GFAP point-of-care measurement for prehospital diagnosis of intracranial hemorrhage in acute coma.

BACKGROUND: Prehospital triage and treatment of patients with acute coma is challenging for rescue services, as the underlying pathological conditions are highly heterogenous. Recently, glial fibrillary acidic protein (GFAP) has been identified as a biomarker of intracranial hemorrhage. The aim of this prospective study was to test whether prehospital GFAP measurements on a point-of-care device have the potential to rapidly differentiate intracranial hemorrhage from other causes of acute coma. METHODS: This study was conducted at the RKH Klinikum Ludwigsburg, a tertiary care hospital in the northern vicinity of Stuttgart, Germany. Patients who were admitted to the emergency department with the prehospital diagnosis of acute coma (Glasgow Coma Scale scores between 3 and 8) were enrolled prospectively. Blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min) shortly after hospital admission. RESULTS: 143 patients were enrolled (mean age 65 ± 20 years, 42.7% female). GFAP plasma concentrations were strongly elevated in patients with intracranial hemorrhage (n = 51) compared to all other coma etiologies (3352 pg/mL [IQR 613-10001] vs. 43 pg/mL [IQR 29-91.25], p < 0.001). When using an optimal cut-off value of 101 pg/mL, sensitivity for identifying intracranial hemorrhage was 94.1% (specificity 78.9%, positive predictive value 71.6%, negative predictive value 95.9%). In-hospital mortality risk was associated with prehospital GFAP values. CONCLUSION: Increased GFAP plasma concentrations in patients with acute coma identify intracranial hemorrhage with high diagnostic accuracy. Prehospital GFAP measurements on a point-of-care platform allow rapid stratification according to the underlying cause of coma by rescue services. This could have major impact on triage and management of these critically ill patients.

Development and validation of a clinical prediction model for prognostic factors in patients with primary pontine hemorrhage.

We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P<0.05). The U test showed no statistical difference (P=0.892) between the training cohort and the validation cohort, suggesting the model fitted well. The new model showed good discrimination (area under the curve=0.833). The decision curve analysis of the nomogram of the training cohort indicated a great net benefit. The PPH nomogram comprising the Glasgow Coma Scale score, normalized pixels, and mechanical ventilation may facilitate predicting a 90-day good outcome.

Semi-supervised Learning for Generalizable Intracranial Hemorrhage Detection and Segmentation.

Purpose To develop and evaluate a semi-supervised learning model for intracranial hemorrhage detection and segmentation on an out-of-distribution head CT evaluation set. Materials and Methods This retrospective study used semi-supervised learning to bootstrap performance. An initial "teacher" deep learning model was trained on 457 pixel-labeled head CT scans collected from one U.S. institution from 2010 to 2017 and used to generate pseudo labels on a separate unlabeled corpus of 25 000 examinations from the Radiological Society of North America and American Society of Neuroradiology. A second "student" model was trained on this combined pixel- and pseudo-labeled dataset. Hyperparameter tuning was performed on a validation set of 93 scans. Testing for both classification (n = 481 examinations) and segmentation (n = 23 examinations, or 529 images) was performed on CQ500, a dataset of 481 scans performed in India, to evaluate out-of-distribution generalizability. The semi-supervised model was compared with a baseline model trained on only labeled data using area under the receiver operating characteristic curve, Dice similarity coefficient, and average precision metrics. Results The semi-supervised model achieved a statistically significant higher examination area under the receiver operating characteristic curve on CQ500 compared with the baseline (0.939 [95% CI: 0.938, 0.940] vs 0.907 [95% CI: 0.906, 0.908]; P = .009). It also achieved a higher Dice similarity coefficient (0.829 [95% CI: 0.825, 0.833] vs 0.809 [95% CI: 0.803, 0.812]; P = .012) and pixel average precision (0.848 [95% CI: 0.843, 0.853]) vs 0.828 [95% CI: 0.817, 0.828]) compared with the baseline. Conclusion The addition of unlabeled data in a semi-supervised learning framework demonstrates stronger generalizability potential for intracranial hemorrhage detection and segmentation compared with a supervised baseline. Keywords: Semi-supervised Learning, Traumatic Brain Injury, CT, Machine Learning Supplemental material is available for this article. Published under a CC BY 4.0 license. See also the commentary by Swimburne in this issue.

STEMI in a patient with recent intracranial hemorrhage.

