Acute Neurological Disorders Research Articles

Specific features of bilateral otolith manifestations in patients with vestibular balance disorder

Bilateral asymmetry in the function of the semicircular canals underlies dizziness and vestibular balance disorders. According to the traditional view, otolith dysfunction does not have a significant effect on the clinical picture in individuals with peripheral vestibular disorders. In recent years, interest in studying the contribution of vestibular function to the control of posture and movements has increased. However, we have not identified any studies addressing the reactivity of otolith organs in vestibular balance disorders in the available literature.Aim: To study bilateral otolith reactions in patients with vestibular balance disorders using the method of cervical vestibular evoked myogenic potentials (cVEMP) in patients with episodic and chronic vestibular disorders.Material and Methods. A clinical examination was carried out in 63 patients complaining of dizziness and balance problems. They were hospitalized on an emergency and planned basis in the neurological departments of the clinics of the Siberian State Medical University and the Medical and Sanitary Unit No 2 in Tomsk. From the total group, 28 patients (8 men and 20 women aged from 22 to 84 years) were selected for assessment of vestibular function; the average age was 63.87 ± 11.52 years and 57.2 ± 18.5 years for men and women respectively. They had chronic and episodic vestibular dysfunction unrelated to acute or progressive neurological disease and inflammatory pathology of the inner ear.Results. 27 patients (96.4%) complained of dizziness. Systemic dizziness, characterized by a feeling of objects rotating around the subject, was detected in 29.63% of patients; non-systemic dizziness, including a feeling of “failing” – in 81.48%. Both types of complaints appeared in 10.71% of those examined, which made it possible to identify 2 groups of patients: Group A – with chronic vestibular disorders (7 patients) and Group B – with episodic vestibular disorders (21 patients). During the study of the groups of patients, differences were found in the amplitudes of cVEMP latency P13 and the coefficient of vestibular asymmetry between Groups A and B, as well as the absence of a difference in amplitudes in Group A and the presence of a difference in Group B on the right.Conclusion. Despite the fact that patients presented with predominantly one complaint of dizziness, clinical and instrumental tests of vestibular dysfunction showed the presence of damage to both the semicircular canals and otolithic organs; asymmetry of vestibular reflexes and/or bilateral damage to the vestibular organs. The results of the study allow us to consider the cVEMP method as one of the methods for objectively assessing the condition of the otolithic apparatus in patients with impaired vestibular function. In this regard, it is recommended to use this method in routine neurological practice.

Pattern of Injuries in Children with Epilepsy: A Hospital-Based Case-Control Study

Abstract Objective The aim of this study is to examine the profile and pattern of injuries in children with epilepsy (CWE) as compared with healthy controls. Methods This prospective, cross-sectional study conducted over 1 year in a tertiary care pediatric center included consecutive CWE aged 4 to 16 years who had active seizures during the preceding 1 year. A similar number of age- and sex-matched healthy controls were enrolled. Children with acute symptomatic seizures or degenerative neurologic disorders were excluded. Standardized scales were used to assess intelligent quotient, psychopathology, seizure severity, and restriction of daily activities. Results Two hundred and eight CWE (mean age: 107 ± 37months; range: 3.5–16 years) and an equal number of healthy controls (mean age: 108 ± 43 months; range: 3.5–16 years; p = 0.07) were evaluated. The majority of CWE had generalized epilepsy (n = 117, 59.6%) followed by focal epilepsy (n = 84, 40.3%). The mean duration of epilepsy was 47.4 ± 36.3 months. The prevalence of injury was significantly greater in CWE (n = 118/208, 56.7%) compared with controls (n = 56/208, 26.9%; p < 0.001). CWE suffered significantly greater number of 293 injuries in the past 1 year in contrast to 83 injuries in controls (p < 0.001). In CWE, the majority of injuries were unrelated to seizures (n = 85/118, 72%, 211 injuries), while only one-third (n = 33/118, 27.9%, 82 injuries) suffered seizure-related injuries. The incidence of injures unrelated to seizures and that of seizure-related injuries were similar (2.48 seizure-related injuries per person per year). Among CWE, a comparison of the injury versus noninjury group showed a significantly longer duration of epilepsy (53 ± 34 vs. 40 ± 38 months, p < 0.007), higher prevalence of underlying structural etiology in generalized epilepsy (34.7 vs. 13.3%, p < 0.001), higher mean seizure severity and restriction of daily activity scores, and higher prevalence of hyperactivity (36.4 vs. 18.9%, p = 0.006) and intellectual disability (35.6 vs. 10%, p < 0.001) in the injury group. Injuries on the head, face, and upper limb were significantly more in CWE as compared with controls, and tongue injuries were found only in CWE (p =< 0.05), and were seen significantly more as seizure-related injury (n = 7 vs. 1, p < 0.001) compared with non-seizure-related injuries. The majority of injuries in children with CWE and controls were mild in nature (n = 112, 53.8% vs. n = 54, 26%; p < 0.001). Conclusions The prevalence of injuries among CWE aged between 4 and 16 years is high and is significantly greater than in healthy controls, although the majority of injuries are mild in severity in both and are non-seizure-related injuries. Longer duration of epilepsy, higher seizure severity, and restriction of daily activities, and higher prevalence of underlying structural etiology, hyperactivity, and intellectual disability are associated with injuries in CWE.

