum and prognosis of autoimmune CNS diseases in PLWH. [ABSTRACT FROM AUTHOR]

The aim of the present study was to perform a comparative quantitative analysis of natural neurotropic autoantibodies (Nabs) in blood serum of patients with COVID-19 associated ischemic strokes (IS) in dynamics of disease. A total of 150 consecutive patients with acute primary IS were included, being divided in two groups: 100 patients with IS on the background of COVID-19 pneumonia (main group No. 1) and 50 patients with IS without COVID-19 symptoms and positive viral test (comparison group No. 2). The stroke severity and consciousness were measured by NIHSS and Glasgow coma scale. In blood serum of patients (n = 110), we have studied the levels of IgG Nabs to NF-200, GFAP, S100β, MBP, receptors to dopamine, serotonin, choline, glutamate, GABA by means of ELISA technique. The blood samples for analyses were taken at the 5th, 14th and 28th days of disease. In group 1 (n = 80), the Nabs levels have been increased as follows: antibodies to NF-200 (132.9±4.1 CU), by 1.09 and 1.8 times; for GFAP (118.9±3.9 CU), by 1.4 and 2 times; S100β antibodies (129.5±10.2 CU), by 1.05 and 1.6 times; MBP antibodies (97.3±4.5 CU) were 1.14 and 1.6 times higher; antibodies to dopamine receptors (77.9±4.4 CU) in 1.2 and 1.6 times; to serotonin receptors (81.96±3.25 CU) in 1.2 and 1.4 times; choline receptor antibodies (61.42±3.6 CU) were increased 1.4- and 1.8-fold; to glutamate (85.28±4.25 CU) by 1.19 and 1.4 times; to GABA (82.4±5.2 CU) the increase was 1.5- and 1.8-fold, respectively, when compared with group 2 and controls. The time-dependent monitoring of Nabs level in patients with COVID-19 associated ischemic stroke showed the highest increase in Nabs to the S-100, NF-200 and MBP proteins at the day +28 following the brain stroke. In patients with COVID-19 associated IS, more enhanced production of serum autoantibodies to neuroproteins and neurotransmitter receptors was detected, which accompanied a worse course of IS and can be considered as a predictor of unfavorable outcome of disease.

Abstract Background To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. Case presentation A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. Conclusions This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.

Abstract Background Neurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity. Case Report A 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in β2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found. Conclusions This case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits.

Abstract Therapeutics for traumatic brains injuries constitute a global unmet medical need. Despite the advances in neurocritical care, which have dramatically improved the survival rate for the ~ 70 million patients annually, few treatments have been developed to counter the long-term neuroinflammatory processes and accompanying cognitive impairments, frequent among patients. This review looks at gene delivery as a potential therapeutic development avenue for traumatic brain injury. We discuss the capacity of gene delivery to function in traumatic brain injury, by producing beneficial biologics within the brain. Gene delivery modalities, promising vectors and key delivery routes are discussed, along with the pathways that biological cargos could target to improve long-term outcomes for patients. Coupling blood-brain barrier crossing with sustained local production, gene delivery has the potential to convert proteins with useful biological properties, but poor pharmacodynamics, into effective therapeutics. Finally, we review the limitations and health economics of traumatic brain injury, and whether future gene delivery approaches will be viable for patients and health care systems.

Abstract Objective Overlap syndromes have been described between N‐methyl‐ d‐aspartate receptor encephalitis (NMDARE) and other neuroinflammatory conditions, although rarely involving neurosarcoidosis. Molecularly targeted immunotherapy may be helpful in the empiric treatment of these conditions. Methods We describe a 9‐year‐old boy with new‐onset seizures and worsening encephalopathy. Results Initial evaluation was concerning for neurosarcoidosis, including elevated cerebrospinal fluid (CSF) and serum angiotensin‐converting enzyme and leptomeningeal with multiple cranial nerve enhancement on magnetic resonance imaging. CSF and serum cytokine profiles were used to choose targeted empiric immunotherapy, and the boy's seizure burden and encephalopathy improved after treatment with tocilizumab. The NMDA receptor antibody titer was later found to be elevated, raising suspicion for a novel overlap syndrome. Interpretation Our patient met the criteria for definite NMDARE and possible neurosarcoidosis. Given the mixed radiographic and serologic markers in this child, cytokine levels were used to direct the choice of empiric treatment, resulting in excellent clinical response. This case suggests that targeted immunotherapy informed by cytokine testing may be helpful in cases of high‐acuity pediatric neuroinflammatory disease with limited diagnostic clarity.

