Neurological Functional Outcome Research Articles

Plasma Levels of Neuron/Glia-Derived Apoptotic Bodies, an In Vivo Biomarker of Apoptosis, Predicts Infarct Growth and Functional Outcome in Patients with Ischemic Stroke.

Evidence demonstrating the involvement of apoptosis in the death of the potentially salvageable area (penumbra zone) in patients during stroke remains limited. Our aim was to investigate whether apoptotic processes occur in penumbral brain tissue by analyzing circulating neuron- and glia-derived apoptotic bodies (CNS-ApBs), which are vesicles released into the bloodstream during the late stage of apoptosis. We have also assessed the clinical utility of plasma neuronal and glial apoptotic bodies in predicting early neurological evolution and functional outcome. The study included a total of 71 patients with acute hemispheric ischemic stroke (73 ± 10years; 30 women). Blood samples were collected from these patients immediately upon arrival at the hospital (within 9h) and at 24 and 72h after symptom onset. Subsequently, isolation, quantification, and phenotypic characterization of CNS-ApBs during the first 72h post-stroke were performed using centrifugation and flow cytometry techniques. We found a correlation between infarct growth and final infarct size with the amount of plasma CNS-ApBs detected in the first 72h after stroke. In addition, patients with neurological worsening (progressive ischemic stroke) had higher plasma levels of CNS-ApBs at 24h after symptom onset than those with a stable or improving course. Circulating CNS-ApB concentration was further associated with patients' functional prognosis. In conclusion, apoptosis may play an important role in the growth of the cerebral infarct area and plasma CNS-ApB quantification could be used as a predictive marker of penumbra death, neurological deterioration, and functional outcome in patients with ischemic stroke.

Simplifying venous outflow: Prolonged venous transit as a novel qualitative marker correlating with acute stroke outcomes.

Prolonged venous transit (PVT), defined as presence of time-to-maximum 10 s within the superior sagittal sinus (SSS) and/or torcula, is a novel, qualitatively assessed computed tomography perfusion surrogate parameter of venous outflow with potential utility in pretreatment acute ischemic stroke imaging for neuroprognostication. We aim to characterize the correlation between PVT and neurological functional outcomes in thrombectomy-treated patients. A prospectively-collected database of large vessel occlusion acute ischemic stroke patients treated with thrombectomy was retrospectively analyzed. Spearman's rank correlation coefficient and point-biserial correlations were performed between PVT status (i.e., no region, either SSS or torcula, or both), 90-day modified Rankin score (mRS), mortality (mRS 6), and poor functional outcome (mRS 4-6 vs 0-3). Of 128 patients, correlation between PVT and 90-day mRS ( = 0.35, p < 0.0001), mortality (r = 0.26, p = 0.002), and poor functional outcome (r = 0.27, p = 0.002) were significant. There is a modest, significant correlation between PVT and severity of neurological functional outcome. Consequently, PVT is an easily-ascertained, qualitative metric that may be useful as an adjunct for anticipating a patient's clinical course. Future analyses will determine the significance of incorporating PVT in clinical decision-making.

Hybrid Clot Histomic-Transcriptomic Models Predict Functional Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke.

