Carbon dioxide is a key determinant of cerebral blood flow and is needed to prevent secondary damage in neurocritical care; however, optimal targets across the heterogeneous spectrum of acute brain injury (ABI) remain to be elucidated. The aim of this study was to evaluate the association between arterial hypocapnia and mortality and neurological outcomes in adult patients with ABI. Six electronic databases were systematically searched from inception to January 2025. Observational and randomized controlled trials comparing exposure to hypocapnia, defined as an arterial partial pressure of carbon dioxide (PaCO2) lower than 35 mmHg, and no-hypocapnia in adult patients with ABI-related conditions (including traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, central nervous system infections, brain tumors, and post-cardiac arrest encephalopathy) were included. Random-effects meta-analyses were conducted using the restricted maximum likelihood (REML) method to pool unadjusted odds ratios (ORs). The primary outcome was all-cause mortality, and the secondary outcome was the occurrence of poor neurological outcomes defined using validated scales. Prespecified subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. A total of 8,637 records were identified after duplicate removal, of which 37 studies met inclusion criteria for the systematic review. Twenty-seven studies (51,373 patients) were included for mortality outcomes, and thirteen studies (3,814 patients) were included for neurological outcomes. Hypocapnia was associated with higher odds of mortality in adult patients with ABI (OR 1.29, 95% CI 1.05-1.59). Subgroup analyses demonstrated variability across ABI types, with stronger associations observed in subarachnoid hemorrhage and ischemic stroke populations. Hypocapnia was also associated with increased odds of poor neurological outcomes (OR 2.09, 95% CI 1.24-3.54), particularly in the traumatic brain injury population. Subgroup analyses suggested that the association with neurological outcomes was more consistent in studies defining exposure as severe hypocapnia (PaCO2<32 mmHg). Arterial hypocapnia was associated with increased mortality and poor neurological outcomes in adults with acute brain injury, although the evidence is predominantly observational and limited randomized data are available. These findings underscore the need for cautious, individualized PaCO2 management and further high-quality prospective research.
A continuous flow insufflation of oxygen (CFIO) device through a face mask has been developed to minimize chest compression interruptions and optimize ventilation during cardiopulmonary resuscitation (CPR). The objective of this study was to assess the association between CFIO versus bag-valve-mask (BVM) ventilation with favorable neurological outcome at day 30 in adults with out-of-hospital cardiac arrest (OHCA). A multicenter observational cohort study was performed. Adult patients from the French Northern Alps Emergency Network cardiac arrest registry who experienced OHCA in three different Emergency Medical Systems between 2017 and 2021 were included. The Emergency Medical Systems employed different ventilation practices, thus enabling the establishment of two distinct groups for comparison: the exposure group that underwent CFIO through a face mask (using a Boussignac valve device), and a control group that underwent ventilation with a BVM. The primary outcome was the 30-day neurological status according to the Cerebral Performance Category (CPC) scale (favorable: CPC 1 or 2). Of the 2,237 included patients, 967 (43%) received CFIO and 1,270 (57%) were ventilated with a BVM. In multivariable analysis, CFIO was associated with a significantly lower odds ratio (OR) of favorable 30-day neurological outcome in comparison to the control (BVM) group (adjusted OR: 0.61 [95%CI: 0.41-0.9] ; p = 0.01). The use of CFIO during OHCA was associated with significantly lower odds of favourable neurological outcome at day 30 compared to BVM.
Early identification of patients with preserved neurological recovery after cardiac arrest remains challenging. We evaluated whether mid-latency somatosensory evoked potentials (SSEPs) provide additional prognostic information during the acute post-cardiac arrest period. In this retrospective cohort study, we included comatose adult cardiac arrest patients treated with targeted temperature management between 2009 and 2023 who underwent SSEP recording within 24 hours after return of spontaneous circulation (ROSC). Short- and mid-latency SSEP amplitudes (N13-P15, N20, N20-P25, P25, P25-N30, and N30-P45) and latencies were quantified. Favorable neurological outcome was defined as a 6-month Cerebral Performance Category (CPC) score of 1-2. Discriminative performance was compared with other early prognostic variables obtained within the same time window, including neurological examination, brain computed tomography, electroencephalography, and neuron-specific enolase. Among 73 patients, 29 (40%) achieved favorable neurological outcome. Cortical SSEP amplitudes were consistently higher in patients with favorable outcomes. P25-N30 amplitude demonstrated strong discrimination (AUC 0.943, 95% CI 0.862-0.984), achieving 100% sensitivity (95% CI 88.1-100%) and 84.1% specificity (95% CI 69.9-93.4%). Its performance was comparable to that of the conventional N20-P25 amplitude (AUC 0.922, 95% CI 0.836-0.972; p = 0.417). The addition of non-SSEP predictors did not significantly improve overall discrimination. Quantitative assessment of the P25-N30 amplitude within 24 hours after cardiac arrest was associated with favorable neurological outcome and may contribute to early multimodal prognostication.