A 63-year-old male patient with a history of hypertension presented to the emergency department with a one-day history of dizziness, nausea, and vomiting.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

Glial Fibrillary Acidic Protein as a Potential Indicator for Symptomatic Intracranial Hemorrhage in Acute Ischemic Patients Undergoing Endovascular Thrombectomy.

Background: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH. Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification. Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150-0.576] versus 0.065 [0.041-0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150-0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269-1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153-2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070-0.295, p = 0.001). Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT.

Intravenous Thrombolysis in Patients 90 Years or Older with Moderate to Severe Acute Ischemic Stroke Increases Ambulation at Discharge and Is Safe: A Prospective Cohort Study from a Single Center in Santiago, Chile.

INTRODUCTION: The World Health Organization predicts that the global population aged 60 years and older will double by 2050, leading to a significant rise in the public health impact of acute ischemic stroke (AIS). Existing stroke guidelines do not specify an upper age limit for the administration of intravenous thrombolysis (IVT), although some suggest a relative exclusion criterion in patients aged ≥80 in the 3-4.5-h window. Many physicians avoid treating these patients with IVT, argumenting high risk and little benefit. Our aim was to investigate the efficacy and safety of IVT treatment in patients with non-minor AIS aged ≥90, admitted to our institution. The primary efficacy endpoint was the ability to walk at discharge (mRS 0-3), and the primary safety endpoints were death and symptomatic intracranial hemorrhagic transformation (sIHT) at discharge. METHODS: Patients with AIS aged ≥90 admitted to our center from January 2003 to December 2022 were included. They were selected if had an NIHSS ≥5, were previously ambulatory (prestroke mRS score 3 or less), and arrived within 6 h from symptom onset. Those treated or not with IVT were compared with univariate analysis. RESULTS: The mean age was 93.2 (2.4) years, and 51 (73.9%) were female. The admission mRS and NIHSS were 1 (IQR 0-2) and 14 (IQR 7-22), respectively. Thrombolyzed patients had a shorter time from symptom onset to door and lower glycemia on admission. IVT was associated with a higher proportion of patients achieving mRS 0-3 at discharge (p = 0.03) and at 90 days (p = 0.04). There were no differences between groups in the risk of death (p = 0.55) or sIHT (p = 0.38). CONCLUSION: In this small sample, ambulatory patients aged ≥90 with moderate or severe AIS treated with IVT had increased odds of being able to walk independently at discharge than those not treated, without safety concerns.

Development and Validation of a Prediction Model for 30-Day Mortality and Functional Outcome in Patients with Primary Brainstem Hemorrhage.

INTRODUCTION: Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is associated with poor prognosis. We aimed to develop a prediction model for predicting 30-day mortality and functional outcome in patients with PBSH. METHODS: We reviewed records of 642 consecutive patients with first-time PBSH from three hospitals between 2016 and 2021. Multivariate logistic regression was used to establish a nomogram in a training cohort. Cutoff points of the variables were determined by receiver operating characteristic curve analysis, and certain points were assigned to these predictors to produce the PBSH score. The nomogram and PBSH score were compared with other scoring systems for PBSH. RESULTS: Five independent predictors, comprised of temperature, pupillary light reflex, platelet-to-lymphocyte ratio, Glasgow Coma Scale (GCS) score on admission, and hematoma volume, were incorporated to construct the nomogram. The PBSH score consisted of 4 independent factors with individual points assigned as follows: temperature, ≥38°C (=1 point), <38°C (=0 points); pupillary light reflex, absence (=1 point), presence (=0 points); GCS score 3-4 (=2 points), 5-11 (=1 point), and 12-15 (=0 points); PBSH volume >10 mL (=2 points), 5-10 mL (=1 point), and <5 mL (=0 points). Results showed that the nomogram was discriminative in predicting both 30-day mortality (area under the ROC curve [AUC] of 0.924 in the training cohort, and 0.931 in the validation cohort) and 30-day functional outcome (AUC of 0.887). The PBSH score was discriminative in predicting both 30-day mortality (AUC of 0.923 in the training cohort and 0.923 in the validation cohort) and 30-day functional outcome (AUC of 0.887). The prediction performances of the nomogram and the PBSH score were superior to the intracranial hemorrhage (ICH) score, primary pontine hemorrhage (PPH) score, and new PPH score. CONCLUSIONS: We developed and validated two prediction models for 30-day mortality and functional outcome in patients with PBSH. The nomogram and PBSH score could predict 30-day mortality and functional outcome in PBSH patients.

