Is C-reactive protein to albumin ratio an indicator of poor prognosis in Bell's palsy?

Abstract

Purpose
The aim of this study was to determine whether the C-reactive protein to albumin ratio was associated with the prognosis in patients with Bell’s palsy.

Methods
Reviewing records of 79 patients diagnosed with Bell’s palsy, 3 groups were constituted: recovered group (with a House Brackman grade of 1 or 2 after treatment, 56 patients), unrecovered group (23 patients) and control group (60 healthy individuals). Age, hemoglobin, C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, white blood cell and hemoglobin values were compared among the groups.

Results
Age, hemoglobin and platelet to lymphocyte ratio were not significantly different between the groups (p = 0.12, p = 0.31, p = 0.86 and p = 0.87, respectively). Median C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio and white blood cell were significantly greater both in non-recovery group (p < 0.001) and recovery group (p = 0.001 and p < 0.001, respectively) compared to the control group. Additionally, median C-reactive protein to albumin ratio and neutrophil to lymphocyte ratio were significantly greater in the non-recovery group, compared to the recovery group (p = 0.002, and p < 0.001, respectively). However, median white blood cell did not significantly differ between the non-recovery and the recovery groups (p = 0.89).

Conclusion
Higher C-reactive protein to albumin ratio and neutrophil to lymphocyte ratio were associated with poor prognosis in patients with Bell’s palsy. C-reactive protein to albumin ratio might be the most significant indicator of poor prognosis in patients with Bell’s palsy.

Full text

Vol.:(0123456789)
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European Archives of Oto-Rhino-Laryngology
https://doi.org/10.1007/s00405-019-05691-3
OTOLOGY
Is C‑reactive protein toalbumin ratio anindicator ofpoor prognosis
inBell’s palsy?
SerkanCayir1 · OmerHizli2 · SerkanKayabasi3
Received: 26 July 2019 / Accepted: 8 October 2019
© Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract
Purpose The aim of this study was to determine whether the C-reactive protein to albumin ratio was associated with the
prognosis in patients with Bell’s palsy.
Methods Reviewing records of 79 patients diagnosed with Bell’s palsy, 3 groups were constituted: recovered group (with a
House Brackman grade of 1 or 2 after treatment, 56 patients), unrecovered group (23 patients) and control group (60 healthy
individuals). Age, hemoglobin, C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte
ratio, white blood cell and hemoglobin values were compared among the groups.
Results Age, hemoglobin and platelet to lymphocyte ratio were not significantly different between the groups (p = 0.12,
p = 0.31, p = 0.86 and p = 0.87, respectively). Median C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio
and white blood cell were significantly greater both in non-recovery group (p < 0.001) and recovery group (p = 0.001 and
p < 0.001, respectively) compared to the control group. Additionally, median C-reactive protein to albumin ratio and neu-
trophil to lymphocyte ratio were significantly greater in the non-recovery group, compared to the recovery group (p = 0.002,
and p < 0.001, respectively). However, median white blood cell did not significantly differ between the non-recovery and
the recovery groups (p = 0.89).
Conclusion Higher C-reactive protein to albumin ratio and neutrophil to lymphocyte ratio were associated with poor progno-
sis in patients with Bell’s palsy. C-reactive protein to albumin ratio might be the most significant indicator of poor prognosis
in patients with Bell’s palsy.
Keywords Bell’s palsy· Paralysis· C-reactive protein· Albumin· Prognosis
Introduction
Bell’s palsy (idiopathic facial paralysis) is the most common
form of facial nerve paralysis with a rate of 60–75% [1].
Although many factors have been identified in the etiology
of Bell’s palsy, inflammation and viral infections may play
the major role in the pathogenesis. The mechanism of Bell’s
palsy might be based on the inflammatory processes com-
pressing the facial nerve in the fallopian canal [2]. Evidences
reported in the prior literature revealed that Bell’s palsy was
an inflammatory disorder of the facial nerve [3–5]. Herpes
simplex type 1 genome was detected in endo-neural fluids
and posterior auricular muscles of the patients with Bell’s
palsy [6]. Additionally, this virus was considered to bring
about an inflammation resulting in acute cranial neuropathy
[7]. Moreover, the inflammation of the facial nerve is inter-
related to a novel virus or to the reactivation of a virus that
had already present [8]. Another proof about inflammatory
* Serkan Cayir
drserkancayir@hotmail.com
Omer Hizli
hizliomer@gmail.com
Serkan Kayabasi
drserkankayabasi@gmail.com
1 Department ofENT, Aksaray University, Aksaray Education
andResearch Hospital, 68100Aksaray, Turkey
2 Department ofENT, Giresun University, Prof Dr. A. Ilhan
Ozdemir Education andResearch Hospital, 28200Giresun,
Turkey
3 Department ofENT, Aksaray University, Faculty
ofMedicine, 68100Aksaray, Turkey

