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Background and aim: Invasion of the central nervous system by Treponema pallidum can occur at any stage of syphilis. In the event that T. pallidum is not cleared promptly, certain individuals may experience progression to neurosyphilis, which manifests as cognitive and behavioral abnormalities, limb paralysis, and potentially fatal outcomes. Early identification or prevention of neurosyphilis is therefore crucial. The aim of this paper is to conduct a critical and narrative review of the latest information focusing exclusively to the pathogenesis and clinical management of neurosyphilis. Methodology: To compile this review, we have conducted electronic literature searches from the PubMed database relating to neurosyphilis. Priority was given to studies published from the past 10 years (from 2013 to 2023) and other studies if they were of significant importance (from 1985 to 2012), including whole genome sequencing results, cell structure of T. pallidum, history of genotyping, and other related topics. These studies are classic or reflect a developmental process. Results: Neurosyphilis has garnered global attention, yet susceptibility to and the pathogenesis of this condition remain under investigation. Cerebrospinal fluid examination plays an important role in the diagnosis of neurosyphilis, but lacks the gold standard. Intravenous aqueous crystalline penicillin G continues to be the recommended therapeutic approach for neurosyphilis. Considering its sustained prominence, it is imperative to develop novel public health tactics in order to manage the resurgence of neurosyphilis. Conclusion: This review gives an updated narrative description of neurosyphilis with special emphasis on its pathogenesis, susceptibility, diagnosis, treatment, and prevention. [ABSTRACT FROM AUTHOR]

Hypoxia is characterized by low oxygen levels in the body or environment, resulting in various physiological and pathological changes. The brain, which has the highest oxygen consumption of any organ, is particularly susceptible to hypoxic injury. Exposure to low-pressure hypoxic environments can cause irreversible brain damage. Hypoxia can occur in healthy individuals at high altitudes or in pathological conditions such as trauma, stroke, inflammation, and autoimmune and neurodegenerative diseases, leading to severe brain damage and impairments in cognitive, learning, and memory functions. Exosomes may play a role in the mechanisms of hypoxic injury and adaptation and are a current focus of research. Investigating changes in exosomes in the central nervous system under hypoxic conditions may aid in preventing secondary damage caused by hypoxia. This paper provides a brief overview of central nervous system injury resulting from hypoxia, and aimed to conduct a comprehensive literature review to assess the pathophysio-logical impact of exosomes on the central nervous system under hypoxic conditions. [ABSTRACT FROM AUTHOR]

Advances in our understanding of postural control have highlighted the need to examine the influence of higher brain centers in the modulation of this complex function. There is strong evidence of a link between emotional state, autonomic nervous system (ANS) activity and somatic nervous system (somatic NS) activity in postural control. For example, relationships have been demonstrated between postural threat, anxiety, fear of falling, balance confidence, and physiological arousal. Behaviorally, increased arousal has been associated with changes in velocity and amplitude of postural sway during quiet standing. The potential links between ANS and somatic NS, observed in control of posture, are associated with shared neuroanatomical connections within the central nervous system (CNS). The influence of emotional state on postural control likely reflects the important influence the limbic system has on these ANS/somatic NS control networks. This narrative review will highlight several examples of behaviors which routinely require coordination between the ANS and somatic NS, highlighting the importance of the neurofunctional link between these systems. Furthermore, we will extend beyond the more historical focus on threat models and examine how disordered/altered emotional state and ANS processing may influence postural control and assessment. Finally, this paper will discuss studies that have been important in uncovering the modulatory effect of emotional state on postural control including links that may inform our understanding of disordered control, such as that observed in individuals living with Parkinson's disease and discuss methodological tools that have the potential to advance understanding of this complex relationship. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD), characterized by the loss of dopaminergic neurons, is a progressive neurodegenerative disorder. Recent research has revealed a significant connection between gut microbiota and PD. To gain insight into research interests, disciplinary contexts, and potential future directions, a comprehensive bibliometric analysis was conducted on the brain-gut axis and PD literature published between 2014 and 2023. Methods: Relevant literature records were gathered from the Web of Science Core Collection on August 11, 2023. The data were then analyzed by Biblioshiny R packages and VOSviewer (version 1.6.19). Results: The dataset revealed an upward trend in annual scientific publications on the brain-gut axis and PD, with an annual growth rate of 50.24%. China, the United States, and Italy were the top three most productive countries/regions. The journal "International Journal Of Molecular Sciences" published the most articles, while "Movement Disorders" received the highest number of citations. Professor Keshavarzian A emerged as the most prolific author, while Professor Scheperjans F held the highest h-index. Keyword analysis highlighted "alphasynuclein" as the most frequent term, with "mouse model," "inflammation," and "risk" as emerging research topics. Additionally, "central nervous system" and "intestinal bacterial overgrowth" attracted increasing attention. Conclusion: This study examined current trends and hotspots in the bibliometric landscape of the brain-gut axis and PD research. Future research directions should explore the functional and metabolic activities of gut microbiota. Additionally, transitioning from observational to interventional study designs offers the potential for personalized interventions and disease prediction. These findings can guide researchers in navigating the latest developments and shaping the future directions of this field. [ABSTRACT FROM AUTHOR]

Background: Relapsing–remitting multiple sclerosis (RRMS) is a subtype of degenerative inflammatory demyelinating disease of multifactorial origin that affects the central nervous system and leads to multifocal neurological impairment. Objectives: To develop a clinical pathway (CP) for the management of Peruvian patients with RRMS. Methods: First, we performed a literature review using Medline, Embase, Cochrane, ProQuest, and Science direct. Then, we structured the information as an ordered and logical series of five topics in a defined timeline: (1) How should MS be diagnosed? (2) How should a relapse be treated? (3) How should a DMT be initiated? (4) How should each DMT be used? and (5) How should the patients be followed? Results: The personnel involved in the care of patients with RRMS can use a series of flowcharts and diagrams that summarize the topics in paper or electronic format. Conclusions: We propose the first CP for RRMS in Peru that shows the essential steps for diagnosing, treating, and monitoring RRMS patients based on an evidence-based medicine method and local expert opinions. This CP will allow directing relevant clinical actions to strengthen the multidisciplinary management of RRMS in Peru. [ABSTRACT FROM AUTHOR]

Adults with childhood-onset disabilities, particularly those with central nervous system impairment, commonly experience pain. Because many such individuals have difficulties in communication, caregivers and medical professionals must identify and interpret non-verbal behaviors as indicators of pain. This process is challenging and can lead to poor outcomes through delayed or incorrect diagnosis and treatment. Most research in the evaluation of pain in individuals with neurologic impairment has focused on the pediatric population, and evidence-based guidelines do not exist for adults. The purpose of this paper is to review current recommendations for pain assessment in adults with communication impairment. This approach includes guidance for history-taking, pharmacologic review, physical examination, and the judicious use of laboratory and imaging tests. Finally, we discuss adult-specific diagnoses to consider when evaluating pain in adults with childhood-onset disabilities and communication difficulties. [ABSTRACT FROM AUTHOR]

