Neurocritical Care

Background: There are currently no therapies proven to accelerate recovery of consciousness for patient with acute severe traumatic brain injury (TBI) in the intensive care unit (ICU). Methods: We performed an open-label, Phase 1 safety and dose-finding study of intravenous methylphenidate (IV MPH) in ICU patients with acute disorders of consciousness (DoC) caused by severe TBI. IV MPH was administered in daily doses of 0.5, 1.0, and 2.0 mg/kg. The primary outcome measure was the number of adverse events (AEs) at each dose. IV MPH pharmacokinetics were measured for 24 hours after each dose. The effect of IV MPH on brain networks was measured using EEG and resting-state functional MRI (rs-fMRI). A pharmacodynamic response was defined by change-point analysis of EEG and rs-fMRI time-series data. Behavioral responses were assessed using the Coma Recovery Scale-Revised (CRS-R). Findings: Between August 24, 2020, and April 1, 2024, we screened 488 ICU patients with TBI and enrolled 9 males (age 23-79 years) with acute traumatic DoC: coma (n=3), vegetative state/unresponsive wakefulness syndrome (n=3), and minimally conscious state (n=3). There were no serious AEs at any dose. Mild-moderate AEs observed at 1.0 mg/kg or 2.0 mg/kg included insomnia, emesis, paroxysmal sympathetic hyperactivity, and transaminitis. Maximum plasma MPH concentration ranged from mean (SD) 312.7 (100.6) ng/mL to 1319.5 (433.8) ng/mL and occurred within a median of 7-14 minutes across doses. Pharmacodynamic responses were observed via EEG in 7/8 participants who received 0.5 mg/kg (1/9 did not undergo EEG), 6/9 who received 1.0 mg/kg, and 4/6 who received 2.0 mg/kg. One of two patients who completed rs-fMRI showed a pharmacodynamic response. CRS-R level of arousal increased within 15 min of the IV MPH bolus for 6/9 participants at 0.5 mg/kg, 5/9 at 1.0 mg/kg, and 0/6 at 2.0 mg/kg. Interpretation: For patients with acute severe TBI, IV MPH may be safe at doses of 0.5-2.0 mg/kg. Pharmacodynamic and behavioral responses suggest that IV MPH promotes recovery of arousal, a prerequisite of consciousness, in the ICU.

BackgroundPerihematomal edema (PHE) expansion exacerbates neurological outcomes in hypertensive intracerebral hemorrhage (HICH). This study investigates the role of fibrinogen in PHE progression. MethodsWe analyzed 94 HICH patients stratified by fibrinogen quartiles (Q1-Q4). Primary outcome was PHE volume on follow-up imaging. Generalized additive models (GAM) and mixed-effects models evaluated associations between fibrinogen, clinical variables, and edema dynamics. ResultsFibrinogen levels differed significantly across quartiles (P<0.001). The highest quartile (Q4: 29.15{+/-}24.38 mL) exhibited larger edema volumes versus Q1-Q3 (23.70{+/-}14.19 mL). Adjusted models revealed fibrinogen ({beta}=1.32, 95%CI 0.87-1.77), hemoglobin ({beta}=-0.45), aspartate aminotransferase ({beta}=0.21), and apolipoprotein B ({beta}=2.15) as independent predictors (all P<0.05), with model R2=0.41-0.42. Coagulation markers (PTA, D-dimer) and imaging features (blend sign) showed secondary associations. ConclusionElevated fibrinogen independently predicts PHE expansion in HICH, suggesting potential therapeutic targeting of hyperfibrinogenemia.