European Archives of Oto-Rhino-Laryngology
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etiology is higher neutrophil tolymphocyte ratio (NLR)
values reported in patients with Bell’s palsy. NLR was con-
sidered as a marker of inflammation and also being used to
evaluate the risk of cardiovascular diseases and the prog-
nosis of the patients with cardiovascular diseases and with
various types of cancer [9, 10].
C-reactive protein (CRP) is a positive acute-phase reac-
tant used for diagnosis in patients with infection/inflamma-
tion and for assessment of the efficacy of treatment [11].
Albumin is a negative acute-phase protein. Even though
albumin decreases mainly in acute inflammation, it is known
to decrease also in chronic process of inflammation and in
patients with malnutrition [12]. CRP and albumin may have
a prognostic value together, either in the short term or in the
long term of inflammation [13, 14].
Although the association between NLR and Bell’s palsy
was investigated [15], yet to the best of our knowledge,
thus far, no studies have addressed the association between
C-reactive proteintoalbumin ratio (CAR) and Bell’s palsy.
The goal of this retrospective cross-sectional study was
to determine whether C-reactive protein to albumin ratio
was associated with the prognosis in patients with Bell’s
palsy. We investigated the association of various blood test
parameters including CAR, NLR, and platelet to lymphocyte
ratio (PLR), white blood cell count (WBC) and hemoglobin
(Hbg) with the prognosis of Bell’s palsy.
Materials andmethods
Subjects andstudy design
This retrospective, archival, cross-sectional study was con-
ducted in line with the dictates of the World Medical Asso-
ciation Declaration of Helsinki and approved by the local
ethical committee. We searched the medical archive of our
institution to identify the cases of Bell’s palsy. Excluded
from the study were the patients with any inflammatory and/
or nutritional disease that might affect the level of blood
parameters, facial palsy of central origin, Ramsay–Hunt syn-
drome, traumatic facial palsy, previous history of otologic
surgery or active otologic disease, and the patients who were
admitted 5days (or later) after the first appearance of Bell’s
palsy.
We constituted the study groups from the patients with
Bell’s palsy (with a House Brackman [16] grade over 3 at the
time of first admission), and the control group from healthy
individuals. All patients with Bell’s palsy included in the
study group received corticosteroid treatment (at an initial
dose of prednisone of 1mg/kg/day), with a gradual dose
reduction maintained for at least 2weeks and the patients
were categorized according to the response to the treat-
ment: the recovery group and the non-recovery group. We
considered the patients with a House Brackman grade of 1
or 2 as recovered after receiving the treatment.
Laboratory evaluation
An automated blood cell counter was used for complete
blood count measurements (Mindray BC-6000, Shenzhen,
China). Serum albumin levels were analyzed using Abbott
C8000i (Abbott Park, IL, USA) automatic photometry com-
mercial kits. Serum CRP levels were measured using neph-
elometric method (AU5800 System; Beckman Coulter Inc,
Brea, CA, USA). We noted the blood test parameters includ-
ing Hbg, WBC, CRP, neutrophil count, lymphocyte count,
platelet count and albumin. Then, we calculated CAR, NLR
and PLR values of the study groups and the control group.
First, we compared the CAR, NLR, PLR, WBC, andHbg
of the groups. Then, we investigated the most significant
indicator parameter associated with the poor prognosis of
Bell’s palsy (non-recovery).
Statistical analysis
Results are presented as median (min–max). We inves-
tigated the distribution pattern of the data using Kol-
mogorov–Smirnov normality test (p < 0.05). We used
Kruskal–Wallis test to compare the median CAR, NLR,
WBC, Hbg and PLR values of three groups. For advanced
comparisons of CAR, NLR, WBC, Hbg and PLR, we used
Mann–Whitney U test, as post hoc test. To detect the most
significantly associated parameter with the poor progno-
sis of Bell’s palsy, and to determine a cut-off values, we
used receiving operator characteristics curve (ROC) analy-
sis test. For statistical analysis of all data, we used SPSS
software for Windows (SPSS Inc., Chicago, IL, USA). A p
value less than 0.05 was considered statistically significant.
Additionally, for post hoc comparison tests, we used Bonfer-
roni correction of three groups (triple combination) and a p
value less than 0.017 (0.05/3) was considered statistically
significant.
Results
One hundred thirty-nine individuals were eligible for this
study. Non-recovery group consisted of 23 patients (9 males
and 14 females, mean age 49 ± 3 years) with a non-recov-
ered Bell’s palsy, recovery group consisted of 56 patients
(27 males and 29 females, mean age 49 ± 3years) with a
recovered Bell’s palsy, and the control group consisted of
60 healthy individuals (29 males and 31 females, mean age
50 ± 3). The groups were age-matched (p = 0.06).
The median values of CAR, NLR, PLR, WBC and
Hbg are presented in the Table1. In the Kruskal–Wallis