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is a debilitating but extremely common form of brain injury that affects a substantial number of people each year. mTBI is especially common in children and adolescents. Our understanding of mTBI pathophysiology is limited, and there is currently no accepted marker for disease severity. A potential marker for disease severity may be cerebrovascular dysfunction. Recent findings have implicated cerebrovascular alteration as an important component of mTBI and suggest it contributes to the development of persistent, long-term symptoms. In this paper, we conducted two studies to investigate whether mTBI affects venous drainage patterns in the central nervous system using alterations in the size of venous sinuses as a marker of changes in drainage. Using a closed head vertical weight-drop model and a lateral impact injury model of mTBI, we imaged and quantified the size of three major draining vessels in the adolescent rat brain using 9.4T MRI. Areas and volumes were quantified in the superior sagittal sinus and left and right transverse sinuses using images acquired from T2w MRI in one study and post-gadolinium T1w MRI in another. Our results indicated that the three venous sinuses were significantly larger in mTBI rats as compared to sham rats 1-day post injury but recovered to normal size 2 weeks after. Acutely enlarged sinuses post-mTBI may indicate abnormal venous drainage, and this could be suggestive of a cerebrovascular response to trauma. [ABSTRACT FROM AUTHOR]

During neurorehabilitation, clinical measurements are widely adopted to evaluate behavioral improvements after treatment. However, it is not able to identify or monitor the change of central nervous system (CNS) of each individual patient. Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to investigate brain functions in healthy controls (HCs) and patients with neurological diseases, which could find functional changes following neurorehabilitation. In this paper, a distance-based rehabilitation evaluation method based on rs-fMRI was proposed. Specifically, we posit that in the functional connectivity (FC) space, patients and HCs distribute separately. Linear support vector machines (SVM) were trained on the brain networks to firstly separate patients from HCs. Second, the FC similarity between patients and HCs was measured by the L2 distance of each subject's feature vector to the separating hyperplane. Finally, statistical analysis of the distance revealed rehabilitation program induced improvements in patients and predicted rehabilitation outcomes. An rs-fMRI dataset with 22 HCs and 18 spinal cord injury (SCI) patients was utilized to validate our method. We built whole-brain networks using five atlases to test the robustness of the method and search for features under different node resolutions. The classifier successfully separated patients and HCs. Significant improvements in FC after treatment were found for the patients for all five atlases using the proposed method, which was consistent with clinical measurements. Furthermore, distance obtained from individual patient's longitudinal data showed a similar trend with each one's clinical scores, implying the possibility of individual rehabilitation outcome tracking and prediction. Our method not only provides a novel perspective of applying rs-fMRI to neurorehabilitation monitoring but also proves the potential in individualized rehabilitation prediction. [ABSTRACT FROM AUTHOR]

Background: Neuroplasticity as a mechanism to overcome central nervous system injury resulting from different neurological diseases has gained increasing attention in recent years. However, deficiency of these repair mechanisms leads to the accumulation of neuronal damage and therefore long-term disability. To date, the mechanisms by which remyelination occurs and why the extent of remyelination differs interindividually between multiple sclerosis patients regardless of the disease course are unclear. A member of the neurotrophins family, the brain-derived neurotrophic factor (BDNF) has received particular attention in this context as it is thought to play a central role in remyelination and thus neuroplasticity, neuroprotection, and memory. Objective: To analyse the current literature regarding BDNF in different areas of multiple sclerosis and to provide an overview of the current state of knowledge in this field. Conclusion: To date, studies assessing the role of BDNF in patients with multiple sclerosis remain inconclusive. However, there is emerging evidence for a beneficial effect of BDNF in multiple sclerosis, as studies reporting positive effects on clinical as well as MRI characteristics outweighed studies assuming detrimental effects of BDNF. Furthermore, studies regarding the Val66Met polymorphism have not conclusively determined whether this is a protective or harmful factor in multiple sclerosis, but again most studies hypothesized a protective effect through modulation of BDNF secretion and anti-inflammatory effects with different effects in healthy controls and patients with multiple sclerosis, possibly due to the pro-inflammatory milieu in patients with multiple sclerosis. Further studies with larger cohorts and longitudinal follow-ups are needed to improve our understanding of the effects of BDNF in the central nervous system, especially in the context of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background: Infratentorial siderosis (iSS) is a progressive degenerative disorder targeting primarily the cerebellum and cranial nerve eighth; therefore, progressive ataxia and its neuro-otological findings are common. Toxicity from hemosiderin involves selectively vulnerable neurons and glia in these posterior fossa structures. Other neurologic findings may be present, though our focus relates to the cochlea-vestibular cerebellar involvement. Radiographic evidence of siderosis may be the result of recurrent, albeit covert bleeding in the subarachnoid space, or the consequence of an overt post-traumatic or aneurysmal subarachnoid hemorrhage (SAH). The radiographic iSS appearance is identical regardless of the SAH cause. A recent study provides compelling evidence to search and correct possible hemorrhage sources in the spinal canal. The removal of residual existing hemosiderin deposits that may potentially cause clinical symptoms remains as a major therapeutic challenge. methods: We reviewed large data sources and identified salient papers that describe the pathogenesis, clinical and neurotologic manifestations, and the radiographic features of iSS. Results: The epidemiology of iSS is unknown. In a recent series, clinically evident iSS was associated with recurrent SAH; by contrast, in a follow-up period ranging from weeks up to 11 years after a monophasic episode of SAH, radiographic siderosis was clinically silent. However, the post-aneurysmal or post-trauma SAH sample size in this single study was small and their observation period relatively short; moreover, the burden of intraneuronal hemosiderin is likely greater with recurrent SAH. There are a few reports of late iSS, several decades after traumatic SAH. A recent report found subjective hearing loss in aneurysmal SAH individuals with radiographic siderosis. Only in recent years, it is safe to perform magnetic resonance imaging (MRI) in post-aneurysmal SAH, because of the introduction of titanium, MRI-compatible aneurysm clips. conclusion: iSS can be associated with significant neurotologic and cerebellar morbidity; the recurrent SAH variant is frequently clinically symptomatic, has a shorter latency and greater neurotologic disability. In these cases, a thorough search and management of a covert source of bleeding may stop clinical progression. The frequency and clinical course of radiographic iSS after traumatic and post-aneurysmal SAH is largely unknown. Detection of radiographic iSS after trauma or aneurysm bleeding suggests that the slower clinical course could benefit from an effective intervention if it became available. The use of cochlear implants is a valid alternative with advanced hearing impairment. [ABSTRACT FROM AUTHOR]