IMPORTANCEPoint-of-care, non-invasive brain monitoring in critically ill patients following cardiac arrest could provide earlier detection of neurological injury and, when combined with earlier treatments, limit brain injury. Point-of-care monitoring could also enable better neuro-prognostication. OBJECTIVESThe study assessed the time to detection of brain injury using optical brain pulse monitoring (OBPM) compared to routine brain monitoring. The association of OBPM signals with more severe forms of brain injury was also assessed. DESIGNRetrospective analysis of patients enrolled in an observational study. SETTINGCritical care unit of a tertiary academic hospital. PARTICIPANTSAdult patients requiring mechanical ventilation in a critical care unit following a cardiac arrest. MAIN OUTCOMES AND MEASURESOBPM uses red and infrared light to capture brain pulse waveforms whose morphology reflects the relative arteriole and venous pressure levels driving microvascular blood flow in the brain. The OBPM sensors were placed bilaterally on the anterior temporal region of the scalp, over the middle cerebral artery territories. Time to brain injury detection was defined as the period from cardiac arrest to the first detection of brain injury by OBPM or routine monitoring. RESULTSTwelve patients were enrolled, three required veno-arterial extra-corporeal membrane oxygenator support. In-hospital mortality was 83% and eight patients developed global hypoxic-ischemic brain injury. The median time to detection of brain injury was 57 hours earlier using OBPM compared to routine monitoring (P < 0.01). In brain injured patients OBPM brain pulse morphologies changed over time and were often different between hemispheres, high amplitude respiratory waves were also present. Known poor prognostic brain pulse waveform morphologies were present in some patients with severe brain injury. CONCLUSIONS AND RELEVANCEOBPM detected brain injury earlier compared to routine brain monitoring. Earlier detection of neurological injury could improve patient outcomes through earlier treatment and better neuro-prognostication. KEY POINTSO_ST_ABSQuestionC_ST_ABSCan point-of-care non-invasive optical brain pulse monitoring (OBPM) in critically ill patients following cardiac arrest provide earlier detection of brain injury compared to routine monitoring? FindingsIn this observational study of 12 patients the median time to detection of brain injury was 57 hours earlier using OBPM compared to routine monitoring. MeaningEarlier detection of brain injury could improve patient outcomes through earlier treatment and better neuro-prognostication.

ObjectiveThe objective of this scoping review is to understand the extent and type of evidence in relation to the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) for neuroprotection in aneurysmal subarachnoid haemorrhage (aSAH). IntroductionThe individual and societal costs of aSAH remain high. Effective neuroprotection would reduce morbidity and mortality but there are uncertainties around both established and emerging therapies. GLP-1RA show promise as neuroprotective drugs in other forms of acute and chronic brain injury and could be repurposed for aSAH. Inclusion criteriaAnimal and human studies of the use of GLP-1RA for aSAH will be included. Key exclusions are traumatic or non-aneurysmal subarachnoid haemorrhage, or the use of multi-agonist drugs. MethodsSearches were conducted in Embase (Ovid), Medline (Ovid), Cochrane Central Register of Controlled Trials (Wiley) and the World Health Organisations International Clinical Trials Registry Platform on 13th June 2025 with no limits applied. Screening and data extraction was performed by two independent reviewers. ResultsAfter de-duplication 593 records were screened, 50 selected for full text review and 5 included in this review. GLP-1R were shown to be highly expressed in neurones and microvascular endothelial cells after aSAH. Administration of GLP-1RAs to rats affected by aSAH improved functional recovery. Furthermore, aSAH was reported to increase cerebral hemisphere oedema, blood-brain barrier permeability, cell death and inflammation, all of which were reversed by GLP-1RA treatment. Murine studies highlight potential mechanisms for these beneficial effects including inhibition of ferroptosis, downregulation of apoptosis, and upregulation of SIRT1 pathways. A human observational studies shows a correlation between higher SIRT1 levels and better neurological outcomes. ConclusionThe limited available evidence suggests a potential neuroprotective role for GLP-1RAs after aSAH. There is a need for extensive further research to determine the efficacy and safety of GLP1-RAs for neuroprotection in aSAH.

IntroductionVentriculostomy related infection (VRI) or ventriculitis is a common and serious complication related to the placement of an external ventricular drain. Numerous sets of diagnostic criteria for VRI have been reported. We sought to estimate the variation in the incidence of VRI in a cohort of patients according to published diagnostic criteria. Materials and MethodsWe conducted a retrospective cohort study. We included adult patients admitted to the Neuroscience intensive care unit with traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) who required an EVD. We estimated the incidence of VRI according to published diagnostic criteria. We compared the incidence to clinicians diagnoses of VRI. The primary outcome was the estimated incidence of VRI. ResultsThere were 190 study participants, median age (interquartile range) of 58 (48 - 72), 106 (55.8%) were female. Admitting diagnoses was ICH in 30 (15.8%), TBI in 49 (25.8%) and SAH in 111 (58.4%) of cases respectively. There were 158 (83.2%) who required mechanical ventilation for a median of 6 (2-13) days. There were 29 (15.3%) who were treated for VRI by clinicians, with 6 (3.2%) having a positive culture. Variation in the diagnostic criteria led to an estimated incidence of VRI that ranged from 1 (0.5%) to 178 (93.7%). ConclusionIn this critically ill cohort, the estimated incidence of VRI varied widely depending on which diagnostic criteria for VRI were applied. A comprehensive, consistent, objective and universal set of diagnostic criteria for ventriculostomy related infection is needed.

