Background Traumatic brain injury (TBI) involves systemic inflammation, oxidative stress, and metabolic disturbances. The systemic inflammation response index (SIRI) and serum uric acid (UA) are both linked to inflammatory and oxidative processes, but their relationship in acute TBI is unclear. Objective To examine the association between SIRI and serum UA in adults with acute TBI, including potential nonlinear patterns and differences by sex and injury severity. Methods This retrospective cross-sectional study included 1,930 adults with CT-confirmed acute TBI admitted between March 2018 and April 2024. Laboratory data were collected within 24 h of admission. SIRI was calculated as neutrophil × monocyte/lymphocyte. Multivariable linear regression, generalized additive models, and piecewise linear regression were used to assess the association between SIRI and UA. Subgroup analyses were conducted by sex and Glasgow Coma Scale (GCS) category. Results Higher SIRI was independently associated with higher UA levels. In the fully adjusted model, each 1-unit increase in SIRI corresponded to a 0.88 μmol/L increase in UA ( β = 0.88, 95% CI: 0.29–1.47). The relationship was approximately linear, and the threshold model did not significantly improve fit. The association was significant in both sexes, stronger in females, and significant only in patients with severe TBI (GCS 3–8). Conclusion Higher SIRI was associated with increased serum UA in acute TBI, suggesting a link between systemic inflammation and purine metabolism after injury. This relationship may be stronger in females and in severe TBI. Further longitudinal multicenter studies are needed.

Objective To develop and validate a multimodal model integrating neuroimaging and plasma biomarkers for predicting the risk of cognitive progression in preclinical Alzheimer’s disease (AD). Methods This retrospective study enrolled 320 patients with Aβ-positive preclinical AD or AD-related mild cognitive impairment. Participants were randomly allocated into training and validation sets at a 7:3 ratio. In the training set, univariable analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariable Logistic regression were employed to identify core predictive variables. Subsequently, four machine learning models were constructed based on these variables. Model performance was evaluated using the area under the receiver operating characteristic Curve (AUC), calibration curves, and decision curve analysis. Interpretability was assessed using SHapley Additive exPlanations (SHAP) values. Results The baseline characteristics were balanced between the training and validation sets. LASSO regression identified five core variables: Mini-Mental State Examination total score, Rey Auditory Verbal Learning Test delayed recall, normalized hippocampal volume, plasma phosphorylated tau181, and apolipoprotein E ε4 allele status. Multivariable analysis confirmed these as independent predictors ( p < 0.01). The logistic regression model demonstrated robust predictive performance, achieving the highest area under the curve (AUC) in the independent validation set (0.818, 95% confidence interval: 0.703–0.933). Calibration and decision curve analyses conducted on the validation set indicated that the model was accurate and possessed clinical utility. SHAP analysis applied to the optimal model showed that normalized hippocampal volume was the most influential contributor to the predictions. Conclusion The developed multimodal model exhibits robust predictive performance and clinical utility. It may serve as a quantitative tool for individualized risk management in preclinical AD.

Sleep is a complex process thought to be regulated by both a circadian system closely tied to ambient light and a homeostatic process characterized by increasing pressure to sleep commensurate with increasing duration of wakefulness. Critical illness is often a complex, multi-system physiological insult characterized by high levels of stress hormones and inflammatory biomarkers as well as pain and anxiety which negatively impacts sleep. Sleep loss may potentiate physiological disturbances and is increasingly being linked to poor ICU outcomes. The current gold standard for improving the sleep of ICU patients is to bundle multiple non-pharmacologic interventions; medication should only be prescribed for sleep when those measures failed to produce the desired results. Medication administered to facilitate sleep has had disappointing results in the ICU and may have unintended consequences such as increasing the risk of delirium and falls. In general, pharmacotherapies used to induce sleep (hypnotics) have focused on targeting specific points along the arousal/sleep pathway. Another approach has been to enhance chronotropy both by non-pharmacologic measures as well as by melatonin supplementation or administration of melatonin receptor agonists. There have been some efforts to promote wakefulness as an effort to leverage the homeostatic pressure to sleep at night rather than allowing sleep to occur intermittently throughout the 24 h day as occurs during critical illness. This review will summarize the current data regarding the pharmacologic management of sleep in the ICU and propose one potential approach.

