|Year : 2019 | Volume
| Issue : 3 | Page : 785-791
Correlation of neuron-specific enolase with radiological findings and degree of disability in acute ischemic stroke
Nabil H Ibrahim1, Mohamed A Abboud2, Wael R Hablas3, Khaled M Sobh1, Mohamed A Zaki1, Mohamed Safwat K Youssif1
1 Department of Neurology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Radiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||29-Nov-2019|
|Date of Decision||29-Nov-2019|
|Date of Acceptance||17-Dec-2019|
|Date of Web Publication||10-Feb-2020|
MBBCH Mohamed Safwat K Youssif
Master of Neurology, Al Mansoura, Dakahlia, 35511
Source of Support: None, Conflict of Interest: None
Introduction Neuron-specific enolase (NSE) is a blood marker released in acute neuronal injury and can be estimated in serum of patients with acute ischemic stroke (AIS) to assess neurological outcome.
Aim To demonstrate the relationship between serum NSE levels in patients with AIS and National Institute of Health Stroke Scale (NIHSS) score and apparent diffusion coefficient (ADC) changes to predict the prognosis and outcome.
Patients and methods This clinical observational study was performed on 50 patients with AIS who attended the emergency and inpatient unit of Al-Azhar University Hospitals, Nabarouh Central hospital, and Mansoura University Hospitals, during a period of 2 years from January 2017 to 2019. Serum NSE was checked within 72 h from admission. NIHSS score was calculated within the same period and then after 1 and 6 months. MRI of brain with diffusion-weighted imaging was done. ADC was calculated up to 1 week from admission.
Results There was a statistically significant strong negative correlation between NSE and ADC, and a statistically significant strong positive correlation between NSE and NIHSS on admission and after 1 and 6 months (P=0.000).
Conclusion Serum NSE can reflect the severity of AIS and predict the short-term and long-term outcomes.
Keywords: acute ischemic stroke, apparent diffusion coefficient, National Institute of Health Stroke Scale, neuron-specific enolase
|How to cite this article:|
Ibrahim NH, Abboud MA, Hablas WR, Sobh KM, Zaki MA, Youssif MK. Correlation of neuron-specific enolase with radiological findings and degree of disability in acute ischemic stroke. Sci J Al-Azhar Med Fac Girls 2019;3:785-91
|How to cite this URL:|
Ibrahim NH, Abboud MA, Hablas WR, Sobh KM, Zaki MA, Youssif MK. Correlation of neuron-specific enolase with radiological findings and degree of disability in acute ischemic stroke. Sci J Al-Azhar Med Fac Girls [serial online] 2019 [cited 2020 Oct 24];3:785-91. Available from: http://www.sjamf.eg.net/text.asp?2019/3/3/785/278031
| Introduction|| |
Neuron-specific enolase (NSE) is the neuronal form of the intracytoplasmic glycolytic enzyme enolase. It is found in the cytoplasm of neurons and cells with neuroendocrine differentiation . NSE is present in very low amount in the serum of normal healthy participants at ∼8.7±3.9 ng/ml, with cerebrospinal fluid (CSF)-NSE concentration of ∼17.3±4.6 ng/ml . Several previous studies have shown that serum NSE levels in patients with acute ischemic stroke (AIS) were significantly higher than in the control groups and that NSE might be a reliable marker for AIS . In cerebral infarction, its half-life has been reported to be ∼48 h . The National Institute of Health Stroke Scale (NIHSS) is one of the most commonly used scoring scales in acute stroke, where admission scores may be predictive of subsequent neurological status . Diffusion-weighted magnetic resonance of the brain and apparent diffusion coefficient (ADC) value are of particular interest in the diagnosis of AIS . Statistically significant correlations between the acute lesion volume and both acute and chronic neurological assessment scales, including NIHSS, have been demonstrated . NIHSS score was found to have a strong correlation with NSE . The aim of this study is to demonstrate the use of NSE as a marker to assess the short-term and long-term outcomes in AIS, through its correlation with NIHSS and ADC value.
| Patients and methods|| |
A written informed consent was obtained from all participants according to the ethical committee, after proper explanation of the study.
