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Year : 2022  |  Volume : 28  |  Issue : 2  |  Page : 139-143

Ischemia-Modified Albumin Levels in Patients with Bell's palsy

1 Department of Otorhinolaryngology, University of Health Sciences, Umraniye Training and Research Hospital, İzmit, Turkey
2 Department of Otorhinolaryngology, Faculty of Medicine, Istanbul Medipol University, İzmit, Turkey
3 Department of Biochemistry, Istanbul Medipol University, Istanbul, Turkey
4 Department of Otolaryngology, Kocaeli State Hospital, İzmit, Turkey

Date of Submission03-Jan-2022
Date of Decision26-Jan-2022
Date of Acceptance06-Mar-2022
Date of Web Publication21-Sep-2022

Correspondence Address:
Dr. Ahmet Adnan Cirik
Department of Otorhinolaryngology, University of Health Sciences, Umraniye Training and Research Hospital, Istanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/indianjotol.indianjotol_4_22

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Background: Although several causes have been regarded as possible including viral, autoimmune, inflammatory, and vascular ischemia, the accurate etiology and pathophysiology of Bell's palsy (BP) remain unclear. The aim of the present article was to determine whether serum levels of ischemia-modified albumin (IMA) are associated with BP and if there is a posttreatment change in IMA levels. Materials and Methods: This was a prospective study enrolling 23 patients (10 males and 13 females; mean age: 44.71 ± 16.72 years; and range, 20–57 years) and 23 healthy individuals (12 males and 11 females; mean age: 37.91 ± 9.16 years; and range, 9–73 years) as the control group. Blood samples were obtained from the antecubital vein from all of the volunteers. Albumin cobalt binding test was used to obtain the IMA levels. Results: The mean IMA level was 0.38 ± 0.06 absorbance units in the study group at the time of diagnosis, 0.35 ± 0.07 absorbance units at the posttreatment period, and 0.35 ± 0.06 absorbance units in the control group. IMA levels of patients in posttreatment period were lower than the onset of illness. The result was statistically significant (P = 0.01). Conclusion: The data demonstrate that IMA decreased in BP with treatment. This is a preliminary study and we could not obtain results that clearly support the ischemic hypothesis of pathogenesis of BP; we think it gives an idea for further studies.

Keywords: Bell's palsy, idiopathic facial paralysis, ischemia-modified albumin

How to cite this article:
Cirik AA, Evcimik MF, Ülfer G, Yiğitbaşi T, Aktaş &. Ischemia-Modified Albumin Levels in Patients with Bell's palsy. Indian J Otol 2022;28:139-43

How to cite this URL:
Cirik AA, Evcimik MF, Ülfer G, Yiğitbaşi T, Aktaş &. Ischemia-Modified Albumin Levels in Patients with Bell's palsy. Indian J Otol [serial online] 2022 [cited 2022 Nov 27];28:139-43. Available from: https://www.indianjotol.org/text.asp?2022/28/2/139/356453

  Introduction Top

Idiopathic facial paralysis, also known as Bell's palsy (BP), is an acute, generally unilateral, and isolated lower motor neuron facial neuropathy of unknown etiology.[1] The clinical presentation of BP is an acute-onset, weakness or paralysis of facial muscles on the influenced side with concomitant symptoms of postauricular pain, taste disorders, tear flow, dry eye, hyperacusis, and subjective change in facial sensation. Annual incidence of BP is reported ranging from 11 to 40/per 100 000 people in different studies.[2] Although it may influence all ages, it is more commonly seen between 15 and 45 years old.[1] 60–75% of all cases are unilateral facial paralysis.[3] The precise etiology and pathogenesis of BP remain unclear. However, reactivation of latent herpes simplex virus infection has been asserted as its major cause.[4],[5] Several causes such as viral (such as herpes simplex or herpes zoster virus), ischemic, hypoxic, and autoimmune pathologies have been hypothesized as etiologies.[6],[7] The ischemic hypothesis has suggested that circulatory disorder-induced ischemia in the vasa nervorum leads to facial nerve injury where the facial nerve courses through narrow bony canal in the temporal bone. Several surgeons advocate that ischemia resulting from inflammation due to viral infection, vascular disturbance or autoimmune pathologies may cause facial paralysis by creating focal edema, demyelination, and secondary ischemia.[1] Within the temporal bone, where the facial nerve goes through the narrow passage, a swelling may lead to nerve compression and result in nerve damage.[8],[9]

Ischemia-modified albumin (IMA) is a marker of oxidative stress and tissue ischemia.[10],[11],[12] IMA is used as a biomarker for identifying myocardial ischemia. The elemental procedure of this test is based on measuring the binding capacity of serum albumin for cobalt is reduced after oxidation.[10] Framework of the N-terminal amino location of serum albumin is altered and disrupted by oxidative stress, ischemia, and hypoxia. The N-terminal region of the albumin molecules is bound to transitional metals such as nickel, copper, and cobalt.[11],[13] N terminus of albumin is reunited as a result of the interaction between albumin and reactive oxygen species. This interplay weakens its affinity for metals and causes the formation of IMA. Propounded changing mechanisms of serum albumin to IMA due to superoxide-radical injury, exposing to free metals, hypoxia, and dysfunction of the cell membrane.[10],[14] Increased amount of IMA levels have been reported in multifarious diseases which related with ischemia, inflammation, and oxidative stress such as acute coronary syndrome, peripheral vascular disease, cerebrovascular-ischemic stroke, acute infections, systemic sclerosis, malignancies, intrauterine disorders, nasal polyps, and obstructive sleep apnea.[12],[15],[16] Based on all this data, we are able to express IMA generation relevant strongly on the increased oxidative stress condition affect many other organs not only myocardium.

