The NAG scale: Noble Predictive Scale for Hematoma Expansion in Intracerebral Hemorrhage

doi:10.1016/j.jstrokecerebrovasdis.2018.05.020

Journal of Stroke and Cerebrovascular Diseases

Volume 27, Issue 10, October 2018, Pages 2606-2612

https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.020 Get rights and content

Abstract

Background and Purpose

Early hematoma expansion (HE) is not rare in intracerebral hemorrhage (ICH) patients, but detecting those patients with high risk of HE is challenging. The aim of this retrospective study was to investigate the factors associated with HE in acute ICH patients, and to develop a simple predictive scale for HE.

Methods

We retrospectively reviewed consecutive patients with primary ICH, who received an initial non-contrast computed tomography (CT) scan within 24 hours from symptom onset. Patients underwent follow-up CT scans at 6 hours, 24 hours, and 7 days after admission. We compared the clinical characteristics of patients with and without HE (defined as an increase in intracerebral hemorrhage volume >33% or an absolute increase >6 mL on follow-up CT scans), and performed a logistic regression analysis to determine the predictors of HE.

Results

A total of 118 patients (78 men; median age 63 years; interquartile range 54–73) were included in our study. HE was observed in 30 patients (25%). HE patients showed higher rates of anticoagulant use (20% vs. 2%, respectively; P=0.003), high National Institutes of Health Stroke Scale on admission (13 vs. 7, respectively; P=0.001), and high plasma glucose (141 mg/dl vs. 113 mg/dl, respectively; P=0.001) compared with patients without HE. After multivariate logistic regression analysis, we selected three factors for defining the NAG scale (1 point as baseline National Institutes of Health Stroke Scale ≥10, 1 point as anticoagulant use, and 1 point as plasma glucose ≥133 mg/dL). The frequencies of HE associated with the NAG scale scores were as follows: score 0, 4%; score 1, 25%; score 2, 60%; score 3, 100%.

Conclusion

Stroke severity, hyperglycemia, and anticoagulation use were factors independently associated with HE. The NAG scale consists of readily available factors and can predict HE.

Introduction

Intracerebral hemorrhage (ICH) is one of the major type of stroke worldwide, accounting for approximately 15% of all strokes, with a mortality rate of 40% at 1 month.1, 2 Although initial ICH volume and hematoma location remain strong predictors of 30-day mortality and functional outcome, neither factor is modifiable on presentation.3, 4 Hematoma expansion (HE) occurs in approximately 30% of patients during hospitalization, and is strongly associated with neurological deterioration and poor functional outcome. Furthermore, as HE can be potentially mitigated, it is considered a therapeutic target.5, 6, 7, 8

Several prediction scales for HE were previously reported with reasonable estimation.9, 10 However, these scales require a variety of patient data and a computed tomography (CT) scan, such as contrast-enhanced imaging for spot sign.⁹ However, in the emergency department, physicians must quickly decide on the treatment plan using limited information, and contrast CT cannot be available for all patients because of their renal impairment or allergic reaction for contrast.

Therefore, in the present study we validated the factors associated with HE, with the aim to devise a simple prediction scale (the ‘NAG scale’) consisting of clinical factors to identify higher risk patients suffering HE.

Section snippets

Study Design

This retrospective study included patients who presented with spontaneous ICH and were admitted between November 2011 and August 2016 to Jikei University Hospital, Japan. Patients were eligible for the study if the initial non-contrast CT (NCCT) scan was performed within 24 hours after symptom onset. Our institutional protocol recommended a follow-up NCCT scan at 6 hours, 24 hours, and 7 days after admission or in case of neurological deterioration. Exclusion criteria were as follows: (1)

Patients

A total of 118 patients (78 men and 40 women; median age 63 years; IQR 54–73) with primary ICH met our inclusion criteria, and were included in the present study. Disposition of patients is shown in Figure 1. The median NIHSS was 8 (IQR 3–14), and the median baseline ICH volume was 9.7 mL (IQR 4.2–19.2). The average time of NCCT assessment from stroke onset was 2.1 hours (IQR 1.5–5.9). There were 74 patients (62%) who received initial CT scan within 3 hours from symptom onset, and 90 patients

Discussion

The present study demonstrated that baseline NIHSS ≥10, anticoagulant use, and plasma glucose ≥133 mg/dL were factors independently associated with HE on multivariate logistic regression analysis. Using these factors, we developed the NAG scale, a very simple scale to predict HE. The NAG scale may be useful in the clinical setting as it can be rapidly calculated by physicians, or even nurses.

