Impact of prophylactic echinocandin on the development of neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation: A single-center retrospective study.

BACKGROUND: Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan-based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation. METHODS: We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). RESULTS: Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. CONCLUSION: Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Paraneoplastic neurologic manifestations of neuroendocrine tumors.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from the transformation of neuroendocrine cells in several organs, most notably the gastro-entero-pancreatic system and respiratory tract. The classification was recently revised in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. NENs can rarely spread to the central or peripheral nervous systems. Neurologic involvement is determined by the rare development of paraneoplastic syndromes, which are remote effects of cancer. Mechanisms depend on immunologic response to a tumor, leading to the immune attack on the nervous system or the production of biologically active ("functioning") substances, which can determine humoral (endocrine) effects with neurologic manifestations. Paraneoplastic neurologic syndromes (PNS) are immunologically mediated and frequently detected in small cell lung cancer but rarely seen in other forms of NEN. PNS and Merkel cell carcinoma is increasingly reported, especially with Lambert Eaton myasthenic syndrome. Endocrine manifestations are found in a wide spectrum of NENs. They can develop at any stage of the diseases and determine neurologic manifestations. Patient outcomes are influenced by tumor prognosis, neurologic complications, and the severity of endocrine effects.

Epidemiology of paraneoplastic neurologic syndromes.

Paraneoplastic neurologic syndromes (PNS), initially depicted as seemingly cryptic remote manifestations of malignancy, were first described clinically in the early 20th century, with pathophysiologic correlates becoming better elucidated in the latter half of the century. There remain many questions not only about the pathophysiology but also regarding the epidemiology of these conditions. The continuous discovery of novel autoantigens and related neurologic disease has broadened the association in classical PNS to include conditions such as paraneoplastic cerebellar degeneration. It has also brought into focus several other neurologic syndromes with a putative neoplastic association. These conditions are overall rare, making it difficult to capture large numbers of patients to study, and raising the question of whether incidence is increasing over time or improved identification is driving the increased numbers of cases. With the rise and increasing use of immunotherapy for cancer treatment, the incidence of these conditions is additionally expected to rise and may present with various clinical symptoms. As we enter an era of clinical trial intervention in these conditions, much work is needed to capture more granular data on population groups defined by socioeconomic characteristics such as age, ethnicity, economic resources, and gender to optimize care and clinical trial planning.

Association between cytomegalovirus infection and neurological disorders: A systematic review.

Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.

Early Surgery for Infective Endocarditis Complicated With Neurologic Injury.

OBJECTIVES: To estimate the association between early surgery and the risk of mortality in patients with left-sided infective endocarditis in the context of stroke. DESIGN: Retrospective cohort study. SETTING: This study was a multiinstitution study based on the Chang Gung Research Database, which contains electronic medical records from 7 hospitals in northern and southern Taiwan; these include 2 medical centers, 2 regional hospitals, and 3 district hospitals. PARTICIPANTS: Patients with active left-sided infective endocarditis who underwent valve surgery between September 2002 and December 2018. INTERVENTIONS: The authors divided patients into 2 groups, with versus without preoperative neurologic complications, had undergone early (within 7 d) or later surgery, and with brain ischemia or hemorrhage. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-two patients with a median time from diagnosis to surgery of 6 days were included. No significant differences in postoperative stroke, in-hospital mortality, or follow-up outcomes were observed between the patients with and without neurologic complications. Among the patients with preoperative neurologic complications, patients who underwent early surgery had a lower 30-day postoperative mortality rate (13.1% v 25.8%; hazard ratio, 0.21; 95% CI 0.07-0.67). In the subgroup analysis of the comparison between brain ischemia and hemorrhage groups, there was no significant between-group difference in the in-hospital outcomes or outcomes after discharge. CONCLUSIONS: Early cardiac surgery may be associated with more favorable clinical outcomes in patients with preoperative neurologic complications. Thus, preoperative neurologic complications should not delay surgical interventions.

Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

[Bibliometric and visual analysis of neurological damage caused by electrical welding operations].