MiRNA506 Activates Sphk1 Binding with Sirt1 to Inhibit Brain Injury After Intracerebral Hemorrhage via PI3K/AKT Signaling Pathway.

Intracerebral hemorrhage (ICH) is an acute neurological disorder characterized by high mortality and disability rates. Previous studies have shown that 75% of patients who survive ICH experience varying degrees of neurological deficits. Sphk1 has been implicated in a multitude of phylogenetic processes, including innate immunity and cell proliferation. An in vivo rat model of ICH and an in vitro model of neuronal oxyhemoglobin (OxyHb) were constructed. The expression level of Sphk1 was assessed using western blotting and immunofluorescence, whereas cell death following ICH was evaluated using fluoro-Jade B and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Immunofluorescence facilitated the examination of microglial phenotypic alterations, while enzyme-linked immunosorbent assays were used to determine the concentrations of inflammatory markers. Behavioral assays were employed to assess the overall behavioral modifications of animals. Neuronal Sphk1/Sirt1 protein levels gradually increased following the induction of ICH. Elevated Sphk1 expression resulted in increased levels of anti-inflammatory microglia and reduced levels of pro-inflammatory factors. In contrast, suppression of Sphk1 expression resulted in an increased number of dead cells, thereby exacerbating neurological deficits. In vitro findings indicated that the levels of phosphorylated PI3K and AKT proteins increased in conjunction with Sphk1 expression. This study established that after ICH, Sphk1 interacts with Sirt1 to mitigate neuroinflammation, cell death, oxidative stress, and brain edema via the PI3K/AKT signaling pathway. Augmenting expression of Sphk1 significantly can ameliorate neurological impairments induced by ICH, offering novel targets and perspectives for therapeutic interventions in ICH treatment.

Ferroptosis: Potential therapeutic targets and prognostic predictions for acute myeloid leukemia (Review).

Ferroptosis is a relatively recently discovered type of regulated cell death that is induced by iron-dependent lipid peroxidation. The key contributing factors to ferroptosis are the loss of glutathione peroxidase 4 which is required for reversing lipid peroxidation, the buildup of redox-active iron and the oxidation of phospholipids containing polyunsaturated fatty acids. Ferroptosis has been associated with a number of diseases, including cancers such as hepatocellular carcinoma, breast cancer, acute renal damage and neurological disorders such as Alzheimer's disease and Alzheimer's disease, and there may be an association between ferroptosis and acute myeloid leukemia (AML). The present review aims to describe the primary regulatory pathways of ferroptosis, and the relationship between ferroptosis and the occurrence and development of AML. Furthermore, the present review comprehensively summarizes the latest advances in the treatment and prognosis of ferroptosis in AML.

Astrocytic centrin-2 expression in entorhinal cortex correlates with Alzheimer's disease severity.

Astrogliosis is a condition shared by acute and chronic neurological diseases and includes morphological, proteomic, and functional rearrangements of astroglia. In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium-binding protein centrin-2 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted-mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2-positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL-40, indicating a human-specific role in AD-induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.

