The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions.

Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.

The safety profile of mesenchymal stem cell therapy administered through intrathecal injections for treating neurological disorders: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs). METHODS: Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed. RESULTS: 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events-CTCAE version 5.0) (RR: 1.61, 95% CI 1.19-2.19, I2 = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004-2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416-0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate. CONCLUSIONS: Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings.

Current Concepts in Early Mobilization of Critically Ill Patients Within the Context of Neurologic Pathology.

Neurocritical patients (NCPs) in the intensive care unit (ICU) rapidly progress to respiratory and peripheral muscle dysfunctions, which significantly impact morbidity and death. Early mobilization in NCPs to decrease the incidence of ICU-acquired weakness has been showing rapid growth, although pertinent literature is still scarce. With this review, we summarize and discuss current concepts in early mobilization of critically ill patients within the context of neurologic pathology in NCPs. A narrative synthesis of literature was undertaken trying to answer the following questions: How do the respiratory and musculoskeletal systems in NCPs behave? Which metabolic biomarkers influence physiological responses in NCPs? Which considerations should be taken when prescribing exercises in neurocritically ill patients? The present review detected safety, feasibility, and beneficial response for early mobilization in NCPs, given successes in other critically ill populations and many smaller intervention trials in neurocritical care. However, precautions should be taken to elect the patient for early care, as well as monitoring signs that indicate interruption for intervention, as worse outcomes were associated with very early mobilization in acute stroke trials.

Racial Inequities in Palliative Referral for Children with High-Intensity Neurologic Impairment.

OBJECTIVE: To evaluate whether racial and socioeconomic inequities in pediatric palliative care utilization extend to children with high-intensity neurologic impairment (HI-NI), which is a chronic neurological diagnosis resulting in substantial functional morbidity and mortality. STUDY DESIGN: We conducted a retrospective study of patients with HI-NI who received primary care services at a tertiary care center from 2014 through 2019. HI-NI diagnoses that warranted a palliative care referral were identified by consensus of a multidisciplinary team. The outcome was referral to palliative care. The primary exposure was race, categorized as Black or non-Black to represent the impact of anti-Black racism. Additional exposures included ethnicity (Hispanic/non-Hispanic) and insurance status (Medicaid/non-Medicaid). Descriptive statistics, bivariate analyses, and multivariable logistic regression models were performed to assess associations between exposures and palliative care referral. RESULTS: A total of 801 patients with HI-NI were included; 7.5% received a palliative referral. There were no differences in gestational age, sex, or ethnicity between patients who received a referral and those who did not. In multivariable analysis, adjusting for ethnicity, sex, gestational age, and presence of complex chronic conditions, Black children (aOR 0.47, 95% CI 0.26, 0.84) and children with Medicaid insurance (aOR 0.40, 95% CI 0.23, 0.70) each had significantly lower odds of palliative referral compared with their non-Black and non-Medicaid-insured peers, respectively. CONCLUSIONS: We identified inequities in pediatric palliative care referral among children with HI-NI by race and insurance status. Future work is needed to develop interventions, with families, aimed at promoting more equitable, antiracist systems of palliative care.

Alternative medicine therapies in neurological disorders: Prevalence, reasons and associated factors. A systematic review.

OBJECTIVE: This systematic review aimed to identify the prevalence of CAM use in patients with neurological disorders, and also to know most frequent types of CAM used. METHODS: Five databases: PubMed, Science Direct, EBSCO, Latindex and Scielo (in English and Spanish) were searched from January 2010 to May 2021. Only original cross-sectional, retrospective and cohort studies were included, whose primary objective was to describe the frequency of CAM use in neurological disorders and/or the related factors to its use in adults. Based on the data, a descriptive analysis was performed, covering the characteristics of studies, measuring methods, prevalence, types and related factors. To control the risk of bias, a quality assessment of each study was performed using STROBE checklist. RESULTS: For the final analysis, 40 studies were included. Most common pathologies observed in the studies were multiple sclerosis, headache, stroke, Parkinson and epilepsy. The STROBE score of studies ranged from 13 to 22 points, with an average of 18.2. Prevalence of CAM use was highly variable from one study to another (16% in stroke patients, to 100% in amyotrophic lateral sclerosis or spinal cord injury patients). Biological therapies (dietary supplements and herbal medicine) were the most commonly CAM types used. The associated factors identified were female sex, an age between 40 and 50 years, and higher socioeconomic level. Not all studies investigated about the results of CAMs but these ranged from 35% to more than 80% of reporting positive effects. CONCLUSIONS: The prevalence of CAM use in neurological diseases is highly variable (16%-100%); the most used type of CAM was biological therapies and the associated factors were female sex, age between 40 and 50 years old and high socioeconomic level.