Summary/Conclusions

We found that baseline NIHSS ≥10, anticoagulant use, and plasma glucose ≥133 mg/dL were independent factors associated with HE. The NAG scale may be useful for predicting HE in ICH patients.

Acknowledgments

None.

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Cited by (14)

Effects and safety of high-frequency rTMS in acute intracerebral hemorrhage patients: A pilot study
2022, Journal of the Neurological Sciences
Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in chronic intracerebral hemorrhage (ICH) is beneficial, it has been poorly investigated in rTMS for acute ICH. Our aim is to investigate the effects and safety of rTMS in acute spontaneous ICH.
We prospectively performed HF-rTMS on consecutive patients with ICH within 24 h from onset between April 2019 and August 2021. The inclusion criterion was (1) persistent paralysis, with an NIHSS scale of 1 or higher for at least 3 days after onset. The exclusion criteria were (1) cortical, subcortical, and cerebellar ICH, (2) disturbance of consciousness, and (3) over 80 years of age. For the purpose of comparison, we used a conventional rehabilitation group whose patients met the same criteria between April 2016 and March 2019. We evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. We also compared the two groups regarding clinical background and outcome.
Enrolled in the study were a total of 44 patients. Of the patients, 22 (50%) were in the rTMS group. The median (IQR) time from onset to the start of rTMS was 9 (6–12) days. There were no cases of epilepsy or exacerbation of NIHSS after the start of rTMS. Favorable outcome (modified Rankin Scale score of between 0 and 2) at 3 months was frequently observed in the rTMS group (73% vs 27%, p = 0.006). HF-rTMS was independently associated with favorable outcome at 3 months (OR = 11.5, 95% CI = 2.194–60.447, p = 0.004).
HF-rTMS may be safe and effective in acute ICH patients.
Prediction of hematoma expansion in spontaneous intracerebral hemorrhage: Our institutional experience
2021, Journal of Clinical Neuroscience
Spontaneous intracerebral hemorrhage (sICH) is a disease process with high morbidity and mortality. In particular, hematoma expansion (HE) is a feared complication of sICH. With 15–40% of patients experiencing HE, it has become increasingly important to predict which sICH will remain stable and which will expand.
With new treatment options being developed, it is becoming increasingly important to be able to predict which hemorrhages are at high versus low risk for expansion. The authors of this study hope to reexamine variables associated with hematoma expansion in hopes of generating newer data on risk factors for expansion.
A retrospective analysis identified 334 patients who presented with sICH. The primary outcome was HE on follow up head CT. HE was defined as a greater than 33% increase or an absolute increase in 6 mL or more in overall volume between the two sets of CT images. Analysis was performed using unpaired t-test, Chi-square, and Fisher’s exact tests, as appropriate.
Of the 334 patients, 247 (74.0%) did not experience an expansion of their ICH while 87 (26.0%) did. Multivariable logistic regression was performed demonstrating ICH score of 3 or greater (4.76 (95% CI 2.60–8.72, p < 0.001) , cortical location of the sICH (1.77 (95% CI 1.03–3.04, p = 0.038), and presence of a fluid level (6.46 (95% CI 2.28–18.3, p < 0.001) as significant predictors of HE.
Our study found that fluid–fluid levels on non-contrast CT, an ICH score 3 or greater, and lobar sICH were all more likely to expand.
Proposal of a prediction score for hematoma expansion after intracerebral hemorrhage
2021, Medicina Intensiva
Citation Excerpt :
Consistent with the validation cohort of our score, Sakuta9 reported that the majority of the study population had mild symptoms, suggesting that different models may be compatible according to different clinical characteristics. Although the NAG score9 was simpler and more portable, it did not include imaging data. Since CT is the gold standard for the diagnosis of cerebral hemorrhage, its reliability needs to be further verified.
To propose and validate a prediction score for intracerebral hemorrhage (ICH) patients at risk of hematoma expansion (HE).
A retrospective observational study was designed to propose and validate the score.
Sanxiang Road branch and Xuguan branch belonging to the Second Affiliated Hospital of Soochow University (China).
A total of 317 ICH patients in Sanxiang Road branch were registered as the development cohort, and 109 ICH patients in Xuguan branch were enrolled as the validation cohort.
Independent risk factors for HE were identified using multiple logistic regression analysis. A prediction score was then proposed based on β coefficients and preliminarily verified in the validation cohort.
All clinical data of the patients were compiled from the electronic medical records. Hematoma expansion was defined as an increase in hematoma volume >33% or absolute hematoma growth >6 ml from the initial scan. Specific non-contrast CT(NCCT) signs were identified by two observers independently.