Transition to end-of-life care in patients with neurological diseases in an acute hospital ward

BackgroundTransitioning to end-of-life care and thereby changing the focus of treatment directives from life-sustaining treatment to comfort care is important for neurological patients in advanced stages. Late transition to end-of-life care for neurological patients has been described previously.ObjectiveTo investigate whether previous treatment directives, primary medical diagnoses, and demographic factors predict the transition to end-of-life care and time to eventual death in patients with neurological diseases in an acute hospital setting.MethodAll consecutive health records of patients diagnosed with stroke, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease or other extrapyramidal diseases (PDoed), who died in an acute neurological ward between January 2011 and August 2020 were retrieved retrospectively. Descriptive statistics and multivariate Cox regression were used to examine the timing of treatment directives and death in relation to medical diagnosis, age, gender, and marital status.ResultsA total of 271 records were involved in the analysis. Patients in all diagnostic categories had a treatment directive for end-of-life care, with patients with haemorrhagic stroke having the highest (92%) and patients with PDoed the lowest (73%) proportion. Cox regression identified that the likelihood of end-of-life care decision-making was related to advancing age (HR = 1.02, 95% CI: 1.007–1.039, P = 0.005), ischaemic stroke (HR = 1.64, 95% CI: 1.034–2.618, P = 0.036) and haemorrhagic stroke (HR = 2.04, 95% CI: 1.219–3.423, P = 0.007) diagnoses. End-of-life care decision occurred from four to twenty-two days after hospital admission. The time from end-of-life care decision to death was a median of two days. Treatment directives, demographic factors, and diagnostic categories did not increase the likelihood of death following an end-of-life care decision.ConclusionsResults show not only that neurological patients transit late to end-of-life care but that the timeframe of the decision differs between patients with acute neurological diseases and those with progressive neurological diseases, highlighting the particular significance of the short timeframe of patients with the progressive neurological diseases ALS and PDoed. Different trajectories of patients with neurological diseases at end-of-life should be further explored and clinical guidelines expanded to embrace the high diversity in neurological patients.

Exploring Microorganisms Associated to Acute Febrile Illness and Severe Neurological Disorders of Unknown Origin: A Nanopore Metagenomics Approach.

Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical cases. In this study, we aim to shed light on the etiological agents underlying AFI and SND cases that conventional diagnostic methods have not been able to fully elucidate. Our approach involved analyzing samples from fourteen hospitalized patients using a comprehensive nanopore metagenomic approach. This process included RNA extraction and enrichment using the SMART-9N protocol, followed by nanopore sequencing. Subsequent steps involved quality control, host DNA/cDNA removal, de novo genome assembly, and taxonomic classification. Our findings in AFI cases revealed a spectrum of disease-associated microbes, including Escherichia coli, Streptococcus sp., Human Immunodeficiency Virus 1 (Subtype B), and Human Pegivirus. Similarly, SND cases revealed the presence of pathogens such as Escherichia coli, Clostridium sp., and Dengue virus type 2 (Genotype-II lineage). This study employed a metagenomic analysis method, demonstrating its efficiency and adaptability in pathogen identification. Our investigation successfully identified pathogens likely associated with AFI and SNDs, underscoring the feasibility of retrieving near-complete genomes from RNA viruses. These findings offer promising prospects for advancing our understanding and control of infectious diseases, by facilitating detailed genomic analysis which is critical for developing targeted interventions and therapeutic strategies.

Efficacy and Safety of Rescue Treatment with Plasma Exchange in Patients with Acute Inflammatory Neurological Disorders: A Single Center Experience.

Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain-Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.

Brain Expression Levels of Commonly Measured Blood Biomarkers of Neurological Damage Differ with Respect to Sex, Race, and Age

It is increasingly evident that blood biomarkers have potential to improve the diagnosis and management of both acute and chronic neurological conditions. The most well-studied candidates, and arguably those with the broadest utility, are proteins that are highly enriched in neural tissues and released into circulation upon cellular damage. It is currently unknown how the brain expression levels of these proteins is influenced by demographic factors such as sex, race, and age. Given that source tissue abundance is likely a key determinant of the levels observed in the blood during neurological pathology, understanding such influences is important in terms of identifying potential clinical scenarios that could produce diagnostic bias. In this study, we leveraged existing mRNA sequencing data originating from 2,642 normal brain specimens harvested from 382 human donors to examine potential demographic variability in the expression levels of genes which code for 28 candidate blood biomarkers of neurological damage. Existing mass spectrometry data originating from 26 additional normal brain specimens harvested from 26 separate human donors was subsequently used to tentatively assess whether observed transcriptional variance was likely to produce corresponding variance in terms of protein abundance. Genes associated with several well-studied or emerging candidate biomarkers including neurofilament light chain (NfL), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), neuron-specific enolase (NSE), and synaptosomal-associated protein 25 (SNAP-25) exhibited significant differences in expression with respect to sex, race, and age. In many instances, these differences in brain expression align well with and provide a mechanistic explanation for previously reported differences in blood levels.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