Abstract Background and purpose The immune response changes during aging and the progression of Alzheimer’s disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults. Methods Study participants from a University of Kentucky Alzheimer’s Disease Research Center (UK-ADRC) community-based cohort of aging and dementia were used to test our hypothesis. There were 84 participants, 44 women and 40 men. Participants underwent physical examination, neurological examination, medical history, cognitive testing, and blood collection to determine plasma biomarker levels (Aβ42/Aβ40 ratio, total tau, Neurofilament Light chain (Nf-L), Glial Fibrillary Acidic Protein (GFAP)) and to isolate peripheral blood mononuclear cells (PBMCs). Flow cytometry was used to analyze PBMCs from study participants for effector and memory T cell populations, including CD4+ and CD8+ central memory T cells (TCM), Naïve T cells, effector memory T cells (TEM), and effector memory CD45RA+ T cells (TEMRA) immune cell markers. Results CD8+ TEMRAs were positively correlated with Nf-L and GFAP. We found no significant difference in CD8+ TEMRAs based on cognitive scores and no associations between CD8+ TEMRAs and AD-related biomarkers. CD4+ TEMRAs were associated with cognitive impairment on the MMSE. Gender was not associated with TEMRAs, but it did show an association with other T cell populations. Conclusion These findings suggest that the accumulation of CD8+ TEMRAs may be a response to neuronal injury (Nf-L) and neuroinflammation (GFAP) during aging or the progression of AD and ADRD. As our findings in a community-based cohort were not clinically-defined AD participants but included all ADRDs, this suggests that TEMRAs may be associated with changes in systemic immune T cell subsets associated with the onset of pathology.

Background: Neurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity. Case Report: A 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in β2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found. Conclusions: This case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits. [ABSTRACT FROM AUTHOR]

The meninges, choroid plexus (CP) and blood-brain barrier (BBB) are recognized as important gateways for peripheral immune cell trafficking into the central nervous system (CNS). Accumulation of peripheral immune cells in brain parenchyma can be observed during aging and Alzheimer's disease (AD). However, the mechanisms by which peripheral immune cells enter the CNS through these three pathways and how they interact with resident cells within the CNS to cause brain injury are not fully understood. In this paper, we review recent research on T cells recruitment in the brain during aging and AD. This review focuses on the possible pathways through which T cells infiltrate the brain, the evidence that T cells are recruited to the brain, and how infiltrating T cells interact with the resident cells in the CNS during aging and AD. Unraveling these issues will contribute to a better understanding of the mechanisms of aging and AD from the perspective of immunity, and hopefully develop new therapeutic strategies for brain aging and AD. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To create and implement a brief, self-directed course on immunotherapy (IT) best practices for trainees on a neuroimmunology elective rotation. METHODS: A working group of neurology faculty developed a curriculum covering the mechanism of action, indications, and necessary monitoring for different IT used in neurology practice. The content was presented as a web-based course and hosted on local servers. Neurology residents and fellows participating in a neuroimmunology elective were given access to the curriculum over a 2-week period. A multiple-choice assessment and questionnaire assessing learner confidence with IT was administered prior to starting the course, and again upon course completion. Twelve months after implementation, the pretest and posttest were revised following an item analysis. RESULTS: Twenty-two neurology residents and fellows completed the course since July 2022. The average score on the first version of the pretest and posttest was 78% versus 92% (P =.02), and 51% versus 70% (P =.02) on the revised version. Trainee self-reported confidence with IT also improved, although only 59.1% of trainees completed the postcourse questionnaire. Respondents provided positive feedback on the format and content of the course and expressed a desire for a reference to the material for future use. CONCLUSION: In this pilot study, our course improved resident confidence and knowledge of IT best practices. The course was well-received, and our methods can be implemented in a variety of clinical environments to supplement trainee learning. [ABSTRACT FROM AUTHOR]

