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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 223-227

Admission leukocytosis, C-reactive protein and erythrocyte sedimentation rate in acute noncardioembolic cerebral ischemia: influence on early outcome


1 Department of Neurology, Ain Shams University, Cairo, Egypt
2 Department of Clinical Pathology, Ain Shams University, Cairo, Egypt

Date of Submission30-Apr-2015
Date of Acceptance26-Jun-2015
Date of Web Publication27-Nov-2015

Correspondence Address:
Magdy A Mostafa
Department of Neurology, Ain Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1083.170651

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  Abstract 

Background
There is growing evidence regarding the role of inflammation in the pathogenesis of ischemic stroke, especially nonembolic types of ischemic stroke. Despite this, there is a need to investigate the direct impact of inflammatory markers on the early outcome in nonembolic ischemic stroke.
Objective
The aim of the present study was to determine whether positive inflammatory markers such as raised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and leukocytosis could be used as biochemical predictors for poor early outcome in patients with acute noncardioembolic ischemic stroke.
Patients and methods
A total of 60 patients(40 men and 20 women; median age: 64.5 years) with first attack of noncardioembolic ischemic stroke were included in the study. Full clinical assessment and routine laboratory investigation were conducted for all patients. MRI of brain, ECG, and cardiac echo were carried out to confirm the diagnosis and exclude cases with embolic stroke. Blood samples for all patients within the first 24 h of onset of symptoms were taken for assessment of ESR, qualitative CRP, and leukocyte count on admission. National Institute of Health Stroke Scale was used for all patients after 7 days. On the basis of their scores patients were divided into two groups: 40 patients with favorable outcome were included in the first group and 20 patients with bad outcome in the second group.
Results
There was significant difference between the two groups regarding ESR value, and the leukocyte count was higher in the group with bad prognosis. In addition, positive CRP was associated more with the same group in statistically significant way.
Conclusion
Inflammatory markers play an important role in detecting the early outcome of noncardioembolic stroke.

Keywords: cerebral ischemia, C-reactive protein, erthrocyte sedimentation rate, leukocytosis


How to cite this article:
Mostafa MA, Elewa MK, Mohamed NA. Admission leukocytosis, C-reactive protein and erythrocyte sedimentation rate in acute noncardioembolic cerebral ischemia: influence on early outcome. Egypt J Neurol Psychiatry Neurosurg 2015;52:223-7

How to cite this URL:
Mostafa MA, Elewa MK, Mohamed NA. Admission leukocytosis, C-reactive protein and erythrocyte sedimentation rate in acute noncardioembolic cerebral ischemia: influence on early outcome. Egypt J Neurol Psychiatry Neurosurg [serial online] 2015 [cited 2017 Jun 26];52:223-7. Available from: http://www.ejnpn.eg.net/text.asp?2015/52/4/223/170651


  Introduction Top


The development and progression of atherosclerotic plaques depends on both genetic and acquired factors. The inflammatory pathway is an essential component of the process of atherosclerosis. Inflammatory markers have been found in the blood of patients with cerebral and cardiac ischemia. In addition, it was found that these inflammatory markers may be used to monitor and predict the prognosis of the patients. However, there is extensive variability between patients regarding the impact of these factors on the process of atherosclerotic vasculopathy and the development of ischemia [1] .

One of these inflammatory markers is C-reactive protein (CRP). It is involved in production of both adhesion molecules and chemokine factors. CRP is a component of the human innate immunity involved in complement activation. The use of elevated CRP as a predictor of the susceptibility to ischemia, whether cerebral, cardiac or peripheral, was emphasized by numerous cohort studies [2] .

Erythrocyte sedimentation rate (ESR) is a simple, widely used and inexpensive laboratory test to assess an acute inflammatory response. Higher ESR values in acute phase of stroke may indicate a greater increase in fibrinogen concentration and blood viscosity, a more pronounced reduction in cerebral blood flow. Clinical studies have suggested that increased ESR levels are associated with poor clinical outcome, early clinical worsening, and extent of brain damage [3] .