Clinical characteristics and risk factors of in-hospital mortality in patients with Takotsubo syndrome

Takotsubo cardiomyopathy is a condition of transient systolic dysfunction triggered by emotional or physical stress. Nowadays, Takotsubo cardiomyopathy is gaining attention and has been detected more frequently. However, there is no collected data on Vietnamese subjects. This study aims to describe the clinical characteristics of patients diagnosed with Takotsubo cardiomyopathy and determine of rates and independent risk factors for in-hospital mortality. A retrospective andobservational study was conducted at the University Medical Center Ho Chi Minh City, involved 103 patients diagnosed with Takotsubo cardiomyopathy between January 2015 and June 2022. The diagnosis was made based on the revised Mayo Clinic diagnostic criteria. The average age of the study population was 71.2±15.3 years, with females accounting for 64.1% of the patients. The most common comorbidities among the patients were hypertension (57.3%), diabetes mellitus (30.1%), ischemic heart disease (15.5%), and chronic obstructive pulmonary disease (15.5%). Acute heart failure was observed in 30.1% of the patients, while ventricular arrhythmias were present in 17.6% of cases. The majority of triggers were attributed to physical factors, including infection (37.9%), respiratory failure (18.4%), postoperative status (3.9%), and acute neurological disease (2.9%). The in-hospital mortality rate was 17.5%, and the independent risk factors were identified as acute heart failure (OR=20.657, 95%CI 2.306–185.008, p=0.007) and respiratory failure (OR=10.397, 95% CI 1.117–96.795, p=0.040). Takotsubo cardiomyopathy patients have many comorbidities and are often triggered by physical factors. The in-hospital mortality rate is significant, with acute heart failure and respiratory failure identified as independent risk factors.

Clinical characteristics and risk factors of in-hospital mortality in patients with Takotsubo syndrome

Takotsubo cardiomyopathy is a condition of transient systolic dysfunction triggered by emotional or physical stress. Nowadays, Takotsubo cardiomyopathy is gaining attention and has been detected more frequently. However, there is no collected data on Vietnamese subjects. This study aims to describe the clinical characteristics of patients diagnosed with Takotsubo cardiomyopathy and determine of rates and independent risk factors for in-hospital mortality. A retrospective andobservational study was conducted at the University Medical Center Ho Chi Minh City, involved 103 patients diagnosed with Takotsubo cardiomyopathy between January 2015 and June 2022. The diagnosis was made based on the revised Mayo Clinic diagnostic criteria. The average age of the study population was 71.2±15.3 years, with females accounting for 64.1% of the patients. The most common comorbidities among the patients were hypertension (57.3%), diabetes mellitus (30.1%), ischemic heart disease (15.5%), and chronic obstructive pulmonary disease (15.5%). Acute heart failure was observed in 30.1% of the patients, while ventricular arrhythmias were present in 17.6% of cases. The majority of triggers were attributed to physical factors, including infection (37.9%), respiratory failure (18.4%), postoperative status (3.9%), and acute neurological disease (2.9%). The in-hospital mortality rate was 17.5%, and the independent risk factors were identified as acute heart failure (OR=20.657, 95%CI 2.306–185.008, p=0.007) and respiratory failure (OR=10.397, 95% CI 1.117–96.795, p=0.040). Takotsubo cardiomyopathy patients have many comorbidities and are often triggered by physical factors. The in-hospital mortality rate is significant, with acute heart failure and respiratory failure identified as independent risk factors.

Risk Assessment of hematoma expansion in patients with hemorrhagic Stroke based on Stochastic Forest Prediction Model

This paper discusses the prediction model of hematoma expansion probability in patients with hemorrhagic stroke. Hemorrhagic stroke is an acute and critical neurological disease. High mortality and disability make it a major challenge in the field of public health. Hematoma dilatation and peri-hematoma edema are important factors leading to secondary brain injury. therefore, accurate prediction of the risk of hematoma expansion in patients with hemorrhagic stroke has important guiding significance for clinical diagnosis and treatment. First of all, this study carries on the matching integration and abnormal processing of the patient data in order to improve the data quality. Then, a classification model based on support vector machine (SVM) and random forest is constructed to predict the probability of hematoma expansion. Through the comparative analysis of the classification accuracy, it is found that the prediction effect of the classification model based on random forest is better than that based on SVM. This result provides clinicians with a more accurate prediction tool, which is helpful to identify high-risk patients early, reduce the incidence of secondary brain injury, and improve the quality of life and prognosis of patients. This study provides a new idea for the clinical diagnosis, treatment and research direction of hemorrhagic stroke, and has important theoretical and practical value.