• ASCs mainly contribute to the NR1-IgGs production in NMDAR encephalitis. • Pre-germinal centres defect in B cell tolerance checkpoint in some patients. • This study reveals the pathogenesis and helps develop tailored treatments. The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis. [ABSTRACT FROM AUTHOR]

Progressive ataxia and palatal tremor (PAPT) and anti-IgLON5 disease share possible clinical presentations. Furthermore, both have been associated to a tauopathy mainly affecting the brainstem. Nonetheless, anti-IgLON5 antibodies have never been tested in PAPT. We report on two PAPT cases without evidence of anti-IgLON5 antibodies in both CSF and serum. Despite common clinical and pathological characteristics, PAPT and IgLON5 disease are two distinct entities. [ABSTRACT FROM AUTHOR]

S100 proteins comprise a family of structurally related proteins that are calcium‐sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti‐microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal‐epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies. [ABSTRACT FROM AUTHOR]

Therapeutics for traumatic brains injuries constitute a global unmet medical need. Despite the advances in neurocritical care, which have dramatically improved the survival rate for the ~ 70 million patients annually, few treatments have been developed to counter the long-term neuroinflammatory processes and accompanying cognitive impairments, frequent among patients. This review looks at gene delivery as a potential therapeutic development avenue for traumatic brain injury. We discuss the capacity of gene delivery to function in traumatic brain injury, by producing beneficial biologics within the brain. Gene delivery modalities, promising vectors and key delivery routes are discussed, along with the pathways that biological cargos could target to improve long-term outcomes for patients. Coupling blood-brain barrier crossing with sustained local production, gene delivery has the potential to convert proteins with useful biological properties, but poor pharmacodynamics, into effective therapeutics. Finally, we review the limitations and health economics of traumatic brain injury, and whether future gene delivery approaches will be viable for patients and health care systems. [ABSTRACT FROM AUTHOR]

This editorial published in the journal Frontiers in Immunology discusses the importance of understanding the interactions between brain-resident and peripheral immune cells in both health and disease. It highlights several research articles included in a special volume on this topic, covering diverse central nervous system pathologies. The document explores the role of immune cells in various neurological disorders, such as Parkinson's disease and multiple sclerosis, as well as their potential as therapeutic targets. It also discusses the interplay between immune cells and the enteric nervous system in maintaining gastrointestinal homeostasis. The authors hope that this research will encourage further investigation into immunity and the brain for potential clinical interventions in neurological diseases. [Extracted from the article]

Background and objective: Autoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups. Methods: Fifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence–Second Edition. The results were standardised with normative data. Results: The mean age of our cohort was 52.5 years old, with the average time from hospital admission to recruitment being 38.41 months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004). Discussion: While, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial. [ABSTRACT FROM AUTHOR]

In 2023, there was a significant increase in the number of articles published on microglia, the primary immune cells of the brain. These articles explored the role of microglia in brain development, health, and disease. One study identified the role of the Rho GTPase Rac1 in microglia biology and brain plasticity, while another study focused on the cell-autonomous effects of APOE4 expression in microglia in Alzheimer's disease. Additionally, a new protocol called FEAST was introduced to study microglia phagocytosis. These advancements have the potential to greatly impact biomedical research and our understanding of microglia biology. [Extracted from the article]

Since its recent discovery, the meningeal lymphatic system has reshaped our understanding of central nervous system (CNS) fluid exchange, waste clearance, immune cell trafficking, and immune privilege. Meningeal lymphatics have also been demonstrated to functionally modify the outcome of neurological disorders and their responses to treatment, including brain tumors, inflammatory diseases such as multiple sclerosis, CNS injuries, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review, we discuss recent evidence of the contribution of meningeal lymphatics to neurological diseases, as well as the available experimental methods for manipulating meningeal lymphatics in these conditions. Finally, we also provide a discussion of the pressing questions and challenges in utilizing meningeal lymphatics as a prime target for CNS therapeutic intervention and possibly drug delivery for brain disorders. [ABSTRACT FROM AUTHOR]