Primary familial brain calcification (PFBC), also known as Fahr's disease, is a central nervous system calcium deposition disorder with symmetrical basal ganglia calcification. Most PFBC cases are caused by SLC20A2 gene variant. We report a Chinese female patient with PFBC and dopamine-responsive parkinsonism who had motor fluctuations and dyskinesia and recovered effectively after symptomatic medication adjustment. A novel heterozygous missense variant was found by whole-exome sequencing and proven harmful by family validation and genetic analysis. This example expands the phenotype of SLC20A2-associated PFBC patients and shows the clinical efficacy of dopaminergic replacement treatment. [ABSTRACT FROM AUTHOR]

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Introduction: Functional disorders are prevalent in all medical fields and pose a tremendous public health problem, with pain being one of the most common functional symptoms. Understanding the underlying, potentially unifying mechanism in functional (pain) disorders is instrumental in facilitating timely diagnosis, stigma reduction, and adequate treatment options. Neuroscientific models of perception suggest that functional symptoms arise due to dysregulated sensorimotor processing in the central nervous system, with brain-based predictions dominating the eventual percept. Experimental evidence for this transdiagnostic mechanism has been established in various functional symptoms. The goal of the current study was to investigate whether erroneous sensorimotor processing is an underlying transdiagnostic mechanism in chronic (functional) pain. Method: A total of 13 patients with chronic (functional) pain [three patients with chronic (functional) pain disorder, F45.40, ICD-10; 10 patients with chronic pain disorder with somatic and psychological factors, F45.41, ICD-10]; and 15 healthy controls performed large combined eye-head gaze shifts toward visual targets, naturally and with increased headmoment of inertia.We simultaneouslymeasured participants' eye and headmovements to assess head oscillations at the end of the gaze shift, which are an established indicator of (transdiagnostic) sensorimotor processing deficits of head control. Results: Using a Bayesian analysis protocol, we found that patients with chronic (functional) pain and control participants stabilized their heads equally well (Bayes Factor 01 = 3.7, Bayes Factor exclusion = 5.23; corresponding to substantial evidence) during all sessions of the experiment. Conclusion: Our results suggest that patients with chronic (functional) pain do not show measurable symptom-unspecific sensorimotor processing deficits. We discuss outcome parameter choice, organ system specificity, and selection of patient diagnoses as possible reasons for this result and recommend future avenues for research. [ABSTRACT FROM AUTHOR]

Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most prevalent carcinoma linked to SPSSDs, followed by lung cancer and lymphoma. Furthermore, classic SPS was the most common SPSSD subtype, followed by stiff limb syndrome and progressive encephalomyelitis with rigidity and myoclonus. GAD65 was the most common autoantigen in patients with cancer and SPSSDs, followed by amphiphysin and GlyR. Patients with cancer subtypes might have multiple SPSSD subtypes, and conversely, patients with SPSSD subtypes might have multiple carcinoma subtypes. The first aim of this review was to highlight the complex nature of the relationships among cancers, autoantigens, and SPSSDs as new information in this field continues to be generated globally. The adoption of an open-minded approach to updating information on new cancer subtypes, autoantigens, and SPSSDs is recommended to renew our database. The second aim of this review was to discuss SPS animal models, which will help us to understand the mechanisms underlying the pathogenesis of SPS. In future, elucidating the relationship among cancers, autoantigens, and SPSSDs is critical for the early prediction of cancer and discovery of new therapeutic modalities. [ABSTRACT FROM AUTHOR]

Diquat (DQ), chemically known as 1,1 '-ethylene-2,2' -bipyridine, is a nonselective herbicide for leaf removal and drying. It has toxic effects on central nervous system cells, and toxic neurological lesions include axonal degeneration and pontine myelolysis. At the same time, DQ can also affect the activity of dopaminergic nerve cells through oxidative stress, causing degeneration and reducing dopamine uptake. With the increasing application of DQ in agricultural production, the clinical reports of neurotoxicity caused by acute DQ poisoning are also increasing. At present, DQ rapid-phase-related toxic encephalopathy mainly involves the pons, midbrain, basal ganglia, thalamus and other brain regions. However, this case is unusual in that the lesion mainly involved the splenium of the corpus callosum. It is also the first time to be reported. [ABSTRACT FROM AUTHOR]

With a rapidly aging global population and improvement of outcomes with newer multiple sclerosis (MS)-specific disease-modifying therapies (DMTs), the epidemiology of MS has shifted to an older than previously described population, with a peak prevalence of the disease seen in the 55-65 years age group. Changes in the pathophysiology of MS appear to be age-dependent. Several studies have identified a consistent phase of disability worsening around the fifth decade of life. The latter appears to be independent of prior disease duration and inflammatory activity and concomitant to pathological changes from acute focal active demyelination to chronic smoldering plaques, slow-expanding lesions, and compartmentalized inflammation within the central nervous system (CNS). On the other hand, decreased CNS tissue reserve and poorer remyelinating capacity with aging lead to loss of relapse recovery potential. Aging with MS may imply longer exposure to DMTs, although treatment efficacy in patients >55 years has not been evaluated in pivotal randomized controlled trials and appears to decrease with age. Older individuals are more prone to adverse effects of DMTs, an important aspect of treatment individualization. Aging with MS also implies a higher global burden of comorbid illnesses that contribute to overall impairments and represent a crucial confounder in interpreting clinical worsening. Discontinuation of DMTs after age 55, when no evidence of clinical or radiological activity is detected, is currently under the spotlight. In this review, we will discuss the impact of aging on MS pathobiology, the effect of comorbidities and other confounders on clinical worsening, and focus on current therapeutic considerations in this age group. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a complex neurological disorder that involves demyelination, lesions and atrophy in both white and gray matter. Such changes in the central nervous system are diagnostic in MS and has a strong relationship with both physical and cognitive symptoms. As a result, magnetic resonance imaging (MRI) scans as a metric of brain atrophy have emerged as an important outcome measure in MS studies. Recently, research has begun to focus on the contribution of aging to the structural changes in the brain associated with MS; prompting questions about whether there is an amplifying effect of aging superimposed on MS-related brain atrophy. To examine current evidence of how the brain ages in individuals with MS, a systematic review of the literature was performed. Specific questions were focused on how aging affects gray and white matter structure, whether patterns of brain atrophy differ in younger and older cohorts and if there are structural differences in the brain as a function of sex in aging people with MS. This review considered studies that used MRI to examine the effects of aging in adults with MS. Twenty-one studies met eligibility criteria. Findings across these studies revealed that gray matter atrophy was more pronounced in older adults with MS, particularly in subcortical regions such as the thalamus; that the rates of atrophy were similar but varied by region for younger and older cohorts; and that males may experience more brain atrophy than females. Further studies that use multimodal MRI acquisition methods are needed to capture changes in both males and females over time, particularly in middle to older adulthood. [ABSTRACT FROM AUTHOR]