Leukocytes are the first cells that arrive in the stroke region(s), and they increase in peripheral blood. The contribution or leukocytes in the early acute phase of cerebral ischemia has not yet been investigated [4] . Neurologic deterioration is thought to arise from penumbral excitotoxic cell death caused in part by leukocyte infiltration [5] .


  Aim of work Top


The aim of the present study was to investigate the impact of early inflammatory response on the prognosis of ischemic noncardioembolic stroke patients through studying the correlation between ESR, leukocytosis, and CRP as early positive inflammatory markers in patients with ischemic noncardioembolic stroke and the short-term outcome in such patients.


  Patients and methods Top


The present prospective follow-up study comprised 60 patients admitted with the diagnosis of first-ever ischemic noncardioembolic stroke within the first 24 h from onset of symptoms. The patients were recruited from Ain Shams Specialized Hospital. The only inclusion criteria were onset of symptoms within the last 24 h. On the other hand, the following exclusion criteria were applied:

  1. Stroke patients younger than 40 years of age,
  2. Patients with recurrent ischemic stroke,
  3. Presence of possible cardiac source of embolic stroke according to modified TOAST criteria [6] , and
  4. Patients with diseases and medical conditions (recent clinical infection, concurrent major renal hepatic or cancerous disease, recent surgery or major trauma, acute osteoarthritis, or inflammatory disease) that might substantially affect their levels of CRP, ESR, and white blood cells.


The patients were subjected to full clinical evaluation including history taking and complete general and neurological examination, routine laboratory investigations including complete blood count, ESR, qualitative CRP using latex agglutination technique, fasting blood sugar (FBS), 2 h postprandial blood sugar levels (PPBS), lipid profile including serum cholesterol, triglycerides, HDL and LDL levels, serum uric acid, liver and kidney functions and serum electrolytes. MRI brain stroke protocol (including T1, T2, T2 star, flair and diffusion films, and magnetic resonance arteriography) was carried out to confirm diagnosis, to detect the size of the infarction, and to determine the state of intracranial cerebral blood vessels through magnetic resonance arteriography. In addition, all patients were subjected to ECG and transthoracic echocardiography to exclude patients with possible cardiac source of embolism. Patients were followed up for 7 days and National Institute of Health Stroke Scale (NIHSS) was done for all patients after 7 days from admission to determine the short-term outcome.

On the basis of a study by Muir and colleagues, NIHSS score of 13 or below was considered to indicate favorable outcome where patients were likely to be independent, whereas a score higher than 13 indicated poor outcome. Therefore, according to that we divided the patients into two groups: the first group comprised 40 patients with favorable outcome (NIHSS ≤13) and the second comprised the remaining 20 patients with bad outcome (NIHSS >13) [7] .

Statistical analysis

IBM SPSS statistics (version 22.0, 2013; USA) was used for data analysis. Data were expressed as median and percentiles for quantitative nonparametric measures. The Wilcoxon rank sum test was used for comparison between two independent groups for nonparametric data. Comparison of proportion between two groups was carried out using χ2 -test. The level P value less than 0.05 was considered the cutoff value for significance.


  Results Top


A total of 60 patients - 20 women (33%) and 40 men (67%) - diagnosed with noncardioembolic ischemic stroke according to modified TOAST criteria 6 were included in the study. They were divided into two groups according to NIHSS score after 1 week from admission. The first group consisted of 40 patients with short-term good outcome. Of them, there were 32 men and nine women. Their age ranged from 42 to 84 years with median value of 63.5 years. The second group consisted of 20 patients with short-term bad outcome. In this group, there were nine men and 11 women. Their age ranged from 52 to 79 years with median value of 65.5 years. Serum levels of different laboratory risk factors were measured including ESR and leukocyte count in all patients in both groups. For both groups, the range, median value, and the 25th and the 75th percentiles for each parameter are shown in [Table 1] and [Table 2].
Table 1 Descriptive data of the first group


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Table 2 Descriptive data of the second group


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On comparing the different laboratory risk factors in both groups, it was found that ESR and leukocyte count were significantly higher in patients with poor prognosis (P < 0.05) [Figure 1] and [Figure 2]. In addition, FBS and PPBS were significantly higher in patients with poor prognosis (P < 0.05). On the other hand, other risk factors were higher among patients with bad prognosis but the differences were not statistically significant (P > 0.05) [Table 3].
Figure 1 Comparison between the two groups as regards WBCs count. WBC, white blood cell.