Histologic and transcriptomic analyses of retrieved stroke clots have identified features associated with patient outcomes. Previous studies have demonstrated the predictive capacity of histology or expression features in isolation. Few studies, however, have investigated how paired histologic image features and expression patterns from the retrieved clots can improve understanding of clot pathobiology and our ability to predict long-term prognosis. We hypothesized that computational models trained using clot histomics and mRNA expression can predict early neurological improvement (ENI) and 90-day functional outcome (modified Rankin Scale Score, mRS) better than models developed using histological composition or expression data alone. We performed paired histological and transcriptomic analysis of 32 stroke clots. ENI was defined as a delta-National Institutes of Health Stroke Score/Scale > 4, and a good long-term outcome was defined as mRS ≤2 at 90 days after procedure. Clots were H&E-stained and whole-slide imaged at 40×. An established digital pathology pipeline was used to extract 237 histomic features and to compute clot percent composition (%Comp). When dichotomized by either the ENI or mRS thresholds, differentially expressed genes were identified as those with absolute fold-change >1.5 and q < 0.05. Machine learning with recursive feature elimination (RFE) was used to select clot features and evaluate computational models for outcome prognostication. For ENI, RFE identified 9 optimal histologic and transcriptomic features for the hybrid model, which achieved an accuracy of 90.8% (area under the curve [AUC] = 0.98 ± 0.08) in testing and outperformed models based on histomics (AUC = 0.94 ± 0.09), transcriptomics (AUC = 0.86 ± 0.16), or %Comp (AUC = 0.70 ± 0.15) alone. For mRS, RFE identified 7 optimal histomic and transcriptomic features for the hybrid model. This model achieved an accuracy of 93.7% (AUC = 0.94 ± 0.09) in testing, also outperforming models based on histomics (AUC = 0.90 ± 0.11), transcriptomics (AUC = 0.55 ± 0.27), or %Comp (AUC = 0.58 ± 0.16) alone. Hybrid models offer improved outcome prognostication for patients with stroke. Identified digital histology and mRNA signatures warrant further investigation as biomarkers of patient functional outcome after thrombectomy.

Prognostic value of early EEG abnormalities in severe stroke patients requiring mechanical ventilation: a pre-planned analysis of the SPICE prospective multicenter study

IntroductionPrognostication of outcome in severe stroke patients necessitating invasive mechanical ventilation poses significant challenges. The objective of this study was to assess the prognostic significance and prevalence of early electroencephalogram (EEG) abnormalities in adult stroke patients receiving mechanical ventilation.MethodsThis study is a pre-planned ancillary investigation within the prospective multicenter SPICE cohort study (2017–2019), conducted in 33 intensive care units (ICUs) in the Paris area, France. We included adult stroke patients requiring invasive mechanical ventilation, who underwent at least one intermittent EEG examination during their ICU stay. The primary endpoint was the functional neurological outcome at one year, determined using the modified Rankin scale (mRS), and dichotomized as unfavorable (mRS 4–6, indicating severe disability or death) or favorable (mRS 0–3). Multivariable regression analyses were employed to identify EEG abnormalities associated with functional outcomes.ResultsOf the 364 patients enrolled in the SPICE study, 153 patients (49 ischemic strokes, 52 intracranial hemorrhages, and 52 subarachnoid hemorrhages) underwent at least one EEG at a median time of 4 (interquartile range 2–7) days post-stroke. Rates of diffuse slowing (70% vs. 63%, p = 0.37), focal slowing (38% vs. 32%, p = 0.15), periodic discharges (2.3% vs. 3.7%, p = 0.9), and electrographic seizures (4.5% vs. 3.7%, p = 0.4) were comparable between patients with unfavorable and favorable outcomes. Following adjustment for potential confounders, an unreactive EEG background to auditory and pain stimulations (OR 6.02, 95% CI 2.27–15.99) was independently associated with unfavorable outcomes. An unreactive EEG predicted unfavorable outcome with a specificity of 48% (95% CI 40–56), sensitivity of 79% (95% CI 72–85), and positive predictive value (PPV) of 74% (95% CI 67–81). Conversely, a benign EEG (defined as continuous and reactive background activity without seizure, periodic discharges, triphasic waves, or burst suppression) predicted favorable outcome with a specificity of 89% (95% CI 84–94), and a sensitivity of 37% (95% CI 30–45).ConclusionThe absence of EEG reactivity independently predicts unfavorable outcomes at one year in severe stroke patients requiring mechanical ventilation in the ICU, although its prognostic value remains limited. Conversely, a benign EEG pattern was associated with a favorable outcome.