BackgroundThe inflammatory response within the central nervous system is a key driver of secondary brain injury after hemorrhagic stroke, both in patients with intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to characterize inflammatory molecules in the blood and cerebrospinal fluid (CSF) of patients within 72 hours of hemorrhage to understand how such molecules vary across disease types and disease severity. MethodsBiological samples were collected from patients admitted to a single-center Neurosciences Intensive Care Unit with a diagnosis of ICH or aSAH between 2014 and 2022. Control CSF samples were collected from patients undergoing CSF diversion for normal pressure hydrocephalus. A panel of immune molecules in the plasma and CSF samples was analyzed using Cytometric Bead Array assays. Clinical variables, including demographics, disease severity, and intensive care unit length of stay were collected. ResultsPlasma and/or CSF samples were collected from 260 patients (188 ICH patients, 54 aSAH patients, 18 controls). C-C motif chemokine ligand-2 (CCL2), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF), were detectable in the CSF within the first 3 days after hemorrhage, and all were elevated compared to plasma. Compared with controls, CCL2, IL-6, IL-8, G-CSF, and VEGF were elevated in the CSF of both ICH and aSAH patients (p<0.01 for all comparisons). VEGF was increased in ICH patients compared to aSAH patients (p<0.01). CCL2, G-CSF, and VEGF in the CSF were associated with more severe disease in aSAH patients only. ConclusionsWithin 3 days of hemorrhagic stroke, proinflammatory molecules can be detected in the CSF at higher concentrations than in the plasma. Early concentrations of some pro-inflammatory molecules may be associated with markers of disease severity.

ObjectiveTo compare early cerebrospinal fluid (CSF) cytokine profiles in intracerebral hemorrhage (ICH) versus subarachnoid hemorrhage (SAH), with a focus on angiography-negative SAH (anSAH). MethodsWe conducted a retrospective observational cohort study of adults with spontaneous hemorrhagic stroke (ICH or SAH). For cytokine analyses, we included patients with external ventricular drains (EVDs) and analyzed the first CSF sample obtained within 72 hours of symptom onset. Cytokines were measured using a multiplex bead-based assay and included interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A (VEGF-A), C-C motif chemokine ligand-2 (CCL2), and granulocyte colony-stimulating factor (G-CSF). Cytokine concentrations were log-transformed due to non-normal distribution. Functional outcomes were assessed using the modified Rankin Scale (mRS) at discharge and 3 months. ResultsCSF cytokine analyses included 120 patients with available CSF samples (43 ICH and 77 SAH), while functional outcome analyses included a broader cohort of 490 patients with ICH or SAH to characterize discharge and 3-month outcomes across hemorrhage subtypes. Compared with SAH, ICH demonstrated higher early CSF log[IL-8] and log[VEGF-A] and had worse functional outcomes at discharge and 3 months. Within SAH, anSAH had higher log[IL-8] and log[VEGF-A] than aSAH, and its cytokine profile more closely aligned with that of primary ICH in hemorrhages without vascular malformations. DiscussionEarly CSF cytokine patterns suggest anSAH shares a more ICH-like inflammatory signature than aneurysmal SAH, supporting anSAH as a potentially biologically distinct SAH phenotype.

BackgroundBrain injury is pathophysiologically diverse, with many cases presenting with mixed pathologies. Utilizing objective measures to investigate the pathophysiology of injury would aid in understanding prognosis and targeting therapeutics. ObjectiveThe goal of this study is to develop a traumatic brain injury classification scheme based on open source deep learning computer tomography (CT) analysis and the two serum biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal L1 (UCH-L1). MethodsMachine learning was utilized to develop a novel algorithm capable of classifying the type of brain injury based on a CT scan analysis algorithm and GFAP and UCH-L1 concentrations. Injury was stratified into one of four groups: spontaneous hemorrhage, oxygen deprivation, trauma resulting in vascular injury or high-velocity trauma with negative CT scan. Outcomes100 research subjects were enrolled. Using a combination of CT analysis and serum markers, the subjects with CT positive trauma were distinguishable from those with spontaneous hemorrhage, ischemic injury, CT negative trauma and controls with AUCs of 0.96, 0.99., 0.98 and 1.00 respectively. Ischemic injury was distinguishable from CT positive trauma with an AUC of 0.98. All forms of brain injury could be distinguished from controls with AUC = 1.00. DiscussionAn open source algorithmic CT scan analysis algorithm and serum biomarkers accurately classified the nature of brain injury across major etiologies. Further implementation of such algorithms and addition of other objective measures will enable better prognostication of injury and improved development of therapeutics.