Population-Level Analysis of Appropriateness of End-of-Life Care for Children with Neurologic Conditions.

OBJECTIVE: The objective of this study was to measure the appropriateness of end-of-life care for children who died with neurologic conditions. STUDY DESIGN: Based on linked routinely collected databases, we conducted a population-level decedent retrospective cohort study of children with neurologic conditions who died in Belgium between 2010 and 2017. We measured a set of 22 face-validated quality indicators. The set concerns 12 indicators of potentially appropriate end-of-life care (eg, specialized comfort medication, physician contact, continuous care) and 10 indicators of potentially inappropriate end-of-life care (eg, diagnostic tests, phlebotomy). We performed ANOVA for predictors (age, sex, disease category, nationality, having siblings, year of death) for scales of appropriate and inappropriate care. RESULTS: Between 2010 and 2017, 139 children with neurologic conditions died in Belgium. For potentially appropriate care, in the last 30 days, 76% of children received clinical care, 55% had continuous care relationships, 17% had contact with a general physician, 8% of children received specialized comfort medication, and 14% received care from a palliative care team. For potentially inappropriate care, in the last 14 days, 45% had blood drawn and 27% were admitted to intensive care unit. CONCLUSIONS: Our study found indications of appropriate as well as inappropriate end-of-life care for children who died with neurologic conditions. These findings reveal a substantial margin for potential quality improvement, in regard to palliative care provision, multidisciplinary care, financial support, specialized comfort medication, clinical follow-up, general physician contact, diagnostics, and blood drawing.

Transcranial direct current stimulation for balance rehabilitation in neurological disorders: A systematic review and meta-analysis.

Postural instability is common in neurological diseases. Although transcranial direct current stimulation (tDCS) seems to be a promising complementary therapy, emerging evidence indicates mixed results and protocols' characteristics. We conducted a systematic review and meta-analysis on PubMed, EMBASE, Scopus, and Web of Science to synthesize key findings of the effectiveness of single and multiple sessions of tDCS alone and combined with other interventions on balance in adults with neurological disorders. Thirty-seven studies were included in the systematic review and 33 in the meta-analysis. The reviewed studies did not personalize the stimulation protocol to individual needs/characteristics. A random-effects meta-analysis indicated that tDCS alone (SMD = -0.44; 95%CI = -0.69/-0.19; p < 0.001) and combined with another intervention (SMD = -0.31; 95%CI = -0.51/-0.11; p = 0.002) improved balance in adults with neurological disorders (small to moderate effect sizes). Balance improvements were evidenced regardless of the number of sessions and targeted area. In summary, tDCS is a promising therapy for balance rehabilitation in adults with neurological disorders. However, further clinical trials should identify factors that influence responsiveness to tDCS for a more tailored approach, which may optimize the clinical use of tDCS.

Training of neurologists for the 21st century: cultural and professional skills.

Training of neurologists for the near future is a challenge due to the likely advances in neuroscientific methods, which will change much of our knowledge on diagnosis and treatment of neurological diseases. OBJECTIVE: to comment on what may be more likely to be a constant in the very near future and to recommend how to prepare the neurologist for the 21st century. METHODS: through a critical review of recent articles on the teaching of Neurology, to present a personal view on the subject. RESULTS: Diagnostic methods and therapeutic resources in Neurology will be greatly improved, but the central core of teaching young neurologists will continue to be the clinical/anatomical correlation. The neurologist must be prepared to be the primary physician in the care of patients with neurological disorders, although the roles of consultant and clinical neuroscientist must also be considered. In addition to technical knowledge, the neurologist must be prepared to discuss not only distressing issues related to the specialty, such as the risks of genetic diseases for family members of their patients, the inexorable progression of some diseases and the need for palliative care, but also problems not directly related to Neurology that cause anxiety and depression in the patient or that are the main reason for the initial consultation. CONCLUSION: neurology will be an even more important area of medicine and the neurologist must be well prepared to be the primary doctor to diagnose, treat and follow the patient with neurological disorders. In addition to technical knowledge, training in doctor-patient relations should be highlighted.

Neurologic adverse events of cancer immunotherapy.

Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neurologists, oncologists, hematologists, and other healthcare professionals who deal with cancer patients will not encounter this type of neurologic complication in their practice in the following years. This article aims to review the epidemiology, clinical manifestations, diagnosis, and management of neurological complications associated with ICI and CAR T-cell therapy.

The Utilization of Critical Care Resources in Pediatric Neurocritical Care Patients.