Joblessness, decreased income, and disability in intensive care unit survivors of nontraumatic intracranial hemorrhage in South Korea.

OBJECTIVES: To examine the proportions of unemployment, decreased household income, and newly acquired disability, and their impact on long-term mortality after intensive care unit (ICU) admission due to nontraumatic intracranial hemorrhage (IH). MATERIALS AND METHODS: This nationwide population-based retrospective cohort study enrolled adult patients admitted to the ICU because of nontraumatic IH between 2010 and 2018 in South Korea. Patients who were alive ≥365 days after ICU admission were defined as nontraumatic IH survivors. RESULTS: In total, 104,086 nontraumatic IH survivors were included in the final analysis. Among them, 7,225 (6.9 %) experienced job loss, 25,709 (24.7 %) experienced decreased household income, and 20,938 (20.1 %) had newly acquired disabilities, of whom 14,188 (13.6 %) had newly acquired brain disabilities. Male sex, increased duration of intensive care unit stay, comorbid status, hospital admission through the emergency room, nontraumatic intracerebral hemorrhage, receipt of surgery, mechanical ventilatory support, and increased total cost of hospitalization were associated with job loss, decreased household income, and newly acquired disabilities. However, these changes were not significantly associated with 2-year all-cause mortality (adjusted hazard ratio: 1.00, 95 % confidence interval: 0.95, 1.06; P = 0.997). CONCLUSIONS: Many nontraumatic IH survivors experienced unemployment, decreased household income, and newly acquired disability one year after ICU admission in South Korea. Some factors were potential risk factors for these changes, but the changes were not associated with 2-year all-cause mortality.

Postmortem diagnosis of severe factor X deficiency in a fetus with intracranial hemorrhage resulting in intrauterine death.

In patients with severe congenital factor X deficiency, spontaneous intracranial hemorrhage (ICH) is particularly frequent in early childhood. We describe a case of fetal death at 26 weeks due to massive ICH. Gene panel analysis of postmortem samples revealed homozygosity for a pathologic F10 gene variant (c.1210T>C, p.Cys404Arg), which impedes correct folding of the catalytic serine protease domain and, therefore, causes a significant reduction in FX levels. The parents, not consanguineous but of the same ethnic community, were found to be heterozygous for this variant and did not have any personal or family history of abnormal bleeding. To the best of our knowledge, this is the first reported case of severe FX deficiency resulting in ICH diagnosed through postmortem genetic analysis. It illustrates the importance of exploring the etiology of fetal or neonatal ICH, which may impact future pregnancies, and the treatment of a potential coagulopathy in the child.

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

BACKGROUND: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH risk stratification. METHODS: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Predictive validity of the All Patients Refined Diagnosis Related Group modifiers for costs and outcomes from intracranial hemorrhage.

OBJECTIVE: The All Patients Refined Diagnosis Related Group (APR-DRG) modifiers-severity of illness (SOI) and risk of mortality (ROM)-inform hospital reimbursement nationally. The ubiquitous APR-DRG data bear the potential to inform public health research; however, the algorithms that generate these modifiers are proprietary and therefore should be independently verified. This study evaluated the predictive value of APR-DRG modifiers for the outcomes and costs of intracranial hemorrhage. METHODS: The New York Statewide Planning and Research Cooperative System databases were accessed and searched for the intracranial hemorrhage Diagnosis Related Group in records from 2012 to 2020. Receiver operating characteristic and multiple logistic regressions characterized the predictive validity of the APR-DRG modifiers for patient outcomes. One-way ANOVA compared costs and charges between SOI and ROM designations. RESULTS: Among 46,019 patients, 12,627 (27.4%) died. The mean ± SEM costs per patient were $21,342 ± $145 and the mean ± SEM charges per patient were $68,117 ± $408. For prediction of mortality, the area under the curve (AUC) was 0.74 for SOI and 0.83 for ROM. For prediction of discharge to a facility, AUC was 0.62 for SOI and 0.64 for ROM. Regression analysis showed that ROM was a strong predictor of mortality, while SOI was a weak predictor; both were modest predictors of discharge to a facility. SOI and ROM were significant predictors of costs and charges. CONCLUSIONS: Compared with the prior studies, the authors identified several limitations of APR-DRG modifiers, including low specificity, modest AUC, and limited outcomes prediction. This report supports the limited use of APR-DRG modifiers in independent research on intracranial hemorrhage epidemiology and reimbursement and advocates for general caution in their use for evaluation of neurosurgical disease.