BACKGROUNDEarly brain injury attributable to initial or recurrent bleeding is the leading cause of poor outcomes in patients with subarachnoid hemorrhage (SAH). This study investigated rebleeding immediately after SAH ictus, focusing on its timing and associated blood pressure (BP). METHODSConsecutive patients with spontaneous SAH treated from January 1999 to June 2022 were reviewed. Rebleeding was defined as a sudden decline in consciousness to a coma, sudden pupillary dilation with elevated BP, or increased SAH on head computed tomography (CT). The rebleeding timing was examined during each management phase. Demographic, radiological, and initial evaluation data were assessed for rebleeding and outcomes. RESULTSAmong 940 patients (64% women, mean age 63.6 {+/-} 13.2, 73% with a World Federation of Neurological Societies grade [&ge;]4), rebleeding occurred in 221 cases (23.5%); 139 episodes in 121 patients (13.7%) before and 134 episodes in 112 patients after hospitalization (11.9%), and 19 patients (2.0%) in both. Rebleeding occurred more frequently in patients with worse neurological state, higher CT grades, and earlier arrivals. Systolic BP (SBP) was higher in patients with rebleeding (178 mmHg, IQR 140-204 mmHg) than in those without rebleeding (148 mmHg, IQR 100-180 mmHg) (P<0.001). Higher SBP was associated with increased rebleeding (OR 9.843; P<0.0001) and lower mortality (OR 0.0281; P=0.0084) but not with favorable outcomes (OR 1.686; P=0.22). When comparing the groups divided into 20 mmHg increments, the incidence of rebleeding, unfavorable outcomes, and mortality increased in the groups with SBP [&ge;]181 mmHg, SBP [&le;]100 mmHg and >160 mmHg, and SBP [&le;]100 mmHg, respectively. CONCLUSIONSRebleeding occurred in 23.5% of patients with SAH in the hyperacute phase, primarily before hospital arrival. Higher SBP was associated with rebleeding, and SBP of 101-160 mmHg was associated with favorable outcomes.

BackgroundPrediction of which traumatic and hypoxic brain injuries will progress to brain death is currently based predominantly on history, physical examination and radiographic findings. We investigated how accurately purely objective measures including three neurologic serum markers and algorithmic CT (computed tomograph) scan analysis can predict brain death and differentiate its etiology. MethodsThis prospective observational study enrolled 51 isolated trauma subjects and 19 clinically brain dead subjects that were further divided by mechanism of injury into high-velocity trauma with presumed diffuse axonal injury, cardiopulmonary/respiratory arrest, and found down groups. Levels of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 Calcium-Binding Protein B (S100B) were compared, and algorithmic analysis of CT scan imaging was performed using an open-source deep learning software (BLAST-CT). FindingsThe prognostic value of various biomarker combinations in identifying subjects progressing to brain death was assessed using machine learning. Prediction accuracy for GFAP, UCH-L1, and S100B and algorithmic CT analysis in combination to predict brain death from among all other cohorts yielded an area under the receiver operator curve of 0.98 versus all other brain injury subjects. This model was also able to distinguish brain death attributed to cardiopulmonary/respiratory arrest from combined non-trauma controls and diffuse axonal injury with an area under the curve of 0.99. InterpretationSerum concentrations of GFAP, UCH-L1, and S100B measured within 32 hours of traumatic and hypoxic brain injury (cardiopulmonary/respiratory arrest) and algorithmic CT analysis have utility in prognosticating brain death and predicting its mechanism of injury as either hypoxic or traumatic/unknown (diffuse axonal injury/found down). FundingAbbott Labs and the Minnesota State Office of Higher Education.

