Neurocritical Care最新文献

Background: Despite advancements in the neuroscience of consciousness, no new medications for disorders of consciousness (DOC) have been discovered in more than a decade. Repurposing existing US Food and Drug Administration (FDA)-approved drugs for DOC is crucial for improving clinical management and patient outcomes.

Methods: To identify potential new treatments among existing FDA-approved drugs, we used a deep learning-based drug screening model to predict the efficacy of drugs as awakening agents based on their three-dimensional molecular structure. A retrospective cohort study from March 2012 to October 2024 tested the model's predictions, focusing on changes in Glasgow Coma Scale (GCS) scores in 4047 patients in a coma from traumatic, vascular, or anoxic brain injury.

Results: Our deep learning drug screens identified saxagliptin, a dipeptidyl peptidase-4 inhibitor, as a promising awakening drug for both acute and prolonged DOC. The retrospective clinical analysis showed that saxagliptin was associated with the highest recovery rate from acute coma among diabetes medications. After matching patients by age, sex, initial GCS score, coma etiology, and glycemic status, brain-injured patients with diabetes on incretin-based therapies, including dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 analogues, recovered from coma at significantly higher rates compared to both brain-injured patients with diabetes on non-incretin-based diabetes medications (95% confidence interval of 1.8-14.1% higher recovery rate, P = 0.0331) and brain-injured patients without diabetes (95% confidence interval of 2-21% higher recovery rate, P = 0.0272). Post matching, brain-injured patients with diabetes on incretin-based therapies also recovered at a significantly higher rate than patients treated with amantadine (95% confidence interval for the difference 2.4-25.1.0%, P = 0.0364). A review of preclinical studies identified several pathways through which saxagliptin and other incretin-based medications may aid awakening from both acute and chronic DOC: restoring monoaminergic and GABAergic neurotransmission, reducing brain inflammation and oxidative damage, clearing hyperphosphorylated tau and amyloid-β, normalizing thalamocortical glucose metabolism, increasing neural plasticity, and mitigating excitotoxic brain damage.

Conclusions: Our findings suggest incretin-based medications in general, and saxagliptin in particular, as potential novel therapeutic agents for DOC. Further prospective clinical trials are needed to confirm their efficacy and safety in DOC.

Background: Understanding the risk factors for hematoma expansion (HE) in different regions of intracerebral hemorrhage (ICH) can help in the development of more accurate HE prediction tools and in implementing more effective clinical treatment interventions. This study aims to investigate the risk factors for HE in patients with lobar and deep ICH.

Methods: A retrospective analysis was conducted on 558 cases of primary supratentorial ICH from Tongji Hospital Affiliated to Tongji University. Patients were categorized into lobar ICH and deep ICH groups. Differential analysis of ICH characteristics at different locations was performed, followed by subgroup analysis based on HE occurrence. Binary logistic regression was used to identify independent risk factors for HE in each group.

Results: Among the 404 patients with ICH who underwent follow-up noncontrast computed tomography (NCCT) scans, the proportion with HE was similar in the deep ICH group (23.2%) and the lobar ICH group (22.7%). Binary logistic regression analysis revealed that fluid level (odds ratio [OR] 4.77, 95% confidence interval [CI] 1.74-13.06), admission Glasgow Coma Scale score (OR 0.87, 95% CI 0.80-0.96), and time from onset to NCCT examination (OR 0.84, 95% CI 0.75-0.94) were independently associated with HE in the deep ICH group. In the lobar ICH group, irregular shape (OR 4.96, 95% CI 1.37-18.01) and fibrinogen level (OR 0.42, 95% CI 0.21-0.86) were significant risk factors.

Conclusions: Fluid level, low admission Glasgow Coma Scale score, and shorter time from onset to NCCT are independent predictors of HE in deep ICH, whereas irregular shape and low fibrinogen levels are independent predictors of HE in lobar ICH. These findings are of great significance for elucidating the mechanisms underlying HE in different locations of ICH and for developing precise predictive models of HE.

Background: The objective of this study was to assess the prognostic significance of identical bursts (IBs) in cardiac arrest survivors with burst suppression on continuous electroencephalogram (cEEG) monitoring. Burst suppression with IBs is associated with poor neurological outcomes and mortality.

Methods: We conducted a retrospective analysis of cardiac arrest survivors admitted to a US academic medical center between 2013 and 2021 who had an EEG background of burst suppression. EEG and clinical features were extracted from our institutional review board-approved repositories. EEG features were qualitatively and quantitatively rated at 0, 12, 24, 48, and 72 h following initiation of monitoring. Qualitative visual assessment occurred, blinded to all clinical features, including outcomes, and in accordance with the current American Clinical Neurophysiology Society definition. Quantitative assessment involved manual marking of 50 consecutive pairs of bursts and interburst intervals (IBIs) for analysis. Similarity of bursts/IBIs were assessed with correlation coefficients. The primary clinical outcome was survival to hospital discharge. Comparisons were performed between groups, and a multivariate model was generated for significant variables.

Results: Of 593 cardiac arrest patients, 203 (34.2%) had burst suppression. Thirty-one (15.3%) patients with burst suppression survived. IBs were detected in 80 patients (39.4% of burst suppression). No patient with qualitatively identified IBs had a good neurological outcome (76 deceased, 4 in a state of unresponsive wakefulness). Whereas 11 of 123 (8.9%) with burst suppression without IB had Cerebral Performance Category scores of 1-2. Quantitative analysis of 268 instances of burst suppression demonstrated that mortality was associated with longer bursts, longer IBIs, and higher burst correlation coefficients (i.e., bursts that were more similar to each other) only when allowing analysis of the first 2 s of bursts. Binary logistic regression showed that the only independent EEG predictor of mortality was the burst correlation coefficient measured over 2 s (adjusted odds ratio 4.82 [95% confidence interval 1.21-8.42], p = 0.009).