Clinical Performance Measures for Emergency Department Care for Adults With Intracranial Hemorrhage.

Though select inpatient-based performance measures exist for the care of patients with nontraumatic intracranial hemorrhage, emergency departments lack measurement instruments designed to support and improve care processes in the hyperacute phase. To address this, we propose a set of measures applying a syndromic (rather than diagnosis-based) approach informed by performance data from a national sample of community EDs participating in the Emergency Quality Network Stroke Initiative. To develop the measure set, we convened a workgroup of experts in acute neurologic emergencies. The group considered the appropriate use case for each proposed measure: internal quality improvement, benchmarking, or accountability, and examined data from Emergency Quality Network Stroke Initiative-participating EDs to consider the validity and feasibility of proposed measures for quality measurement and improvement applications. The initially conceived set included 14 measure concepts, of which 7 were selected for inclusion in the measure set after a review of data and further deliberation. Proposed measures include 2 for quality improvement, benchmarking, and accountability (Last 2 Recorded Systolic Blood Pressure Measurements Under 150 and Platelet Avoidance), 3 for quality improvement and benchmarking (Proportion of Patients on Oral Anticoagulants Receiving Hemostatic Medications, Median ED Length of Stay for admitted patients, and Median Length of Stay for transferred patients), and 2 for quality improvement only (Severity Assessment in the ED and Computed Tomography Angiography Performance). The proposed measure set warrants further development and validation to support broader implementation and advance national health care quality goals. Ultimately, applying these measures may help identify opportunities for improvement and focus quality improvement resources on evidence-based targets.

Differences between males and females following endovascular therapy for stroke: A systematic review and meta-analysis.

BACKGROUND: Endovascular therapy (EVT) represents the standard of care for eligible patients with acute ischemic stroke (AIS) and large vessel occlusion. To better understand differences in baseline characteristics and outcomes between males and females following EVT, we conducted a systematic review and meta-analysis. METHODS: We identified, using the Nested Knowledge AutoLit platform, prospective studies that reported 90-day outcomes in males and females treated with EVT for AIS. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0-2. Secondary outcome variables included mRS 0-1, symptomatic intracranial hemorrhage (sICH), thrombolysis in cerebral infarction (TICI) score 2b-3, and mortality. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: We included 10 studies with 10,209 patients. There was no difference between males and females in rate of mRS 0-2 (OR= 1.16; 95% CI= 0.87-1.56; P-value= 0.316); however, after removing outliers, males had higher rates of mRS 0-2 (OR= 1.40; 95% CI= 1.19-1.66; P-value< 0.001). Similar results were reported for mRS 0-1 (OR= 1.21; 95% CI= 0.93-1.56; P-value= 0.15), after removing outliers (OR= 1.32; 95% CI= 1.17-1.50; P-value< 0.001). There was no difference between males and females in rate of sICH (OR= 0.89; 95% CI= 0.74-1.08; P-value= 0.246), mortality (OR= 0.88; 95% CI= 0.74-1.05; P-value= 0.15), or TICI 2b-3 (OR= 1.19; 95% CI= 0.85-1.67; P-value= 0.309). CONCLUSIONS: Males tend to experience better outcomes following EVT for AIS, even in the setting of similar reperfusion. The mechanisms underlying this phenomenon remain unclear, and further research is warranted. EVT remains a safe and effective option for both males and females with AIS.

Serum S-100B adds incremental value for the prediction of symptomatic intracranial hemorrhage and brain edema after acute ischemic stroke.

Background: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications. Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4. Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log10S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7-6.9, p = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3-7.1, p < 0.001) in multivariable logistic regression models. Adding S-100B to the clinical prediction model increased the AUC from 0.72 to 0.75 (p = 0.001) for symptomatic intracranial hemorrhage and from 0.78 to 0.81 (p < 0.0001) for symptomatic brain edema. Conclusions: Serum S-100B levels measured within 24 h after symptom onset are independently associated with the development of symptomatic intracranial hemorrhage and symptomatic brain edema in acute ischemic stroke patients. Thus, S-100B may be useful for early risk-stratification regarding stroke complications.

