Editor’s Choice Articles

On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of death. Due to the extent of this problem and the percentage of patients suffering from brain tumors, innovative therapeutic treatment methods are constantly being sought. One such innovative therapeutic method is photodynamic therapy (PDT). Photodynamic therapy is an alternative and unique technique widely used in dermatology and other fields of medicine for the treatment of oncological and nononcological lesions. Photodynamic therapy consists of the destruction of cancer cells and inducing inflammatory changes by using laser light of a specific wavelength in combination with the application of a photosensitizer. The most commonly used photosensitizers include 5-aminolevulinic acid for the enzymatic generation of protoporphyrin IX, Temoporfin—THPC, Photofrin, Hypericin and Talaporfin. This paper reviews the photosensitizers commonly used in photodynamic therapy for brain tumors. An overview of all three generations of photosensitizers is presented. Along with an indication of the limitations of the treatment of brain tumors, intraoperative photodynamic therapy and its possibilities are described as an alternative therapeutic method. Full article

Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who have no detectable auto-antibodies, a condition termed “seronegative MG” (SnMG). Several factors contribute to this, including laboratory test inaccuracies, decreased antibody production, immunosuppressive therapy, immunodeficiencies, antigen depletion, and immune-senescence. The diagnosis of SnMG is more challenging and is based on clinical features and neurophysiological tests. The early identification of these patients is needed in order to ensure early treatment and prevent complications. This narrative review aims to examine the latest updates on SnMG, defining the clinical characteristics of affected patients, diagnostic methods, management, and therapeutic scenarios. Full article

The COVID-19 pandemic had a significant impact on neurology training programs, leading to disruptions and changes that may have long-term implications for neurological education. The objective of this study was to investigate the impact of COVID-19 on neurological training programs, collecting available data relating to residents’ experience worldwide. We performed a systematic search of the literature published on PubMed from January 2020 to March 2023, including studies referring to quantitative analysis of residents’/trainees’ perspectives. Specifically, we included studies that examined how the pandemic has affected clinical and research activities, the use of telemedicine, the delivery of education and the psychological status of residents. Of the 95460 studies identified through database searching, 12 studies met the full criteria and underwent data extraction. In conclusion, the COVID-19 pandemic has had significant impacts on neurology training programs, highlighting the need for resilience and flexibility in medical education. Future research should focus on the long-term outcomes of these adaptations in the quality of neurology education and patient care. Full article

Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink rate, saccadic eye movement abnormalities, smooth pursuit deficits, and impaired voluntary and reflexive eye movements. Furthermore, visuoperceptive impairments affect the ability to perceive and recognize visual stimuli accurately, including impaired contrast sensitivity and reduced visual acuity, color discrimination, and object recognition. Visuospatial impairments are also remarkable, including difficulties perceiving and interpreting spatial relationships between objects and difficulties judging distances or navigating through the environment. Moreover, PD patients can present visuospatial attention problems, with difficulties attending to visual stimuli in a spatially organized manner. Moreover, PD patients also show perceptual disturbances affecting their ability to interpret and determine meaning from visual stimuli. And, for instance, visual hallucinations are common in PD patients. Nevertheless, the neurobiological bases of visual-related disorders in PD are complex and not fully understood. This review intends to provide a comprehensive description of visual disturbances in PD, from sensory to perceptual alterations, addressing their neuroanatomical, functional, and neurochemical correlates. Structural changes, particularly in posterior cortical regions, are described, as well as functional alterations, both in cortical and subcortical regions, which are shown in relation to specific neuropsychological results. Similarly, although the involvement of different neurotransmitter systems is controversial, data about neurochemical alterations related to visual impairments are presented, especially dopaminergic, cholinergic, and serotoninergic systems. Full article

Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal folds. SANS serves a large barrier to planetary spaceflight such as a mission to Mars and has been noted by the National Aeronautics and Space Administration (NASA) as a high risk based on its likelihood to occur and its severity to human health and mission performance. While it is a large barrier to future spaceflight, the underlying etiology of SANS is not well understood. Current ophthalmic imaging onboard the International Space Station (ISS) has provided further insights into SANS. However, the spaceflight environment presents with unique challenges and limitations to further understand this microgravity-induced phenomenon. The advent of artificial intelligence (AI) has revolutionized the field of imaging in ophthalmology, particularly in detection and monitoring. In this manuscript, we describe the current hypothesized pathophysiology of SANS and the medical diagnostic limitations during spaceflight to further understand its pathogenesis. We then introduce and describe various AI frameworks that can be applied to ophthalmic imaging onboard the ISS to further understand SANS including supervised/unsupervised learning, generative adversarial networks, and transfer learning. We conclude by describing current research in this area to further understand SANS with the goal of enabling deeper insights into SANS and safer spaceflight for future missions. Full article

The role of the endoscopic transplanum–transtuberculum approach (ETTA) in the treatment of pituitary adenomas/PitNETs (PAs) is sparsely analyzed in the literature, and its use is still debated in the current practice. The aim of this study was to report our experience with this approach. Our institutional registry was retrospectively reviewed, and patients who underwent ETTA for a PA from 1998 to 2022 were included. Fifty-seven cases were enrolled over a time span of 25 years, corresponding to 2.4% of our entire PA caseload. Radical resection was achieved in 57.9% of cases, with re-do surgery (p = 0.033) and vessel encasement/engulfment (p < 0.001) as predictors of partial resection. CSF leak incidence stood at 8.8%, with higher BMI (p = 0.038) as its only significant predictor. Partial or full improvement of the visual field deficits was achieved in 73.5% of cases. No surgical mortality was observed. According to our results, ETTA for the treatment of PAs is characterized by a satisfactory surgical outcome but with greater morbidity than the conventional endoscopic approach. Therefore, it should be reserved for the few selected cases otherwise unsuitable for the endoscopic trans-sphenoidal route, representing a valid alternative and an effective complementary route for the transcranial approach for these challenging PAs. Full article

Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, such as microvascular alterations in brain tissue, ionic imbalances, blood–brain barrier disruption, immune–inflammatory responses, oxidative stress, and activation of cell death pathways. Research progress presents a variety of promising therapeutic approaches for the preservation of neurological function following SAH, including calcium channel antagonists, endothelin-1 receptor blockers, antiplatelet agents, anti-inflammatory agents, and anti-oxidative stress agents. EBI can be mitigated following SAH through neuroprotective measures. To enhance our comprehension of the relevant molecular pathways involved in brain injury, including brain ischemia–hypoxic injury, neuroimmune inflammation activation, and the activation of various cell-signaling pathways, following SAH, it is essential to investigate the evolution of these multifaceted pathophysiological processes. Facilitating neural repair following a brain injury is critical for improving patient survival rates and quality of life. Full article

Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses electromagnetic pulses for focal modulate ion of neuronal activity in brain cortical regions. When pulses are applied repeatedly (repetitive transcranial magnetic stimulation—rTMS), they are thought to induce long-lasting neuroplastic effects, proposed to be a therapeutic mechanism for rTMS, with efficacy and safety initially demonstrated for treatment-resistant depression (TRD). Since then, many rTMS treatment protocols emerged for other difficult to treat psychiatric conditions. Moreover, multiple clinical studies, including large multi-center trials and several meta-analyses, have confirmed its clinical efficacy in different neuropsychiatric disorders, resulting in evidence-based guidelines and recommendations. Currently, rTMS is cleared by multiple regulatory agencies for the treatment of TRD, depression with comorbid anxiety disorders, obsessive compulsive disorder, and substance use disorders, such as smoking cessation. Importantly, current research supports the potential future use of rTMS for other psychiatric syndromes, including the negative symptoms of schizophrenia and post-traumatic stress disorder. More precise knowledge of formal indications for rTMS therapeutic use in psychiatry is critical to enhance clinical decision making in this area. Full article

Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical treatments are urgently needed. The middle cerebral artery occlusion (MCAO) model is currently the most widely used animal model of ischemic stroke. This review discusses various methods for constructing the MCAO model and compares their advantages and disadvantages in order to provide better approaches for studying ischemic stroke. Full article

This paper delves into the intricate structure and functionality of the brain’s glymphatic system, bringing forth new dimensions in its neuroscientific understanding. This paper commences by exploring the cerebrospinal fluid (CSF)—its localization, production, and pivotal role within the central nervous system, acting as a cushion and vehicle for nutrient distribution and waste elimination. We then transition into an in-depth study of the morphophysiological aspects of the glymphatic system, a recent discovery revolutionizing the perception of waste clearance from the brain, highlighting its lymphatic-like characteristics and remarkable operations. This paper subsequently emphasizes the glymphatic system’s potential implications in Alzheimer’s disease (AD), discussing the connection between inefficient glymphatic clearance and AD pathogenesis. This review also elucidates the intriguing interplay between the glymphatic system and the circadian rhythm, illustrating the optimal functioning of glymphatic clearance during sleep. Lastly, we underscore the hitherto underappreciated involvement of the glymphatic system in the tumoral microenvironment, potentially impacting tumor growth and progression. This comprehensive paper accentuates the glymphatic system’s pivotal role in multiple domains, fostering an understanding of the brain’s waste clearance mechanisms and offering avenues for further research into neuropathological conditions. Full article

Social exclusion refers to the experience of rejection by one or more people during a social event and can induce pain-related sensations. Cyberball, a computer program, is one of the most common tools for analyzing social exclusion. Regions of the brain that underlie social pain include networks linked to the dorsal lateral prefrontal cortex (DLPFC). Specifically, self-directed negative socially induced exclusion is associated with changes in DLPFC activity. Direct manipulation of this area may provide a better understanding of how the DLPFC can influence the perception of social exclusion and determine a causal role of the DLPFC. Transcranial magnetic stimulation (TMS) was applied to both the left and right DLPFC to gauge different reactions to the Cyberball experience. It was found that there were elevated exclusion indices following right DLPFC rTMS; participants consistently felt more excluded when the right DLPFC was excited. This may relate to greater feelings of social pain when the right DLPFC is manipulated. These data demonstrate that direct manipulation of the DLPFC results in changes in responses to social exclusion. Full article

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings. Full article

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1–80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS. Full article

Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several clinical studies have converged on the hypothesis of microglia hyperactivation and a consequent neuroinflammatory state as a pathogenic substrate of schizophrenia. Prenatal, perinatal, and postnatal factors can cause microglia to switch from M2 anti-inflammatory to M1 pro-inflammatory states. A continuous mild neuroinflammatory state progressively leads to neuronal loss, a reduction in dendritic spines, and myelin degeneration. The augmentation of drugs that reduce neuroinflammation to antipsychotics could be an effective therapeutic modality in managing schizophrenia. This review will consider studies in which drugs with anti-inflammatory and neuroprotective properties have been used in addition to antipsychotic treatment in patients with schizophrenia. Full article

Total sleep deprivation (TSD) leads to cognitive decline; however, the neurophysiological mechanisms underlying resting-state electroencephalogram (EEG) changes after TSD remain unclear. In this study, 42 healthy adult participants were subjected to 36 h of sleep deprivation (36 h TSD), and resting-state EEG data were recorded at baseline, after 24 h of sleep deprivation (24 h TSD), and after 36 h TSD. The analysis of resting-state EEG at baseline, after 24 h TSD, and after 36 h TSD using source localization analysis, power spectrum analysis, and functional connectivity analysis revealed a decrease in alpha-band power and a significant increase in delta-band power after TSD and impaired functional connectivity in the default mode network, precuneus, and inferior parietal lobule. The cortical activities of the precuneus, inferior parietal lobule, and superior parietal lobule were significantly reduced, but no difference was found between the 24 h and 36 h TSD groups. This may indicate that TSD caused some damage to the participants, but this damage temporarily slowed during the 24 h to 36 h TSD period. Full article