Background: Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated. Objectives: We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment. Methods: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society--Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively. Results: Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = -0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004). Conclusions: Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of disability with limited effective interventions that improve recovery in the subacute phase. This protocol aims to evaluate the safety and efficacy of a non-invasive, extremely low-frequency, low-intensity, frequency-tuned electromagnetic field treatment [Electromagnetic Network Targeting Field (ENTF) therapy] in reducing disability and promoting recovery in people with subacute ischemic stroke (IS) with moderate-severe disability and upper extremity (UE) motor impairment. Following a sample-size adaptive design with a single interim analysis, at least 150 and up to 344 participants will be recruited to detect a 0.5-point (with a minimum of 0.33 points) difference on the modified Rankin Scale (mRS) between groups with 80% power at a 5% significance level. This ElectroMAGnetic field Ischemic stroke-Novel subacutE treatment (EMAGINE) trial is a multicenter, double-blind, randomized, sham-controlled, parallel two-arm study to be conducted at approximately 20 United States sites, and enroll participants with subacute IS and moderate-severe disability with UE motor impairment. Participants will be assigned to active (ENTF) or sham treatment, initiated 4-21 days after stroke onset. The intervention, applied to the central nervous system, is designed for suitability in multiple clinical settings and at home. Primary endpoint is change in mRS score from baseline to 90 days post-stroke. Secondary endpoints: change from baseline to 90 days post-stroke on the Fugl-Meyer Assessment - UE (lead secondary endpoint), Box and Block Test, 10-Meter Walk, and others, to be analyzed in a hierarchical manner. EMAGINE will evaluate whether ENTF therapy is safe and effective at reducing disability following subacute IS. [ABSTRACT FROM AUTHOR]

Microglia are the principal resident immune cells in the central nervous system (CNS) and play important roles in the development of CNS disorders. In recent years, there have been significant developments in our understanding of microglia, and we nowhave greater insight into the temporal and spatial patterns of microglia activation in a variety of CNS disorders, as well as the interactions between microglia and neurons. A variety of signaling pathways have been implicated. However, to date, all published clinical trials have failed to demonstrate efficacy over placebo. This review summarizes the results of recent important studies and attempts to provide a mechanistic view of microglia activation, inflammation, tissue repair, and CNS disorders. [ABSTRACT FROM AUTHOR]

Objectives: It is still a challenge to differentiate space-occupying brain lesions such as tumefactive demyelinating lesions (TDLs), tumefactive primary angiitis of the central nervous system (TPACNS), primary central nervous system lymphoma (PCNSL), and brain gliomas. Convolutional neural networks (CNNs) have been used to analyze complex medical data and have proven transformative for image-based applications. It can quickly acquire diseases' radiographic features and correct doctors' diagnostic bias to improve diagnostic efficiency and accuracy. The study aimed to assess the value of CNN-based deep learning model in the differential diagnosis of space-occupying brain diseases on MRI. Methods: We retrospectively analyzed clinical and MRI data from 480 patients with TDLs (n = 116), TPACNS (n = 64), PCNSL (n = 150), and brain gliomas (n = 150). The patients were randomly assigned to training (n = 240), testing (n = 73), calibration (n = 96), and validation (n = 71) groups. And a CNN-implemented deep learning model guided by clinical experts was developed to identify the contrast-enhanced T1-weighted sequence lesions of these four diseases. We utilized accuracy, sensitivity, specificity, and area under the curve (AUC) to evaluate the performance of the CNN model. The model's performance was then compared to the neuroradiologists' diagnosis. Results: The CNN model had a total accuracy of 87% which was higher than senior neuroradiologists (74%), and the AUC of TDLs, PCNSL, TPACNS and gliomas were 0.92, 0.92, 0.89 and 0.88, respectively. Conclusion: The CNN model can accurately identify specific radiographic features of TDLs, TPACNS, PCNSL, and gliomas. It has the potential to be an effective auxiliary diagnostic tool in the clinic, assisting inexperienced clinicians in reducing diagnostic bias and improving diagnostic efficiency. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Sleep disorders in neuromuscular diseases: treatable conditions: the evolving scenario of sleep in neuromuscular disorders," discusses the importance of sleep in individuals with neuromuscular disorders (NMD). Sleep plays a crucial role in muscle repair and recovery, which is essential for individuals with NMD who may experience muscle weakness. The article highlights the need for further evaluation of sleep-related breathing disorders in NMD patients, such as spinal muscular atrophy (SMA) and Charcot-Marie-Tooth disease (CMT). It also mentions the impact of sleep on conditions like myotonic dystrophy and the potential benefits of new therapies in treating sleep disorders in NMDs. [Extracted from the article]

Antibody-mediated central nervous system (CNS) disorders including those associated with aquaporin-4 or myelin oligodendrocyte glycoprotein IgG and autoimmune encephalitis often affect women of childbearing age. Pathogenic antibodies of these diseases can potentially alter reproductive functions and influence fetal development. Hormonal changes occurring during pregnancy may modify the course of autoimmune diseases by influencing relapse risk, attack severity, and affect the delivery and postpartum period. Moreover, balancing treatment related safety issues with the risk of potentially disabling relapses during pregnancy and breastfeeding are major challenges. Intentional prenatal, gestational, and post-partum counseling is paramount to address these issues and mitigate these risks. Fortunately, new insights on risk factors for adverse pregnancy outcomes and possible preventive strategies are emerging. This review aims to summarize the interplay between antibody-mediated CNS disorders and pregnancy during the prenatal, gestational, and postpartum periods, highlight current treatment recommendations, and discuss future areas of research. [ABSTRACT FROM AUTHOR]

Purpose and Background: Distinguishing primary central nervous system lymphoma (PCNSL) and glioma on computed tomography (CT) is an important task since treatment options differ vastly from the two diseases. This study aims to explore various machine learning and deep learning methods based on radiomic features extracted from CT scans and end-to-end convolutional neural network (CNN) model to predict PCNSL and glioma types and compare the performance of different models. Methods: A total of 101 patients from five Chinese medical centers with pathologically confirmed PCNSL and glioma were analyzed retrospectively, including 50 PCNSL and 51 glioma. After manual segmentation of the region of interest (ROI) on CT scans, 293 radiomic features of each patient were extracted. The radiomic features were used as input, and then, we established six machine learning models and one deep learning model and three readers to identify the two types of tumors. We also established a 2D CNN model using raw CT scans as input. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models. Results: The cohort was split into a training (70, 70% patients) and validation cohort (31,30% patients) according to the stratified sampling strategy. Among all models, the MLP performed best, with an accuracy of 0.886 and 0.903, sensitivity of 0.914 and 0.867, specificity of 0.857 and 0.937, and AUC of 0.957 and 0.908 in the training and validation cohorts, respectively, which was significantly higher than the three primary physician’s diagnoses (ACCs ranged from 0.710 to 0.742, p < 0.001 for all) and comparable with the senior radiologist (ACC 0.839, p = 0.988). Among all the machine learning models, the AUC ranged from 0.605 to 0.821 in the validation cohort. The end-to-end CNN model achieved an AUC of 0.839 and an ACC of 0.840 in the validation cohort, which had no significant difference in accuracy compared to the MLP model (p = 0.472) and the senior radiologist (p = 0.470). Conclusion: The established PCNSL and glioma prediction model based on deep neural network methods from CT scans or radiomic features are feasible and provided high performance, which shows the potential to assist clinical decision-making. [ABSTRACT FROM AUTHOR]