MRI is essential for diagnosing and monitoring neurological diseases. Conventional protocols require multiple sequences to obtain complementary contrasts, increasing scan time, cost, and tolerability. Generating multiple contrasts from a single acquisition may streamline workflow while maintaining clinical utility. To train attention-based convolutional neural networks (ACNNs) to generate clinical-quality Fluid-Attenuated-Inversion-Recovery (FLAIR), Magnetization-Prepared-Rapid-Gradient-Echo (MPRAGE), R2* maps, and derived contrasts from a single Gradient Echo Plural Contrast Imaging (GEPCI) acquisition. Retrospective. 43 MRI scans from individuals with multiple sclerosis (25/18 F/M, 49 ± 11 years-of-age). 3 T MRI, 3D GEPCI, MPRAGE, and FLAIR. Technical quality of AI-generated contrasts was evaluated against directly acquired MRI using structural similarity index (SSIM). Clinical image quality was assessed by physicians. Lesion volumes and counts were obtained using automated segmentation. One-sample one-sided Wilcoxon signed-rank test was used to establish the clinical quality of images. Agreement between native- and AI-derived lesion volume and lesion count measurements was assessed using intraclass correlation coefficients (ICC). Quantitative accuracy for R2* maps was evaluated using normalized root-mean-square error (NRMSE). AI-generated FLAIR and MPRAGE achieved mean SSIM values of 0.923 ± 0.028 and 0.935 ± 0.022, respectively. Generated R2* maps achieved a mean SSIM of 0.996 ± 0.006 and NRMSE of 0.031 ± 0.020. Physicians-assigned mean clinical quality ratings of 4.2 for GEPCI-FLAIR and 4.5 for GEPCI-MPRAGE exceeded the 4.0 clinical standard on a 1-to-5 scale. Lesion volume and count comparisons from automated segmentation showed strong agreement between AI-generated and ground-truth measurements: R2 = 0.988 and R2 = 0.933, ICC = 0.988 and ICC = 0.967, respectively. AI-GEPCI generated multiple clinically relevant MRI contrasts from a single GEPCI acquisition with high similarity to corresponding acquired images, supporting high-quality, intrinsically co-registered multi-contrast brain evaluation. 2. Stage 1. This study developed a new MRI method called AI‐GEPCI that can create many important brain images from a single scan. Normally, people with neurological diseases need several different MRI scans, which take a long time, are costly, and can be hard to tolerate. We trained artificial intelligence (AI) to turn one GEPCI scan into several clinical images (called FLAIR, MPRAGE, and R2*) that doctors routinely use. The AI‐generated images looked very similar to standard MRI images and were rated as high quality by physicians. This approach may allow faster, more comfortable, and more consistent MRI exams for brain diseases.
PANoptosis is an emerging programmed cell death (PCD) pathway that integrates the key features of pyroptosis, apoptosis, and necroptosis, and is coordinately regulated by a multi-protein complex known as the PANoptosome. This pathway plays a significant role in various neurological disorders, including cerebral ischemia-reperfusion injury, spinal cord injury, glioma, and other neuroinflammatory diseases. By synthesizing the latest bioinformatics and substantial experimental evidence, this review provides a comprehensive overview of the PANoptosome's composition and its dynamic regulatory networks, and further dissect the immunoregulatory functions of PANoptosis. Distinct from previous descriptive summaries, we propose a refined framework focusing on the spatiotemporal and cell-type-specific dynamics of PANoptosis, specifically highlighting the functional transition from acute neuronal stress (VDAC1-mediated) to chronic glial-mediated inflammation (TAK1-dependent). Furthermore, we evaluate the methodological standards for detection and discuss the translational feasibility and safety of targeting this pathway. By outlining these prospective research avenues, this work underscores the critical value of PANoptosis in clinical translation and provides an updated conceptual roadmap for future therapeutic strategies in neurological diseases.
Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism presenting with acute liver failure, cirrhosis, or neurologic involvement. Liver transplantation (LT) is the definitive treatment; however, data remain limited, particularly from regions reliant on living donor LT (LDLT). We retrospectively analyzed a prospectively collected transplant database, identifying all patients (≥ 14 years) who underwent LT for WD between January 2001 and December 2023. Data on demographics, LT indications, disease characteristics, pre-transplant therapy, complications, and outcomes were collected. Survival was assessed using Kaplan-Meier methods, and neurologic outcomes from clinical documentation. Forty-one patients underwent LT for WD (median age: 23 years; 51.2% female). Ascites was present in 68.4%, encephalopathy in 32.4%, and hepatocellular carcinoma in 5.1%. Acute liver failure was the initial presentation in 17.9%. LDLT comprised 53.7%. Acute cellular rejection occurred in 29.7% but was manageable; no patient required re-transplantation. Neurologic involvement was present in 17.1%, with 71% improving post-LT. One-, five-, and ten-year survival rates were 94%, 94%, and 82%. LT for WD yields excellent long-term survival. Neurologic improvement occurred in most Neuro-Wilson patients, supporting LT even in neurologically affected cases. LDLT plays a crucial role in regions with limited deceased donors.
Recent randomized controlled trials comparing extracorporeal cardiopulmonary resuscitation (ECPR) with conventional cardiopulmonary resuscitation (CCPR) reveal mixed outcomes; however, current data support an association between ECPR and neurologically intact survival, particularly within a meticulously trained and highly functional extracorporeal membrane oxygenation (ECMO) delivery system. Rapid deployment of ECPR is critical to achieving favorable outcomes. We describe the implementation of a single-center ECPR program at Mayo Clinic, incorporating an ECPR emergency backpack, clinical lead ECMO specialists, and an emergency ECPR checklist to enhance deployment efficiency and outcomes. Data were extracted from electronic medical records to assess clinical outcomes, including survival to hospital discharge with favorable neurologic status. A tertiary and quaternary care academic medical center. Fifty-eight adult patients who underwent ECPR between October 3, 2020, and December 31, 2023. Implementation of a structured ECPR program incorporating an emergency ECPR backpack, clinical lead ECMO specialists, and an emergency ECPR checklist to streamline deployment and improve outcomes. Of 58 patients treated with ECPR, the overall rate of neurologically intact survival to hospital discharge was 34.5%, including 41.2% for out-of-hospital cardiac arrest and 31.7% for in-hospital cardiac arrest. This single-center experience demonstrates the feasibility and impact of a streamlined ECPR program emphasizing rapid deployment, standardized processes, and dedicated personnel. Our model provides a reproducible framework for institutions seeking to enhance ECPR timeliness and neurologically intact survival following cardiac arrest.
Achondroplasia (ACH) is the most common skeletal dysplasia characterized by disproportionate short stature due to impaired endochondral ossification. One of the most critical and potentially fatal complications of ACH is foramen magnum and upper cervical canal stenosis. Compression at the cervicomedullary junction may lead to myelopathy, hypotonia, developmental delay, and central sleep apnea. Early detection and timely surgical intervention are essential to prevent permanent neurological injury. This retrospective study evaluated 15 pediatric patients with ACH (9 girls, 6 boys; age range 3-42 months, mean 17.2 months) who underwent foramen magnum decompression and C1 laminectomy at Marmara University Neurosurgery Department between 2016 and 2025. All patients underwent comprehensive neurological and radiological evaluation, including MRI and 3D CT of the craniovertebral junction, and were classified by the Achondroplasia Foramen Magnum Score (AFMS). Nine patients had AFMS level 4 stenosis and six had level 3. The anteroposterior diameter of the foramen magnum ranged from 4.03 to 11.03 mm, with an area between 17.40 and 105.16 mm2. Presenting symptoms included motor delay (n = 4), respiratory disturbances or central apnea (n = 4), and macrocephaly (n = 3). Postoperative imaging confirmed adequate decompression in all patients. Neurological and respiratory improvement occurred in all patients except one with persistent hypotonia. One patient died early postoperatively due to recurrent pneumonia and sepsis. Complications were minimal. Foramen magnum decompression with C1 laminectomy is a safe and effective procedure for infants and children with achondroplasia presenting with cervicomedullary compression. Early radiological and neurological evaluation, particularly with AFMS, facilitates accurate surgical decision-making and improves outcomes.