Oral nimodipine is the only drug approved in North America for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow capsules. An oral liquid formulation exists but causes gastrointestinal complications. An intravenous nimodipine formulation (GTX-104) has been developed that has bioavailability approaching 100% and is not affected by feeding or gastointestinal absorption. GTX-104 causes less hypotension and has more consistent peak plasma concentrations than oral nimodipine in healthy human volunteers. Herein we describe the protocol of a prospective, randomized, open-label safety and tolerability study of GTX-104 compared to oral nimodipine in patients with aSAH (STRIVE-ON, NCT05995405). Inclusion and exclusion criteria match the prescribing information for oral nimodipine and include adult patients with aSAH of all Hunt and Hess grades who can receive investigational product within 96 hours of aSAH. Subjects at imminent risk of death are excluded. Subjects are randomized 1:1 to GTX-104 or oral nimodipine for up to 21 days. The primary endpoint is the proportion of subjects in each group with clinically significant hypotension, defined as hypotension requiring any medical treatment, with a reasonable likelihood of being due to investigational product as determined by an independent, blinded endpoint adjudication committee. No statistical analysis of the endpoint is planned. Secondary endpoints include all episodes of hypotension, all adverse events, delayed cerebral ischemia, rescue therapy and suicidal ideation. Clinical and health economic outcomes include quality of life using the EQ-5D-3L, modified Rankin scale at 30 and 90 days after aSAH and hospital resource use. The planned sample size is 100 subjects across 25 sites in the United States and Canada. DETAILS PAGEO_LIWe confirm that manuscript complies with all instructions to authors. C_LIO_LIWe confirm that authorship requirements have been met and the final manuscript is approved by all authors. C_LIO_LIWe confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. It is planned to post it on C_LIO_LIWe confirm adherence to ethical guidelines and indicate ethical approvals and use of informed consent. C_LIO_LIAll conflicts of Interest for all authors are disclosed. C_LIO_LIWe confirm the use of the Standard Protocol Items: Recommended for Interventional Trials (SPIRIT) checklist. C_LIO_LIThe source of funding for the study is disclosed. It is Acasti Pharma. C_LI

BackgroundIntracranial hemorrhage (ICH) is a serious complication associated with oral anticoagulant use and is associated with significant morbidity and mortality. Although anticoagulation reversal agents are utilized as standard of care, practitioners are limited in their ability to assess degree of anticoagulation reversal for direct oral anticoagulants (DOACs). There is a clinical need identify biomarkers to assess anticoagulation status in patients with DOAC-associated ICH to ensure hemostatic efficacy of anticoagulation reversal agents in the acute setting. The purpose of this study was to assess the utility of thromboelastography (TEG) to assess the impact of anticoagulation reversal in patients presenting to the emergency department (ED) with DOAC-associated ICH. MethodsWe conducted a prospective, observational cohort study in adult patients presenting to the ED with acute DOAC-associated ICH. Patients were excluded if last DOAC dose was >48 hours prior to hospital arrival, if they experienced polytrauma, were pregnant, incarcerated, had a history of hepatic failure or coagulopathy, or received anticoagulation reversal with products other than prothrombin complex concentrates (PCCs). We collected baseline TEG samples from participants prior to anticoagulation reversal, as well as 30-minutes, 12-hours, and 24-hours post-reversal. TEG samples were also collected from participants who transferred to our facility after reversal at ED presentation, as well as 12- and 24-hours post-reversal. ResultsPre-reversal TEG was collected on 10 participants prior to DOAC reversal. A significant decrease in TEG R-time was observed at 30 minutes post-reversal. R-time increased at 12- and 24-hours to baseline levels. Significant changes were not observed in K-time, clot strength, maximum amplitude, or coagulation index. ConclusionsTEG R-time may be able to detect a change in anticoagulation activity of DOACs in ICH after anticoagulation reversal. R-time decreases acutely after anticoagulation reversal and rebounds at 12- and 24-hours post-reversal.

Background/ObjectiveThe reliability of electronic medical records (EMR) for exposure to sedative and analgesic medications in patients with acute disorders of consciousness is unknown. Our objective was to quantify the accuracy of sedative and analgesic infusion rates derived from the EMR to support its use in big data clinical research. MethodsWe conducted a prospective cohort study enrolling critically ill patients who were unresponsive to verbal commands after acute brain injury. During standardized behavioral assessments, research coordinators documented infusing sedative and analgesic medications in case report forms (CRF; reference standard). We extracted infusion rates from the EMR (index) and calculated concordance correlation coefficients for drugs with [&ge;] 10 EMR-CRF infusion rate pairs. ResultsAmong 63 included patients (median age: 61 [46-72]; 22 [35%] female), we collected 404 pairs (225 fentanyl, 86 propofol, 70 dexmedetomidine, 19 midazolam, 4 ketamine). Correlation coefficients were 0.82 (95% CI: 0.69-0.91) for propofol, 0.93 (95% CI: 0.85-0.97) for fentanyl, 0.92 (95% CI: 0.81-0.98) for dexmedetomidine and 0.94 (95% CI: 0.55-1.00) for midazolam. ConclusionsEMR derived data on sedative and analgesic infusion rates has variable but overall adequate accuracy to support big data research. External validation is required to support its routine use in clinical research.