Acupuncture improves neurological function and anti-inflammatory effect in patients with acute ischemic stroke: A double-blinded randomized controlled trial

Background and purposeAcupuncture exerts an anti-inflammatory effect and is recommended by the World Health Organization as a complementary therapy for stroke. This study investigated the improvement in neurological function outcome in acute-stage intervention of acute ischemic stroke (AIS), and the anti-inflammatory effect of early acupuncture. MethodsFifty patients with AIS were randomly assigned to either a control group (CG, 25 patients, received sham acupuncture) or treatment group (TG, 25 patients, received acupuncture treatment). Acupuncture intervention was administered twice a week for a total of 8 sessions over 4 consecutive weeks. The primary outcome was the changes in the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) scores. The secondary outcome was the changes in serum inflammation-related biomarker levels.(ANAIS trial) ResultsA total of 35 patients (18 patients in the CG and 17 patients in the TG) completed the trial. The reduction in NIHSS scores was greater in the TG than in the CG between V2 (second assessment administered after acupuncture intervention) and V1 (first assessment administered before acupuncture intervention; 4.33 ± 1.91 vs. 2.68 ± 1.42, p = 0.005) and between V3 (third assessment administered 28 days after last acupuncture intervention) and V1 (6.00 ± 2.53 vs. 3.83 ± 2.31, p = 0.012). The increase in BI scores was greater in the TG than in the CG between V2 and V1 (28.89 ± 15.39 vs. 14.21 ± 19.38, p = 0.016) and between V3 and V1 (39.41 ± 20.98 vs. 25.00 ± 18.47, p = 0.038). Among participants with high inflammation, the increase in serum IL-12p70 level between V2 and V1 was greater in the TG than in the CG (0.20 ± 0.19 vs. −0.14 ± 0.30, pg/mL p = 0.006). ConclusionsAcupuncture improved the neurological function of patients with AIS, and the relationship between acupuncture improving neurological function and anti-inflammatory effect needs further study. In addition, studies with larger sample sizes and longer follow-ups as well as multicenter clinical trials are expected in the future.

Safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.

To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia. Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤3 and a platelet count <100×109/L were obtained from a multicenter register. Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was a 1-year all-cause death. The short-term neurological outcomes were evaluated by modified Rankin scale (mRS) score at discharge. A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled. Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge (OR=1.657, 95%CI: 1.253-2.192, P<0.01) and did not increase the risk of intracranial hemorrhage (OR=2.359, 95%CI: 0.301-18.503, P>0.05), compared with those without antiplatelet therapy. However, dual-antiplatelet therapy did not bring more neurological benefits (OR=0.923, 95%CI: 0.690-1.234, P>0.05), but increased the risk of gastrointestinal bleeding (OR=2.837, 95%CI: 1.311-6.136, P<0.01) compared with those with mono-antiplatelet therapy. For patients with platelet counts ≤75×109/L and >90×109/L, antiplatelet therapy significantly improved neurological functional outcomes (both P<0.05). For those with platelet counts (>75-90)×109/L, antiplatelet therapy resulted in a significant improvement of 1-year survival (P<0.05). For patients even with concurrent coagulation abnormalities, mono-antiplatelet therapy did not increase the risk of various types of bleeding (all P>0.05) but improved neurological functional outcomes (all P<0.01). There was no significant difference in the occurrence of bleeding events, 1-year all-cause mortality risk, and neurological functional outcomes between aspirin and clopidogrel (all P>0.05). For non-cardioembolic mild stroke patients with thrombocytopenia, antiplatelet therapy remains a reasonable choice. Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Total cerebral small vessel disease burden and stroke outcomes in large vessel occlusion stroke receiving endovascular treatment: A systematic review and meta-analysis

BackgroundCerebral small vessel disease (CSVD) is prevalent in the population, especially among the elderly. Various types of CSVD markers commonly coexist, and the neurological function outcome is affected by their combined effect. Studies investigating the association between total CSVD burden and stroke outcomes in large vessel occlusion (LVO) stroke receiving endovascular treatment (EVT) are expanding but have not been systematically assessed. MethodsWe systematically searched the PubMed, Embase, and Cochrane databases for relevant clinical studies. The total CSVD burden score summarized the markers of CSVD, including lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVSs), which was a comprehensive index of overall CSVD burden. The pooled odds ratios (ORs) were used to calculate the association between high total CSVD burden score and outcomes of EVT in patients with LVO stroke. The primary outcome was poor functional outcome, which was defined as a modified Rankin Scale score (mRS) ≥ 3 at 90 days after EVT. The secondary outcomes were symptomatic intracranial hemorrhage (sICH) and poor collateral flow. ResultsOverall, 6 eligible studies with 1,774 patients with LVO stroke undergoing EVT were pooled in meta-analysis. High overall CSVD burden score was significantly associated with increased risks of poor functional outcome at 90 days (pooled OR 2.86, 95 % CI 1.31–6.25, p = 0.008). Besides, high overall CSVD burden score was associated with sICH (pooled OR 2.07, 95 % CI 0.38–5.17; p = 0.118) and poor collateral flow (pooled OR 1.57, 95 % CI 0.75–3.27; p = 0.232), but were not statistically significant. ConclusionsHigh overall CSVD burden was associated with increased risks of unfavorable outcomes in patients with LVO stroke undergoing EVT.