Our score demonstrated satisfactory discrimination ability for HE (area under the ROC curve 0.854 in the development cohort versus 0.893 in the validation cohort). Appropriate calibration was found in the development cohort, whereas calibration in the validation cohort was slightly lower but still within the accuracy range (maximum deviation, average deviation and P were 0.070, 0.028, 0.773, respectively, versus 0.114, 0.056, 0.156). Decision curve analysis of the score from two samples were both far from the curve of treat all and curve of treat none, which verified its security and reliability. Patients with a total score ≥4.5 were at greatest risk of HE.
The score may provide some reference and help in accurately identifying individuals at high risk of HE, allowing rapid guidance of clinical management and also serving as an aid in clinical trials.
Proponer y validar una puntuación de predicción de hemorragia cerebral (HC) en paciente con riesgo de expansión del hematoma (EH).
Se diseñó un estudio observacional retrospectivo para proponer y validar la puntuación.
ramas de Sanxiang Road y Xuguan pertenecientes al Segundo Hospital Afiliado de la Universidad de Soochow.
317 pacientes con HE de la rama de Sanxiang Road fueron incluidos como la cohorte de desarrollo, y 109 pacientes con HC de la rama de Xuguan fueron incluidos como la cohorte de validación.
Se obtuvieron los factores de riesgo independientes de EH de a partir de un análisis de regresión múltiple. A continuación, se propuso una puntuación de predicción basada en coeficientes β y se verificó de forma preliminar en la cohorte de validación.
Todos los datos clínicos de los pacientes se registraron consultando historias electrónicas. La EH se definió como un aumento del volumen del hematoma >33% o un crecimiento absoluto del hematoma >6 ml respecto a la exploración inicial. Los signos específicos de la tomografía computerizada sin contraste (TCSC) fueron identificados de manera independiente por dos observadores.
Nuestra puntuación demostró de manera satisfactoria su capacidad de discriminación para la EH (el área bajo la curva ROC fue 0.854 en la cohorte de desarrollo frente a 0.893 en la cohorte de validación). Se observó un calibrado adecuado en la cohorte de desarrollo, mientras que el calibrado de la cohorte de validación fue ligeramente inferior, si bien se mantuvo dentro del intervalo de precisión (la desviación máxima, la desviación promedio y el valor P fueron respectivamente 0.070, 0.028 y 0.773, frente a 0.114, 0.056 y 0.156). Las curvas de análisis de la curva de decisión de la puntuación a partir de las dos muestras se situaron alejadas de la curva de tratar a todos y de la curva de no tratar a ninguno, lo cual verificó su seguridad y fiabilidad. Los pacientes con una puntuación total ≥ 4.5 corrían un mayor riesgo de EH.
Es posible que la puntuación sirva de referencia y ayuda para identificar con precisión a las personas con alto riesgo de EH, además de ofrecer una guía rápida sobre el tratamiento y de poder utilizarse en ensayos clínicos.
The NAG scale can screen for hematoma expansion in acute intracerebral hemorrhage–a multi-institutional validation
2020, Journal of the Neurological Sciences
Citation Excerpt :
The following clinical data were collected from all patients: age, sex, time of onset (defined as the time last seen well), the location and volume of the hematoma, laboratory data, and the presence of traditional cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease. We used the NIHSS and Glasgow coma scale (GCS) scores to assess stroke severity and calculated the NAG score in all patients [7]. The modified Rankin scale (mRS) scores at discharge were assessed.
Early hematoma expansion (HE) is seen in approximately 30% of patients with intracerebral hemorrhage (ICH), but detecting patients with a high HE risk is challenging.
The NAG scale is a simple predictive scale for HE in acute ICH patients. Multi-institutional validation of the usefulness of this scale was the aim of this study.
We retrospectively reviewed 142 consecutive primary ICH patients admitted to our hospital between September 2016 and December 2018. The NAG scale consists of three factors: National Institutes of Health Stroke Scale (NIHSS) score ≥ 10, anticoagulant use, and glucose ≥133 mg/dl (1 point each). Patients underwent non-contrast computed tomography (CT) within 24 h of symptom onset and follow-up CT 6 h, 24 h, and 7 days after admission. We defined HE as increased hemorrhage volume > 33% or an absolute increase of >6 mL on follow-up CT. Poor prognosis was defined as a modified Rankin scale score of 4–6 at discharge. We performed logistic regression analysis and created receiver operating characteristic curves to determine the discrimination ability of the NAG score.
Patients constituted 96 men and 46 women (median age: 64 years; median NIHSS: 11), and HE was observed in 38/142 patients (27%). Higher NAG sores were associated with HE (P < .001), poor prognosis (P < .001), and in-hospital death (P < .001). The C statistic was 0.72 (95% confidence interval [CI]: 0.63–0.82) for HE, 0.67 (95% CI: 0.58–0.76) for poor prognosis, and 0.85 (95% CI: 0.74–0.95) for in-hospital death. Multivariate logistic regression analysis with known risk factors showed that NAG scale score was an independent risk factor for HE (odds ratio: 2.95; 95% CI: 1.57–5.52; P = .001).
The NAG scale showed good discrimination in our multi-institutional validation.
Response to “The NAG Scale: Noble Predictive Scale for Hematoma Expansion in Intracerebral Hemorrhage”
2018, Journal of Stroke and Cerebrovascular Diseases
Establishment of a Scale for Predicting Early Hematoma Enlargement of Spontaneous Intracerebral Hemorrhage Based on Non-Contrast CT Signs
2023, Turkish Neurosurgery