BackgroundNeonatal cerebral venous sinus thrombosis (CVST) is associated with intracranial hemorrhage (ICH) and ischemic lesions. There is no scale to characterize the spectrum of brain injury secondary to neonatal CVST. ObjectiveTo develop the Neonatal CVST Hemorrhage Score (NeoCVST Score) to characterize ICH and brain injury in neonates with CVST. MethodsThis was a retrospective cohort study of neonates with CVST diagnosed using brain MRI/MRV. The NeoCVST Score was developed using the study cohort, integrating elements from previous hemorrhage classification systems and expert consensus. Logistic regression examined associations between NeoCVST score and neurodevelopmental outcomes (Pediatric Stroke Outcome Measure). Interrater reliability was assessed with intraclass correlation coefficient. ResultsThe study included 100 neonates (77% term and 23% preterm) with CVST. Thrombosis of multiple venous sinuses was present in 62%. ICH was present in 63%. Supratentorial hemorrhage was present in 57% and included germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) grades 1-2 (22%), GMH-IVH grade 3 (15%), parenchymal (43%) and thalamic (18%) hemorrhage. Infratentorial hemorrhage was present in 19% and included cerebellar (18%) and brainstem (4%) hemorrhage. Extra-axial hemorrhage was present in 32% and included epidural (2%), subdural (26%) and subarachnoid hemorrhage (6%). Ischemic brain injury was present in 67% and included lesions in the medullary vein distribution (13%), white matter (54%), basal ganglia (17%) and thalamus (25%). Neurodevelopmental outcomes included 40% with normal outcomes and 60% with neurodevelopmental impairments. NeoCVST total score (OR=1.1, P=0.02) and subscores for thalamic hemorrhage (OR=1.9, P=0.04), thalamic ischemia (OR=2.2, P=0.005) and bilateral thalamic ischemia (OR=2.8, P=0.01) were predictors of adverse neurodevelopmental outcome. Inter-rater reliability showed moderate-good agreement between reviewers with an intraclass correlation coefficient of 0.71. ConclusionsThe NeoCVST Score is a simple clinical tool to characterize ICH and brain injury secondary to neonatal CVST. Increasing NeoCVST total score and subscores for thalamic hemorrhage and ischemia were associated with worse neurodevelopmental outcomes.

BackgroundWe developed a simple quantifiable scoring system that predicts aneurysmal subarachnoid hemorrhage (aSAH) mortality, delayed cerebral ischemia (DCI) and modified Rankin Scale outcomes using readily available SAH admission clinical data with a new radiographic quantitative volumetric SAH method. MethodsWe analyzed 277 patients with aneurysmal SAH (aSAH) admitted at our Comprehensive Stroke Center (CSC) at Mayo Clinic Florida between 2012 and 2022. We developed a mathematical model that measures aSAH basal cisternal subarachnoid hemorrhage volume (SAHV) using a derivation of the ABC/2 ellipsoid formula, where A = width/thickness, B = length, C = vertical extension) on non-contrast CT (NCCT), which we previously demonstrated comparable to pixel based manual segmentation on NCCT scans. Data was analyzed using t-test, chi-square, receiver operator characteristics (ROC) curve, and area under curve analysis. Multivariate logistic regression analysis with stepwise elimination of variables not contributing to the model (0.05 significance level for entry into the model) was used to develop an enhanced SAH (eSAH) scoring system. ResultsUsing regression and logistic regression, we found that age, GCS score and SAHV were significantly associated with final discharge outcome, prediction on in-hospital DCI, and in-hospital mortality. A weighted eSAH score was developed using these factors that ranged between 0-5 and was strongly predictive of outcome (AUC=0.88), DCI (AUC=0.75) and in-hospital mortality (AUC=0.87). ConclusionsA volumetrically-enhanced SAH (eSAH) score is a simple quantitative model based on SAH volumetrics, GCS and age and appears to predict mortality and outcomes in SAH patients. A larger cohort validation study is planned.