Neurofilament Light Chain Concentration in Cerebrospinal Fluid in Children with Acute Nontraumatic Neurological Disorders.

(1) Introduction: This pilot study aimed to analyze neurofilament light chain levels in cerebrospinal fluid (cNfL) in a cohort of children with different acute nontraumatic neurological conditions. (2) Methods: This prospective observational cohort study consisted of 35 children aged 3 months to 17 years and was performed from November 2017 to December 2019. Patients' clinical data were reviewed, and patients were assigned to the following groups: n = 10 (28.6%) meningitis, 5 (14.3%) Bell's palsy, 7 (20.0%) febrile non-CNS infection, 3 (8.6%) complex febrile seizure, 4 (11.4%) idiopathic intracranial hypertension, and 6 (17.1%) others. cNfL levels were measured using a sensitive single-molecule array assay. (3) Results: The cNfL levels [median (range)] in children with meningitis were 120.5 pg/mL (58.1-205.4), in Bell's palsy 88.6 pg/mL (48.8-144.5), in febrile non-CNS infection 103.9 pg/mL (60.1-210.8), in complex febrile seizure 56 pg/mL (53.2-58.3), and in idiopathic intracranial hypertension 97.1 pg/mL (60.1-124.6). Within the meningitis group, children with Lyme neuroborreliosis (LNB) had significantly higher cNfL concentrations (median 147.9 pg/mL; range 87.8-205.4 pg/mL) than children with enterovirus meningitis (72.5 pg/mL; 58.1-95.6 pg/mL; p = 0.048) and non-significantly higher cNfL levels when compared to Bell's palsy (88.6 pg/mL; 48.8-144.5 pg/mL; p = 0.082). There was no correlation between cNfL levels and age. (4) Conclusions: Although the number of patients in this pilot study cohort is limited, higher cNfL levels in children with LNB compared to those with viral meningitis (significant) and Bell's palsy (trend) may indicate the potential of cNfL as a biomarker in the differential diagnosis of pediatric meningitis and facial palsy.

The risk of delirium after sedation with propofol or midazolam in intensive care unit patients.

Knowledge of risk factors may provide strategies to reduce the high burden of delirium in intensive care unit (ICU) patients. We aimed to compare the risk of delirium after deep sedation with propofol versus midazolam in ICU patients. In this prospective cohort study, ICU patients who were in an unarousable state for ≥24 h due to continuous sedation with propofol and/or midazolam were included. Patients admitted ≤24 h, those with an acute neurological disorder and those receiving palliative sedation were excluded. ICU patients were assessed daily for delirium during the 7days following an unarousable state due to continuous sedation. Among 950 included patients, 605 (64%) subjects were delirious during the 7days after awaking. The proportion of subsequent delirium was higher after midazolam sedation (152/207 [73%] patients) and after both propofol and midazolam sedation (257/377 [68%] patients), compared to propofol sedation only (196/366 [54%] patients). Midazolam sedation (adjusted cause-specific hazard ratio [adj. cause-specific HR] 1.32, 95% confidence interval [CI] 1.05-1.66) and propofol and midazolam sedation (adj. cause-specific HR 1.29, 95% CI 1.06-1.56) were associated with a higher risk of subsequent delirium compared to propofol sedation only. This study among sedated ICU patients suggests that, compared to propofol sedation, midazolam sedation is associated with a higher risk of subsequent delirium. This risk seems more apparent in patients with high cumulative midazolam intravenous doses. Our findings underpin the recommendations of the Society of Critical Care Medicine Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guidelines to use propofol over benzodiazepines for sedation in ICU patients.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver.

Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity. A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), ; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 ). Beat-to-beat rBV and CBFv were also strongly correlated, , but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Clinical observations in acute neurology: A historical explanation of the present.