Investigating the Roles of Gut Microbiome in the Progression of Neurodegenerative Diseases: Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS)

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS), pose global health burdens due to their incurable and degenerative nature. Emerging evidence highlights the complex interplay between the gut microbiome and the central nervous system (CNS), revealing novel mechanisms of ND pathogenesis and progression. This review integrates current literature, correlation analyses, and inferential statistics to elucidate the impact of gut microbiome dysbiosis on NDs and identify potential diagnostic biomarkers and therapeutic targets. The gut-brain axis (GBA), a bidirectional communication network between the gut and the brain, modulates neurological function and disease outcomes. Correlation analyses demonstrated significant associations between gut microbiome perturbations and ND parameters, implying a causal role for gut dysbiosis in ND pathogenesis. Inferential statistics revealed distinct microbial profiles between ND cohorts and healthy controls, indicating a shared gut dysbiosis across diverse NDs. Studies investigating microbial taxa, metabolites, and signaling pathways have provided insights into the molecular mechanisms underlying gut microbiome-mediated effects on neurodegeneration. Elucidating the reciprocal interactions between the gut microbiome and the host physiology is essential for deciphering the GBA’s role in NDs. Despite advances, knowledge gaps remain. Longitudinal studies are required to monitor gut microbiome dynamics over ND progression. Mechanistic studies are needed to establish how gut microbiome composition affects disease. Methodological standardization for gut microbiome assessment is imperative for rigorous research. Future endeavors should aim to translate findings into clinical applications to exploit microbiome-based interventions for enhanced neurological outcomes in NDs.

Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination

Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders. By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO) mouse stroke model, we examined the effects and underlying mechanisms of genetic and pharmacological inhibition of the cGAS-STING pathway on long-term post-stroke neurological functional outcomes. Blocking the cGAS-STING pathway, even 3days after tMCAO, significantly promoted functional recovery in terms of white matter structural and functional integrity as well as sensorimotor and cognitive functions. Mechanistically, the neuroprotective effects via inhibiting the cGAS-STING pathway were contributed not only by inflammation repression at the early stage of tMCAO but also by modifying the cell state of phagocytes to facilitate remyelination at the sub-acute phase. The activation of the cGAS-STING pathway significantly impeded post-stroke remyelination through restraining myelin debris uptake and degradation and hindering oligodendrocyte differentiation and maturation. Manipulating the cGAS-STING pathway has an extended treatment window in promoting long-term post-stroke functional recovery via facilitating remyelination in a mouse stroke model. Our results highlight the roles of the cGAS-STING pathway in aggregating stroke pathology and propose a new way for improving functional recovery after ischemic stroke. This work was primarily funded by the National Key R&D Program of China.

Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study

BackgroundThe study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD).MethodsThis study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups.ResultsA total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031–362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259–92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005).ConclusionNAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.

Clinical outcomes in patients with neurological disorders following periacetabular tumor removal and endoprosthetic reconstruction of the hemipelvis.