A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations in specific domains can also occur. The aim of this study was to evaluate the effects of semi-immersive virtual reality (VR) cognitive training (using the BTS Nirvana, Italy) in promoting global functional recovery in patients with SCI. Forty-two SCI patients were included in this retrospective case-control study, and the analysis was carried out using an electronic data retrieval system. The enrolled patients were divided into two groups with the same demographic and medical characteristics: the control group (CG: 21 patients) participated in traditional therapy, whereas the experimental group (EG: 21 patients) received training using semi-immersive VR. In both groups, there were patients with A- or B-grade impairments according to the American Spinal Injury Association (ASIA) scale. Both study groups underwent the same amount of cognitive training (but using a different type of training: conventional vs. innovative), consisting of three weekly sessions for eight weeks (24 sessions in total), each session lasting approximately sixty minutes, as well as the same amount of physiotherapy. The effect of the two treatments (EG/CG) was significantly different in global cognitive functioning (MOCA: p = 0.001), mood (BDI: p = 0.006), and overall quality of life (SF12 Total: p < 0.001), especially in physical perception (SF12-Physics: p = 0.004). Our results suggest that SCI patients could benefit from cognitive training using semi-immersive VR. Indeed, the integration of cognitive exercises that require movement and provide increased feedback could allow for better motor and cognitive recovery in people with SCI. Full article

Motoric cognitive risk syndrome (MCR) is defined by the presence of slow gait and subjective cognitive decline. It is well recognized as a prodrome for dementia, but the biological mechanism and trajectory for MCR are still lacking. The objective of this study was to explore the association of MCR with body composition, including sarcopenia and systemic inflammation, in pre-frail older adults in a cross-sectional study of 397 pre-frail community-dwelling older adults. Data on demographics, physical function, frailty, cognition (Montreal Cognitive Assessment (MoCA)), perceived health and depression were collected. Body composition was measured using a bioelectrical impedance analyzer. Systemic inflammatory biomarkers, such as progranulin, growth differentiation factor-15 (GDF-15), interleukin-10 (IL-10), interleukin-6 and tumor necrosis factor-α (TNF-α), were collected. Univariate and multivariate logistic regression were used to analyze the association between MCR, body composition, sarcopenia and systemic inflammatory biomarkers. The prevalence of MCR was 14.9%. They were significantly older and there were more females, depression, functional impairment, lower education, physical activity and MoCA scores. Body fat percentage (BF%), fat mass index, fat to fat free mass ratio (FM/FFM) and sarcopenia prevalence were significantly higher in MCR. Serum GDF-15 and TNF-α levels were highest with progranulin/TNF-α and IL-10/TNF-α ratio lowest in MCR. Compared to healthy patients, MCR was significantly associated with sarcopenia (aOR 2.62; 95% CI 1.46–3.17), BF% (aOR 1.06; 95% CI 1.01–1.12), FMI (aOR 1.16; 95% CI 1.02–1.30) and FM/FFM (aOR 6.38; 95% CI 1.20–33.98). The association of IL-10 to TNF-α ratio (aOR 0.98, 95% CI 0.97–0.99) and IL-10 (aOR 2.22, 95% CI 0.05–0.98) with MCR were independent of sarcopenia and BF%. Longitudinal population studies are needed to understand the role of body fat indices and IL-10 in pre-frail older adults with MCR and trajectory to dementia. Full article

Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, which have become a great challenge for today’s physicians. The studies suggest that among glial cells, iron has the highest concentration in oligodendrocytes, copper in astrocytes and zinc in the glia of hippocampus and cortex. Previous studies have shown neurotoxic effects of copper, iron and manganese, while zinc can have a bidirectional effect, i.e., neurotoxic but also neuroprotective effects depending on the dose and disease state. Recent data point to the association of metals with neurodegeneration through their role in the modulation of protein aggregation. Metals can accumulate in the brain with aging and may be associated with age-related diseases. Full article

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression. Full article

Background: The advance in imaging techniques is useful for 3D models and printing leading to a real revolution in many surgical specialties, in particular, neurosurgery. Methods: We report on a clinical study on the use of 3D printed models to perform cranioplasty in patients with craniosynostosis. The participants were recruited from various medical institutions and were divided into two groups: Group A (n = 5) received traditional surgical education (including cadaveric specimens) but without using 3D printed models, while Group B (n = 5) received training using 3D printed models. Results: Group B surgeons had the opportunity to plan different techniques and to simulate the cranioplasty. Group B surgeons reported that models provided a realistic and controlled environment for practicing surgical techniques, allowed for repetitive practice, and helped in visualizing the anatomy and pathology of craniosynostosis. Conclusion: 3D printed models can provide a realistic and controlled environment for neurosurgeons to develop their surgical skills in a safe and efficient manner. The ability to practice on 3D printed models before performing the actual surgery on patients may potentially improve the surgeons’ confidence and competence in performing complex craniosynostosis surgeries. Full article

Background: The standard reperfusion therapy for acute ischemic stroke (AIS) is considered to be thrombolysis, but its application is limited by the high risk of hemorrhagic transformation (HT). This study aimed to analyze risk factors and predictors of early HT after reperfusion therapy (intravenous thrombolysis or mechanical thrombectomy). Material and methods: Patients with acute ischemic stroke who developed HT in the first 24 h after receiving rtPA thrombolysis or performing mechanical thrombectomy were retrospectively reviewed. They were divided into two groups, respectively, the early-HT group and the without-early-HT group based on cranial computed tomography performed at 24 h, regardless of the type of hemorrhagic transformation. Results: A total of 211 consecutive patients were enrolled in this study. Among these patients, 20.37% (n = 43; age: median 70.00 years; 51.2% males) had early HT. Multivariate analysis of independent risk factors associated with early HT found that male gender increased the risk by 2.7-fold, the presence of baseline high blood pressure by 2.4-fold, and high glycemic values by 1.2-fold. Higher values of NIHSS at 24 h increased the risk of hemorrhagic transformation by 1.18-fold, while higher values of ASPECTS at 24 h decreased the risk of hemorrhagic transformation by 0.6-fold. Conclusions: In our study, male gender, baseline high blood pressure, and high glycemic values, along with higher values of NIHSS were associated with the increased risk of early HT. Furthermore, the identification of early-HT predictors is critical in patients with AIS for the clinical outcome after reperfusion therapy. Predictive models to be used in the future to select more careful patients with a low risk of early HT need to be developed in order to minimize the impact of HT associated with reperfusion techniques. Full article