Background and PurposePatients admitted for subarachnoid hemorrhage (SAH) may require cerebrospinal fluid (CSF) diversion. The rate and indications for CSF diversion are highly variable. This study aimed to identify factors associated with CSF diversion in low-grade SAH in clinical practice. MethodsWe used a prospectively collected multicentric database (Neurobase(R)) cohort of patients with severe acute cerebral injuries, in three intensive care units (ICU) in France between March 2022 and June 2024. We included patients with aneurysmal or sine materia SAH with WFNS grades 1 to 3. Clinical and radiological variables were analyzed in patients with a CSF diversion during ICU stay. Hydrocephalus, cerebral hemorrhage and edema were quantified on admission CT-scans. ResultsOur cohort included 219 patients, mainly women (61%), on average 53 years old, mostly WFNS grade 1 (68%). Shunts were placed in 45% of patients, of which 92% were external ventricular drains, and 75% were placed in the first 24 hours. The predictors of CSF diversion in the first 24 hours in multivariate analysis were the delay between symptoms and first CT-scan (adjusted OR [aOR], 0.67 [95% CI, 0.45-0.99]), a GCS in the first 24 hours < 15 (aOR, 3.17 [95% CI, 1.42-7.10]), the ventricular Hijdra score (aOR, 1.48 [95% CI, 1.19-1.85]), temporal horn dilation (aOR, 1.89 [95% CI, 1.25-2.87]), and a Subarachnoid hemorrhage Early Brain Edema Score (SEBES) of 2 (aOR, 4.83 [95% CI, 1.57-14.87]). These predictors were also associated with CSF diversion at any time of ICU stay. We tested the centers and found a statistical significance (p < 0.001). ConclusionThe decision to place a CSF shunt depends not only on hydrocephalus, altered mental status, and intraventricular hemorrhage, but also on cerebral edema and the delay between the first symptoms and CT-scan. The variability of practice in the included centers highlights a gray zone in the indication of CSF diversion.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is frequently complicated by delayed cerebral ischaemia (DCI), for which current therapies incompletely target the underlying multifactorial pathophysiology. Transauricular vagus nerve stimulation (taVNS) modulates inflammatory, vasoactive and autonomic pathways and may attenuate secondary brain injury after aSAH. Methods: We conducted a prospective, single-centre, single-blind, randomised, sham-controlled pilot trial in adults within 5 days of aneurysm securing for non-traumatic aSAH. Participants were allocated 1:1 to active taVNS (left tragus) or sham (left earlobe) using a portable device delivered for 45 minutes twice daily over 5 days. Primary outcomes were safety (taVNS-related serious adverse events), acceptability, and compliance; secondary outcomes included inflammatory biomarkers, DCI, in-hospital complications, and functional outcomes to 1 month. Results: Thirty patients were randomised (16 taVNS, 14 sham), with numerically more severe aSAH at baseline in the taVNS arm. No taVNS-related serious adverse events occurred; side effects were generally mild and transient, and over 80% of planned sessions were completed. TaVNS produced greater reductions in serum tumour necrosis factor- and trends towards reductions in interleukin-1{beta} and interleukin-10, with numerically fewer DCI events (6.6% vs 35.7%) and neurological impairments (16.7% vs 53.8%), although functional outcomes were not statistically different at 1 month. Conclusions: Early taVNS after aSAH is safe, acceptable, and feasible in the neurocritical care setting and shows biologically plausible signals warranting evaluation in larger multi-centre trials.

ObjectiveCognitive motor dissociation (CMD) is associated with long-term recovery in acute brain injury, but CMD testing is only available in few centers. Our objective was to identify surface EEG patterns with high sensitivity or positive predictive value (PPV) for CMD in patients with acute disorders of consciousness to refine allocation of this resource-intensive test. MethodsIn this observational cohort study, we enrolled clinically unresponsive, acutely brain injured patients who underwent continuous surface EEG and CMD assessments. CMD was detected by applying a machine learning algorithm to EEG acquired during a motor command paradigm presentation. Electroencephalographers blinded to CMD test results applied standardized ACNS criteria to the EEGs acquired during CMD assessments. We calculated accuracy measures of surface EEG findings for CMD test results using generalized estimating equations, with an exchangeable matrix and accounting for repeated measures per patient. ResultsWe included 185 patients (mean age: 62 {+/-} 17; 85 [46%] female) and 282 CMD assessments. CMD testing was positive in 39 (14%) assessments. Sensitivity and PPV of normal background voltage, symmetry and continuity were respectively 77% (95%-CI: 60-88%) and 19% (95%-CI: 13-26%), 74% (95%-CI: 58-86%) and 14% (95%-CI: 10-20%), and 74% (95%-CI: 58-86%) and 14% (95%-CI: 9-19%). All EEGs with burst suppression, suppression, sporadic epileptiform discharges, lateralized periodic discharges, bilateral independent periodic discharges, electrographic seizures and brief potentially ictal rhythmic discharges had negative CMD tests. InterpretationSurface EEG findings are not reliable to screen for CMD or to identify patterns conferring higher CMD pretest probability.