A clinical observational study was done on 50 patients (males and females) recruited from the emergency and inpatient unit of Al-Azhar University Hospitals, Nabarouh Central Hospital, and Mansoura University Hospitals, admitted within 3–7 days from the insult, diagnosed as having AIS, during a period of 2 years from January 2017 to 2019.
The following were the inclusion criteria: age more than 21 years, diagnosed as AIS by clinical examination and radiology (CT brain or MRI brain with diffusion), anterior circulation ischemic stroke, and within 72 h from onset of symptoms.
Patients with posterior circulation ischemic stroke; more than 72 h from onset of symptoms regarding blood samples taken (NSE); more than 1 week from onset of symptoms regarding radiology done [diffusion-weighted imaging (DWI) MR]; documented or clinical evidence of brain infarction, hemorrhage, head trauma, or central nervous system infection within 3 months before admission; a history of nervous system tumor or other neurological disorders; patients with history of cancer or infectious disease within 15 days before admission, and those with previous disability were excluded.
Clinical and laboratory data were collected from patients on admission. Serum NSE was checked within 72 h from admission, stored at −20°C until evaluation by the quantitative sandwich enzyme immunoassay technique, using Quantikine enzyme-linked immunosorbent assay kit. The NIHSS was calculated within the same period of admission and then after 1 and 6 months. DWI brain was done. ADC was calculated up to 1 week from admission using Siemens (Erlangen, Germany) NOVUS 1.5 superconducting MR scanning system. Relative apparent diffusion coefficient (rADC) value was calculated by the following equation: rADC=(average ADC value in infarcted side/average ADC value in healthy side)×100%.
Data were fed to the computer and analyzed using IBM SPSS software package, version 22.0, applying Kolmogorov–Smirnov test, χ2 test, Monte–Carlo test, Fisher exact test, Student t test, one-way analysis of variance test, post-hoc Tukey test, Mann–Whitney U test, and Kruskal–Wallis test and using the P value and the rs (Spearman correlation coefficient).
| Results|| |
A total of 50 patients with AIS fulfilled the criteria for inclusion in this study. The mean age was 64.18 years. Male patients (n=30) were more than female patients (n=20) ([Figure 1]).
Twenty one cases had affection of the right side of the brain, whereas 29 cases had affection of the left side. Thirteen cases had cortical infarcts only, whereas 27 cases had subcortical infarcts only. More than half of the cases (54%) had parietal lobe affection.
The mean values for NSE, ADC, and rADC were 71.66, 0.56, and 53.38, respectively. On admission and after 1 and 6 months, the mean values of NIHSS were 12.9, 9.24, and 3.82, respectively.
Using the P value and the rs in the study, there was a statistically significant strong negative correlation between NSE and ADC (P=0.000, rs=−0.803) and also between NSE and rADC (P=0.000, rs=−0.792), whereas a statistically significant strong positive correlation between NSE and NIHSS on admission (P=0.000, rs=0.670), after 1 (P=0.000, rs=0.763), and 6 months (P=0.000, rs=0.783) of follow-up ([Figure 2],[Figure 3],[Figure 4] and [Table 1]).
|Figure 2 Scatter diagram showing correlation between NSE and NIHSS 0 (on admission). NIHSS, National Institute of Health Stroke Scale; NSE, neuron-specific enolase.|
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|Figure 3 Scatter diagram showing correlation between NSE and NIHSS 1 (after 1 month). NIHSS, National Institute of Health Stroke Scale; NSE, neuron-specific enolase.|
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|Figure 4 Scatter diagram showing correlation between NSE and NIHSS 6 (after 6 months). NIHSS, National Institute of Health Stroke Scale; NSE, neuron-specific enolase.|
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|Table 1 Correlation between neuron-specific enolase and apparent diffusion coefficient, relative apparent diffusion coefficient, and National Institute of Health Stroke Scale|
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There was a statistically significant difference between patients who had a history of diabetes mellitus (DM) (Z=2.59, P=0.009) and atrial fibrillation (AF) (Z=2.27, P=0.02) and those who did not, in association with NSE, where Z represents Mann–Whitney test.