The concept of early brain injury (EBI) is based on the assumption of a global reduction in brain perfusion following aneurysmal subarachnoid hemorrhage (aSAH). However, the heterogeneity of computed tomography perfusion (CTP) imaging in EBI has not yet been investigated. In contrast, increased mean transit time (MTT) heterogeneity, a possible marker of microvascular perfusion heterogeneity, in the delayed cerebral ischemia (DCI) phase has recently been associated with a poor neurological outcome after aSAH. Therefore, in this study, we investigated whether the heterogeneity of early CTP imaging in the EBI phase is an independent predictor of the neurological outcome after aSAH. We retrospectively analyzed the heterogeneity of the MTT using the coefficient of variation (cvMTT) in early CTP scans (within 24 h after ictus) of 124 aSAH patients. Both linear and logistic regression were used to model the mRS outcome, which were treated as numerical and dichotomized values, respectively. Linear regression was used to investigate the linear dependency between the variables. No significant difference in cvMTT between the patients with and those without EVD could be observed (p = 0.69). We found no correlation between cvMTT in early CTP imaging and initial modified Fisher (p = 0.07) and WFNS grades (p = 0.23). The cvMTT in early perfusion imaging did not correlate significantly with the 6-month mRS for the entire study population (p = 0.15) or for any of the subgroups (without EVD: p = 0.21; with EVD: p = 0.3). In conclusion, microvascular perfusion heterogeneity, assessed by the heterogeneity of MTT in early CTP imaging, does not appear to be an independent predictor of the neurological outcome 6 months after aSAH. Full article

Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis may be difficult, as the disease may present with unspecific symptoms and signs. We hypothesize that the diagnostic process may benefit from the use of machine learning (ML). Methods: 397 patients referring to neuromuscular clinics in 4 centers from the south of Italy with neuropathy and at least 1 more red flag, as well as undergoing genetic testing for ATTRv, were considered. Then, only probands were considered for analysis. Hence, a cohort of 184 patients, 93 with positive and 91 (age- and sex-matched) with negative genetics, was considered for the classification task. The XGBoost (XGB) algorithm was trained to classify positive and negative TTR mutation patients. The SHAP method was used as an explainable artificial intelligence algorithm to interpret the model findings. Results: diabetes, gender, unexplained weight loss, cardiomyopathy, bilateral carpal tunnel syndrome (CTS), ocular symptoms, autonomic symptoms, ataxia, renal dysfunction, lumbar canal stenosis, and history of autoimmunity were used for the model training. The XGB model showed an accuracy of 0.707 ± 0.101, a sensitivity of 0.712 ± 0.147, a specificity of 0.704 ± 0.150, and an AUC-ROC of 0.752 ± 0.107. Using the SHAP explanation, it was confirmed that unexplained weight loss, gastrointestinal symptoms, and cardiomyopathy showed a significant association with the genetic diagnosis of ATTRv, while bilateral CTS, diabetes, autoimmunity, and ocular and renal involvement were associated with a negative genetic test. Conclusions: Our data show that ML might potentially be a useful instrument to identify patients with neuropathy that should undergo genetic testing for ATTRv. Unexplained weight loss and cardiomyopathy are relevant red flags in ATTRv in the south of Italy. Further studies are needed to confirm these findings. Full article

Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D₄ receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients. Full article

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative stress and mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation is increasingly understood to contribute to the pathogenesis of epilepsy. Mitochondrial dysfunction is also recognized for its contributions to neuronal excitability and apoptosis, which can lead to neuronal loss in epilepsy. This review focuses on the roles of oxidative damage, mitochondrial dysfunction, NAPDH oxidase, the blood–brain barrier, excitotoxicity, and neuroinflammation in the development of epilepsy. We also review the therapies used to treat epilepsy and prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, and antioxidant therapies. In addition, we review the use of neuromodulation and surgery in the treatment of epilepsy. Finally, we present the role of dietary and nutritional strategies in the management of epilepsy, including the ketogenic diet and the intake of vitamins, polyphenols, and flavonoids. By reviewing available interventions and research on the pathophysiology of epilepsy, this review points to areas of further development for therapies that can manage epilepsy. Full article

An understanding of the neurocognitive profile underlying the use of social networking sites (SNSs) can help inform decisions about the classification of problematic SNS use as an addictive disorder and elucidate how/when ‘SNS addiction’ might develop. The present review aimed to synthesize structural and functional MRI research investigating problematic/compulsive forms of SNS use or regular (non-addicted) SNS use behaviours. We conducted a systematic search for research articles published in English using the Web of Science, PubMed, and Scopus databases up to October 2022. Studies meeting our inclusion criteria were assessed for quality and a narrative synthesis of the results was conducted. Twenty-eight relevant articles were identified comprising structural MRI (n = 9), resting-state fMRI (n = 6) and task-based fMRI studies (n = 13). Current evidence suggests that problematic SNS use might be characterised by (1) reduced volume of the ventral striatum, amygdala, subgenual anterior cingulate cortex, orbitofrontal cortex and posterior insula; (2) increased ventral striatum and precuneus activity in response to SNS cues; (3) abnormal functional connectivity involving the dorsal attention network; (4) inter-hemispheric communication deficits. Regular SNS use behaviours appear to recruit regions involved in the mentalising network, the self-referential cognition network, the salience network, the reward network and the default mode network. Such findings are at least partially consistent with observations from the substance addiction literature and provide some provisional support for the addictive potential of SNSs. Nonetheless, the present review is limited by the small number of eligible studies and large heterogeneity in the methods employed, and so our conclusions should remain tentative. Moreover, there is a lack of longitudinal evidence suggesting SNSs cause neuroadaptations and thus conclusions that problematic SNS use represents a disease process akin to substance use addictions are premature. More well-powered longitudinal research is needed to establish the neural consequences of excessive and problematic SNS use. Full article

The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such as the anterior cingulate cortex, nucleus accumbens, and amygdala, its involvement in stress responses has become a matter of great interest. While chronic stress has been proposed as a trigger of pain chronification and related psychiatric comorbidities due to maladaptive stress responses, acute stress triggers analgesia and other adaptative responses. Here we reviewed and highlighted the critical role of the RVM in stress responses, mainly in acute stress-induced analgesia (SIA) and chronic stress-induced hyperalgesia (SIH), providing insights into pain chronification processes and comorbidity between chronic pain and psychiatric disorders. Full article