ObjectiveDespite substantial variability in the severity of post-anoxic encephalopathy, all comatose patients after cardiac arrest are usually treated according to the same standardized intensive care protocol, including sedation, mechanical ventilation, and targeted temperature management (TTM). We hypothesize that patients with a favourable EEG pattern (continuous EEG within 12 hours after cardiac arrest) may not benefit from prolonged sedation and TTM. We studied the feasibility and safety of early cessation of sedation and TTM in this subgroup. MethodsWe conducted a non-randomized, controlled intervention study including 40 adult patients admitted to the ICU with postanoxic encephalopathy after cardiac arrest and an early (< 12 hours) favourable EEG pattern. The control group received standard care with sedation and TTM for at least 24-48 hours, whereas the intervention group underwent early cessation of sedation and TTM as soon as possible after establishing a favourable EEG, followed by weaning from mechanical ventilation. The primary outcome was duration of mechanical ventilation. Secondary outcomes included ICU length of stay, total sedation time, number of ICU complications, and neurological outcomes at 3 and 6 months. ResultsDuration of mechanical ventilation was significantly shorter in the intervention than in the control group (median 12 vs 28 h, p < 0.001). Median ICU length of stay and median total sedation time were also reduced by more than 50% in the intervention group, from respectively 2.5 to 1.2 days (p = 0.001) and 27 to 12 h (p < 0.001). There was no increase in ICU complications in the intervention group. No statistically significant differences in neurological outcomes at 3 or 6 months were observed. ConclusionEarly withdrawal of sedation is feasible and safe in patients with an early favourable EEG following cardiac arrest. The study was underpowered to detect possible differences in long-term neurological recovery. SignificanceShortening sedation and mechanical ventilation is likely to result in direct reductions in healthcare costs and contribute to more appropriate care. Larger studies are needed to evaluate the impact on long-term neurological outcomes.

BackgroundHyperglycemia after intracerebral hemorrhage (ICH) may be associated with worse outcomes. In this study, we evaluated the association of early post-ICH glucose trajectories and clinical outcomes. MethodsWe performed a secondary analysis of the ATACH-2 trial dataset. Hyperglycemia was defined as a blood glucose of [&ge;]140 mg/dl. Glucose levels at 0h, 24h, 48h, and 72h were analyzed using a linear mixed effects model, with fixed effects for time and random intercept/slopes. Patient-specific estimates were used to predict glucose values at 0h and 72h, informed by all four timepoints, to classify patients into the following glycemic trajectory groups: (1) early hyperglycemia, (2) late hyperglycemia, (3) persistent hyperglycemia, and (4) persistent normoglycemia. Outcomes were compared using univariate analysis and log-rank test survival analysis. Good outcomes were defined as a modified Rankin Score of 0 to 2. The association between glycemic trajectories and functional outcomes was tested using logistic regression models adjusted for patient demographics and clinical variables. ResultsOf 1000 patients (median age 62 [IQR 52-71]; 38% female) in the study, 81 (8.1%) had early hyperglycemia, 59 (5.9%) late hyperglycemia, 225 (22.5%) persistent hyperglycemia, and 635 (63.5%) persistent normoglycemia. On univariate analysis, 45.8% of patients with persistent normoglycemia had favorable 90-day functional outcomes compared to 30.9% in early, 30.5% in late, and 32.0% in persistent hyperglycemia patients (p<0.001). The late hyperglycemia patients had the highest rate of hematoma expansion (35.3%, p=0.029) and the lowest Kaplan Meier-estimated survival (86%, p=0.015). In adjusted multivariable regression models, early hyperglycemia was significantly associated with a poor functional outcome (OR 2.27, 95% CI 1.10-4.68, p=0.026). ConclusionEarly hyperglycemia was associated with worse functional outcomes, while late and persistent hyperglycemia were associated with worse survival rates. These findings suggest that glycemic trajectories may affect or predict prognosis. This highlights the importance of continuous glucose monitoring and glycemic control strategies after ICH.