The present study intends to evaluate serum IMA levels in patients with BP and to compare with that of healthy subjects. This study also aims to evaluate the change in IMA levels after treatment.

  Materials and Methods Top

This study was conducted at departments of otorhinolaryngology of two tertiary hospitals between January 2016 and January 2020. A total of 23 patients (10 males and 13 females; mean age: 44.71 ± 16.72 years; and range, 20–57 years) with BP and 23 age- and sex-matched healthy individuals (12 males and 11 females; mean age: 37.91 ± 9.16 years; and range, 9–73 years) as the control group were evaluated in the study. Inclusion criteria were as follows: unilateral acute-onset peripheral facial nerve palsy with no previous treatment, without known causes, and the time elapsed between the onset of disease and applying to the clinic not more than 24 h. Exclusion criteria were as follows: Having a history of acute or chronic middle ear diseases and facial palsy with a recognizable cause such as trauma, iatrogenic, infectious, neoplastic, neurological autoimmune, or metabolic diseases. Patients were not included in the study if they had any concurrent acute ischemic cardiovascular or cerebrovascular disease.

All patients underwent a thorough otolaryngologic history taking and detailed physical examination. All clinical data were saved. The House–Brackmann grading score was used to assess the degree of facial nerve palsy.[17]

Methylprednisolone (Prednol, Mustafa Nevzat İlaç Sanayi, İstanbul, Turkey) was used for all patients. It was administered at a dose of 1 mg/kg per oral for the first 4 days and, then, its dose was tapered daily. Systemic corticosteroids treatment was terminated at the minimum dose on day 10. All patients were concomitantly administered an oral proton-pump inhibitor.

This prospective study was approved by the Ethics Committee of the XXX Hospital (Date: January 07, 2016, number: 10840098-604.01.01-E.314). The study was conducted in accordance with the principles of the Declaration of Helsinki. A written informed consent was obtained from all of the participants after informing details of the study.

Analysis of blood samples

To compute serum IMA levels, venous blood samples were obtained from the antecubital vein of all volunteers. The samples were placed into biochemical separator-containing tubes and centrifuged at 4000 rpm for 10 min to obtain serum, and then stored at −80°C until assayed. All specimens were transported under fit conditions.

The IMA measurement was performed using rapid and calorimetric method described by Bar-Or et al.[14] This colorimetric assay calculates complexes of dithiothreitol (DTT) with unbound cobalt. The test was performed by adding 50 μL 0.1% exogenous cobalt chloride to 200-μL serum and mixed then it was incubated for 10 min to allow albumin cobalt binding. Next, 50 μL 1.5 mg/mL DTT (Sigma-Aldrich) was added to give way to the reaction of free cobalt. After 2 min, the reaction was halted by adding 0.9% sodium chloride. The same method was applied to the sample blank. Meanwhile, water was used to prepare the sample blank not DTT. The absorbance values (ABSU) were calculated at 470 nm in spectrophotometry (Shimadzu UV-1201: Shimadzu Corp., Kyoto, Japan). IMA value was accepted as the difference between the sample and sample blank. The intra-assay and inter-assay coefficient of variation and percentage values of the method were 3.20 and 3.91, respectively.

Statistical analysis

Data analysis was performed using the Statistical SPSS version 20.0 software (IBM Corp., Armonk, NY, USA). Parametric data were expressed in mean ± standard deviation. Shapiro–Wilk and Kolmogorov–Smirnov tests were used to determine the normality of variables. Qualitative data were evaluated using the Chi-square test. Quantitative variables with normal standard distribution were compared using the independent sample t-test, whereas nonnormally distributed variables were compared using the Mann–Whitney U test. Paired sample t-test was used to compare two related variables. P < 0.05 was considered statistically significant.

  Results Top

The patients and healthy controls groups were statistically similar with regard to age and sex (P = 0.122 and P = 0.999, respectively). The mean IMA quantity was 0.38 ± 0.06 ABSU (range, 0.201–0.471) in the patient group at the time of diagnosis and 0.35 ± 0.06 ABSU (range, 0.281–0.434) in the healthy controls. The patients' IMA levels at the time of diagnosis were higher than the control groups; however, this was not statistically significant (P = 0.059).