Circadian rhythm disruption (CRD) is a major driver of immune dysregulation; however, whether CRD promotes ischemic stroke (IS) progression through immune imbalance and the underlying molecular mechanisms remain unclear. Transcriptomic data from human IS brain tissues were analyzed to identify CRD associated regulators using machine-learning approaches. A CRD score model was constructed to quantify circadian disruption. Circadian timing-dependent stroke models were established to evaluate diurnal variation in stroke severity and gene rhythmicity in vivo. Single-cell transcriptomic analysis of peripheral blood mononuclear cell -derived scRNA-seq data was performed to characterize CRD-associated immune remodeling. Virtual gene knockdown analysis using the scTenifoldKnk framework, together with experimental validation including microglial gene silencing and T cell co-culture in vitro, as well as adeno-associated virus (AAV)-mediated gene intervention in a transient middle cerebral artery occlusion (tMCAO) model in vivo, were conducted to assess immunoregulatory effects and neurological recovery. We identified seven hub genes associated with CRD in IS patients. Circadian timing significantly influenced stroke severity, with marked differences in infarct volume across Zeitgeber time points. In parallel, coronin 1C (CORO1C) exhibited rhythmic expression in the brain under physiological conditions, which was disrupted following ischemic stroke. High CRD scores were associated with enhanced CD8+ T-cell activation and reduced M0 macrophages, indicating a proinflammatory immune phenotype. Single-cell analysis revealed activation of PD-1/PD-L1 signaling and Th17 polarization within T-cell subsets, consistent with immune overactivation and functional exhaustion. Virtual knockdown analysis highlighted CORO1C as a central regulator linking neuronal and immune transcriptional programs. In microglia, CORO1C knockdown reduced IL-6 and IFN-γ secretion. In vivo, AAV-shCORO1C treatment decreased cerebral CORO1C expression, attenuated CD8+ T-cell infiltration and inflammatory signaling, enhanced Claudin-5 expression, improved neurological function, and promoted post-stroke recovery. This study indicates that CORO1C acts as a pivotal regulator that mediates circadian rhythm disruption-driven immune dysregulation, thereby influencing stroke progression and neurological recovery.
Seizure forecasting and affective state analysis using EEG-ECG data play a pivotal role in advancing neurological and mental health monitoring. However, existing methods such as Fed-Transformer, Res-1D CNN, and Fed-ESD suffer from privacy risks, inefficient feature extraction, and high computational overhead, limiting their effectiveness in real-world applications. To overcome these challenges, this study proposes NeuroFedSense, a novel Federated Learning-enabled Privacy-Preserving Framework that integrates a Temporal Convolutional Network (TCN) with an Attention Mechanism for accurate seizure forecasting and affective state analysis using EEG-ECG data, ensuring enhanced feature selection, interpretability and efficient decentralized training. The model leverages adaptive attention-based optimization and weighted feature selection to improve classification performance while ensuring data privacy. Implemented using TensorFlow, NeuroFedSense achieves 99.54% accuracy, 99.62% precision, 99.34% recall, and a 99.46% F1-score, outperforming Fed-Transformer (97.10% accuracy), Res-1D CNN (81.62% accuracy), and FML (99.10% accuracy). The ROC-AUC score of 0.99 further establishes its superiority over competing models. Additionally, the federated approach reduces energy consumption per node by 30% and optimizes communication efficiency by minimizing data transmission by 15% over 100 rounds. By ensuring high accuracy, improved privacy, reduced computational overhead, and enhanced energy efficiency, NeuroFedSense sets a new benchmark for decentralized, real-time seizure prediction and affective state monitoring. These findings underscore its potential for deployment in intelligent, privacy-preserving healthcare applications, addressing critical challenges in remote neurological monitoring.