Conclusions: Using a single-center US cohort, IBs within 72 h post cardiac arrest were strongly associated with poor outcomes. Quantitative analysis revealed that including the first 2 s of the bursts was superior to limiting the analysis to 0.5-1 s.

Background: Phosphorylated Tau (p-Tau), an early biomarker of neuronal damage, has emerged as a promising candidate for predicting neurological outcomes in cardiac arrest (CA) survivors. Despite its potential, the correlation of p-Tau with other clinical indicators remains underexplored. This study assesses the predictive capability of p-Tau and its effectiveness when used in conjunction with other predictors.

Methods: In this single-center retrospective study, 230 CA survivors had plasma and brain computed tomography scans collected within 24 h after the return of spontaneous circulation (ROSC) from January 2016 to June 2023. The patients with prearrest Cerebral Performance Category scores ≥ 3 were excluded (n = 33). The neurological outcomes at discharge with Cerebral Performance Category scores 1-2 indicated favorable outcomes. Plasma p-Tau levels were measured using an enzyme-linked immunosorbent assay, diastolic blood pressure (DBP) was recorded after ROSC, and the gray-to-white matter ratio (GWR) was calculated from brain computed tomography scans within 24 h after ROSC.

Results: Of 197 patients enrolled in the study, 54 (27.4%) had favorable outcomes. Regression analysis showed that higher p-Tau levels correlated with unfavorable neurological outcomes. The levels of p-Tau were significantly correlated with DBP and GWR. For p-Tau to differentiate between neurological outcomes, an optimal cutoff of 456 pg/mL yielded an area under the receiver operating characteristic curve of 0.71. Combining p-Tau, GWR, and DBP improved predictive accuracy (area under the receiver operating characteristic curve = 0.80 vs. 0.71, p = 0.008).

Conclusions: Plasma p-Tau levels measured within 24 h following ROSC, particularly when combined with GWR and DBP, may serve as a promising biomarker of neurological outcomes in CA survivors, with higher levels predicting unfavorable outcomes.

Background: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA.

Methods: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs).

Results: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients.

Conclusions: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.

Background: Identical bursts on electroencephalography (EEG) are considered a specific predictor of poor outcomes in cardiac arrest, but its relationship with structural brain injury severity on magnetic resonance imaging (MRI) is not known.

Methods: This was a retrospective analysis of clinical, EEG, and MRI data from adult comatose patients after cardiac arrest. Burst similarity in first 72 h from the time of return of spontaneous circulation were calculated using dynamic time-warping (DTW) for bursts of equal (i.e., 500 ms) and varying (i.e., 100-500 ms) lengths and cross-correlation for bursts of equal lengths. Structural brain injury severity was measured using whole brain mean apparent diffusion coefficient (ADC) on MRI. Pearson's correlation coefficients were calculated between mean burst similarity across consecutive 12-24-h time blocks and mean whole brain ADC values. Good outcome was defined as Cerebral Performance Category of 1-2 (i.e., independence for activities of daily living) at the time of hospital discharge.

Results: Of 113 patients with cardiac arrest, 45 patients had burst suppression (mean cardiac arrest to MRI time 4.3 days). Three study participants with burst suppression had a good outcome. Burst similarity calculated using DTW with bursts of varying lengths was correlated with mean ADC value in the first 36 h after cardiac arrest: Pearson's r: 0-12 h: - 0.69 (p = 0.039), 12-24 h: - 0.54 (p = 0.002), 24-36 h: - 0.41 (p = 0.049). Burst similarity measured with bursts of equal lengths was not associated with mean ADC value with cross-correlation or DTW, except for DTW at 60-72 h (- 0.96, p = 0.04).

Conclusions: Burst similarity on EEG after cardiac arrest may be associated with acute brain injury severity on MRI. This association was time dependent when measured using DTW.

Background: Hypoxic-ischemic brain injury is a common cause of mortality after cardiac arrest (CA) and cardiopulmonary resuscitation; however, the specific underlying mechanisms are unclear. This study aimed to explore postresuscitation changes based on multi-omics profiling.

Methods: A CA swine model was established, and the neurological function was assessed at 24 h after resuscitation, followed by euthanizing animals. Their fecal, blood, and hippocampus samples were collected to analyze gut microbiota, metabolomics, and transcriptomics.

Results: The 16S ribosomal DNA sequencing showed that the microbiota composition and diversity changed after resuscitation, in which the abundance of Akkermansia and Muribaculaceae_unclassified increased while the abundance of Bifidobacterium and Romboutsia decreased. A relationship was observed between CA-related microbes and metabolites via integrated analysis of gut microbiota and metabolomics, in which Escherichia-Shigella was positively correlated with glycine. Combined metabolomics and transcriptomics analysis showed that glycine was positively correlated with genes involved in apoptosis, interleukin-17, mitogen-activated protein kinases, nuclear factor kappa B, and Toll-like receptor signal pathways.

Conclusions: Our results provided novel insight into the mechanism of hypoxic-ischemic brain injury after resuscitation, which is envisaged to help identify potential diagnostic and therapeutic markers.