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test, the median Hbg and PLR values did not significantly
differ among three groups (p = 0.86 and p = 0.87, respec-
tively). However, a significant difference of median CAR
(p < 0.001), NLR (p < 0.001) and WBC (p < 0.001) was evi-
dent among three groups.
In post hoc comparisons, median CAR, NLR and WBC
values were significantly greater both in non-recovery group
(p < 0.001) and recovery group (p = 0.001 and p < 0.001,
respectively) compared to the control group (Table1). Addi-
tionally, median CAR and NLR values were significantly
greater in the non-recovery group, compared to the recov-
ery group (p = 0.002, and p < 0.001, respectively). However,
median WBC did not significantly differ between the non-
recovery and the recovery group (p = 0.89) (Table1). Thus,
we found that WBC was not associated with the recovery
of Bell’s palsy, while CAR and NLR might be associated.
Figure1 represents the graph of the ROC analysis of the
parameters included CAR, NLR and WBC. ROC analysis
of poor prognosis of Bell’s palsy revealed that, CAR had a
greater AUC value (0.831) compared to NLR (0.785) and
WBC (0.723) (p < 0.001 and p = 0.001). Thus, CAR might
be an indicator parameter for poor prognosis in Bell’s palsy.
The cut-off value of CAR for poor prognosis in Bell’s palsy
was found as 0.82, with a sensitivity of 95% and specificity
of 78%.
Discussion
Bell’s palsy is identified as a sudden paresis/paralysis of all
facial muscles on one side of the face. Patients with Bell’s
palsy have several complaints such as dry eye, pain around
the ear, altered sense of taste and tear reduction not asso-
ciated with any other cranial neuropathy [17]. The annual
incidence of Bell’s palsy is 15–20 per 100,000 with 40,000
new cases each year. The recurrence rate of Bell’s palsy is
8–12%. There is no gender or racial preference and palsy
can occur at any age, but more cases are seen in mid- and
late life. Risk factors include diabetes mellitus, pregnancy,
preeclampsia, obesity, and hypertension [18].
Even though the pathophysiology of Bell’s palsy is still
unclear, ischemic neuropathy, autoimmune diseases, and
viral inflammation of the facial nerve were suspected. The
viral inflammatory/immune mechanism was considered to
play the major role in the pathogenesis of Bell’s palsy [19].
Inflammatory changes due to the viral infection may result in
edema of the facial nerve in the facial canal, compressing the
nerve and causing the paralysis. Vein reflux occurs owing
to increased pressure on the facial nerve, the congestion of
blood vessels causes edema and compression, as a result of
the ischemia of the facial nerve which is an important factor
related to poor prognosis in patients with facial paralysis
[20].
NLR and the CAR were reported to have prognostic value
as markers of inflammation [14, 15]. NLR, a novel potential
marker for identifying inflammation in various diseases, is
a valuable, easily accessible and inexpensive parameter like
the high-cost inflammatory markers such as IL-6, IL-1b,
Table 1 Comparison of the median values of CAR, NLR, PLR, WBC and Hbg
CAR C-reactive protein to albumin ratio, NLR neutrophil to lymphocyte ratio, PLR platelet to lymphocyte ratio, WBC white blood cell count,
Hbg hemoglobin
* of Kruskal–Wallis test
CAR NLR PLR WBC (×1000/ml) Hbg (mg/Dl)
Non-recovery20.89 (0.82–1.27) 2.9 (1.5–3) 136.3 (115–141.4) 8.76 (8.12–9.38) 14 (13.7–14.2)
Recovery10.71 (0.25–1.3) 1.95 (1.7–2.8) 135.7 (79–149.6) 8.84 (7.96–9.64) 14 (12.7–15.4)
Control00.62 (0.18–1.12) 1.75 (1.65–2.8) 137.3 (108.5–152.6) 6.12 (6.01–8.98) 14 (13.5–14.6)
p value* < 0.001 < 0.001 0.87 < 0.001 0.86
p2–0 < 0.001 < 0.001 –< 0.001 –
p1–0 0.001 < 0.001 –< 0.001 –
p2–1 0.002 < 0.001 – 0.89 –
Fig. 1 The graph of the ROC analysis