Over the last years, a constantly increasing number of genetic diseases associated with epilepsy and movement disorders have been recognized. An emerging group of conditions in this field is represented by genetic disorders affecting G-protein-coupled receptors (GPCRs)–cAMP signaling. This group of postsynaptic disorders includes genes encoding for proteins highly expressed in the central nervous system and involved in GPCR signal transduction and cAMP production (e.g., GNAO1, GNB1, ADCY5, GNAL, PDE2A, PDE10A, and HPCA genes). While the clinical phenotype associated with ADCY5 and GNAL is characterized by movement disorder in the absence of epilepsy, GNAO1, GNB1, PDE2A, PDE10A, and HPCA have a broader clinical phenotype, encompassing movement disorder, epilepsy, and neurodevelopmental disorders. We aimed to provide a comprehensive phenotypical characterization of genetic disorders affecting the cAMP signaling pathway, presenting with both movement disorders and epilepsy. Thus, we reviewed clinical features and genetic data of 203 patients from the literature with GNAO1, GNB1, PDE2A, PDE10A, and HPCA deficiencies. Furthermore, we delineated genotype–phenotype correlation in GNAO1 and GNB1 deficiency. This group of disorders presents with a highly recognizable clinical phenotype combining distinctive motor, epileptic, and neurodevelopmental features. A severe hyperkinetic movement disorder with potential life-threatening exacerbations and high susceptibility to a wide range of triggers is the clinical signature of the whole group of disorders. The existence of a distinctive clinical phenotype prompting diagnostic suspicion and early detection has relevant implications for clinical and therapeutic management. Studies are ongoing to clarify the pathophysiology of these rare postsynaptic disorders and start to design disease-specific treatments. [ABSTRACT FROM AUTHOR]

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic. [ABSTRACT FROM AUTHOR]

The inflammatory processes observed in the central nervous system in multiple sclerosis (MS) could damage the endothelium of the cerebral vessels and lead to a dysfunctional regulation of vessel tonus and recruitment, potentially impairing cerebrovascular reactivity (CVR) and neurovascular coupling (NVC). Impaired CVR or NVC correlates with declining brain health and potentially plays a causal role in the development of neurodegenerative disease. Therefore, we examined studies on CVR or NVC in MS patients to evaluate the evidence for impaired cerebrovascular function as a contributing disease mechanism in MS. Twenty-three studies were included (12 examined CVR and 11 examined NVC). Six studies found no difference in CVR response between MS patients and healthy controls. Five studies observed reduced CVR in patients. This discrepancy can be because CVR is mainly affected after a long disease duration and therefore is not observed in all patients. All studies used CO2 as a vasodilating stimulus. The studies on NVC demonstrated diverse results; hence a conclusion that describes all the published observations is difficult to find. Future studies using quantitative techniques and larger study samples are needed to elucidate the discrepancies in the reported results. [ABSTRACT FROM AUTHOR]

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord. Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling. The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder. [ABSTRACT FROM AUTHOR]

Migraine is the most common neurological disorder in the world, affecting 12% of the population. Migraine involves the central nervous system, trigeminal nerves and meninges. Recent advances have shown that targeting calcitonin gene-related peptide (CGRP) through either antibodies or small molecule receptor antagonists is effective at reducing episodic and chronic migraine episodes, but these therapeutics are not effective in all patients. This suggests that migraine does not have a singular molecular cause but is likely due to dysregulated physiology of multiple mechanisms. An often-overlooked part of migraine is the potential involvement of the immune system. Clinical studies have shown that migraine patients may have dysregulation in their immune system, with abnormal plasma cytokine levels either during the attack or at baseline. In addition, those who are immunocompromised appear to be at a higher risk of migraine-like disorders. A recent study showed that migraine caused changes to transcription of immune genes in the blood, even following treatment with sumatriptan. The dura mater is densely packed with macrophages, mast and dendritic cells, and they have been found to associate with meningeal blood vessels and trigeminal afferent endings. Recent work in mice shows activation and morphological changes of these cells in rodents following the migraine trigger cortical spreading depression. Importantly, each of these immune cell types can respond directly to CGRP. Since immune cells make up a large portion of the dura, have functional responses to CGRP, and interact with trigeminal afferents, CGRP actions on the dural immune system are likely to play key roles in migraine. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are physiologically expressed in the central nervous system in neurons, astrocytes and microglia, and their aberrant elevation contributes to a number of diseases. Amongst the MMP members, MMP−9 has generated considerable attention because of its possible involvement in inflammatory responses, blood-brain barrier permeability, the regulation of perineuronal nets, demyelination, and synaptic long-term potentiation. Emerging evidence indicate an association between MMP−9 and the syndrome of depression. This review provides an updated and comprehensive summary of the probable roles of MMP−9 in depression with an emphasis on the mechanisms and potential of MMP−9 as a biomarker of depression. [ABSTRACT FROM AUTHOR]

Neurosurgery has traditionally been overtly focused on the study of anatomy and functions of cortical areas with microsurgical techniques aimed at preserving eloquent cortices. In the last two decades, there has been ever-increasing data emerging from advances in neuroimaging (principally diffusion tensor imaging) and clinical studies (principally from awake surgeries) that point to the important contribution of white matter tracts (WMT) that influence neurological function as part of a brain network. Major scientific consortiums worldwide, currently working on this human brain connectome, are providing evidence that is dramatically altering the manner in which we view neurosurgical procedures. The development of the telencephalic flexure, a major landmark during the human embryogenesis of the central nervous system (CNS), severely affects the cortical/subcortical anatomy in and around the sylvian fissure and thus the different interacting brain networks. Indeed, the telencephalic flexure modifies the anatomy of the human brain with the more posterior areas becoming ventral and lateral and associative fibers connecting the anterior areas with the previous posterior ones follow the flexure, thus becoming semicircular. In these areas, the projection, association, and commissural fibers intermingle with some WMT remaining curved and others longitudinal. Essentially the ultimate shape and location of these tracts are determined by the development of the telencephalic flexure. Five adult human brains were dissected (medial to lateral and lateral to medial) with a view to describing this intricate anatomy. To better understand the 3D orientation of the WMT of the region we have correlated the cadaveric data with the anatomy presented in the literature of the flexure during human neuro-embryogenesis in addition to cross-species comparisons of the flexure. The precise definition of the connectome of the telencephalic flexure is primordial during glioma surgery and for disconnective epilepsy surgery in this region. [ABSTRACT FROM AUTHOR]