The history of the development of acute neurologic disease as a biologic mechanism is of interest. Equally important is how it translated to the bedside and how the clinical examination differentiated itself. This paper reviews primary sources pertaining to acute neurologic conditions described mostly in the 19th and 20th century. A review of monographs, treatises, textbooks, and peer-reviewed articles was conducted. The evolution of clinical signs and syndromes associated with dynamic intracranial pathologies was predicated on the idea that animal studies informed clinicians, who then linked clinical signs to these observations. A dominant theme is that innovative technologies could trace acute processes through all their various stages, affording a complete picture of the disease process. Just as clinical descriptors of central nervous system processes evolved, the presentation of acute neuromuscular respiratory failure became better defined. Once practices incorporated these acute clinical signs, textbooks cemented their "gold standard" status with relative impunity. The practise of acute neurology and neurocritical care must find out what, historically, others were seeking but could not find. Patterns of clinical presentation in acute neurology are sufficiently recognizable to guide practise decisions. Although, the currently well-documented clinical syndromes of acute neurologic conditions (at presentation and during deterioration) have been taught for generations, practitioners have noted that they lack consistency and predictability. History also taught us that part of this improved knowledge came with designated units-a clear example of how protean systems (not always innovative neurologists or neuroscientists or technologies) shaped the history of neurology.

Practice patterns in pediatric infectious encephalopathy in four centers in Africa.

Infectious encephalopathy (IE), including meningitis, infectious encephalitis, and cerebral abscess, remains prevalent and carries high mortality and morbidity in children, especially in low and middle income countries (LMIC). This study aims to describe the usual care and outcomes of pediatric IE in four LMIC hospitals in sub-Saharan Africa to support evidence-based care guideline development. This is a secondary analysis of the Prevalence of Acute Critical Neurological disease in children: A Global Epidemiological Assessment-Developing Countries study, a 4-week, prospective, observational study in children (1 week to 17 years) with IE presenting to referral hospitals in Ethiopia, Kenya, Rwanda, and Ghana. Data collection included diagnostic testing, interventions, and patient outcomes [e.g., mortality, Pediatric Cerebral and Overall Performance Category Scores (PCPC and POPC)]. Seventy-two children with IE were enrolled. Most patients were diagnosed with undifferentiated IE (78%, n = 56). Specific etiologies included cerebral malaria (10%, n = 7), viral encephalitis (4%, n = 3), tuberculosis (4%, n = 3), bacterial meningitis (3%, n = 2), and cerebral abscess (1%, n = 1). Fourteen patients (20%) had a head computed tomography performed. Thirty two (44%) children had a lumbar puncture but only 9 samples (28%) were sent for culture. Median time from diagnosis to antimicrobial therapy was 3 h (IQR 1-12 h). Half (51%, n = 33) of inpatients received intracranial pressure (ICP)-directed treatment but none underwent ICP monitoring. Mortality was 13% (n = 9). The percentage of children with a favorable cognitive score decreased from 95% (n = 62) prior to admission to 80% (n = 52) and 77% (n = 50) at discharge for PCPC and POPC respectively. IE led to considerable morbidity and mortality in this cohort, and evaluation and management varied across the care continuum. Resource limitations and diagnostic constraints may have affected diagnosis-directed therapy and other aspects of management. Further studies are needed to describe the epidemiology and management of IE in LMICs to inform future treatment protocols, the role of technological and human capacity building to support both basic monitoring and interventions, as well as creative new solutions to emergency and critical care in these settings.

The start-up of a neurosurgical service in an East Indonesian archipelagic province: The first 2-year experience of North Maluku Database in Neurosurgery (NOMADEN).

Despite encouraging developments after its initial founding in Indonesia more than seven decades ago, inequity in access and availability of neurosurgical services throughout the country continues to pose a challenge. We aimed to elaborate on the start-up of a previously inactive neurosurgical service in North Maluku, an archipelagic province in East Indonesia, and describe cases managed within the first two years of service. In the North Maluku Database in the Neurosurgery register, demographic and clinical information of neurosurgical patients admitted to Chasan Boesoirie General Hospital, Ternate, from January 2021 to December 2022, were analyzed. Surgically managed patients were rendered visually according to their decades of life and districts of events. There were 998 new patients (mean age ± standard deviation [SD]: 34.7 ± 19.6 years, 60.3% male) managed and 216 neurosurgical procedures (mean age ± SD: 33 ± 20.4 years, 67.1% male) performed. The majority of patients operated were within the 1st decade of life (18.5%), presented to the emergency room (56.5%), covered by national health insurance (69.4%), from outside Ternate (62.5%), diagnosed with neurotrauma (40.7%), and discharged alive (80.1%). Ternate was the only district where all seven types of neurological diseases were encountered. No surgeries were performed for patients from Taliabu, the farthest district from Ternate. A large portion of neurosurgical patients in North Maluku were those young and at productive age who were transported from outside Ternate with acute neurological disease (particularly neurotrauma). Distance and geographical circumstances may have a profound effect on access to neurosurgical services.