European Archives of Oto-Rhino-Laryngology
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IL-8 and TNF-α [15, 21]. Neutrophils are important for
cytokine production and usually increases in inflammatory
disorders, but a reduction in the number of lymphocytes is
possible during inflammation [22, 23]. NLR may provide
an information about whether the present pathology was a
result of an inflammatory event. Consistent with the prior
literature, we found the median NLR significantly higher in
patients with Bell’s palsy compared to the control group.
Additionally, our results showed that recovery of Bell’s
palsy resulted in a significant NLR decrease.
CRP is a well-known acute-phase protein produced by
hepatocytes in response to cytokines during inflammatory
processes, and significantly increases due to the infection
and inflammation. Increase in CRP levels usually depends
on the severity of the inflammation or infection [24]. On
the other hand, albumin is a negative acute-phase protein
providing an insight into the prognosis of diseases related to
infection and inflammation, and is associated with oxidative
stress [25]. Many prior studies demonstrated the prognos-
tic value of CAR in different cancer types and inflamma-
tory disorders [13, 14]. In this study, we found significantly
greater CAR values in patients with Bell’s palsy compared
to the control group. Based on our results, greater CAR
values might be an indicator of the inflammatory base of
Bell’s palsy. Additionally, CAR values showed a significant
decrease in patients with a recovered disease after receiving
a corticosteroid treatment. Thus, we can hypothesize that
extremely increased levels of CAR might be an indicator
of poor prognosis in patients with Bell’s palsy. Moreover,
the ROC analysis in our study provided the cut off value of
CAR for poor prognosis as 0.82 with a sensitivity of 95%
and specificity of 78%. Thus, physicians could consider the
patients with a CAR value over 0.82 as associated with poor
prognosis.
Our results showed the association of Bell’s palsy not
only with CAR values, but also with NLR values and WBC
levels. However, the WBC was not significantly associated
with recovery. In addition, higher NLR might also be an
indicator of poor prognosis in patients with Bell’s palsy, but
CAR had a greater area under curve in the ROC analysis.
This result suggests that CAR might be a more precious
parameter related to the poor prognosis in patients with
Bell’s palsy.
To the best of our knowledge, this is the first study inves-
tigating the predictive value of CAR in patients with Bell’s
palsy and providing a cut off value for poor prognosis. How-
ever, the major limitation was the retrospective nature of
the study, since we had to include only a limited number
of parameters obtained from the medical records of the
patients. Nevertheless, this study may provide an inspiration
for further prospective investigations of many other blood
test parameters associated with inflammation in patients with
Bell’s palsy.
Conclusion
In conclusion, higher CAR and NLR were associated
with poor prognosis in patients with Bell’s palsy. CAR
might be the most significant indicator of poor prognosis
in patients with Bell’s palsy and physicians could consider
the patients with a CAR value over 0.82 as associated with
poor prognosis.
Author contributions SC: collected and analyzed data, wrote article,
approved the final version. OH: designed and supervised study, inter-
preted data, made statistics, wrote and revised article, approved the
final version. SK: collected and analyzed data, revised article, approved
the final version
Funding The authors declared that this study has received no financial
support.
Compliance with ethical standards
Conflict of interest The authors have no conflict of interest to declare.
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