Microglia are the resident immune cells in the central nervous system (CNS). After traumatic spinal cord injury (SCI), microglia undergo activation, proliferation, and changes in gene and protein expression and morphology, with detrimental and beneficial effects. Activated microglia cause secondary neuronal injury via the production of proinflammatory cytokines, reactive oxygen species, and proteases. However, activated microglia also promote neuronal repair through the secretion of anti-inflammatory growth factors and cytokines. Proinflammatory cytokines increase endothelial permeability, promote A1 astrocyte activation and axonal demyelination, and reduce neural stem/progenitor cells (NSPCs), leading to the exacerbation of neuronal injury. In contrast, anti-inflammatory factors facilitate angiogenesis, reduce reactive astrocytes, and promote axonal remyelination and the propagation of NSPCs, contributing to tissue repair and locomotor recovery. Due to its limited regenerative capacity, the CNS requires beneficial microglia for continuous protection against injury. Understanding and regulating microglial activation status are beneficial to reducing detrimental effects and promoting repair behaviors and to obtain more information on efficient therapies for traumatic SCI. This review discusses microglial activation and the differences between microglia and similar immune cells, microglial interactions with other cells in the spinal cord, and the progress in the development of therapies targeting microglia in SCI. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a neurodegenerative disease associated with demyelination and neuroinflammation in the central nervous system. There is an urgent need to develop remyelinating therapies to better treat multiple sclerosis and other demyelinating diseases. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating therapies; however, prototypical KOR agonists, such as U50,488 have side effects, which limit clinical use. In the current study, we investigated a Salvinorin A analog, ethoxymethyl ether Salvinorin B (EOM SalB) in two preclinical models of demyelination in C57BL/6J mice. We showed that in cellular assays EOM SalB was G-protein biased, an effect often correlated with fewer KOR-mediated side effects. In the experimental autoimmune encephalomyelitis model, we found that EOM SalB (0.1–0.3 mg/kg) effectively decreased disease severity in a KOR-dependent manner and led to a greater number of animals in recovery compared to U50,488 treatment. Furthermore, EOM SalB treatment decreased immune cell infiltration and increased myelin levels in the central nervous system. In the cuprizone-induced demyelination model, we showed that EOM SalB (0.3 mg/kg) administration led to an increase in the number of mature oligodendrocytes, the number of myelinated axons and the myelin thickness in the corpus callosum. Overall, EOM SalB was effective in two preclinical models of multiple sclerosis and demyelination, adding further evidence to show KOR agonists are a promising target for remyelinating therapies. [ABSTRACT FROM AUTHOR]

Background: Gray matter pathology plays a central role in the progression of multiple sclerosis (MS). The occurrence of synaptic loss appears to be important but, to date, still poorly investigated aspect of MS pathology. In this systematic review, we drew from the recent knowledge about synaptic loss in human post-mortem studies. Methods: We conducted a systematic search with PubMed to identify relevant publications. Publications available from15 June 2021 were taken into account. We selected human post-mortem studies that quantitatively assessed the synapse number in MS tissue. Results: We identified 14 relevant publications out of which 9 reported synaptic loss in at least one investigated subregion. The most commonly used synaptic marker was synaptophysin; non-etheless, we found substantial differences in the methodology and the selection of reference tissue. Investigated regions included the cortex, the hippocampus, the cerebellum, the thalamus, and the spinal cord. Conclusion: Synaptic loss seems to take place throughout the entire central nervous system. However, the results are inconsistent, probably due to differences in the methodology. Moreover, synaptic loss appears to be a dynamic process, and thus the nature of this pathology might be captured using in vivo synaptic density measurements. [ABSTRACT FROM AUTHOR]

Recent findings showing that epidermal growth factor (EGF) is significantly decreased in the cerebrospinal fluid (CSF) and spinal cord (SC) of living or deceased multiple sclerosis (MS) patients, and that its repeated administration to rodents with chemically- or virally-induced demyelination of the central nervous system (CNS) or experimental allergic encephalomyelitis (EAE) prevents demyelination and inflammatory reactions in the CNS, have led to a critical reassessment of the MS pathogenesis, partly because EGF is considered to have little or no role in immunology. EGF is the only myelinotrophic factor that has been tested in the CSF and spinal cord of MS patients, and it has been shown there is a good correspondence between liquid and tissue levels. This review: (a) briefly summarises the positive EGF effects on neural stem cells, oligodendrocyte cell lineage, and astrocytes in order to explain, at least in part, the biological basis of the myelin loss and remyelination failure in MS; and (b) after a short analysis of the evolution of the principle of cause-effect in the history of Western philosophy, highlights the lack of any experimental immune-, toxin-, or virus-mediated model that precisely reproduces the histopathological features and "clinical" symptoms of MS, thus underlining the inapplicability of Claude Bernard's crucial sequence of "observation, hypothesis, and hypothesis testing." This is followed by a discussion of most of the putative non-immunologically-linked points of MS pathogenesis (abnormalities in myelinotrophic factor CSF levels, oligodendrocytes (ODCs), astrocytes, extracellular matrix, and epigenetics) on the basis of Popper's falsification principle, and the suggestion that autoimmunity and phologosis reactions (surely the most devasting consequences of the disease) are probably the last links in a chain of events that trigger the reactions. As it is likely that there is a lack of other myelinotrophic growth factors because myelinogenesis is controlled by various CNS and extra-CNS growth factors and other molecules within and outside ODCs, further studies are needed to investigate the role of non-immunological molecules at the time of the onset of the disease. In the words of Galilei, the human mind should be prepared to understand what nature has created. [ABSTRACT FROM AUTHOR]

We addressed postural instability during stance with eyes closed (EC) on a compliant surface in healthy young people. Spectral analysis of the centre of foot pressure oscillations was used to identify the effects of haptic information (light-touch, EC-LT), or vision (eyes open, EO), or both (EO-LT). Spectral median frequency was strongly reduced by EO and EO-LT, while spectral amplitude was reduced by all "stabilising" sensory conditions. Reduction in spectrum level by EO mainly appeared in the high-frequency range. Reduction by LT was much larger than that induced by the vision in the low-frequency range, less so in the high-frequency range. Touch and vision together produced a fall in spectral amplitude across all windows, more so in anteroposterior (AP) direction. Lowermost frequencies contributed poorly to geometric measures (sway path and area) for all sensory conditions. The same subjects participated in control experiments on a solid base of support. Median frequency and amplitude of the spectrum and geometric measures were largely smaller when standing on solid than on foam base but poorly affected by the sensory conditions. Frequency analysis but not geometric measures allowed to disclose unique tuning of the postural control mode by haptic and visual information. During standing on foam, the vision did not reduce low-frequency oscillations, while touch diminished the entire spectrum, except for the medium-high frequencies, as if sway reduction by touch would rely on rapid balance corrections. The combination of frequency analysis with sensory conditions is a promising approach to explore altered postural mechanisms and prospective interventions in subjects with central or peripheral nervous system disorders. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the neuromuscular system for which currently there is no effective therapy. Motoneuron (MN) degeneration involves several complex mechanisms, including surrounding glial cells and skeletal muscle contributions. Neuregulin 1 (NRG1) is a trophic factor present particularly in MNs and neuromuscular junctions. Our previous studies revealed that gene therapy overexpressing the isoform I (NRG1-I) in skeletal muscles as well as overexpressing the isoform III (NRG1-III) directly in the central nervous system are both effective in preserving MNs in the spinal cord of ALS mice, opening novel therapeutic approaches. In this study, we combined administration of both viral vectors overexpressing NRG1-I in skeletal muscles and NRG1-III in spinal cord of the SOD1G93A mice in order to obtain a synergistic effect. The results showed that the combinatorial gene therapy increased preservation of MNs and of innervated neuromuscular junctions and reduced glial reactivity in the spinal cord of the treated SOD1G93A mice. Moreover, NRG1 isoforms overexpression improved motor function of hindlimb muscles and delayed the onset of clinical disease. However, this combinatory gene therapy did not produce a synergic effect compared with single therapies, suggesting an overlap between NRG1-I and NRG1-III activated pathways and their beneficial effects. [ABSTRACT FROM AUTHOR]