Objective: To analyze and summarize the trends and hot spots in the field of neurological damage caused by electric welding operations, and to provide ideas for new researches by searching the domestic and international literature. Methods: In December 2022, using Web of Science Citation Index (Web of Science), China Journal Full-Text Database (CNKI) and Wanfang Database as search databases, literature search was conducted on the Chinese and English search terms related to eletrical welding operations and neurological damage. The bibliometric analysis software VOSviewer 1.6.18 and CiteSpace 6.1.6 were used to visualize the publication year, publication quantity, country, research institution and key words of the literature. Results: A total of 309 articles (112 in Chinese and 197 in English) were included in this study. The first domestic and international papers were published in 1976 and 1994 respectively, and the number of papers reached the peak in 2006 and 2018, and then showed a downward trend to varying degrees. In China, Shandong First Medical University (including Shandong Institute of Occupational Health and Occupational Disease Prevention and Shandong Academy of Medical Sciences) and Wuhan University of Science and Technology had the largest number of publications. The 309 articles were from 52 Chinese journals and 86 English journals. The co-occurrence analysis of key words showed that the domestic research mainly focused on eletrical welding operation, welding workers, neurobehavioral function and manganese, and the nervous system damage caused by manganese in welding smoke was the field of international attention. Long term exposure, risk, and performance were key buzzwords in the field. Conclusion: The research focus in the field of nervous system damage caused by electric welding operation has an obvious trend of time evolution, gradually transiting from clinical manifestations to its toxic mechanism and early biomarkers.

Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders.

BACKGROUND: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND). METHODS: This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival. RESULTS: Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. INTERPRETATION: In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.

Targeting the mammalian target of rapamycin pathway in neurological manifestations of Covid-19.

The diverse and severe nature of neurological manifestations associated with coronavirus disease 2019 (Covid-19) has garnered increasing attention. Exploring the potential to decrease neurological complications in Covid-19 patients involves targeting the mammalian target of rapamycin (mTOR) pathway as a therapeutic strategy. The mTOR pathway, widely recognised for its central role in essential cellular processes like synthesising proteins, facilitating autophagy, and modulating immune responses, has implications in various neurological disorders. Drawing parallels between these disorders and the observed neurological complications in Covid-19, we present a comprehensive review on the current understanding of mTOR signalling in the context of severe acute respiratory syndrome coronavirus 2 infection and neuroinflammation.

Neurological disorders throughout acute SARS-CoV2 infection: A comparative study between vaccinated and non-vaccinated patients.

BACKGROUND: The role of vaccination on Covid-19 severity in neurological patients is still unknown. We aim at describing clinical characteristics and outcomes of breakthrough and unvaccinated Covid-19 patients hospitalized for neurological disorders. METHODS: Two hundred thirty-two Covid-19 patients were admitted to a neuro-Covid Unit form March 1st 2021 to February 28th 2022. Out of the total sample, 74 (32%) were full vaccinated. The prevalence, clinical characteristics, disease severity, expressed by Brescia-COVID Respiratory Severity Scale (BCRSS) and National Early Warning Score 2 (NEWS2), and final outcomes of neurological syndromes were compared between vaccinated and unvaccinated cases. Cox regression analysis was implemented in order to investigate the combined effect of predictors of mortality. RESULTS: Breakthrough vaccinated cases were older (years 72.4 ± 16.3 vs 67.0 ± 18.9 years, p = 0.029), showed higher pre-admission comorbidity score and Clinical Frailty scale score (4.46 ± 1.6 vs 3.75 ± 2.0, p = 0.008) with no differences in terms of disease progression or mortality rate (16.2% vs 15.2%), compared to full-dose vaccinated patients. Cox-regression analysis showed age and NEWS2 score as the variables with a significant relation to mortality between the two groups, independently from pre-morbid conditions and inflammatory response. CONCLUSION: This study on breakthrough COVID-19 infection could help identify vulnerable neurological patients with higher risk of poor outcomes.

Neurological involvement in patients with primary immunodeficiency

Introduction: Primary immunodeficiency diseases (PID) are defined by recurrent infections, allergies, autoimmunity, and malignancies. Neurologic symptoms are one of the major components of some immunodeficiency syndromes, such as Ataxia-Telangiectasia (AT), Nijmegen breakage syndrome (NBS), and Purine Nucleoside Phosphorylase (PNP) deficiency, which are considered as the primary involvement. Various pathological mechanisms, DNA repair disorders, metabolic abnormalities, and autoimmune phenomena have also been linked with neurological conditions. Materials and method: We retrospectively assessed the neurological involvement in 108 patients out of 6000 with PID in this study. Results: The female/male ratio of the cases was 49/59, and the median age was 13 years (min = 1; max = 60). Neurological problems were detected at a median age of 7 years (min = 0.5; max = 30). Di George Syndrome (DGS) and CVID (common variable immunodeficiency) were the most common diseases in our cohort (n = 31, 30% and n = 30, 27%, respectively). The most frequent outcomes were cognitive delay (n = 63, 58%), epilepsy (n = 25, 23%), and ataxia (n = 20, 18%). Central nervous system involvement was found in 99% of the patients (n = 107), and peripheral nervous system complication was found in only one patient with CVID and chronic inflammatory demyelinating polyneuropathy (CDIP). Cranial MRI was found to be abnormal in 74% (n = 80) of the patients. MRI findings included cerebellar atrophy (n = 33, 34%), white matter lesion (n = 27, 28.4%), cerebral atrophy (n = 21, 22.3%), gray matter lesion (n = 6, 6.3%), hydrocephalus (n = 5, 5,3%), and pituitary gland lesion (n = 3, 3.2%), intracranial hemorrhage (n = 3, 3%), intracranial vasculitis (n = 3, 2.7%), and arterio-venous malformation (n = 1, 0,9%) (AU)