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Figure 2 Comparison between the two groups as regards ESR. ESR, erythrocyte sedimentation rate.

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Table 3 Comparison between the two groups as regards different risk factors


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CRP was found to be positive among 85% of the patients with bad prognosis while only 52.5% of the patients with good prognosis were CRP positive. The difference between the two groups was statistically significant (P = 0.014) [Table 4] and [Figure 3].
Figure 3 Comparison between the two groups as regards qualitative C-reactive protein.

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Table 4 Comparison between the two groups as regards qualitative CRP


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  Discussion Top


Atherosclerosis is a complex process starting with endothelial injury followed by a complex inflammatory process. Inflammation precedes atherosclerotic changes that occur in autoimmune diseases, as systemic lupus erytheromatosus and rheumatoid arthritis. The process of chronic inflammation includes subintimal focal recruitment of circulating monocytes and T-lymphocytes that heals by fibrosis and calcification. Both local cellular mechanisms and humoral consequences easily measurable in plasma are involved in the process of atherogenesis. The triggers for both inflammation and endothelial dysfunction are cardiovascular risk factors: hypercholesterolemia, hypertension, smoking, or diabetes [8] .

In this study, we included only the types of ischemic stroke related directly to atherosclerosis; patients with cardioembolic ischemic stroke were excluded. The inflammatory markers used in this study were leukocytosis, increased ESR, and positive CRP. All of them were associated with bad short-term outcome; this corresponded to the results of previous studies. One of them found that mode of clinical presentation, clinical evolution during the first day of stroke, and ESR were independent predictors of short-term stroke outcome [9] . Whereas, Idicula and colleagues found that there was crude association between high CRP and short-term functional outcome, which is likely to be secondary to stroke severity. In this study, high CRP was found to be also independent predictor of long-term mortality after ischemic stroke [10] .

Another study showed that patients with persistent leukocytosis are more likely to present with severe strokes and maintain a high NIHSS score at 24 h after admission, unlike patients without leukocytosis or patients with transient leukocytosis [4] . In addition, Nardi et al. [11] found that an elevated leukocyte count in the acute phase of cerebral ischemia is a significant independent predictor of poor initial-stroke severity, poor clinical outcome after 72 h, and discharge disability.

It is worth to say that most of these studies were done on patients with ischemic stroke in general whereas our study was conducted on patients with noncardioembolic ischemic stroke. In addition, the time interval required and the scale used to measure the outcome were different among studies. However, the results were similar.

A different prospective controlled clinical study compared the association between the serum levels of different inflammatory markers and the severity of clinical manifestation in different types of ischemic stroke using NIHSS; it was found that cardioembolic stroke patients showed increased D-dimer, fibrinogen, and D-dimer/fibrinogen ratio correlated with increased severity. On the other hand, patients with atherothrombotic stroke showed raised fibrinogen and ESR as a marker of severity whereas patients with lacunar and undetermined stroke showed intermediate values of all these markers correlated with stroke severity [12] .

As regards other risk factors, there were no significant differences between the two groups except for FBS and PPBS. A similar finding in an Egyptian study found that hyperglycemia and leukocytosis were considered as bad prognostic factors for both short-term and long-term ischemic stroke outcome [13] . On the other hand; in this study, old age was found to be associated with bad prognosis. This is contradictory to our results but it may be due to the difference in the studied subjects. Our study was confined to subjects with noncardioembolic stroke whereas the other study included patients with thromboembolic stroke.

In fact, the relation of inflammatory mediators and severity and prognosis of different types of ischemic stroke was discussed in many studies. These studies used different inflammatory markers such as serum ferritin, fibrinogen, D-dimer, interleukin 6, matrix metalloproteinases, and adhesion molecules in relation to severity, short-term and long-term outcome of different types of ischemic stroke. The results were contradictory. Despite that, it is clear that the process of inflammation is an important component in the pathogenesis of ischemic stroke. The differences in results between studies could be attributed to different factors. The differences in the study design (some of these studies followed the case control design whereas others were cross-sectional comparative studies), the differences in sample sizes, and the different ways of assessment of ischemic stroke severity and outcome may be responsible for these contradictory results. There is a need for more studies to evaluate the use of the inflammatory markers as predictors of outcome in different types of ischemic stroke.