Objective: Central nervous system infections (CNSIs), especially viral encephalitis and meningitis, are well-recognized causes of medically refractory epilepsy. Although surgery is an effective and durable intervention against these infections, the seizure control outcomes described in previous surgical series have been variable. Accordingly, it is not clear which variables are most valuable in predicting seizure control following surgery for CNSI. The aim of this meta-analysis was to identify the predictors of favorable surgical outcomes in CNSI-related epilepsy. Methods: The PubMed, EMBASE, Cochrane Library, WANGFANG, VIP, CBM, and CNKI databases were searched for studies according to the inclusion criteria. Prognostic factors, surgical outcomes, and patient characteristics were extracted. Heterogeneity was detected by the I2 and Q statistics. Results: Seventeen studies were included in our meta-analysis. Eight predictors of favorable outcomes (Engel Class I/II) were determined, including abnormal MRI findings, meningitis, temporal location only, regional ictal pattern, unilateral ictal pattern, older age at epilepsy, longer silent period, and longer time from infection, as follows: OR = 3.34 (95% CI 1.44–7.74), OR = 0.31 (95% CI 0.13–0.70), OR = 0.34 (95% CI 0.16–0.74), OR = 5.65 (95% CI 1.75–18.30), and OR = 9.53 (95% CI 2.36–38.48), respectively, and MD = 2.15 (95% CI 0.20–4.11), MD = 2.40 (95% CI 0.09–4.70), and MD = 8.49 (95% CI 1.50–15.48), respectively. A subgroup analysis found the following associations: regional and unilateral ictal patterns in viral encephalitis, a younger age at infection in parasitic encephalopathy, an older age at surgery, a longer time from onset, and a longer time from infection in unexplained meningitis. A sensitivity analysis restricted to studies that included each variable yielded robust results. Little evidence of publication bias was observed. Conclusions: This meta-analysis suggests that abnormal MRI findings, meningitis, temporal location only, regional and unilateral ictal patterns, older age at epilepsy, longer silent period, and longer time from infection are predictive factors in patients with favorable surgical outcomes in CNSI-related epilepsy. In addition, different infective agents influenced the results in regional and unilateral ictal patterns in ictal electroencephalography, as well as the relationship between age at infection and surgery and the time from epilepsy onset and infection. [ABSTRACT FROM AUTHOR]

Antibody-mediated disorders of the central nervous system (CNS) are increasingly recognized as neurologic disorders that can be severe and even life-threatening but with the potential for reversibility with appropriate treatment. The expanding spectrum of newly identified autoantibodies targeting glial or neuronal (neural) antigens and associated clinical syndromes (ranging from autoimmune encephalitis to CNS demyelination) has increased diagnostic precision, and allowed critical reinterpretation of non-specific neurological syndromes historically associated with systemic disorders (e.g., Hashimoto encephalopathy). The intracellular vs. cell-surface or synaptic location of the different neural autoantibody targets often helps to predict the clinical characteristics, potential cancer association, and treatment response of the associated syndromes. In particular, autoantibodies targeting intracellular antigens (traditionally termed onconeural autoantibodies) are often associated with cancers, rarely respond well to immunosuppression and have a poor outcome, although exceptions exist. Detection of neural autoantibodies with accurate laboratory assays in patients with compatible clinical-MRI phenotypes allows a definite diagnosis of antibody-mediated CNS disorders, with important therapeutic and prognostic implications. Antibody-mediated CNS disorders are rare, and reliable autoantibody identification is highly dependent on the technique used for detection and pre-test probability. As a consequence, indiscriminate neural autoantibody testing among patients with more common neurologic disorders (e.g., epilepsy, dementia) will necessarily increase the risk of false positivity, so that recognition of high-risk clinical-MRI phenotypes is crucial. A number of emerging clinical settings have recently been recognized to favor development of CNS autoimmunity. These include antibody-mediated CNS disorders following herpes simplex virus encephalitis or occurring in a post-transplant setting, and neurological autoimmunity triggered by TNFα inhibitors or immune checkpoint inhibitors for cancer treatment. Awareness of the range of clinical and radiological manifestations associated with different neural autoantibodies, and the specific settings where autoimmune CNS disorders may occur is crucial to allow rapid diagnosis and early initiation of treatment. [ABSTRACT FROM AUTHOR]

Background: Crutches are the most common walking aids prescribed to improve mobility in subjects with central nervous system (CNS) lesions. To increase adherence to the appropriate level of crutch usage, providing load-related auditory feedback (aFB) may be a useful approach. We sensorized forearm crutches and developed a custom software to provide aFB information to both user and physical therapist (PhT). Aim: Evaluate aFB effects on load control during gait by a self-controlled case series trial. Methods: A single experimental session was conducted enrolling 12 CNS lesioned participants. Load on crutch was recorded during 10 Meter Walk Test performed with and without aFB. In both cases, crutch load data, and gait speed were recorded. Usability and satisfaction questionnaires were administered to participants and PhTs involved. Results: Reliable data were obtained from eight participants. Results showed that compared to the no FB condition, aFB yielded a significant reduction in the mean load on the crutches during gait (p = 0.001). The FB did not influence gait speed or fatigue (p > 0.05). The experience questionnaire data indicated a positive experience regarding the use of aFB from both participants' and PhTs' perspectives. Conclusion: aFB significantly improves compliance with crutch use and does not affect gait speed or fatigue by improving the load placed on crutches. The FB is perceived by users as helpful, safe, and easy to learn, and does not interfere with attention or concentration while walking. Furthermore, the PhTs consider the system to be useful, easy to learn and reliable. [ABSTRACT FROM AUTHOR]