Background: Endothelial dysfunction is implicated in various inflammatory diseases such as ischemic stroke, heart attack, organ failure, and COVID-19. Recent studies have shown that endothelial dysfunction in the brain is attributed to excessive inflammatory responses caused by the SARS-CoV-2 infection, leading to increased permeability of the blood-brain barrier and consequently neurological damage. Here, we aim to examine the single-cell transcriptomic landscape of endothelial dysfunction in COVID-19 and its implications for glioblastoma (GBM) progression. Methods: Single-cell transcriptome data GSE131928 and GSE159812 were obtained from the gene expression omnibus (GEO) to analyze the expression profiles of key players in innate immunity and inflammation between brain endothelial dysfunction caused by COVID-19 and GBM progression. Results: Single-cell transcriptomic analysis of the brain of COVID-19 patients revealed that endothelial cells had undergone significant transcriptomic changes, with several genes involved in immune responses and inflammation upregulated. Moreover, transcription factors were observed to modulate this inflammation, including interferon-regulated genes. Conclusions: The results indicate a significant overlap between COVID-19 and GBM in the context of endothelial dysfunction, suggesting that there may be an endothelial dysfunction link connecting severe SARS-CoV-2 infection in the brain to GBM progression. Full article

Cognitive biases have a significant impact on the etiology and treatment of eating disorders (EDs). These biases, including selective attentional bias (AB) to disliked body parts, may reinforce concerns about body shape, fear of gaining weight and body image disturbances and may contribute to dietary restriction and restraint. Decreasing AB could reduce core symptoms in anorexia nervosa (AN). This study represents a preliminary exploration aiming to assess whether AB towards weight-related (WR) and non-weight-related (NW) body parts could be reduced through an AB modification task in a virtual reality (VR) environment in healthy participants. A total of 54 female participants, aged 22.98 ± 1.89, were recruited. The task consisted of directing the participants’ attention towards all body parts equally in a VR setting. Eye-tracking (ET) measurements (complete fixation time [CFT] and number of fixations [NF]) were made before and after the task. The results showed a significant reduction of the AB in the two groups with an initial AB towards WR body parts or towards NW body parts. Participants showed a tendency to more balanced (non-biased) attention after the intervention. This study provides evidence of the usefulness of AB modification tasks in a non-clinical sample. Full article

Mu rhythm, also known as the mu wave, occurs on sensorimotor cortex activity at rest, and the frequency range is defined as 8–13Hz, the same frequency as the alpha band. Mu rhythm is a cortical oscillation that can be recorded from the scalp over the primary sensorimotor cortex by electroencephalogram (EEG) and magnetoencephalography (MEG). The subjects of previous mu/beta rhythm studies ranged widely from infants to young and older adults. Furthermore, these subjects were not only healthy people but also patients with various neurological and psychiatric diseases. However, very few studies have referred to the effect of mu/beta rhythm with aging, and there was no literature review about this theme. It is important to review the details of the characteristics of mu/beta rhythm activity in older adults compared with young adults, focusing on age-related mu rhythm changes. By comprehensive review, we found that, compared with young adults, older adults showed mu/beta activity change in four characteristics during voluntary movement, increased event-related desynchronization (ERD), earlier beginning and later end, symmetric pattern of ERD and increased recruitment of cortical areas, and substantially reduced beta event-related desynchronization (ERS). It was also found that mu/beta rhythm patterns of action observation were changing with aging. Future work is needed in order to investigate not only the localization but also the network of mu/beta rhythm in older adults. Full article

Identifying predictors for individuals vulnerable to the adverse effects of traumatic brain injury (TBI) remains an ongoing research pursuit. This is especially important for patients with mild TBI (mTBI), whose condition is often overlooked. TBI severity in humans is determined by several criteria, including the duration of loss of consciousness (LOC): LOC < 30 min for mTBI and LOC > 30 min for moderate-to-severe TBI. However, in experimental TBI models, there is no standard guideline for assessing the severity of TBI. One commonly used metric is the loss of righting reflex (LRR), a rodent analogue of LOC. However, LRR is highly variable across studies and rodents, making strict numeric cutoffs difficult to define. Instead, LRR may best be used as predictor of symptom development and severity. This review summarizes the current knowledge on the associations between LOC and outcomes after mTBI in humans and between LRR and outcomes after experimental TBI in rodents. In clinical literature, LOC following mTBI is associated with various adverse outcome measures, such as cognitive and memory deficits; psychiatric disorders; physical symptoms; and brain abnormalities associated with the aforementioned impairments. In preclinical studies, longer LRR following TBI is associated with greater motor and sensorimotor impairments; cognitive and memory impairments; peripheral and neuropathology; and physiologic abnormalities. Because of the similarities in associations, LRR in experimental TBI models may serve as a useful proxy for LOC to contribute to the ongoing development of evidence-based personalized treatment strategies for patients sustaining head trauma. Analysis of highly symptomatic rodents may shed light on the biological underpinnings of symptom development after rodent TBI, which may translate to therapeutic targets for mTBI in humans. Full article

The topic of this narrative review is mood stabilizers. First, the author’s definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author’s criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with “insufficient” ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided. Full article

Background: As the field of sensor-based rehabilitation continues to expand, it is important to gain a comprehensive understanding of its current research landscape. This study aimed to conduct a bibliometric analysis to identify the most influential authors, institutions, journals, and research areas in this field. Methods: A search of the Web of Science Core Collection was performed using keywords related to sensor-based rehabilitation in neurological diseases. The search results were analyzed with CiteSpace software using bibliometric techniques, including co-authorship analysis, citation analysis, and keyword co-occurrence analysis. Results: Between 2002 and 2022, 1103 papers were published on the topic, with slow growth from 2002 to 2017, followed by a rapid increase from 2018 to 2022. The United States was the most active country, while the Swiss Federal Institute of Technology had the highest number of publications among institutions. Sensors published the most papers. The top keywords included rehabilitation, stroke, and recovery. The clusters of keywords comprised machine learning, specific neurological conditions, and sensor-based rehabilitation technologies. Conclusions: This study provides a comprehensive overview of the current state of sensor-based rehabilitation research in neurological diseases, highlighting the most influential authors, journals, and research themes. The findings can help researchers and practitioners to identify emerging trends and opportunities for collaboration and can inform the development of future research directions in this field. Full article

Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. Hence, this study compared the neurotoxicity of OPs, chlorpyrifos-oxon (CPO), and azamethiphos (AZO) and the carbamate pesticide, aldicarb, to undifferentiated versus differentiated SH-SY5Y neuroblastoma cells. OP and carbamate concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and cellular bioenergetic capacity assessed via quantitation of cellular ATP levels. Concentration-response curves for inhibition of cellular AChE activity were also generated and the production of reactive oxygen species (ROS) was monitored using a 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. The OPs and aldicarb reduced cell viability, cellular ATP levels, and neurite outgrowth in a concentration-dependent fashion, from a threshold concentration of ≥10 µM. Neurotoxic potency was in the order AZO > CPO > aldicarb for undifferentiated cells but CPO > AZO > aldicarb for differentiated cells and this toxic potency of CPO reflected its more extensive induction of reactive oxygen species (ROS) and generation of carbonylated proteins that were characterized by western blotting. Hence, the relative neurotoxicity of the OPs and aldicarb in part reflects non-cholinergic mechanisms that are likely to contribute to developmental neurotoxicity. Full article

Stroke is the fourth leading cause of mortality and is estimated to be one of the major reasons for long-lasting disability worldwide. There are limited studies that describe the application of physical therapy interventions to prevent disabilities in stroke survivors and promote recovery after a stroke. In this review, we have described a wide range of interventions based on impairments, activity limitations, and goals in recovery during different stages of a stroke. This article mainly focuses on stroke rehabilitation tactics, including those for sensory function impairments, motor learning programs, hemianopia and unilateral neglect, flexibility and joint integrity, strength training, hypertonicity, postural control, and gait training. We conclude that, aside from medicine, stroke rehabilitation must address specific functional limitations to allow for group activities and superior use of a hemiparetic extremity. Medical doctors are often surprised by the variety of physiotherapeutic techniques available; they are unfamiliar with the approaches of researchers such as Bobath, Coulter, and Brunnstrom, among others, as well as the scientific reasoning behind these techniques. Full article

The mechanism behind the onset of depression has been the focus of current research in the neuroscience field. Silent information regulator 1 (SIRT1) is a key player in regulating energy metabolism, and it can regulate depression by mediating the inflammatory response (e.g., nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)), gene expression in the nucleus accumben (NAc) and CA1 region of the hippocampus (e.g., nescient helix-loop-helix2 (NHLH2), monoamine oxidase (MAO-A), and 5-Hydroxyindole-3-acetic acid (5-HIAA)), and neuronal regeneration in the CA3 region of the hippocampus. Exercise is an important means to improve energy metabolism and depression, but it remains to be established how SIRT1 acts during exercise and improves depression. By induction and analysis, SIRT1 can be activated by exercise and then improve the function of the hypothalamic–pituitary–adrenal (HPA) axis by upregulating brain-derived neurotrophic factors (BDNF), inhibit the inflammatory response (suppression of the NF-κB and TNF-α/indoleamine 2,3-dioxygenase (IDO)/5-Hydroxytryptamine (5-HT) pathways), and promote neurogenesis (activation of the insulin-like growth factor1 (IGF-1) and growth-associated protein-43 (GAP-43) pathways, etc.), thereby improving depression. The present review gives a summary and an outlook based on this finding and makes an analysis, which will provide a new rationale and insight for the mechanism by which exercise improves depression. Full article

The steady-state visually evoked potential (SSVEP) is an important type of BCI that has various potential applications, including in virtual environments using virtual reality (VR). However, compared to VR research, the majority of visual stimuli used in the SSVEP-BCI are plane stimulation targets (PSTs), with only a few studies using stereo stimulation targets (SSTs). To explore the parameter optimization of the SSVEP-BCI virtual SSTs, this paper presents a parameter knowledge graph. First, an online VR stereoscopic stimulation SSVEP-BCI system is built, and a parameter dictionary for VR stereoscopic stimulation parameters (shape, color, and frequency) is established. The online experimental results of 10 subjects under different parameter combinations were collected, and a knowledge graph was constructed to optimize the SST parameters. The best classification performances of the shape, color, and frequency parameters were sphere (91.85%), blue (94.26%), and 13Hz (95.93%). With various combinations of virtual reality stereo stimulation parameters, the performance of the SSVEP-BCI varies. Using the knowledge graph of the stimulus parameters can help intuitively and effectively select appropriate SST parameters. The knowledge graph of the stereo target stimulation parameters presented in this work is expected to offer a way to convert the application of the SSVEP-BCI and VR. Full article

Traumatic brain injury (TBI) is a global health concern, that can leave lasting physical, cognitive, and/or behavioral changes for many who sustain this type of injury. Because of the heterogeneity of this population, development of appropriate intervention tools can be difficult. Social determinants of health (SDoH) are factors that may impact TBI incidence, recovery, and outcome. The purpose of this study is to describe and analyze the existing literature regarding the prevailing SDoH and health disparities (HDs) associated with TBI in adults. A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to explore three electronic databases—PubMed, Medline, and CINAHL. Searches identified peer-reviewed empirical literature addressing aspects of SDoH and HDs related to TBI. A total of 123 records were identified and reduced to 27 studies based on inclusion criteria. Results revealed race/ethnicity was the most commonly reported SDoH impacting TBI, followed by an individual’s insurance status. Health disparities were noted to occur across the continuum of TBI, including TBI risk, acute hospitalization, rehabilitation, and recovery. The most frequently reported HD was that Whites are more likely to be discharged to inpatient rehabilitation compared to racial/ethnic minorities. Health disparities associated with TBI are most commonly associated with the race/ethnicity SDoH, though insurance status and socioeconomic status commonly influence health inequities as well. The additional need for evidence related to the impact of other, lesser researched, SDoH is discussed, as well as clinical implications that can be used to target intervention for at-risk groups using an individual’s known SDoH. Full article