Neuroangiostrongyliasis is a neuroinvasive helminth infection caused primarily by the rat lungworm Angiostrongylus cantonensis, which is the main causative agent of eosinophilic meningitis in humans. The closely related species Angiostrongylus malaysiensis coexists in many endemic regions particularly in Asia and Oceania and shares substantial morphological and genetic similarity with A. cantonensis, yet its pathogenic potential remain poorly understood. Here, we performed a direct comparative investigation of neuropathogenesis and host immune responses following experimental infection with A. cantonensis or A. malaysiensis in a murine model. Both species established central nervous system infection and induced neurological manifestations and inflammatory responses. However, infection with A. malaysiensis resulted in more severe clinical disease, characterized by greater weight loss, higher clinical scores, and extensive cerebral hemorrhage, accompanied by increased parasite invasion into the brain parenchyma. In contrast, A. cantonensis infection elicited stronger neuroimmune activation, including increased leukocyte recruitment and elevated expression of type 2 cytokines and chemokines within the brain and meninges. Despite the more severe neurological complications observed in A. malaysiensis infection, immune cell accumulation in the central nervous system was comparatively reduced, suggesting differences in parasite containment at the neuroimmune interface. Together, these findings demonstrate that closely related Angiostrongylus species can induce distinct patterns of neuropathogenesis and immune regulation. Our results highlight the importance of species-specific host-parasite interactions in shaping disease severity and provide new insight into mechanisms underlying the pathogenesis of neuroangiostrongyliasis.
Phakomatoses, also known as neurocutaneous syndromes are rare disorders characterized by multisystem involvement with variable neurological manifestations in children, including intracranial vascular malformations. Cavernous malformations may present with acute haemorrhage and stroke-like symptoms. Diagnostic difficulty arises when radiologic findings suggest a benign lesion, yet histopathology reveals discordant malignant pathology. An 8-year-old female presented with sudden-onset left hemiparesis and recurrent seizures. Physical examination revealed multiple cutaneous naevi, raising suspicion of a syndromic association. Brain magnetic resonance imaging demonstrated a well-circumscribed right parietal intra-axial lesion with a "popcorn" appearance and hypointense susceptibility blooming, highly suggestive of a cavernous malformation. Cranial computed tomography scan subsequently showed an associated large intracerebral haematoma. The patient underwent right parietal craniotomy with haematoma evacuation and excision of the lesion. The immediate postoperative course was initially satisfactory with neurological improvement. Histopathological examination of the excised specimen, however, revealed a malignant neoplasm, establishing a significant radiologic-histologic discordance which fundamentally altered the diagnostic interpretation. The patient had a relapse of symptoms two months after surgery, with repeat neuroimaging showing multicentric tumour recurrence, necessitating referral for adjuvant neuro-oncologic management. This case illustrates a rare diagnostic pitfall and challenge in paediatric neurosurgery, where a malignant intracranial tumour mimicked a cavernous malformation in the context of cutaneous stigmata. The report emphasizes the limitations of neuroimaging alone and underscores the importance of careful clinicoradiologic correlation, histopathological confirmation, and multidisciplinary evaluation when managing presumed vascular lesions in children, particularly in resource-limited settings.