There was a statistically significant difference between cortical and subcortical groups in association with NSE (P=0.007) ([Table 2]) and also between NSE and patients with cognitive affection (Z=2.29, P=0.02) ([Table 3]). There was a statistically significant difference between cases that received and did not receive tissue plasminogen activator in association with NSE (P=0.01).
|Table 2 Neuron-specific enolase association with infarction location among studied cases|
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|Table 3 Neuron-specific enolase association with cognitive affection in studied cases|
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| Discussion|| |
NSE is a noninvasive marker for neuronal injury which gets elevated in CSF and serum in cases of ischemic stroke . In the current study, there was a statistically significant strong positive correlation between NSE and NIHSS on admission and after 1 and 6 months. Oh et al. , found in a study including 109 patients with AIS that NIHSS on admission and after 1 week and after 3 months was correlated with the initial serum NSE level.
This is congruent with Pandey et al. , who found in their series of 90 patients with AIS admitted within 72 h of the onset of stroke symptoms that higher initial level of NSE was significantly correlated with the severity of neurological deficit on admission (rs=0.901, P<0.01) and with the short-term outcome (rs=0.883, P<0.01).
Moreover, this is congruent with Frankivsk , who included 128 patients of AIS in his study, and on the basis of the comparison of serum levels of NSE with the NIHSS score, more significant increase in NSE was detected in patients with severe neurological deficit.
However, this is incongruent with the study conducted by González-García et al. , where no correlation was found between NSE levels and stroke severity on admission. They attributed this difference in results to the fact that timing of blood withdrawal was different in various studies.
In this study, the results showed a statistically significant difference between patients who had a history of DM and those who had not, in association with NSE (Z=2.59, P=0.009). Pandey and colleagues, found that serum NSE level in patients with hyperglycemic stroke was also positively correlated with the blood sugar level (rs=0.73, P<0.001). This adds further support to the concept that hyperglycemia enhances neuronal necrosis. Hyperglycemia-induced lactic acidosis in the ischemic brain not only damages glial and endothelial cells but may also exacerbate the biochemical events in the penumbra, which lead to neuronal death and release of biochemical markers, as shown by the positive correlation between NSE and the blood sugar level during the acute stage of ischemic stroke .
This also was similar to Frankivsk , who found that the analysis of the concentration of NSE in blood serum of 128 patients with AIS revealed its increase in patients with coexistent type II DM. In contrast, a study done by Sulter et al. , showed that hyperglycemia in patients with pure motor stroke, due to lacunar infarctions, was not associated with increased NSE levels.
The current study revealed a statistically significant difference between patients who had a history of AF and those who did not, in association with NSE (Z=2.27, P=0.02). This is nearly congruent with Kim et al. , who found that AF was observed more frequently in patients with a second peak pattern of NSE.
DWI is more useful than noncontrast CT scanning for the diagnosis of AIS within 12 h of symptoms onset . In the current study, there was a statistically significant strong negative correlation between NSE and ADC (P=0.000, rs=−0.803) and also between NSE and rADC (P=0.000, rs=−0.792).
Shen et al. , performed a study on 98 patients with cerebral infarction, who were imaged with both conventional MRI and DWI. The average ADC and rADC values were calculated. Both decreased obviously in hyperacute and acute infarction lesions. rADC values increased progressively as time passed and appeared as ‘pseudonormal’ values in ∼8–14 days. There was a positive correlation between rADC values and time (P<0.01). The ADC values and the rADC values in hyperacute and acute lesions had gradient signs (increased from the center to the periphery), whereas in subacute lesions, these values had adverse gradient signs (decreased from the center to the periphery).