Gait recovery is a fundamental goal in patients with spinal cord injury to attain greater autonomy and quality of life. Robotics is becoming a valid tool in improving motor, balance, and gait function in this patient population. Moreover, other innovative approaches are leading to promising results. The aim of this study was to investigate new rehabilitative methods for gait recovery in people who have suffered spinal cord injuries. A systematic review of the last 10 years of the literature was performed in three databases (PubMed, PEDro, andCochrane). We followed this PICO of the review: P: adults with non-progressive spinal cord injury; I: new rehabilitative methods; C: new methods vs. conventional methods; and O: improvement of gait parameters. When feasible, a comparison through ES forest plots was performed. A total of 18 RCTs of the 599 results obtained were included. The studies investigated robotic rehabilitation (n = 10), intermittent hypoxia (N = 3) and external stimulation (N = 5). Six studies of the first group (robotic rehabilitation) were compared using a forest plot for 10MWT, LEMS, WISCI-II, and SCIM-3. The other clinical trials were analyzed through a narrative review of the results. We found weak evidence for the claim that robotic devices lead to better outcomes in gait independence compared to conventional rehabilitation methods. External stimulation and intermittent hypoxia seem to improve gait parameters associated with other rehabilitation methods. Research investigating the role of innovative technologies in improving gait and balance is needed since walking ability is a fundamental issue in patients with SCI. Full article

Background: The efficacy of upper limb (UL) robot-assisted therapy (RAT) on functional improvement after stroke remains unclear. However, recently published randomized controlled trials have supported its potential benefits in enhancing the activities of daily living, arm and hand function, and muscle strength. Task-specific and high-intensity exercises are key points in facilitating motor re-learning in neurorehabilitation since RAT can provide an assisted-as-needed approach. This study aims to investigate the clinical effects of an exoskeleton robotic system for UL rehabilitation compared with conventional therapy (CT) in people with subacute stroke. As a secondary aim, we seek to identify patients’ characteristics, which can predict better recovery after UL-RAT and detects whether it could elicit greater brain stimulation. Methods: A total of 84 subacute stroke patients will be recruited from 7 Italian rehabilitation centers over 3 years. The patients will be randomly allocated to either CT (control group, CG) or CT plus UL-RT through an Armeo^®Power (Hocoma AG, CH, Volketswil, Switzerland) exoskeleton (experimental group, EG). A sample stratification based on distance since onset, DSO (DSO ≤ 30; DSO > 30), and Fugl–Meyer Assessment (FM)-UL (FM-UL ≤ 22; 22 < FM-UL ≤ 44) will be considered for the randomization. The outcomes will be recorded at baseline (T0), after 25 + 3 sessions of intervention (T1), and at 6 months post-stroke (T2). The motor functioning assessed by the FM-UL (0–66) will be considered the primary outcome. The clinical assessments will be set based on the International Classification of Function, Disability and Health (ICF). A patient satisfaction questionnaire will be evaluated in the EG at T1. A subgroup of patients will be evaluated at T0 and T1 via electroencephalography. Their brain electrical activity will be recorded during rest conditions with their eyes closed and open (5 min each). Conclusion: The results of this trial will provide an in-depth understanding of the efficacy of early UL-RAT through a whole arm exoskeleton and how it may relate to the neural plasticity process. The trial was registered at ClinicalTrial.gov with the registration identifier NCT04697368. Full article

The prevalence of people over 60 years of age with cognitive impairment has increased in recent decades. As a consequence, numerous computerized cognitive trainings (CCT) have been developed. This pilot study aimed to determine the effectiveness of the CCT with VIRTRAEL in improving older adults’ cognition. Fifty-five participants ($\overline{\mathrm{x}}$ = 72.7 years; SD = 6.5) underwent CCT, and twenty participants ($\overline{\mathrm{x}}$ = 76.1 years; SD = 7.6) received face-to-face cognitive stimulation with a paper-and-pencil methodology. Both trainings were conducted in nine sessions (45–60 min each). Participants completed a pre-post training neuropsychological assessment. ANCOVAs and the standardized clinical change were performed. VIRTRAEL’s group showed a significant and greater improvement in verbal learning (p < 0.006) and delayed recall (p ≤ 0.001), working memory (p < 0.005), abstract (p < 0.002) and semantic reasoning (p < 0.015), and planning (p < 0.021). Additionally, more large clinical changes (d > 0.8) were found in the VIRTRAEL condition (in verbal learning and delayed free and cued recall) than in the standard group. Here we show that the CCT with VIRTRAEL is effective in improving cognitive function in older adults and is superior to the standard format. These preliminary findings indicate that CCT is a useful tool potentially applicable in the fight against cognitive symptomatology associated with aging and neurodegenerative diseases. VIRTRAEL represents a breakthrough in this field as it is inexpensive and easily accessible to any older person, regardless of whether they live far from health care resources. Full article

The Internet of Things (IoT) is a well-known technology that has a significant impact on many areas, including connections, work, healthcare, and the economy. IoT has the potential to improve life in a variety of contexts, from smart cities to classrooms, by automating tasks, increasing output, and decreasing anxiety. Cyberattacks and threats, on the other hand, have a significant impact on intelligent IoT applications. Many traditional techniques for protecting the IoT are now ineffective due to new dangers and vulnerabilities. To keep their security procedures, IoT systems of the future will need AI-efficient machine learning and deep learning. The capabilities of artificial intelligence, particularly machine and deep learning solutions, must be used if the next-generation IoT system is to have a continuously changing and up-to-date security system. IoT security intelligence is examined in this paper from every angle available. An innovative method for protecting IoT devices against a variety of cyberattacks is to use machine learning and deep learning to gain information from raw data. Finally, we discuss relevant research issues and potential next steps considering our findings. This article examines how machine learning and deep learning can be used to detect attack patterns in unstructured data and safeguard IoT devices. We discuss the challenges that researchers face, as well as potential future directions for this research area, considering these findings. Anyone with an interest in the IoT or cybersecurity can use this website’s content as a technical resource and reference. Full article

High-resolution magnetic resonance imaging (HRMRI) is the most important and popular vessel wall imaging technique for the direct assessment of vessel wall and cerebral arterial disease. It can identify the cause of stroke in high-risk plaques and differentiate the diagnosis of head and carotid artery dissection, including inflammation, Moya Moya disease, cerebral aneurysm, vasospasm after subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, blunt cerebrovascular injury, cerebral arteriovenous malformations, and other stenosis or occlusion conditions. Through noninvasive visualization of the vessel wall in vitro, quantified assessment of luminal stenosis and pathological features of the vessel wall can provide clinicians with further disease information. In this report, technical considerations of HRMRI are discussed, and current clinical applications of HRMRI are reviewed. Full article