OBJECTIVES: To define the prevalence of neurologic diagnoses and evaluate the utilization of critical care and neurocritical care (NCC) resources among children admitted to the PICU. DESIGN: Retrospective cohort analysis. SETTING: Data submitted to the Virtual Pediatric Systems (VPS) database. PATIENTS: All children entered in VPS during 2016 (January 1, 2016, to December 31, 2016). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 128,688 patients entered into VPS and were comprised of 24.3% NCC admissions and 75.7% general PICU admissions. The NCC cohort was older, represented more scheduled admissions, and was more frequently admitted from the operating room. The NCC cohort also experienced a greater decline in prehospitalization to posthospitalization functional status and required more frequent use of endotracheal intubation, arterial lines, and foley catheters but had an overall shorter duration of PICU and hospital length of stay with a higher mortality rate. One thousand seven hundred fifteen patients at 12 participating institutions were entered into a novel, pilot NCC module evaluating sources of secondary neurologic injury. Four hundred forty-eight patients were manually excluded by the data entrant, leaving 1,267 patients in the module. Of the patients in the module, 75.8% of patients had a NCC diagnosis as their primary diagnosis; they experienced a high prevalence of pathophysiologic events associated with secondary neurologic insult (ranging from hyperglycemia at 10.5% to hyperthermia at 36.8%). CONCLUSIONS: In children admitted to a VPS-contributing PICU, a diagnosis of acute neurologic disease was associated with greater use of resources. We have identified the most common etiologies of acute neurologic disease in the 2016 VPS cohort, and such admissions were associated with significant decrease in functional status, as well as an increase in mortality.

Therapeutic plasma exchange in critically ill children: experience of the pediatric intensive care unit of two centers in Chile.

INTRODUCTION: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique used in a wide spectrum of diseases. We aim to review the indications, complications, and outcomes of critically ill children who received TPE and to compare a membrane versus centrifugal method in this cohort. METHODS: A retrospective observational study in two pediatric intensive care units in Chile during eight years (2011-2019) Results: A total of 36 patients underwent 167 TPE sessions (20 centrifugation and 16 membrane-based). The more frequent indications for TPE were autoimmune neurological diseases in 14 cases, renal diseases (9), and rheumatological disorders (5). 58 % of children received other immunomodulatory therapy. According to ASFA, 45 % of cases were I-II category, 50 % to III, and 5% not classified. Response to treatment was complete in 64 % (23/36) and partial in 33 % (12/36). Complications occurred in 17.4 % of sessions, and the most frequent was transient hypotension during the procedure. Overall survival at discharge from the PICU was 92 %. Patients who received TPE as a single therapy (n = 26) survived 96 %. The clinical outcomes between the two apheresis methods were similar. Survivors had a significantly lower PELOD score on admission (14.5 vs. 6.5, p = 0.004). CONCLUSIONS: TPE is mainly indicated as a rescue treatment in neurological autoimmune diseases refractory to conventional immunomodulatory treatment. Complications in critically ill children are mild and low. The outcome in children requiring TPE as a single therapy is good, and no differences were observed with centrifugation or membrane method.

Neurologic manifestations in hospitalized patients with COVID-19 in Mexico City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a systemic entity that frequently implies neurologic features at presentation and complications during the disease course. We aimed to describe the characteristics and predictors for developing in-hospital neurologic manifestations in a large cohort of hospitalized patients with COVID-19 in Mexico City. METHODS: We analyzed records from consecutive adult patients hospitalized from March 15 to June 30, 2020, with moderate to severe COVID-19 confirmed by reverse transcription real-time polymerase chain reaction (rtRT-PCR) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neurologic syndromes were actively searched by a standardized structured questionnaire and physical examination, confirmed by neuroimaging, neurophysiology of laboratory analyses, as applicable. RESULTS: We studied 1,072 cases (65% men, mean age 53.2±13 years), 71 patients had pre-existing neurologic diseases (diabetic neuropathy: 17, epilepsy: 15, history of ischemic stroke: eight, migraine: six, multiple sclerosis: one, Parkinson disease: one), and 163 (15.2%) developed a new neurologic complication. Headache (41.7%), myalgia (38.5%), dysgeusia (8%), and anosmia (7%) were the most common neurologic symptoms at hospital presentation. Delirium (13.1%), objective limb weakness (5.1%), and delayed recovery of mental status after sedation withdrawal (2.5%), were the most common new neurologic syndromes. Age, headache at presentation, preexisting neurologic disease, invasive mechanical ventilation, and neutrophil/lymphocyte ratio ≥9 were independent predictors of new in-hospital neurologic complications. CONCLUSIONS: Even after excluding initial clinical features and pre-existing comorbidities, new neurologic complications in hospitalized patients with COVID-19 are frequent and can be predicted from clinical information at hospital admission.