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Purpose of Review: Cardiovascular disease (CVD) is a leading cause of death and chronic disability worldwide. Yet, despite extensive intervention strategies the number of persons affected by CVD continues to rise. Thus, there is great interest in unveiling novel mechanisms that may lead to new treatments. Considering this dilemma, recent focus has turned to the neuroimmune mechanisms involved in CVD pathology leading to a deeper understanding of the brain's involvement in disease pathology. This review provides an overview of new and salient findings regarding the neuroimmune mechanisms that contribute to CVD. Recent Findings: The brain contains neuroimmune niches comprised of glia in the parenchyma and immune cells at the brain's borders, and there is strong evidence that these neuroimmune niches are important in both health and disease. Mechanistic studies suggest that the activation of glia and immune cells in these niches modulates CVD progression in hypertension and heart failure and contributes to the inevitable end-organ damage to the brain. Summary: This review provides evidence supporting the role of neuroimmune niches in CVD progression. However, additional research is needed to understand the effects of prolonged neuroimmune activation on brain function. [ABSTRACT FROM AUTHOR]

Background and purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults. Methods: Study participants from a University of Kentucky Alzheimer's Disease Research Center (UK-ADRC) community-based cohort of aging and dementia were used to test our hypothesis. There were 84 participants, 44 women and 40 men. Participants underwent physical examination, neurological examination, medical history, cognitive testing, and blood collection to determine plasma biomarker levels (Aβ42/Aβ40 ratio, total tau, Neurofilament Light chain (Nf-L), Glial Fibrillary Acidic Protein (GFAP)) and to isolate peripheral blood mononuclear cells (PBMCs). Flow cytometry was used to analyze PBMCs from study participants for effector and memory T cell populations, including CD4+ and CD8+ central memory T cells (TCM), Naïve T cells, effector memory T cells (TEM), and effector memory CD45RA+ T cells (TEMRA) immune cell markers. Results: CD8+ TEMRAs were positively correlated with Nf-L and GFAP. We found no significant difference in CD8+ TEMRAs based on cognitive scores and no associations between CD8+ TEMRAs and AD-related biomarkers. CD4+ TEMRAs were associated with cognitive impairment on the MMSE. Gender was not associated with TEMRAs, but it did show an association with other T cell populations. Conclusion: These findings suggest that the accumulation of CD8+ TEMRAs may be a response to neuronal injury (Nf-L) and neuroinflammation (GFAP) during aging or the progression of AD and ADRD. As our findings in a community-based cohort were not clinically-defined AD participants but included all ADRDs, this suggests that TEMRAs may be associated with changes in systemic immune T cell subsets associated with the onset of pathology. [ABSTRACT FROM AUTHOR]

Gut physiology is the epicenter of a web of internal communication systems (i.e., neural, immune, hormonal) mediated by cell-cell contacts, soluble factors, and external influences, such as the microbiome, diet, and the physical environment. Together these provide the signals that shape enteric homeostasis and, when they go awry, lead to disease. Faced with the seemingly paradoxical tasks of nutrient uptake (digestion) and retarding pathogen invasion (host defense), the gut integrates interactions between a variety of cells and signaling molecules to keep the host nourished and protected from pathogens. When the system fails, the outcome can be acute or chronic disease, often labeled as "idiopathic" in nature (e.g., irritable bowel syndrome, inflammatory bowel disease). Here we underscore the importance of a holistic approach to gut physiology, placing an emphasis on intercellular connectedness, using enteric neuroimmunophysiology as the paradigm. The goal of this opinion piece is to acknowledge the pace of change brought to our field via single-cell and -omic methodologies and other techniques such as cell lineage tracing, transgenic animal models, methods for culturing patient tissue, and advanced imaging. We identify gaps in the field and hope to inspire and challenge colleagues to take up the mantle and advance awareness of the subtleties, intricacies, and nuances of intestinal physiology in health and disease by defining communication pathways between gut resident cells, those recruited from the circulation, and "external" influences such as the central nervous system and the gut microbiota. [ABSTRACT FROM AUTHOR]