The immune system's role is much more than merely recognizing self vs. non-self and involves maintaining homeostasis and integrity of the organism starting from early development to ensure proper organ function later in life. Unlike other systems, the central nervous system (CNS) is separated from the peripheral immune machinery that, for decades, has been envisioned almost entirely as detrimental to the nervous system. New research changes this view and shows that blood-borne immune cells (both adaptive and innate) can provide homeostatic support to the CNS via neuroimmune communication. Neurodegeneration is mostly viewed through the lens of the resident brain immune populations with little attention to peripheral circulation. For example, cognition declines with impairment of peripheral adaptive immunity but not with the removal of microglia. Therapeutic failures of agents targeting the neuroinflammation framework (inhibiting immune response), especially in neurodegenerative disorders, call for a reconsideration of immune response contributions. It is crucial to understand cross-talk between the CNS and the immune system in health and disease to decipher neurodestructive and neuroprotective immune mechanisms for more efficient therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: A major difficulty in treating moyamoya disease is the lack of effective methods to detect novel or progressive disease prior to the onset of disabling stroke. More importantly, a tool to better stratify operative candidates and quantify response to therapy could substantively complement existing methods. Here, we present proof-of-principle data supporting the use of urinary biomarkers as diagnostic adjuncts in pediatric moyamoya patients. Methods: Urine and cerebrospinal fluid specimens were collected from pediatric patients with moyamoya disease and a cohort of age and sex-matched control patients. Clinical and radiographic data were paired with measurements of a previously validated panel of angiogenic proteins quantified by ELISA. Results were compared to age and sex-matched controls and subjected to statistical analyses. Results: Evaluation of a specific panel of urinary and cerebrospinal fluid biomarkers by ELISA demonstrated significant elevations of angiogenic proteins in samples from moyamoya patients compared to matched controls. ROC curves for individual urinary biomarkers, including MMP-2, MMP-9, MMP-9/NGAL, and VEGF, showed excellent discrimination. The optimal urinary biomarker was MMP-2, providing a sensitivity of 88%, specificity of 100%, and overall accuracy of 91%. Biomarker levels changed in response to therapy and correlated with radiographic evidence of revascularization. Conclusions: We report, for the first time, identification of a panel of urinary biomarkers that predicts the presence of moyamoya disease. These biomarkers correlate with presence of disease and can be tracked from the central nervous system to urine. These data support the hypothesis that urinary proteins are useful predictors of the presence of moyamoya disease and may provide a basis for a novel, non-invasive method to identify new disease and monitor known patients following treatment. [ABSTRACT FROM AUTHOR]

Background: Diagnostic delay and neurologic deterioration are still a problem for the treatment of rapidly progressing CNS lymphoma (CNSL); there is an unmet need for a diagnostic test with a high diagnostic yield and limited risk, minimizing the time to the initiation of effective treatment. Methods: In this prospective monocentric study, we analyzed the utility of CXCL13 and CXCL9 as diagnostic, therapeutic and prognostic biomarkers for CNSL. Cerebrospinal fluid (CSF) from 155 consecutive patients admitted with brain lesions of various origins was collected. Levels of CXCL13 and CXCL9 were analyzed by ELISA. Additionally, CSF was analyzed during CNSL disease course (relapse, remission, progress) in 17 patients. Results: CXCL13 and CXCL9 CSF levels were significantly increased in patients with CNSL compared to control patients with lesions of other origin. Using logistic regression and a minimal- p -value approach, a cut-off value of 80 pg/ml for CXCL13 shows high sensitivity (90.7%) and specificity (90.1%) for the diagnosis of active CNSL. CXCL9 at a cut-off value of 84 pg/ml is less sensitive (61.5%) and specific (87.1%). Both cytokines correlate with the clinical course and response to therapy. Conclusions: Our results confirm the excellent diagnostic potential of CXCL13 and introduce CXCL9 as a novel albeit less powerful marker for PCNSL. [ABSTRACT FROM AUTHOR]

Given the important functions that glutamate serves in excitatory neurotransmission, understanding the regulation of glutamate in physiological and pathological states is critical to devising novel therapies to treat epilepsy. Exclusive expression of pyruvate carboxylase and glutamine synthetase in astrocytes positions astrocytes as essential regulators of glutamate in the central nervous system (CNS). Additionally, astrocytes can significantly alter the volume of the extracellular space (ECS) in the CNS due to their expression of the bi-directional water channel, aquaporin-4, which are enriched at perivascular endfeet. Rapid ECS shrinkage has been observed following epileptiform activity and can inherently concentrate ions and neurotransmitters including glutamate. This review highlights our emerging knowledge on the various potential contributions of astrocytes to epilepsy, particularly supporting the notion that astrocytes may be involved in seizure initiation via failure of homeostatic responses that lead to increased ambient glutamate. We also review the mechanisms whereby ambient glutamate can influence neuronal excitability, including via generation of the glutamate receptor subunit GluN2B-mediated slow inward currents, as well as indirectly affect neuronal excitability via actions on metabotropic glutamate receptors that can potentiate GluN2B currents and influence neuronal glutamate release probabilities. Additionally, we discuss evidence for upregulation of System x c - , a cystine/glutamate antiporter expressed on astrocytes, in epileptic tissue and changes in expression patterns of glutamate receptors. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is little information on the acute cerebrovascular complications of coronavirus disease 2019 (COVID-19) in Egypt. The aim of this study was to estimate the proportion of acute cerebrovascular disease (CVD) among COVID-19 patients and evaluate their clinical and radiological characteristics in comparison with non-COVID-19 CVD. Materials and Methods: In a retrospective study, COVID-19 patients whom presented with CVD in Assiut and Aswan University Hospitals were compared with non-COVID-19, CVD patients, admitted to Qena University Hospital, prior to the pandemic. The following data were collected: clinical history and presentation, risk factors, comorbidities, brain imaging (MRI or CT), chest CT, and some laboratory investigations. Results: Fifty-five (12.5%) of the 439 patients with COVID-19 had acute CVD. Of them, 42 (9.6%) had ischemic stroke while 13 patients (2.9%) had hemorrhagic CVD. In the 250 cases of the non-COVID-19 group, 180 had ischemic stroke and 70 had hemorrhagic stroke. A large proportion of patients with COVID-19 who presented with ischemic stroke had large vessel occlusion (LVO), which was significantly higher than in non-COVID-19 patients with CVD (40 vs. 7.2%, P < 0.001). Comorbidities were recorded in 44 (80%) cases. In COVID-19 ischemic stroke patients, risk factors [hypertension and ischemic heart disease (IHD)] and comorbidities (hepatic and renal) were significantly higher than those in non–COVID-19 patients. In addition, 23.5% had hemorrhagic CVD, and six patients with LVO developed hemorrhagic transformation. Conclusion: Acute CVD among patients with COVID-19 was common in our study. LVO was the commonest. Hypertension, IHD, and anemia are the most common risk factors and could contribute to the worsening of clinical presentation. Comorbidities were common among patients with CVD, although a large number had elevated liver enzymes and creatinine that were partially due to COVID-19 infection itself. The current results begin to characterize the spectrum of CVD associated with COVID-19 in patients in Upper Egypt. Registration ID: The ID number of this study is IRB no: 17300470. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia. Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected. Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability. Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery. [ABSTRACT FROM AUTHOR]

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.