The mean IMA level of BP in the posttreatment period, at 4 weeks later onset, was 0.35 ± 0.07 ABSU (range, 0.145–0.444). There was no significant difference between mean IMA levels in the posttreatment period of BP patients and healthy controls (P = 0.809). IMA levels in BP patients in posttreatment period were lower than the onset of illness; this difference was statically significant (P = 0.01). Baseline demographic and clinical characteristics and IMA levels of all groups are shown in [Table 1]. The comparison of serum ischemia-modified albumin levels between the groups is presented in [Figure 1].
Table 1: Demographic, clinical characteristics and IMA results of patients with Bell's palsy and healthy controls

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Figure 1: The comparison of serum ischemia-modified albumin levels between the groups

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At the time of diagnosis, the patients with House–Brackmann grade II and III were regarded as mild, and House–Brackmann grade to grade IV and V were regarded as severe. There were no statistically significant differences for IMA levels between mild and severe groups of BP at the time of diagnosis (P = 0.687), likewise no significant differences for IMA levels between the same groups at posttreatment period (P = 0.316).

  Discussion Top

This study investigated the comparison between the IMA levels of peripheral venous blood samples of patients with BP and healthy individuals. The reasons of BP are still unclear. The research on its etiology is limited due to difficulty in histopathologic exploration. Takeda et al.[18] carried out an animal experimentation with the intention of providing useful information on the pathogenesis of ischemic facial palsy. They have presented that the petrosal artery supplying the facial nerve was blocked causing facial nerve paralysis. Zhao et al.[19] was asserted that increased plasma fibrinogen level associated with impaired facial nerve microcirculation because of increased blood viscosity and that was supported the ischemia hypothesis about BP. Terzi et al.[20] detected that oxidative stress index levels were significantly higher in the patients of BP.

IMA is known as an marker of oxidative stress and ischemia producing as a result of tissue hypoxia.[21] The IMA is accepted the most dependable biomarker for identification of myocardial ischemia where necrosis does not occur.[12] However, it is not an organ-specific ischemic marker. Recently, IMA has been studied in several diseases. Ataş et al.[22] suggested that elevated levels of IMA in patients with vitiligo may result from increased oxidative stress; similarly, Ozdemir et al.[23] and Chandrashekar et al.[24] reported increased IMA level in psoriasis patients. Li et al.[25] concluded that IMA could be used as a reference for early diagnosis and prognosis in acute carbon monoxide poisoning. Erkut et al.[26] reported increased serum IMA levels could be regarded as a marker of increased tissue hypoxia in patients with acute leukemia. There are many articles on the association between hypo/hyperthyroidism and IMA levels, which indicated an increased oxidative stress status.[27],[28] While majority of them show significant correlations between IMA and thyroid hormones, Ersoy et al.[29] found no significant correlation. A study in patients with obstructive sleep apnea has shown that serum levels of IMA increased with the presence and severity of disease.[30] In a recent study by Göker et al.,[31] thirty patients with BP were divided into three groups according to House–Brackmann classification as grades II, III, and IV. Serum IMA levels were compared within the study group and between the control group. Similar to our study, they failed to show a statistically significant difference in serum ischemia-modified albumin levels among the patient groups (their study group did not include any patients with grade V BP). Göker et al., contrary to our study, have detected a significant increase in IMA levels in patients with BP at admission; however, we failed to show such a difference. Nevertheless, we have, for the first time in the literature, shown that there is a significant decrease in serum IMA levels after treatment of BP. In recent years, various studies have been carried out interested in relation of IMA and its possible correlation with diseases such as chronic obstructive pulmonary disease, acute rheumatic fever, and nasal polyposis.

As far as we know, the IMA levels after BP treatment have previously never been enquired. In this study, we have shown that IMA values tend to decrease with the improvement of BP. Although there were no significant relationship between the value of IMA in control group and at the pretreatment or posttreatment study group, posttreatment period IMA levels in BP patient is significantly lower than the pretreatment. IMA is not a specific marker for BP. Indeed, IMA levels also change in facial paralysis cases caused by systemic and infectious diseases. Although facial paralysis due to other causes is not targeted in this study, it would be useful to study these as well. Further studies are needed to assess its practical clinical use. Large case series would be useful to assess IMA levels recorded according to severity of the disease and a follow-up is needed for the IMA levels of resistant BP patients and those who recover quickly should be followed carefully. In this way, it may be possible to predict the response of the BP patient to treatment with IMA values. If the level of ischemia can be predicted, more selective treatment can be used in treatment selection (hyperbaric oxygen therapy, etc.). There are many other causes of facial nerve paralysis. In some cases, it may not be fully understood whether the paralysis is caused by traumatic incision or ischemia caused by edema/compression. IMA values can guide us in the differential diagnosis in such situations.

One major limitation of our study may be the small sample size. Another is that we cannot evaluate ischemic biomarkers or oxidative stress parameters and lack of data for serial IMA levels in the control group. Finally, the time between the real onset of the disease and the awareness of the disease by patients is unknown. There is not enough information about the specificity of IMA as a marker in BP. Further studies are needed to gain knowledge in this area.

  Conclusion Top

The results from this study demonstrated that serum IMA levels were significantly decreased with recovery in patients with BP. This is a preliminary study, and we could not obtain results that clearly support the ischemic hypothesis of pathogenesis of BP; we think it gives an idea for further studies. Additional prospective studies are necessary which must have a large pool of patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

  [Table 1]


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