Children Newly Diagnosed with Fetal and Neonatal Alloimmune Thrombocytopenia: Neurodevelopmental Outcome at School Age.

OBJECTIVE: To evaluate the neurodevelopmental outcome at school age in children newly diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT). STUDY DESIGN: This observational cohort study included children diagnosed with FNAIT between 2002 and 2014. Children were invited for cognitive and neurological testing. Behavioral questionnaires and school performance results were obtained. A composite outcome of neurodevelopmental impairment (NDI) was used, defined, and subdivided into mild-to-moderate and severe NDI. Primary outcome was severe NDI, defined as IQ <70, cerebral palsy with Gross Motor Functioning Classification System level ≥ III, or severe visual/hearing impairment. Mild-to-moderate NDI was defined as IQ 70-85, minor neurological dysfunction or cerebral palsy with Gross Motor Functioning Classification System level ≤ II, or mild visual/hearing impairment. RESULTS: In total, 44 children were included at a median age of 12 years (range: 6-17 years). Neuroimaging at diagnosis was available in 82% (36/44) of children. High-grade intracranial hemorrhage (ICH) was detected in 14% (5/36). Severe NDI was detected in 7% (3/44); two children had high-grade ICH, and one had low-grade ICH and perinatal asphyxia. Mild-to-moderate NDI was detected in 25% (11/44); one child had high-grade ICH, and eight children were without ICH, yet for two children, neuroimaging was not performed. Adverse outcome (perinatal death or NDI) was 39% (19/49). Four children (9%) attended special needs education, three of whom had severe NDI and one had mild-to-moderate NDI. Total behavioral problems within the clinical range were reported in 12%, which is comparable with 10% in the general Dutch population. CONCLUSION: Children who are newly diagnosed with FNAIT are at increased risk for long-term neurodevelopmental problems, even those without ICH. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (Identifier: NCT04529382).

Pregnancy and Child Outcomes Following Fetal Intracranial Hemorrhage.

BACKGROUND: The prenatal and early postnatal outcomes of fetal intracranial hemorrhage (ICH) prenatally diagnosed by fetal magnetic resonance imaging (MRI) have not been well described. METHODS: A retrospective study of cases with fetal ICH diagnosed by fetal MRI at Children's National Hospital, Washington, DC, from 2012 to 2020 was conducted. Maternal characteristics, prenatal imaging, pregnancy outcome, and child developmental outcomes were recorded. Abnormal outcomes were categorized as mild for required physical/occupational therapy without other delays, moderate for intermediate multidomain developmental delays, and severe if nonambulatory, nonverbal, or intellectual disability. RESULTS: Fifty-seven cases with fetal ICH were included. The mean (S.D.) maternal age was 31.1 (6.9) years, gestational age at fetal evaluation was 28.1 (5.3) weeks, and gestational age at birth was 38.2 (1.3) weeks. Pregnancy outcomes were 75% (n = 43) live birth, 14% (n = 8) termination of pregnancy, and 11% (n = 6) intrauterine demise (IUD). Live births decreased from 90% to 33% and IUD increased 10% to 22% when comparing unilateral intraventricular hemorrhage with more extensive hemorrhages. Among the 37 live-born infants with clinical follow-up to age 1.8 (1.6) years, neurodevelopmental outcome was normal in 57%, mildly abnormal in 24%, moderately abnormal in 14%, and severely abnormal in 5%. In five cases, an etiology was identified: two had placental pathologies, two had genetic findings (fetal neonatal alloimmune thrombocytopenia and COL4A1 mutation), and one had congenital cytomegalovirus infection. CONCLUSION: Perinatal and early child outcomes following fetal ICH have a wide spectrum of outcomes. Fetal MRI description of ICH location may aid in pregnancy and postnatal outcome prediction.

Blood proteome of acute intracranial hemorrhage in infant victims of abusive head trauma.