Cost-benefit analysis of intraoperative neuromonitoring for cardiac surgery.

BACKGROUND: Intraoperative neuromonitoring (IONM) can detect large vessel occlusion (LVO) in real-time during surgery. The aim of this study was to conduct a cost-benefit analysis of utilizing IONM among patients undergoing cardiac surgery. METHODS: A decision-analysis tree with terminal Markov nodes was constructed to model functional outcome, as measured via the modified Rankin Scale (mRS), among 65-year-old patients undergoing cardiac surgery. Our cost-benefit analysis compares the use of IONM (electroencephalography and somatosensory evoked potential) against no IONM in preventing neurological complications from perioperative LVO during cardiac surgery. The study was performed over a lifetime horizon from a societal perspective in the United States. Base case and one-way probabilistic sensitivity analyses were performed. RESULTS: At a baseline LVO rate of 0.31%, the mean attributable lifetime expenditure for IONM-monitored cardiac surgeries relative to unmonitored cardiac surgeries was $1047.41 (95% CI, $742.12 - $1445.10). At a critical LVO rate of approximately 3.67%, the costs of both monitored and unmonitored cardiac surgeries were the same. Above this critical rate, implementing IONM became cost-saving. On one-way sensitivity analysis, variation in LVO rate from 0% - 10% caused lifetime costs attributable to receiving IONM to range from $1150.47 - $29404.61; variations in IONM cost, percentage of intervenable LVOs, IONM sensitivity, and mechanical thrombectomy cost exerted comparably minimal influence over lifetime costs. DISCUSSION: We find considerable cost savings favoring the use of IONM under certain parameters corresponding to high-risk patients. This study will provide financial perspective to policymakers, clinicians, and patients alike on the appropriate use of IONM during cardiac surgery.

Potential Neurologic Manifestations of COVID-19 Infection in Neonates.

In contrast to adults, neonates and infants with coronavirus disease 2019 (COVID-19) infection have milder symptoms and are less likely to require hospitalization. However, some neonates with COVID-19 can present with significant symptoms. Recent evidence suggests that neurologic manifestations of neonatal COVID-19 infection may be higher than initially thought. In this comprehensive review of the current literature, we summarize the clinical, laboratory, and radiologic findings, as well as potential management strategies for COVID-19-related neurologic illness in neonates. Although the growing brain may be affected by neurologic disease associated with COVID-19 infection, the few published studies on the long-term outcomes after COVID-19 infection in neonates and infants provide conflicting results. Larger collaborative clinical studies are needed to determine whether COVID-19 infection in neonates has long-term neurodevelopmental outcomes.

Neurological Complications Caused by Human Immunodeficiency Virus (HIV) and Associated Opportunistic Co-infections: A Review on their Diagnosis and Therapeutic Insights.

Neurocognitive disorders associated with human immunodeficiency virus (HIV) infected individuals increase the risk of mortality and morbidity that remain a prevalent clinical complication even in the antiretroviral therapy era. It is estimated that a considerable number of people in the HIV community are developing neurological complications at their early stages of infection. The daily lives of people with chronic HIV infections are greatly affected by cognitive declines such as loss of attention, learning, and executive functions, and other adverse conditions like neuronal injury and dementia. It has been found that the entry of HIV into the brain and subsequently crossing the blood-brain barrier (BBB) causes brain cell damage, which is the prerequisite for the development of neurocognitive disorders. Besides the HIV replication in the central nervous system and the adverse effects of antiretroviral therapy on the BBB, a range of opportunistic infections, including viral, bacterial, and parasitic agents, augment the neurological complications in people living with HIV (PLHIV). Given the immuno-compromised state of PLHIV, these co-infections can present a wide range of clinical syndromes with atypical manifestations that pose challenges in diagnosis and clinical management, representing a substantial burden for the public health system. Therefore, the present review narrates the neurological complications triggered by HIV and their diagnosis and treatment options. Moreover, coinfections that are known to cause neurological disorders in HIV infected individuals are highlighted.