This could be explained by two possibilities: first, vessel-sourced edema causes injury to endothelial cells 5–6 h after brain infarction, and exacerbates in subacute phase, leading to enhanced permeability of blood brain barrier, and increased movement of many molecules including water molecules in extracellular spaces, and second, the cell membrane breaks and releases intracellular water molecules. In chronic phase, the infarcted brain tissues liquidize and are replaced by CSF, which has a free movement of water molecules and high ADC value when compared with normal brain tissues, leading to a rADC value of more than 100%. So, the combined analysis of ADC, rADC, and routine MRI images can be useful in clinical diagnosis of the progression after brain infarction .
The other interesting point is the spatial distribution of ADC and rADC values within infarcted region. In superacute and acute cases, ADC values increase from the center to the side areas, suggesting that the decrease of ADC values can reflect the severity of tissue damage. The surrounding regions of infarction area are considered to be plastic and can be reperfused in proper conditions, or infarcted if not treated. So, the ADC values of infarction lesions have evolution rules with time and space which can be helpful to decide the clinical stage and to provide the evidence in guiding the treatment or judging the prognosis in infarction .
In the present study, there is no significant statistically difference in the association of NSE with the side of infarction in brain (P=0.23). This is congruent with Baidya et al. , who found in their series of 35 patients with AIS that there was no significant difference between the serum NSE in left-sided brain lesion compared with the right-sided brain lesion (P=0.596). The present study revealed a statistically significant difference between cortical and subcortical groups in association with NSE (P=0.007). This is congruent with Wu et al. , who found in a study including 38 patients with AIS that NSE levels were also higher in the cortical group than in the subcortical group (P<0.01), which indicated that the peak NSE level may be correlated with the infarction size. Oh et al. , found in a study including 109 patients with AIS that the initial serum NSE levels were higher in the cortical group than in the subcortical group (P<0.05).
Regarding functional affection among studied cases, this study revealed a statistically significant difference in the association of NSE with cognition affection (Z=2.29, P=0.02). Frankivsk , found that there was a strong correlation between serum level of NSE and the Mini-Mental State Examination score (P<0.05) and between NSE and the Montreal Cognitive Assessment score (P<0.05). The obtained data may indicate the possibility of using the value of NSE serum for the validation of manifestations of post-stroke cognitive impairment and the development of post-stroke dementia.
This is nearly similar to a study done by Shen and Gao , including 42 patients with vascular dementia (VaD), randomized as the VaD group, and 38 stroke patients without dementia, who were in the control group, to estimate whether serum somatostatin and NSE were biochemical markers of the VaD in the early stage. The results showed that serum NSE contents in VaD group were significantly higher than that of control group 3 days after stroke and at 3 and 6 months of follow-up (P<0.01), and had a tendency to increase (P<0.05).
In contrast to these findings, Sulkava et al. , found that CSF NSE was decreased in multi-infarct dementia but unchanged in Alzheimer’s disease in their study including 22 patients with probable Alzheimer’s disease, 35 patients with multi-infarct dementia, and 15 controls. The decrease of CSF NSE in multi-infarct dementia can be explained based on decreased amount of neural tissue as a result of preceding infarcts. The association of moderate to severe central atrophy with lower enzyme levels supports also this assumption. In Alzheimer’s disease, the low levels of CSF NSE owing to cerebral atrophy are probably compensated by the continuous neuronal destruction. CSF NSE reflects a central nervous lesion, and NSE level is lower in serum than in CSF .
The major limitation of our study was that NSE levels were estimated only once, although various studies have reported dynamic changes in NSE levels during the first few days after stroke . Therefore, serial measurement of NSE would have provided a better picture of its correlation with NIHSS and ADC. Another limitation was that sample size was not very large, so future multicenter studies with a large number of participants are required to overcome this limitation. Another shortcoming of the study was exclusion of patients with posterior circulation stroke owing to poor and not precise assessment by NIHSS, so further future studies are needed including patients with anterior and posterior circulation affection and using other various prognostic clinical scales.
| Conclusion|| |
In our study, there was a directly proportional correlation between NSE and NIHSS, but inversely proportional with ADC. In patients with AIS with mainly cognitive affection, NSE has special correlation and can reflect the outcome. So, we recommend to use NSE as an easy noninvasive prognostic marker for short-term and long-term outcomes of AIS.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]