Recent studies have demonstrated that ginsenoside Rb1 (GRb1) exhibits neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury. However, whether GRb1 modulates autophagy and oxidative stress induced by cerebral I/R remains unclear. This study aims to determine whether GRb1 attenuates cerebral I/R injury by suppressing autophagy and oxidative stress via regulation of the ATM-CHK2-Beclin 1 pathway. Middle cerebral artery occlusion/reperfusion (MCAO/R) in 60 SPF C57BL/6 mice and oxygen-glucose deprivation/reperfusion (OGD/R) in rat pheochromocytoma (PC12) cells were employed to evaluate the protective effects of GRb1 on neurological injury, autophagy, and oxidative stress. Molecular mechanisms were validated using Western blot, immunofluorescence, and pharmacological inhibitors. The results showed that GRb1 alleviated neurological impairments, decreased cerebral infarct volume, and reduced histological damage in MCAO/R mice. Besides, GRb1 alleviated cell injury and reduced intracellular ROS production in PC12 cells induced by OGD/R. Furthermore, during MCAO/R and OGD/R, GRb1 suppressed autophagy and oxidative stress. Moreover, GRb1 treatment also decreased p-ATM/ATM and p-CHK2/CHK2 ratio and increased Beclin 1-Bcl-2 interaction both in vivo and in vitro. Molecular docking further elucidated that the mechanism by which GRb1 improves cerebral ischemia maybe related to its direct binding to ATM, which in turn inhibited the phosphorylation of ATM. Additionally, the drug affinity response target stability (DARTS) and cellular thermal shift assay (CETSA) were also performed to suggest that GRb1 directly interacts with ATM. Collectively, these findings demonstrated that GRb1 reduced ischemic stroke-induced oxidative stress and autophagy through ATM-CHK2-Beclin 1 pathway, and GRb1 may be a protective medication for the treatment of cerebral ischemia.
Impaired opisthenar microvessel area (OMA) has been associated with adverse cardiac outcomes in acute myocardial infarction (AMI) patients. Here, we compared the characteristics of OMA of ischemic stroke (AIS) patients, National Institutes of Health Stroke Scale (NIHSS) positive, AIS recurrence, and AMI patients. OMA was investigated using optical coherence tomography (OCT) in AIS patients with mild or no neurological deficit (MND, NND) and recurrence or recurrence-free (RG, RFG). The characteristics of microvessel were compared to those of AMI patients. Brachial-ankle pulse wave velocity (baPWV) was also measured with Omron Instrument. Compared to controls (Con), OMA, total and average vessel length (TVL, AVL) were smaller but End points (EPs) were greater in AIS at room temperature (RT). Both heat and cold stimulation (HS and CS) increased vessel length and area. However, significantly increased EPs and Lacunarity were observed at CS in AIS patients. As for the effect of neurological deficiency, OMA, TVL, and AVL were smaller, and EPs were markedly increased in MND with CS. OMA and TVL were smaller in the RG group at RT, but CS or HS did not change microvascular characteristics. Between AIS and AMI patients, baPWV was significantly greater in AIS, microvessel area and length were comparable between the two groups, and EPs were significantly increased in AIS. Furthermore, baPWV showed a positive correlation with OMA in CON, a negative correlation in AMI, but no correlation in AIS. Greater EPs and lacunarity of microvasculature are indicative of discordancy in AIS patients. Disrupted macrovascular-microvascular association in AIS suggests distinctive pathology to those of AMI.
BACKGROUND Kennedy disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare and incurable X-linked neuromuscular disorder mainly affecting men aged 30 to 60 years. Polymyositis can present similarly, but can be excluded by measuring muscle enzymes, performing muscle imaging, and electromyography. This report describes the case of a 52-year-old man with a 10-year history of progressive limb weakness due to Kennedy disease, established by genetic testing. CASE REPORT A 52-year-old man presented with a 10-year history of gradually progressive proximal limb weakness and persistently elevated creatine kinase levels ranging from 808-2300 U/L (normal 39-308 U/L). One year prior to this admission, the limb weakness had worsened, but initial electromyography, neuroimaging, and muscle biopsy showed no specific abnormalities. Despite a trial of immunosuppressive therapy due to suspected polymyositis, there was no clinical improvement. Neurological examination later revealed gynecomastia, proximal muscle atrophy, and bilateral tongue atrophy with tremor. Electromyography showed chronic neurogenic changes and reduced sensory nerve action potentials. Repeat expansion analysis identified a hemizygous pathogenic CAG repeat expansion in exon 1 of the androgen receptor gene using a short-read next-generation sequencing-based repeat detection algorithm (ExpansionHunter), with an estimated repeat number of 51 (range 50-53). At 6-month follow-up, the patient demonstrated mild progression of motor symptoms but remained functionally stable. CONCLUSIONS This report presents a rare case of Kennedy disease, initially diagnosed as polymyositis, and highlights the importance of follow-up with genetic testing when neurological and electromyography investigations are not typical for polymyositis. Early identification of Kennedy disease helps avoid unnecessary immunosuppressive treatments.