Biofeedback training is a method commonly used in various fields of life, for example, in medicine, sports training or business. In recent studies, it has been shown that biofeedback, and neurofeedback, can affect the performance of professional athletes. Training based on the neurofeedback method includes exercising the brain waves. The aim of the article is to evaluate the influence of neurofeedback training on the physical fitness of professional athletes representing various sports disciplines, such as judo, volleyball and soccer. Based on 10 scientific papers from various sources, including PubMed, the latest research on neurofeedback and its impact on athletes has been reviewed. On the basis of the literature review from 2012 to 2022 on the neurofeedback method in sports training, it can be stated that this type of practice has a significant impact on physical fitness and sports performance. This review comprised 10 research studies with 491 participants in the neurofeedback groups, and 62 participants in the control group. Two reviewers independently extracted data and evaluated the quality of the studies utilising the PEDro scale. Properly planned and conducted neurofeedback training affects stimulation and improvement of many variables (reducing stress levels, increasing the ability to self-control physiological factors, enhancing behavioural efficiency and meliorating the speed of reaction to a stimulus). Full article

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy usually presents as meningoencephalomyelitis. Many patients developed flu-like symptoms preceding the neurologic symptoms. Reversible lesion in the splenium of the corpus callosum (SCC) is a clinical and radiological syndrome secondary to many kinds of etiologies, including infections, which is termed RESLES. Case presentation: we reported a case developing irregularly high fever, both temporal pain, low limbs fatigue with frequent urination admitted to our neurology department. CSF test showed GFAP-IgG positive, elevated WBC counts and protein, with low glucose and chlorine, while MRI showed a reversible lesion on SCC, leading us to diagnose autoimmune GFAP autocytopathy accompanied with RESLES. The boy had significantly improved after anti-virus and steroids therapy. Discussion: Autoimmune GFAP autocytopathy accompanied with RESLES is rarely seen, and pathogenesis for the co-existence has not been clarified. Autoimmune GFAP autocytopathy and RESLES are both related to viral infection. Our case covered infectious symptoms and improved after antiviral treatment, suggesting virus infection may perform a key role in pathogenesis. Full article

Comparison across somatosensory domains, important for clinical and scientific goals, requires prior calibration of impairment severity. Provided test score distributions are comparable across domains, valid comparisons of impairment can be made by reference to score locations in the corresponding distributions (percentile rank or standardized scores). However, this is often not the case. Test score distributions for tactile texture discrimination (n = 174), wrist joint proprioception (n = 112), and haptic object identification (n = 98) obtained from pooled samples of stroke survivors in rehabilitation settings were investigated. The distributions showed substantially different forms, undermining comparative calibration via percentile rank or standardized scores. An alternative approach is to establish comparable locations in the psychophysical score ranges spanning performance from just noticeably impaired to maximally impaired. Several simulation studies and a theoretical analysis were conducted to establish the score distributions expected from completely insensate responders for each domain. Estimates of extreme impairment values suggested by theory, simulation and observed samples were consistent. Using these estimates and previously discovered values for impairment thresholds in each test domain, comparable ranges of impairment from just noticeable to extreme impairment were found. These ranges enable the normalization of the three test scales for comparison in clinical and research settings. Full article

Neural inflammatory response is a crucial pathological change in intracerebral hemorrhage (ICH) which accelerates the formation of perihematomal edema and aggravates neural cell death. Although surgical and drug treatments for ICH have advanced rapidly in recent years, therapeutic strategies that target and control neuroinflammation are still limited. Exosomes are important carriers for information transfer among cells. They have also been regarded as a promising therapeutic tool in translational medicine, with low immunogenicity, high penetration through the blood-brain barrier, and ease of modification. In our previous research, we have found that exogenous administration of miRNA-124-overexpressed microglial exosomes (Exo-124) are effective in improving post-injury cognitive impairment. From this, we evaluated the potential therapeutic effects of miRNA-124-enriched microglial exosomes on the ICH mice in the present study. We found that the gene-edited exosomes could attenuate neuro-deficits and brain edema, improve blood–brain barrier integrity, and reduce neural cell death. Moreover, the protective effect of Exo-124 was abolished in mice depleted of Gr-1⁺ myeloid cells. It suggested that the exosomes exerted their functions by limiting the infiltration of leukocyte into the brain, thus controlling neuroinflammation following the onset of ICH. In conclusion, our findings provided a promising therapeutic strategy for improving neuroinflammation in ICH. It also opens a new avenue for intranasal delivery of exosome therapy using miRNA-edited microglial exosomes. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein–induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD. Full article

Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer’s. Microglia are the brain’s primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds with anti-inflammatory and antioxidant properties, such as epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related neurodegenerative diseases involving activated microglia cells. The objective of the current study was to examine the molecular targets underlying the anti-inflammatory effects of EGCG in activated microglia cells. BV-2 microglia cells were grown, stimulated, and treated with EGCG. Cytotoxicity and nitric oxide (NO) production were evaluated. Immunoassay, PCR array, and WES™ Technology were utilized to evaluate inflammatory, neuroprotective modulators as well as signaling pathways involved in the mechanistic action of neuroinflammation. Our findings showed that EGCG significantly inhibited proinflammatory mediator NO production in LPS-stimulated BV-2 microglia cells. In addition, ELISA analysis revealed that EGCG significantly decreases the release of proinflammatory cytokine IL-6 while it increases the release of TNF-α. PCR array analysis showed that EGCG downregulated MIF, CCL-2, and CSF2. It also upregulated IL-3, IL-11, and TNFS10. Furthermore, the analysis of inflammatory signaling pathways showed that EGCG significantly downregulated mRNA expression of mTOR, NF-κB2, STAT1, Akt3, CCL5, and SMAD3 while significantly upregulating the expression of mRNA of Ins2, Pld2, A20/TNFAIP3, and GAB1. Additionally, EGCG reduced the relative protein expression of NF-κB2, mTOR, and Akt3. These findings suggest that EGCG may be used for its anti-inflammatory effects to prevent neurodegenerative diseases. Full article