View all citing articles on Scopus

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The NAG scale: Noble Predictive Scale for Hematoma Expansion in Intracerebral Hemorrhage☆,☆

Abstract

Background and Purpose

Methods

Results

Conclusion

Introduction

Section snippets

Study Design

Patients

Discussion

Summary/Conclusions

Acknowledgments

Lancet

Lancet Neurol

The Lancet Neurology

The Lancet

The Lancet

Clin Neurol Neurosurg

Journal of the neurological sciences

Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality

Stroke

Long-term mortality after intracerebral hemorrhage

Neurology

Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes

Neurology

Recombinant activated factor VII for acute intracerebral hemorrhage

The New England journal of medicine

Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage

Neurology

Predicting hematoma expansion after primary intracerebral hemorrhage

JAMA neurology

The HEP Score: A Nomogram-Derived Hematoma Expansion Prediction Scale

Neurocrit Care

Report of the committee on the classification and diagnostic criteria of diabetes mellitus

J Diabetes Investig

The ABCs of measuring intracerebral hemorrhage volumes

Stroke

Association Between Hypodensities Detected by Computed Tomography and Hematoma Expansion in Patients With Intracerebral Hemorrhage

JAMA neurology

Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time

Stroke

Ultraearly hematoma growth in active intracerebral hemorrhage

Neurology

Determinants of intracerebral hemorrhage growth: an exploratory analysis

Stroke