Revision total elbow arthroplasty is technically demanding and carries a substantial risk of postoperative neurological complications because of scarring, altered anatomy, implant removal, and repeated humeral and ulnar exposure. The incidence, nerve distribution, and recovery profile of nerve injury after revision total elbow arthroplasty remain incompletely defined. This study aimed to systematically review the literature to define the incidence, recovery profile, and risk factors for nerve injury after revision TEA. A systematic review of the literature was performed in accordance with PRISMA guidance. Thirteen retrospective case series were included, comprising 282 revision total elbow arthroplasties in 271 patients. Random-effects meta-analysis of proportions was undertaken where the data permitted. The primary outcome was postoperative nerve injury following revision total elbow arthroplasty. Secondary outcomes included nerve type, recovery, secondary nerve-related procedures, infection, triceps insufficiency, metallosis, periprosthetic fracture, and re-revision. The pooled incidence of postoperative nerve injury was 22.3% (95% CI 16.3 to 29.6; I2 = 34.6%). The crude incidence was 60 of 282 revisions (21.3%, 95% CI 16.6 to 26.5). The ulnar nerve was involved in 66.7% of all nerve injuries, the radial nerve in 31.7%, and the median nerve in 1.7%. No significant difference in pooled nerve-injury incidence was identified between studies published before 2010 and those published from 2010 onwards (22.9% vs 21.4%, p = 0.837). Recovery reporting was heterogeneous; among injuries with numerically extractable outcomes, 85.4% improved partially or completely (95% CI 72.2 to 93.9). Secondary nerve-related procedures were reported in seven studies. Pooled complication estimates were 10.2% for infection, 13.6% for triceps insufficiency, 25.5% for metallosis, 15.9% for periprosthetic fracture, and 14.0% for re-revision. Postoperative nerve injury is a common and clinically important complication of revision total elbow arthroplasty, affecting approximately one in five cases. The ulnar nerve is most frequently involved, although radial nerve injury accounts for a substantial proportion of cases. Many neuropathies improve during follow-up, but persistent deficits and the need for secondary nerve-related procedures are not uncommon. Future studies should adopt standardised neurological definitions and reporting to improve comparability and guide preventive surgical strategies.
Spinal cord injury (SCI) recovery is variable and can be complicated by concomitant polytrauma. While previous studies suggest worse rehabilitation outcomes in polytrauma patients, comparative analyses remain limited. This study evaluates the impact of polytrauma on motor, sensory, and functional outcomes for patients with SCI. To do so, a retrospective cohort study was done to evaluate patients with polytrauma (poly-SCI) and without polytrauma (SCI-only) in addition to SCI. Polytrauma was defined as the presence of two injuries with an abbreviated injury scale (AIS) severity score ≥ 3 in two distinct body regions. Primary outcomes included changes in International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) injury grade, total motor score (TMS), neurologic level of injury (NLI), and Section GG functional scores from rehabilitation (rehab) admission to discharge. Of the 146 patients identified for study inclusion between 2019 and 2024; 81 patients were SCI-only and 65 were poly-SCI. The poly-SCI cohort was younger (36.0 vs. 52.0 years; p = 0.006), sustained more high-energy injuries, and experienced longer acute hospital stays (9.5 vs. 6 days; p < 0.001). Consequently, the poly-SCI group exhibited a greater proportion of ISNCSCI Grade A injuries compared to the SCI-only group (46% vs. 19%; p = 0.005), although baseline TMS at admission was similar between cohorts (52.34 vs. 51.94; p = 0.899). Regarding recovery across acute rehab, the poly-SCI cohort demonstrated significantly smaller improvements in TMS between admission and discharge compared to the SCI-only group (3.0 vs. 9.0; p < 0.001). However, no significant differences were observed in changes in ISNCSCI grade, NLI, and Section GG functional scores. Multivariable linear regression with analysis of covariance (ANCOVA) further confirmed that polytrauma status was not significantly associated with changes in Section GG scores. Instead, age and admission TMS emerged as the only significant predictors of functional improvement. Further work is needed to clarify domain-specific recovery patterns and long-term effects.