This study used the rabbit facial nerve crush injury model to investigate the time-dependent effects of acupuncture at Hegu (LI04) on facial nerve regeneration and regulatory role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Thirty-two New Zealand rabbits with facial nerve crush injury were randomly assigned to four groups (n = 8 each): sham-operated, model, acute-phase acupuncture (treatment initiated immediately after modeling, daily for 10 days), and chronic-phase acupuncture (treatment initiated 7 days after modeling, daily for 10 days). Simone's 10-point scale was used for behavioral assessment on day 1 and day 17 post-modeling. Hematoxylin & Eosin staining was used for histomorphology analysis. PI3K, Akt, and mTOR protein and mRNA expression levels were assessed by immunohistochemistry and RT-qPCR, respectively. Both acute- and chronic-phase acupuncture interventions significantly improved the facial nerve function scores, reduced myelin sheath edema, and upregulated the expression levels of PI3K, Akt, and mTOR compared to the model group. Compared to the chronic-phase intervention, the acute-phase intervention yielded superior functional recovery, more regular nerve fiber arrangement, and stronger upregulation of PI3K, Akt, and mTOR proteins and mRNAs. In this experimental model, acupuncture at Hegu (LI04) was associated with improved repair of facial nerve crush injury, with acute-phase intervention showing greater efficacy than chronic-phase intervention. This time-dependent effect was accompanied by upregulation of the PI3K/Akt/mTOR signaling pathway, suggesting a potential association. However, given the substantial methodological limitations-including the absence of sham controls, lack of electrophysiological validation, and the partial nature of the injury model-these findings provide preliminary experimental evidence that may help inform the design of future clinical studies, rather than serving as confirmatory evidence.

Recently, several clinical studies have shown that higher systolic blood pressure (SBP) upon admission is associated with poor clinical outcomes in patients with ischemic stroke following endovascular treatment (EVT). However, the effect of the mean systolic blood pressure (MSBP) upon admission on patients with acute anterior circulation large vessel occlusion (ACLVO) who underwent EVT after 24 h is unclear. We sought to assess the association between MSBP at admission and clinical outcomes in patients treated with EVT for acute ACLVO beyond 24 h after onset. Patients with ACLVO treated with EVT more than 24 h after symptom onset were consecutively enrolled during a 3-year period at a tertiary stroke center. MSBP was measured at admission using an automatic cuff recording. The efficacy outcome was a 3-month good functional outcome (modified Rankin Scale score of 0-2). Symptomatic intracerebral hemorrhage (sICH) and mortality at 3 months were the safety outcomes. A total of 57 patients with acute ischemic stroke who met the inclusion criteria were included in the study (mean age 56 ± 12 years, mean National Institute of Health Stroke Scale score 11 ± 5). In the Firth penalized likelihood logistic regression analyses adjusted for confounding factors, higher MSBP levels were significantly negatively correlated with good clinical outcomes (odds ratio: 0.012; 95% confidence interval: 0.000-0.204). There was no significant association between high SBP and sICH or mortality. Our study suggests that higher MSBP at admission is an independent predictor of a poor clinical outcome at 3 months in patients treated with EVT for acute ACLVO beyond 24 h after onset.

Levetiracetam (LEV) is a broad-spectrum, second-generation anti-seizure medication and is commonly used as a first-line therapy for both generalized and focal epilepsies. A wide range of adverse effects has been reported with LEV, including neurological, dermatological, muscular, and hematological effects. However, psychobehavioral adverse effects (PBAEs) are the most frequently reported. The aim of this review is to explore different psychobehavioural adverse effect of LEV, the risk factors and specific available interventions. Serious but uncommon psychiatric adverse effects include psychosis and suicidality, whereas behavioral adverse effects, such as irritability, aggression, and agitation, are more common. The mean reported rates of irritability, anger, and aggressiveness are 9.9, 2.5, and 2.6%, respectively, with reported discontinuation rates of 2.4-3.4% attributable to aggression and irritability. Several risk factors have been associated with an increased likelihood of developing PBAEs, including a prior history of psychiatric illness, male sex, age <60 years, poorly controlled epilepsy, secondary generalized epilepsy, and absence seizures. In pediatric populations, the reported prevalence of PBAEs ranges from 12 to 38.7%, with a discontinuation rate of approximately 16% due to these adverse effects. Early recognition of PBAEs is essential when initiating LEV therapy. Patients who develop significant PBAE may require dose reduction or discontinuation of LEV, depending on symptom severity. In severe cases, temporary treatment with antipsychotic medications may be required to control behavioral or psychotic symptoms.

To explore the changes in brain network functional connectivity (FC) in patients with benign paroxysmal positional vertigo (BPPV) before and after otoconial repositioning treatment, and to analyze the correlation between FC and the Dizziness Handicap Inventory (DHI) score, thereby elucidating the neural basis of BPPV from a central mechanism perspective. A prospective cohort design was adopted, including 29 BPPV patients (BPPV group) and 29 healthy controls (control group). Resting-state brain network data were collected using 44-channel functional near-infrared spectroscopy (fNIRS), and the FC intensity of the whole brain and regions of interest (ROIs) was calculated. FC detection and DHI scoring were performed in the BPPV group before and 7 days after repositioning. Group comparisons were conducted using t-tests or Mann-Whitney U tests, and correlations were analyzed using Pearson analysis. The whole-brain FC in the BPPV group before repositioning (0.52 ± 0.20) was significantly lower than that in the control group (0.64 ± 0.18) (t = -4.32, P < 0.01). Seven days after repositioning, the FC of the visual cortex V1, V2 + V3, and somatosensory cortex increased compared with that before treatment (P < 0.05), but did not return to normal levels (P < 0.05). The DHI score was negatively correlated with whole-brain FC (r = -0.62, P < 0.01). fNIRS revealed characteristic FC alterations in BPPV: acute-phase decreases, partial sensory cortex recovery post-repositioning, and delayed prefrontal recovery. FC correlated negatively with symptom severity, suggesting its potential as an objective biomarker. These findings provide insights into central mechanisms and support neuroregulation-assisted therapy development.