Surgical treatment of musculoskeletal tumors in the periacetabular region present extremely difficult due to the complex anatomy and need for reconstruction. Orthopedic surgeons face more difficulties in patients with neurological conditions, which can cause increased muscle tone, an elevated risk of fractures, and compromised bone quality. There is limited evidence regarding endoprosthetic reconstruction for periacetabular tumors in individuals with neurological disorders. We conducted a single-center retrospective study to examine the outcomes of patients with preexisting neurological conditions who underwent surgery to remove periacetabular tumors and who underwent endoprosthesis reconstruction. Clinical presentation, detailed neurological conditions, complications, and functional outcomes were studied. Sixteen out of the 838 patients were identified (1.91%), with a mean follow-up time of 33 months. The primary neurological conditions encompassed Parkinson's disease, Alzheimer's disease, dementia, and cerebral ischemic stroke. Every patient was diagnosed with periacetabular lesions that were either primary or oligometastatic. They underwent tumor resection and subsequently received endoprosthetic reconstruction of the hemipelvis. Three patients developed metastasis lesions later, and two patients experienced tumor recurrence. Five cases experienced hip dislocation-one with periprosthetic fracture and one with surgical site infection. The position of the prosthetic rotating center was not correlated with dislocation. The reoperation rate was 31.25%. The cohort of patients all presented with more extended hospital stays and rehabilitation. In 3 patients, the general functional score was good, while in 6 patients, it was fair; in 7 patients, it was regarded as poor. The average MSTS93 score was 49.71%. Endoprosthetic reconstruction after periacetabular tumor resection is an effective way to eliminate tumors and salvage limbs. However, this group of patients has an increased likelihood of secondary surgery, complications, extended hospital stay, and no significant improvement in functional outcomes. Despite the diverse nature of the cohort, it is recommended to consider enhanced soft tissue reconstruction, supervised functional recovery and rehabilitation training.

Effect of anesthesia mode during endovascular treatment on neurological functional outcomes in patients with acute posterior circulation stroke.

To compare the effect of anesthesia mode on the neurological functional outcomes in patients undergoing endovascular treatment for acute posterior circulation ischemic stroke. Clinical data of 656 patients undergoing intravascular therapy for acute posterior circulation ischemic stroke registered in online Acute Stroke Patients for Stroke Management Quality Evaluation Database from January 2017 to December 2022 were retrospectively analyzed. The data included 163 cases with conscious sedation and 493 cases with general anesthesia during the procedure. After propensity score matching, 428 patients were included in the analysis, including 155 cases in the conscious sedation group and 273 cases in the general anesthesia group. The differences of operation mode, etiology type, vascular recanalization, hemorrhagic transformation at 24 h, modified Rankin Scale (mRS) score at 3 months and mortality within 3 months were compared between the two groups. Binary logistic regression was used to explore the effect of different anesthesia mode on neurological functional outcomes. There was a significant difference in operation mode between the two groups (P<0.01), while there were no significant differences in etiology type, vascular recanalization, hemorrhagic transformation at 24 h, mRS score at 3 months or mortality within 3 months (all P>0.05). Binary logistic regression analysis revealed that anesthesia modes were not significantly associated with functional outcomes of patients (OR=1.151, 95%CI: 0.751-1.765, P>0.05). Anesthesia mode (conscious sedation or general anesthesia) will not affect the neurological functional outcomes in patients with acute posterior circulation ischemic stroke undergoing endovascular treatment.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

Clinical practice guideline development. Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12hours after acute SCI). A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24hours of acute SCI) or ultra-early (in particular, but not limited to, within 12hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. The GDG recommended that early surgery (≤24hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24hours compared to after 24hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Concomitant traumatic brain injury as a determinant of survival, and neurological and functional outcomes after traumatic spinal cord injury: A retrospective cohort study.

Although concomitant traumatic brain injury (TBI) is not infrequently associated with spinal cord injury (SCI), there is relatively scarce information about the effects of concomitant TBI on outcomes after SCI. To assess the impact of concomitant mild-to-moderate TBI on survival, and neurological and functional outcomes within the first year after acute traumatic SCI. Retrospective cohort study. Acute spine trauma centers in the United States. This study includes all individuals who were enrolled into the Third National Spinal Cord Injury Study (NASCIS-3). The study population was classified into SCI + TBI group and SCI-alone group. TBI was defined as a Glasgow Coma Scale score <15 on admission. Not applicable. Both groups were compared regarding their survival and neurological outcomes (ie, NASCIS motor, sensory and pain scores) and functional outcome (ie, Functional Independence Measure score) within the first year following SCI. Data analyses were adjusted for major potential confounders. There were 413 individuals in the SCI-alone group and 86 individuals in the SCI + TBI group (17.2%). Both groups were comparable regarding gender distribution (p = .621). However, the SCI + TBI group was older (p < .001), had a higher proportion of complete (p = .006) and cervical SCI (p = .003), and had a higher blood alcohol level (p < .001) than the SCI-alone group. The SCI + TBI group did not significantly differ from the SCI-alone group regarding survival within the first year after SCI (p = .768). Among the survivors, concomitant mild-to-moderate TBI did not significantly affect neurological and functional outcomes at 1 year after SCI in the multiple regression analyses after adjusting for major potential confounders. The results of this study suggest that concomitant mild-to-moderate TBI did not have a significant impact on survival, neurological recovery, and functional outcomes at 1 year after SCI, even though there were some epidemiological differences between SCI-alone and SCI + TBI groups.