Hypoxic-ischemic encephalopathy is a major cause of neonatal disability and mortality. Its core pathology involves extensive neuronal apoptosis and persistent inflammatory responses. Microglia play a crucial role in maintaining brain homeostasis and promoting injury repair by recognizing and clearing apoptotic neurons. However, the regulatory mechanisms underlying this process remain unclear. This study employed a co-culture model of apoptotic neurons, phagocytic function assays, cytokine analysis, transcriptome sequencing, Gas6 gene knockout and rescue experiments, combined with a mouse model of hypoxic-ischemic brain injury, to elucidate the role of microglia in the phagocytic process and the regulatory function of Gas6. Injured neurons induced an early phase of pro-inflammatory activation and enhanced phagocytic capacity in microglia, followed by a shift towards an anti-inflammatory function. Transcriptome analysis suggested that co-culture with injured neurons activated pathways such as PI3K-AKT and NF-κB in microglia, concomitant with a significant upregulation of Gas6. Furthermore, we found that Gas6 deficiency significantly reduced the phosphorylation level of TAM receptors, leading to impaired downstream PI3K/AKT activation and a marked decrease in Rac1-GTP, thereby suppressing cytoskeletal rearrangement and phagocytic function. In parallel, Gas6-deficient microglia exhibited a sustained pro-inflammatory response, with both their efferocytic capacity and ability to regulate inflammation being significantly compromised. In vivo experiments showed that Gas6-KO mice displayed more severe neurological deficits, increased neuronal apoptosis, and stronger inflammatory responses after HIE. Supplementation with exogenous Gas6 elevated TAM receptor phosphorylation and the PI3K/AKT-Rac1 signaling pathway, partially restoring the phagocytic capacity of microglia. This study demonstrates the important role of the Gas6-TAM-PI3K/AKT-Rac1 signaling axis in modulating microglial efferocytic function and inflammatory state transition. It provides a potential therapeutic strategy for improving HIE prognosis by targeting the regulation of microglial phagocytosis.
Red flags are clinical indicators that may signal serious underlying spinal conditions, yet there is no consistently applied guidance for identifying red flags specific to serious neck pathologies. While previous studies have outlined red flags for cervical spine pain more broadly (e.g., Feller et al., 2024), there is limited empirical evidence detailing early presenting features that differentiate serious pathology from common musculoskeletal presentations, particularly in non-traumatic contexts. This gap increases the risk of missed or delayed diagnosis. To empirically identify and prioritise red flags for serious neck pathologies to support earlier detection and appropriate management. A qualitative study using the Nominal Group Technique was conducted with ten UK-based clinicians experienced in diagnosing and managing serious neck pathologies. Participants independently generated potential red flags, refined them through structured group discussion, and voted on their inclusion using a predefined consensus threshold. Agreed-upon indicators were then organised into thematic categories. Consensus was achieved on eight categories of red flags across three domains: risk factors, symptoms, and signs. Early indicators prioritised by participants included pain characteristics, functional decline, subtle neurological changes, and patient-reported difficulty supporting the head or neck. Clinicians emphasised that red flags are most informative when interpreted as clusters of evolving features rather than isolated findings. Unlike prior systematic reviews, this study empirically identifies early, clinician-prioritised red flags specific to serious neck pathologies, providing practical guidance for differentiating serious conditions from benign musculoskeletal neck pain. Recognising these early features may support timely detection and improved patient outcomes.
Biallelic variants in SYNJ1 were initially identified in early-onset Parkinson's disease, often accompanied by atypical neurological manifestations. However, their occurrence in patients with a multiple system atrophy-mimicking phenotype has not been well described. A 71-year-old Chinese woman with gradually worsening motor and autonomic symptoms was assessed. The evaluation included clinical examination, genetic testing, and functional studies. The patient exhibited gait instability, cerebellar ataxia, parkinsonism, urinary autonomic dysfunction, and poor levodopa responsiveness. Genetic analysis identified novel compound heterozygous SYNJ1 variants (c.1574 A > G and c.142G > T). Functional assays evaluating each variant individually showed reduced synaptojanin-1 abundance without altered localization. This case expands the clinical context in which biallelic SYNJ1 variants may be implicated and suggests that SYNJ1 analysis could be considered in atypical parkinsonism with cerebellar dysfunction.