Early etiologic discrimination between large-artery atherosclerosis (LAA) and small-vessel occlusion (SVO) is clinically relevant when advanced imaging is unavailable or delayed. We examined whether combining carotid pulse wave velocity (PWV) with the triglyceride-glucose (TyG) index improves early in - hospital discrimination of LAA vs. SVO, and developed a predictive model integrating PWV, TyG, and clinical indicators. We performed a single-centre retrospective study including consecutive acute ischaemic stroke patients from September 2021 to November 2023. Carotid PWV (Wv, m/s) was measured bilaterally and averaged; TyG was calculated from fasting triglycerides and glucose. Restricted cubic splines (RCS) tested non-linearity. Multivariable logistic regression was applied to (i) estimate the adjusted association of PWV and TyG with LAA versus SVO, and (ii) identify independent predictors via backward stepwise selection and establish predictive model. Discrimination was assessed by ROC AUC with DeLong tests; calibration used bootstrap-corrected curves; internal validation used 1,000-bootstrap optimism correction; decision-curve analysis appraised clinical utility. Of 892 admissions screened, 298 were analysed (SVO 179; LAA 119). LAA showed higher PWV (median 17.72 vs. 15.02 m/s; p < 0.001) and higher TyG (8.85 vs. 8.64; p = 0.005) than SVO. RCS supported overall associations of PWV and TyG with LAA versus SVO without evidence of non-linearity. Compared with single markers (AUC: PWV = 0.627; TyG = 0.596), a two-marker model (PWV + TyG) achieved AUC 0.654, while a parsimonious four-variable model (PWV, TyG, sex, eGFR) reached AUC 0.685 and significantly outperformed either single marker (paired DeLong vs. PWV: ΔAUC 0.058, p = 0.043; vs. TyG: ΔAUC 0.089, p = 0.011). Calibration was acceptable after bootstrap correction. PWV and TyG provide complementary, early in - hospital signals for moderate discrimination of LAA vs. SVO, with incremental value when combined. The predictive model constructed by combining PWV, TyG, and clinical indicators also performed well. These bedside markers provide adjunctive, early in-hospital risk stratification for suspected LAA versus SVO.

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system caused by reactivation of latent JC virus in immunocompromised individuals. Despite advances in understanding its pathogenesis, PML remains a diagnostic challenge due to its diverse clinical manifestations, radiographic overlap with other disorders, low incidence and subsequent lack of clinical familiarity. Diagnostic delays, often extending months after symptom onset, are common and contribute to poor outcomes. This review outlines the key clinical features, risk factors, diagnostic and neuroradiographic findings of PML to aid practicing neurologists in timely recognition and expedited diagnosis. We review emerging biomarkers and advanced diagnostic tools to identify PML. We also compare PML with its common mimics to underscore diagnostic pitfalls and how to overcome them. Novel and experimental therapies are beyond the scope of this article; instead, we focus on equipping neurologists with a framework grounded in patient data and clinical experience to establish timely diagnoses of PML.

Australia's native fauna is unique through millions of years of isolated evolution resulting in a significant divergence of marsupial brain anatomy, and thus neural pathways, from eutherian mammals. This study provides a morphometric description of a mature female koala (Phascolarctos cinereus) through segmentation of high-resolution magnetic resonance images. As the availability of brain specimens of the endangered koala is scarce, brain segmentation has been performed on a single specimen. The brain of a naturally deceased koala was removed and fixed in 10% neutral buffered formaldehyde (pH 7.0). The MRI was acquired on a 9.4 T Bruker Biospec MR system with Paravision 7.0 software, using a 3D multigradient echo sequence, with TR/TE = 70 msec/ (8 echoes 4-32 msec), a field of view = 7.0 × 6.4 × 4.0 cm3. AMIRA post image processing software was used to create three-dimensional volume reconstruction of different brain structures, allowing for the calculation of their volumes. The koala brain is lissencephalic and has a volume of 15720.98 mm3. It was found that the olfactory bulbs of the koala were 418 mm3 or 2.66% of the total brain volume (tbv). The cerebral hemispheres were 9336.92 mm3 (59.39% of the tbv). The interhemispheric connections were 148 mm3 (0.94% of tbv). The combined volume of the anterior commissure and fasciculus aberrans, which is specific to marsupials, has also been labeled and segmented. The ventricular system was 172 mm3 (1.09% of tbv). The brainstem was 1874 mm3 (11.92% of tbv). The cerebellum was 2304.69 mm3 (14.66% of tbv). This study can be used as a basis for clinical imaging of koalas and as baseline data for future research into brain development of koalas and other marsupials.