  Conclusion Top


The inflammation plays an important role in the pathogenesis of noncardioembolic ischemic stroke, and inflammatory mediators like ESR, CRP, and leukocytosis can be used as early biochemical predictors of outcome in these types of ischemic stroke, especially the short-term one.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Shoamanesh A, Preis SR, Beiser AS, Vasan RS, Benjamin EJ, Kase CS, et al. Inflammatory biomarkers, cerebral microbleeds, and small vessel disease: Framingham Heart Study. Neurology 2015; 84 :825-832.  Back to cited text no. 1
    
2.
Zeng L, He X, Liu J, Wang L, Weng S, Wang Y, et al. Differences of circulating inflammatory markers between large- and small vessel disease in patients with acute ischemic stroke. Int J Med Sci 2013; 10 :1399-1405.  Back to cited text no. 2
    
3.
Selcuk S, Asl EC, Hayat G. Erythrocytes sedimentation rate: can be a prognostic marker in acute ischemic stroke? Turkish J Cerebrovasc Dis 2013; 19 :18-22.  Back to cited text no. 3
    
4.
Boehme AK, Kumar AD, Lyerly MJ, Gillette MA, Siegler JE, Albright KC, et al. Persistent leukocytosis-is this a persistent problem for patients with acute ischemic stroke? J Stroke Cerebrovasc Dis 2014; 23 :1939-1943.  Back to cited text no. 4
    
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Kumar AD, Boehme AK, Siegler JE, Gillette M, Albright KC, Martin-Schild S. Leukocytosis in patients with neurologic deterioration after acute ischemic stroke is associated with poor outcomes. J Stroke Cerebrovasc Dis 2013; 22 :111-117.  Back to cited text no. 5
    
6.
Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtypes of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST (Trial of Org 10172 in Acute Stroke Treatment). Stroke 1993; 24 :35-41.  Back to cited text no. 6
    
7.
Muir KW, Weir CJ, Murray GD, Povey C, Lees KR. Comparison of neurological scales and scoring systems for acute stroke prognosis. Stroke 1996; 27 :1817-1820.  Back to cited text no. 7
    
8.
Balanescu S, Calmac L, Constantinescu D, Marinescu M, Onut R, Dorobantu M. Systemic inflammation and early atheroma formation: are they related? Maedica (Buchar) 2010; 5 :292-301.  Back to cited text no. 8
    
9.
Chamorro A, Vila N, Ascaso C, Saiz A, Montalvo J, Alonso P, Tolosa E Early prediction of stroke severity. Role of the erythrocyte sedimentation rate. Stroke 1995; 26 :573-576.  Back to cited text no. 9
    
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Idicula TT, Brogger J, Naess H, Waje-Andreassen U, Thomassen L. Admission C-reactive protein after acute ischemic stroke is associated with stroke severity and mortality: the ′Bergen stroke study′. BMC Neurol 2009; 9 :18.  Back to cited text no. 10
    
11.
Nardi K, Milia P, Eusebi P, Paciaroni M, Caso V, Agnelli G. Admission leukocytosis in acute cerebral ischemia: influence on early outcome. J Stroke Cerebrovasc Dis 2012; 21 :819-824.  Back to cited text no. 11
    
12.
Alvarez-Perez FJ, Castelo-Branco M, Alvarez-Sabin J. Usefulness of measurement of fibrinogen, D-dimer, D-dimer/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke. J Neurol Neurosurg Psychiatry 2011; 82 :986-992.  Back to cited text no. 12
    
13.
Hashem S, Fathy H, El-Sayed M, Hassan R, Samir H, Kamal M. Outcome and prognosis after ischemic strokes. Egypt J Neurol Psychiat Neurosurg 2004; 41 :195-212.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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