Currently nearly one-quarter of admissions to pediatric intensive care units (PICUs) worldwide are for neurocritical care diagnoses that are associated with significant morbidity and mortality. Pediatric neurocritical care is a rapidly evolving field with unique challenges due to not only age-related responses to primary neurologic insults and their treatments but also the rarity of pediatric neurocritical care conditions at any given institution. The structure of pediatric neurocritical care services therefore is most commonly a collaborative model where critical care medicine physicians coordinate care and are supported by a multidisciplinary team of pediatric subspecialists, including neurologists. While pediatric neurocritical care lies at the intersection between critical care and the neurosciences, this narrative review focuses on the most common clinical scenarios encountered by pediatric neurologists as consultants in the PICU and synthesizes the recent evidence, best practices, and ongoing research in these cases. We provide an in-depth review of (1) the evaluation and management of abnormal movements (seizures/status epilepticus and status dystonicus); (2) acute weakness and paralysis (focusing on pediatric stroke and select pediatric neuroimmune conditions); (3) neuromonitoring modalities using a pathophysiology-driven approach; (4) neuroprotective strategies for which there is evidence (e.g., pediatric severe traumatic brain injury, post–cardiac arrest care, and ischemic stroke and hemorrhagic stroke); and (5) best practices for neuroprognostication in pediatric traumatic brain injury, cardiac arrest, and disorders of consciousness, with highlights of the 2023 updates on Brain Death/Death by Neurological Criteria. Our review of the current state of pediatric neurocritical care from the viewpoint of what a pediatric neurologist in the PICU needs to know is intended to improve knowledge for providers at the bedside with the goal of better patient care and outcomes. [ABSTRACT FROM AUTHOR]

Maternal autoimmune diseases (AID) are risk factors for Attention Deficit Hyperactivity Disorder (ADHD). Animal studies suggest that maternal immune activation (MIA) is a disease primer for ADHD, with second environmental factor precipitating the onset of the disease. Prematurity is also a major risk factor for ADHD. In this study, we sought to explore the interaction between parental AID and prematurity on ADHD risk in a community sample. Children of AID parents born prematurely appeared at increased odds of ADHD but these two risk factors do not appear to be additive (OR 1.39 [95 CI 0.75; 2.46]). Longitudinal studies with larger numbers of participants are needed. [ABSTRACT FROM AUTHOR]

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE‐mediated diseases and glioma. Allergic disease stems from a Th2‐biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour‐immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro‐Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult‐type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune–glioma interactions to ultimately improve patient prognosis and survival. [ABSTRACT FROM AUTHOR]

Objective. We report here a study seeking to identify the possible influences of measures of cellular immunity and neurobiological variables (frequency of seizures of different types and seizure severity) on comorbid psychopathological symptoms depending on interhemispheric asymmetry profile in patients with focal forms of epilepsy. Materials and methods. The study included 92 patients with epilepsy (38 men, 54 women, mean age 38.7 ± 8.45 years). Focal temporal lobe epilepsy was diagnosed in 36 patients, focal frontal epilepsy in 16, and temporofrontal epilepsy in 40. Severity was assessed for each type of seizure using the National Seizure Severity Scale (NHS3). Patients' mental status was assessed using the SCL-90 self-report scale. The Annett scale was used to assess the interhemispheric asymmetry profile. The numbers of cells of different lymphocyte clusters, including T-lymphocytes (CD3+), T-helpers (CD3+CD4+), T-cytotoxic (CD3+CD8+), T-NK (natural killers, CD3+CD16+CD56+), and B-lymphocytes (CD3–CD19+), were determined, along with the immunoregulatory index (CD4/CD8 ratio). Possible relationships between neurobiological and immune variables on the one hand and SCL-90 constructs on the other were identified by Spearman rank correlation analysis in left- and right-handed groups separately. Results. Differences were found between groups of epilepsy patients with right- and left-sided interhemispheric asymmetry profiles in terms of relationships between the frequency of seizures, their severity, and accompanying psychopathological variables on the one hand and between indicators of immunity and psychopathological constructs on the other. Neurobiological and immune variables in left-handers were found to determine the psychopathological structure of comorbid mental disorders. Conclusions. Concomitant psychopathological syndromes in patients with epilepsy based on clinical data and data on immunity can be predicted, but only in patients with a left-sided interhemispheric asymmetry profile. [ABSTRACT FROM AUTHOR]

Leucine-rich glioma-inactivated 1-antibody-encephalitis is a treatable and potentially reversible cause of cognitive and psychiatric presentations, and may mimic cognitive decline, rapidly progressive dementia and complex psychosis in older patients. This aetiology is of immediate relevance given the alternative treatment pathway required, compared with other conditions presenting with cognitive deficits. [ABSTRACT FROM AUTHOR]