Eur Arch Otorhinolaryngol DOI 10.1007/s00405-016-3937-1
Diagnostic and prognostic value of procalcitonin levels in patients with Bell’s palsy Saffet Kilicaslan1 • Sinan Uluyol1 • Mehmet Hafit Gur1 • Ilker Burak Arslan2 Ozlem Yagiz2
Received: 12 October 2015 / Accepted: 11 February 2016 Ó Springer-Verlag Berlin Heidelberg 2016
Abstract Inflammation is thought to play an important role in the pathogenesis of Bell’s palsy (BP). Procalcitonin (PCT) is currently among the most frequently used proinflammatory biomarkers in clinical practice. In this study, we assessed the serum PCT levels for predicting the severity and prognosis of BP. In total, 32 patients with House–Brackmann (HB) grade II and III BP (low-grade group), 22 patients with HB grade IV and V (high-grade group) and 35 healthy individuals (control group) were included in this prospective study. PCT levels were compared among these three groups at the time of diagnosis. All patients received standard prednisolone and acyclovir treatment. The correlation between PCT levels and recovery was analyzed 3 months after treatment. The PCT levels for control, low-grade and high-grade BP groups were 0.01 ± 0.001, 0.35 ± 0.05, and 0.98 ± 0.41 ng/mL, respectively. The PCT level in low-grade group was significantly higher than that in control group (p \ 0.001), and the PCT level in high-grade BP group was significantly higher than that in low-grade group (p = 0.01, p \ 0.05). The complete recovery rate was 93.7 % in low-grade and 54.5 % in high-grade BP group (p = 0.015, p \ 0.05). There was a strong negative correlation between PCT levels and recovery rates (r = -0.896, p \ 0.001). PCT
& Saffet Kilicaslan [email protected]
Department of Otolaryngology, Van Training and Research Hospital, Van, Turkey
Department of Otolaryngology, Tepecik Training and Research Hospital, Izmir, Turkey
levels were significantly associated with the severity of BP and higher PCT levels were related with poor clinical outcome in terms of recovery. These results support the diagnostic and prognostic significance of PCT in patients with early BP. Keywords Bell’s palsy Inflammation Inflammatory marker Procalcitonin Prognosis
Introduction Bell’s palsy (BP), also known as idiopathic facial nerve paralysis, results in facial motor dysfunction of varying severity . Several other conditions can also cause facial paralysis. The pathogenesis of BP remains unclear; however, inflammation due to viral infection is thought to play an important role . Inflammation of the facial nerve appears to induce pressure on the nerve within bony canal, blocking the transmission of neural signals or damaging the nerve, especially the labyrinthine segment . The severity of symptoms and is generally assessed using the House–Brackmann (HB) grading system . Procalcitonin (PCT), the precursor of the hormone calcitonin, is produced by C cells of the thyroid gland and neuroendocrine cells of the lung or intestine. PCT is currently among the most frequently used proinflammatory biomarkers in clinical practice [5, 6]. The blood level of PCT in healthy individuals is \0.01 ng/ mL . The aim of this study was to assess whether serum PCT levels reflect the severity of BP and assist to estimate the prognosis of BP.
Eur Arch Otorhinolaryngol
Patients and methods This study was performed in accordance with the Helsinki Declaration of the World Medical Association. Informed consent was obtained from all participants, and the study was approved by the Research Ethics Committee of a tertiary referral center (no. 2014/19). This prospective study involved 54 patients, who were diagnosed with BP in a tertiary referral center from October 2014 to May 2015, and a control group of 35 healthy individuals. Patients with a history of any of the following conditions were excluded: otitis media, middle ear effusion, acoustic trauma or barotrauma in the previous 4 weeks, otologic surgery, neurologic disorders predisposing them to facial paralysis or neoplasia within the previous 2 years, and inflammatory diseases leading to high PCT levels such as thyroid disease, diabetes, hypertension, renal failure, chronic liver or intestinal disease, and chronic obstructive pulmonary disease. Patients with BP were divided into two groups according to severity of disease using HB grading system by the same two practitioners. Patients were evaluated at the time of diagnosis and re-evaluated 3–4 days after the initiation of the BP if there was any progress in the facial paralysis degree, and the final results were documented. As a results, 35 healthy individuals comprised the control group, 32 patients with HB grade II and III BP comprised the low-grade group, and 22 patients with HB grade IV and V BP comprised the high-grade group. No patients had HB grade VI BP. PCT levels were measured at the time of diagnosis and 3–4 days after the initiation of BP, the average values were included in the study. The majority of patients (n = 44; 81.5 %) were diagnosed within 24 h of symptoms onset, but 8 (14.8 %) were diagnosed within 48 h, and 2 (3.7 %) were within 72 h. Samples were taken using a sterile needle and syringe, from the antecubital vein at 8:00 a.m. after an overnight fast. The serum PCT levels were measured using an electrochemiluminescence immunoassay (Roche Cobas e411; Roche Diagnostics GmBH, Mannheim, Germany). All patients were treated with 1 mg/kg daily prednisolone for 5 days, then tapering by 5 mg per day for the next 2 weeks and acyclovir 400 mg five times daily for 7 days. The patients were reassessed by the same two practitioners, in terms of recovery rate at the end of the third month of treatment. Complete facial recovery was defined as House–Brackmann grade I. A post-hoc power analysis was performed using G*Power 3.1 software for Windows. Power value was calculated as 89.03 % [k (number of groups) = 3, S (total sample size) = 89, a = 0.05, b = 0.18, medium effect
size = 0.41]. The data were analyzed using the SPSS software package for Windows ver. 20.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were presented as mean ± standard deviation and categorical variables as % ratios. The PCT levels among the control group, low and high grade BP groups were detected using analysis of variances (ANOVAs). The primary outcome measure of complete recovery (House–Brackmann I) at the end of 3 months between the low-grade and high grade BP groups were compared with Yates continuity correction test (Yates Chi square test). Spearman correlation coefficient test (r) was used to analyse the correlations of PCT levels with BP grades and recovery rates. A p value\0.05 was taken to indicate statistical significance.