Association Between Early External Ventricular Drain Insertion and Functional Outcomes 6 Months Following Moderate-to-Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading global cause of morbidity and mortality. Intracranial hypertension following moderate-to-severe TBI (m-sTBI) is a potentially modifiable secondary cerebral insult and one of the central therapeutic targets of contemporary neurocritical care. External ventricular drain (EVD) insertion is a common therapeutic intervention used to control intracranial hypertension and attenuate secondary brain injury. However, the optimal timing of EVD insertion in the setting of m-sTBI is uncertain and practice variation is widespread. Therefore, we aimed to assess if there is an association between timing of EVD placement and functional neurological outcome at 6 months post m-sTBI. We pooled individual patient data for all relevant harmonizable variables from the Erythropoietin in Traumatic Brain Injury (EPO-TBI) and Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR) randomized control trials, and the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) Core Study version 3.0 and Australia-Europe NeuroTrauma Effectiveness Research in TBI (Oz-ENTER) prospective observational studies to create a combined dataset. The Glasgow Coma Scale (GCS) score was used to define TBI severity and we included all patients admitted to an intensive care unit with a GCS ≤12, who were 15 years or older and underwent EVD placement within 7 days of injury. We used hierarchical multi-variable logistic regression models to study the association between EVD insertion within 24 h of injury (early) compared with EVD insertion more than 24 h after injury (late) and 6-month functional neurological outcome measured using the Glasgow Outcome Score Extended (GOSE). In total, 2536 patients were assessed. Of these, 502 (20%) underwent early EVD insertion and 145 (6%) underwent late EVD insertion. Following adjustment for the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) score extended (Core + CT), sex, injury severity score, study and treatment site, patients receiving a late EVD had higher odds of death or severe disability (GOSE 1-4) at 6 months follow-up than those receiving an early EVD adjusted odds ratio; 95% confidence interval, 2.14; 1.22-3.76; p = 0.008. Our study suggests that in patients with m-sTBI where an EVD is needed, early (≤ 24 h post-injury) insertion may result in better long-term functional outcomes. This finding supports future prospective investigation in this area.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Fifteen patients (median age 57years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

CLR (C-Reactive Protein to Lymphocyte Ratio) Served as a Promising Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage (aSAH): A Retrospective Cohort Study.

Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive value of the C-reactive protein to lymphocyte ratio (CLR) for neurological functional outcome and complications after aSAH. Methods: We retrospectively analyzed a total of 166 aSAH patients who met the inclusion criteria enrolled in our study. Multivariate logistic regression analyses were performed to evaluate the independent risk factors. The predictive value of different models was compared by calculating the areas under the receiver operating characteristic (ROC) curve. Results: On-admission levels of CLR in patients with poor outcomes (6 months mRS 3-6), CVS, DCI, and CH were significantly higher than those in patients with good outcomes (6 months mRS 0-2), non-CVS, non-DCI, and non-CH. Multivariate logistic regression analysis revealed that admission CLR was independently associated with CVS (OR [95% CI] 2.116 [1.507-2.971]; p < 0.001), and DCI (OR [95% CI] 1.594 [1.220-2.084]; p = 0.001). In ROC analysis, the area under the curve (AUC) of CLR for poor outcomes (6 months mRS 3-6), CVS, DCI, and CH prediction were (AUC [95% CI] 0.639 [0.555-0.724]; p = 0.002), (AUC [95% CI] 0.834 [0.767-0.901]; p < 0.001), (AUC [95% CI] 0.679 [0.581-0.777]; p < 0.001), and (AUC [95% CI] 0.628 [0.543-0.713]; p = 0.005) revealing that admission CLR had a favorable predictive value for CVS after aSAH. The sensitivity and specificity of admission CLR for CVS prediction were 77.1% and 75.4%. On-admission CLR of 0.757 mg × 10-6 was identified as the best cutoff threshold to discriminate between CVS and non-CVS (CVS: CLR < 0.757 mg × 10-6 11/100 [11.0%] vs. CLR ≥ 0.757 mg × 10-6 37/66 [56.1%]; p < 0.001). Conclusions: High levels of on-admission CLR serve as an independent risk factor for CVS and DCI after aSAH. Admission CLR is an easy-to-quantify laboratory parameter that efficiently predicts the CVS after aSAH, which can provide some guidance for clinicians to evaluate for possible progression and treatment strategies in patients with aSAH.