Precision clinical trials: a framework for getting to precision medicine for neurobehavioural disorders.

The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders. Traditional randomized clinical trial methods are insufficient for advancing precision medicine because of the dynamic complexity of these conditions. We present a pragmatic solution: the precision clinical trial framework, encompassing methods for individually tailored treatments. This framework includes the following: (1) treatment-targeted enrichment, which involves measuring patients' response after a brief bout of an intervention, and then randomizing patients to a full course of treatment, using the acute response to predict long-term outcomes; (2) adaptive treatments, which involve adjusting treatment parameters during the trial to individually optimize the treatment; and (3) precise measurement, which involves measuring predictor and outcome variables with high accuracy and reliability using techniques such as ecological momentary assessment. This review summarizes precision clinical trials and provides a research agenda, including new biomarkers such as precision neuroimaging, transcranial magnetic stimulation-electroencephalogram digital phenotyping and advances in statistical and machine-learning models. Validation of these approaches - and then widespread incorporation of the precision clinical trial framework - could help achieve the vision of precision medicine for neurobehavioural conditions.

Telemedicina para gestión de consultas, evaluaciones y manejo terapéutico en enfermedades neurológicas / Telemedicine for the management of consultations, evaluations and therapeutic management in neurological diseases

INTRODUCCIÓN A nivel mundial, cientos de millones de personas sufren trastornos neurológicos que requieren atención sanitaria prolongada. Tradicionalmente, es el/a paciente quien se desplaza al centro sanitario, habitualmente junto a un acompañante/cuidador, para recibir la atención neurológica. En los últimos años, el desarrollo de las tecnologías de la información y comunicación y su incorporación al ámbito sanitario ha permitido la prestación de servicios de salud a distancia. Recientemente, los problemas de acceso a los servicios sanitarios, provocados por la pandemia por COVID-19, han impulsado el desarrollo de los servicios de telemedicina, en general, y de teleneurología (TN), específicamente; por lo que resulta de interés tratar de reducir la incertidumbre de su efectividad, seguridad y eficiencia, frente al modelo convencional de asistencia sanitaria. OBJETIVO El objetivo principal del presente informe de Evaluación de Tecnología Sanitaria (ETS) es evaluar la seguridad, efectividad clínica y coste efectividad, así como los aspectos éticos, legales, organizativos, sociales y de pacientes, y ambientales, derivado del uso de la TN, comparando la atención habitual presencial sola con la atención habitual realizada junto a la TN para la gestión de consultas, evaluaciones y manejo terapéutico de pacientes con enfermedades neurológicas. METODOLOGÍA Efectividad y seguridad Se realizó una revisión sistemática (RS) de la literatura científica publicada en los últim

INTRODUCTION Worldwide, hundreds of millions of people suffer from neurological disorders that require long-term health care. Traditionally, the patient travels to the health center, usually accompanied by a companion/carer, to receive their neurological care. The recent development of information and communication technology and its incorporation into the health field has meant that health services can be provided online. Problems of access to health services caused by the recent COVID-19 pandemic have promoted the development of telemedicine, in general, and specifically teleneurology (TN); it is therefore of interest to try to reduce the uncertainty surrounding its effectiveness, safety and efficiency, compared to the conventional healthcare model. AIMS The main aim of this Health Technology Assessment report (HTA) is to evaluate the safety, clinical effectiveness and cost-effectiveness, as well as the ethical, legal, organizational, social and environmental aspects as well as those of patients derived from the use of TN, as a complement to the usual face-to-face care for the management of consultations, evaluations and therapeutic management of patients with neurological diseases, compared to usual care. METHOD Effectiveness and safety A systematic review (SR) of the published scientific literature in the last ten years was perforrmed. Randomized

[Blindness and neurological sequelae following carbon monoxide poisoning: effective treatment with hyperbaric oxygen]. / Ceguera y trastornos neurológicos por monóxido de carbono: tratamiento efectivo con oxígeno hiperbárico en dos pacientes pediátricos.

We present two patients who developed visual deterioration due to carbon monoxide poisoning. They were treated with hyperbaric oxygen and recovered not only their vision but also they improved neurological signs and symptoms. We believe that implementation of hyperbaric oxygen, even in a late period of time will be effective in reversing neurological sequelae.

Se presentan dos pacientes que desarrollaron deterioro visual debido a una intoxicación por monóxido de carbono. Ellos fueron tratados con oxígeno hiperbárico y recuperaron no solo su visión, sino que, además, mejoraron su signo-sintomatología neurológica. Se cree que la implementación de oxígeno hiperbárico, incluso en un período tardío, será efectiva para revertir las secuelas neurológicas.