Abusive head trauma (AHT) is a leading cause of mortality and morbidity in infants. While the reported incidence is close to 40 cases per 100'000 births/year, misdiagnoses are commonly observed in cases with atypical, subacute, or chronic presentation. Currently, standard clinical evaluation of inflicted intracranial hemorrhagic injury (ICH) in infants urgently requires a screening test able to identify infants who need additional investigations. Blood biomarkers characteristic of AHT may assist in detecting these infants, improving prognosis through early medical care. To date, the application of innovative omics technologies in retrospective studies of AHT in infants is rare, due also to the blood serum and cerebrospinal fluid of AHT cases being scarce and not systematically accessible. Here, we explored the circulating blood proteomes of infants with severe AHT and their atraumatic controls. We discovered 165 circulating serum proteins that display differential changes in AHT cases compared with atraumatic controls. The peripheral blood proteomes of pediatric AHT commonly reflect: (i) potentially secreted proteome from injured brain, and (ii) proteome dysregulated in the system's circulation by successive biological events following acute ICH. This study opens up a novel opportunity for research efforts in clinical screening of AHT cases.

Low LDL-C level and intracranial haemorrhage risk after ischaemic stroke: a prospective cohort study.

BACKGROUND AND PURPOSE: The Treat Stroke to Target trial has confirmed the benefit of targeting low-density lipoprotein cholesterol (LDL-C) of <1.8 mmol/L in patients who had an ischaemic stroke (IS). However, haemorrhagic risk brought by this target level (<1.8 mmol/L) or even lower level (<1.4 mmol/L) of LDL-C should also be concerned. In this study, we aimed to demonstrate whether low LDL-C could increase the intracranial haemorrhage risk following IS. METHODS: Patients who had an IS from China Stroke Center Alliance programme with complete baseline information were prospectively enrolled. 793 572 patients who had an IS were categorised into 6 groups according to LDL-C level (<1.40 mmol/L, 1.40-1.79 mmol/L, 1.80-2.59 mmol/L, 2.60-2.99 mmol/L, 3.00-4.89 mmol/L, ≥4.90 mmol/L). The study outcome was defined as intracranial haemorrhage identified during hospitalisation. Logistic regression model was used to examine the association between different LDL-C levels and risk of intracranial haemorrhage. RESULTS: Compared with patients of LDL-C=1.80-2.59 mmol/L, both subgroups of LDL-C<1.40 mmol/L and LDL-C=1.40-1.79 mmol/L showed significantly higher risk of intracranial haemorrhage (OR=1.26, 95% CI=1.18 to 1.35; OR=1.22, 95% CI=1.14 to 1.30, respectively). Interaction effect was found to exist between the subgroups of intravenous thrombolytic therapy (p=0.04), rather than the subgroups of age, sex and body mass index. Moreover, the sensitivity analyses indicated that even patients who had an IS with minor stroke still suffered from the increased intracranial haemorrhage risk related to low LDL-C level. CONCLUSIONS: Among patients who had an IS, the low LDL-C level (<1.4 mmol/L or <1.8 mmol/L) at baseline is associated with increased risk of intracranial haemorrhage during acute stage. While actively lowering LDL-C level for patients who had an IS, clinicians should also concern about the haemorrhagic risk associated with low LDL-C level.

Machine learning algorithms for integrating clinical features to predict intracranial hemorrhage in patients with acute leukemia.

BACKGROUND: Intracranial hemorrhage (ICH) in acute leukemia (AL) patients leads to high morbidity and mortality, treatment approaches for ICH are generally ineffective. Thus, early identification of which subjects are at high risk of ICH is of key importance. Currently, machine learning can achieve well predictive capability through constructing algorithms that simultaneously exploit the information coming from clinical features. METHODS: After rigid data preprocessing, 42 different clinical features from 948 AL patients were used to train different machine learning algorithms. We used the feature selection algorithms to select the top 10 features from 42 clinical features. To test the performance of the machine learning algorithms, we calculated area under the curve (AUC) values from receiver operating characteristic (ROC) curves along with 95% confidence intervals (CIs) by cross-validation. RESULTS: With the 42 features, RF exhibited the best predictive power. After feature selection, the top 10 features were international normalized ratio (INR), prothrombin time (PT), creatinine (Cr), indirect bilirubin (IBIL), albumin (ALB), monocyte (MONO), platelet (PLT), lactic dehydrogenase (LDH), fibrinogen (FIB) and prealbumin (PA). Among the top 10 features, INR, PT, Cr, IBIL and ALB had high predictive performance with an AUC higher than 0.8 respectively. CONCLUSIONS: The RF algorithm exhibited a higher cross-validated performance compared with the classical algorithms, and the selected important risk features should help in individualizing aggressive treatment in AL patients to prevent ICH. Efforts that will be made to test and optimize in independent samples will warrant the application of such algorithm and predictors in the future.