Research Advancements on the Correlation Between Spontaneous Intracerebral Hemorrhage of Different Etiologies and Imaging Markers of Cerebral Small Vessel Disease.

The purpose of this review is to identify the correlation between ICH and CSVD imaging markers under SMASH-U classification by searching and analyzing a large number of literatures in recent years, laying a theoretical foundation for future clinical research. At the same time, by collecting clinical data to evaluate patient prognosis, analyzing whether there are differences or supplements between clinical trial conclusions and previous theories, and ultimately guiding clinical diagnosis and treatment through the analysis of imaging biomarkers. In this review, by searching CNKI, Web of Science, PubMed, FMRS and other databases, the use of "spontaneous intracerebral hemorrhage", "hypertensive hemorrhagic cerebral small vessel disease", "cerebral small vessel disease imaging", "Based cerebral small vessel diseases", "SMASH the -u classification" and their Chinese equivalents for the main search term. We focused on reading and analyzing hundreds of relevant literatures in the last decade from August 2011 to April 2020, and also included some earlier literatures with conceptual data sources. After screening and ranking the degree of relevance to this study, sixty of them were cited for analysis and elaboration. In patients with ICH, the number of cerebral microbleeds in lobes, basal ganglia, and the deep brain is positively correlated with ICH volume and independently correlated with neurological functional outcomes; white matter hyperintensity severity is positively correlated with ICH recurrence risk; multiple lacunar infarction independently predict the risk of ICH; severe brain atrophy is an independent risk factor for a poor prognosis in the long term in patients diagnosed with ICH; and the number of enlarged perivascular spaces is correlated with ICH recurrence. However, small subcortical infarct and ICH are the subject of few studies. Higher CSVD scores are independently associated with functional outcomes at 90 days in patients diagnosed with ICH.

Autonomic dysfunction and treatment strategies in intracerebral hemorrhage.

Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients. We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic-parasympathetic balance, would potentially improve clinical outcomes in ICH patients. The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes.

Time-Dependent Changes in Hematoma Expansion Rate after Supratentorial Intracerebral Hemorrhage and Its Relationship with Neurological Deterioration and Functional Outcome.

Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT. We included 567 consecutive patients with supratentorial ICH and baseline head CT within 24 h of onset. ND was defined as a ≥4-point increase on the NIH stroke scale (NIHSS) or a ≥2-point drop on the Glasgow coma scale. Poor outcome was defined as a modified Rankin score of 4 to 6 at 3-month follow-up. The rate of HE was higher among those scanned within 3 h (124/304, 40.8%) versus 3 to 24 h post-ICH onset (53/263, 20.2%) (p < 0.001). However, HE was an independent predictor of ND (p < 0.001), poor outcome (p = 0.010), and mortality (p = 0.003) among those scanned within 3 h, as well as those scanned 3-24 h post-ICH (p = 0.043, p = 0.037, and p = 0.004, respectively). Also, in a subset of 180/567 (31.7%) patients presenting with mild symptoms (NIHSS ≤ 5), hematoma growth was an independent predictor of ND (p = 0.026), poor outcome (p = 0.037), and mortality (p = 0.027). Despite decreasing rates over time after ICH onset, HE remains an independent predictor of ND, functional outcome, and mortality among those presenting >3 h after onset or with mild symptoms.