Results The demographic characteristics of the recruited patients and their sex- and age-matched controls are summarized in Table 1. The PCT levels in control, low-grade and high-grade BP groups were 0.01 ± 0.001 (range 0.001–0.30), 0.35 ± 0.05 (range 0.01–1.05), and 0.98 ± 0.41 (range 0.20–1.50) ng/mL, respectively. The PCT level in lowgrade BP group was significantly higher than that in control group (p \ 0.001), the PCT level in high-grade BP group was significantly higher than that in low-grade group (p = 0.01, p \ 0.05) and there was a significant differences between high-grade and control group (p \ 0.001). PCT levels were positively correlated with the grade of facial paralysis (r = 0.716, p \ 0.001) (Fig. 1). The mean follow-up time was 3.3 ± 0.4 months with a complete recovery rate of 93.7 % (30 of 32 patients) in low-grade and 54.5 % (12 of 22 patients) in high-grade group. There was significant differences in terms of complete recovery between the low-grade and high-grade BP groups (p = 0.015, p \ 0.05) (Fig. 2). There was a strong negative correlation between PCT levels and complete recovery rates (r = -0.896, p \ 0.001).
Table 1 Demographic characteristics Control group (n = 35)
Low-grade group (n = 32)
High-grade group (n = 22)
Age range, years
Age in years, mean ± SD
38.6 ± 18.1
39.1 ± 14.2
36.9 ± 15.9
Female, n (%)
19 (54 %)
14 (43 %)
10 (45 %)
Male, n (%)
16 (46 %)
18 (57 %)
12 (55 %)
SD standard deviation
Eur Arch Otorhinolaryngol
Fig. 1 The association between procalcitonin (PCT) levels and control, low-grade facial paralysis and high-grade facial paralysis groups
Fig. 2 The association between procalcitonin (PCT) levels and recovery rates
Discussion Procalcitonin reportedly has greater specificity and sensitivity than acute-phase proteins such as C-reactive protein [8, 9]. PCT level rises dramatically under conditions of bacterial infection and sepsis, whereas lower levels (but still higher than normal) are present in patients with viral infection or noninfectious inflammatory conditions [10– 12]. Because inflammation is thought to be a precursor to the development of BP, we investigated the PCT levels in patients with BP. To date, very few clinical trials have evaluated the relationship between BP and inflammatory biomarkers. Jonsson et al.  analyzed immune complexes containing IgG-C1q and IgG-C3 and reported significantly elevated levels in the acute and convalescent stages of BP. Larsson et al. 
investigated the level of tumor necrosis factor alpha (TNFalpha), a cytokine associated with demyelination and the inflammatory response, and found significantly higher concentrations in patients with than without BP. Yılmaz et al.  compared levels of inflammatory cytokines between patients with and without BP and found that serum IL-6, IL8, and TNF-alpha concentrations were significantly higher in patients with than without BP. The neutrophil-to-lymphocyte ratio (NLR) represents the most frequently studied inflammatory marker. Bucak et al.  carried out a retrospective review of 54 patients with BP and reported that the mean NLR in patients with BP was significantly higher than that in the control group and NLR may be a potential marker to predict prognosis; similar findings were revealed by Kum et al. ; these authors noticed a significant relationship between the NLR and presence of BP. Atan et al.  reported a significant relationship between NLR and BP, but no significant relationship was detected between the degree of facial paralysis and NLR. The strength of our study depends on the evaluation of the relationship between the PCT level, severity and prognosis of BP for the first time. PCT levels were found to be significantly correlated with the grade of BP and this correlation provides important information about the grade of inflammation on the facial nerve. The mean PCT levels in patients with high-grade BP group was significantly higher than in low-grade group and also the clinical presentation showed a poor outcome in terms of recovery in high-grade BP group. The correlation of PCT levels with the degree of recovery rates indicates the potential prognostic value of PCT in BP. These results emphasize that elevated PCT levels in BP at hospital admission could represent a negative prognostic value. Based on this information, we speculate that corticosteroid therapy in patients with BP may be adjusted from the standard beginning doses that have been frequently suggested in numerous clinical studies and guidelines [19–21]. Further studies of the correlation between PCT levels and the optimal anti-inflammatory treatment modalities are needed to reveal our hypothesis.
Conclusions Procalcitonin levels were significantly associated with the severity of BP and higher PCT levels were found to be related with poor prognosis. Our results show that PCT is more than just a biomarker or predictor in patients with BP; its correlation with the degree of nerve involvement and poor recovery suggest its prognostic importance in early BP and its potential importance in determining optimal anti-inflammatory treatment modalities.
Eur Arch Otorhinolaryngol Compliance with ethical standards Conflict of interest The authors have no conflicts of interest or financial ties to disclose.
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