Original Paper

Eur Neurol 2008;60:253257 DOI: 10.1159/000151701

Received: August 29, 2007 Accepted: March 12, 2008 Published online: August 29, 2008

Independent Role of Hypertension in Bells Palsy: A Case-Control Study

Daryoush Savadi-Oskouei a Ali Abedi b
a

Homayoun Sadeghi-Bazargani a, c

Neuroscience Research Center, Faculty of Medicine, Tabriz University, Tabriz, b Physiology Department, Faculty of Medicine, Ardabil, Iran; c PHS Department, Karolinska Institute, Stockholm, Sweden

Introduction Key Words Facial palsy Bells palsy, etiology Hypertension Diabetes

Abstract Background/Aim: In this case-control study, our aim was to check for a possible independent role of hypertension in increasing the risk of developing Bells palsy. Methods: All patients diagnosed as having Bells palsy referred to a neurology clinic were enrolled as cases. Controls were selected among other patients referred to the same clinic. Data were analyzed using the Stata 8 statistical software package. To detect the independent effect of exposure variables, a multiple logistic regression test was used. Results: Bivariate analysis showed an increased risk of Bells palsy for patients with diabetes or hypertension. Logistic regression results stratified for patients younger than 40 years of age and others showed that diabetes was the independent predictor of Bells palsy in both age groups. Logistic regression results showed that hypertension could not independently predict the occurrence of Bells palsy among patients younger than 40 years but for older ones it could. Conclusion: Hypertension may increase the risk of Bells palsy among those aged above 40 years. Researchers should be very cautious when declaring an independent role of hypertension as a cause of Bells palsy. Copyright 2008 S. Karger AG, Basel

Ever since Sir Charles Bell in 1821 established that the muscles of facial expression were under the control of a separate cranial nerve, his name has been associated with all forms of facial palsy. Bells palsy is an acute, unilateral paresis or paralysis of the face in a pattern consistent with peripheral nerve dysfunction, without detectable causes [1]. Bells palsy accounts for almost three quarters of all acute facial palsies, with the highest incidence in the 15to 45-year-old age group [2]. It causes considerable loss of self-esteem among patients. The annual incidence of this idiopathic disorder is between 11 and 40/100,000, or about 1 in 60 persons in a lifetime [3]. Men and women are equally affected, although the incidence is higher in pregnant women (45 cases/100,000) [4]. The cause is unclear. Viral infection, vascular ischemia, autoimmune inflammatory disorders and heredity have been proposed as the underlying cause. A viral cause has gained popularity since the isolation of the herpes simplex virus 1 genome from facial nerve endoneurial fluid in people with Bells palsy [1]. Focusing on specific diseases underlying Bells palsy, diabetes is the best known. Regarding hypertensions independent role, methodologically acceptable studies are hardly available. In this case-control study, our aim was to check for the possible independent role of hypertension in increasing the risk of developing Bells palsy.
Homayoun Sadeghi-Bazargani Karolinska Institute PHS Department, Norrbacka, 2nd floor SE171 76 Stockholm (Sweden) Tel./Fax +46 8 669 3582, E-Mail homsad@ki.se

2008 S. Karger AG, Basel 00143022/08/06050253$24.50/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: www.karger.com/ene

Control 0.03

Cases

0.02 Density

0.01

0 0 50 100 0 Age (years) 50 100

Fig. 1. Age distribution in the control and

case groups.

Materials and Methods

This case-control study was conducted in Ardabil, a mountainous province in the northwest of Iran. All the patients diagnosed as having Bells palsy referred to a neurology clinic from 2001 to 2004 were enrolled as cases. A complete medical examination was done and the medical history taken for all patients. Patients with a positive history of stroke were excluded. Finally 201 cases who agreed to participate and met the criteria were included in the study. Computerized tomography, magnetic resonance imaging and audiometric tests were used to exclude known causes of facial palsy, and, in cases of ambiguity, ENT consultations were also requested. The main information gathered by a structured questionnaire included e.g. age, sex, clinical signs and symptoms or blood pressure. Controls were selected among other patients referred to the same clinic. These were mainly patients suffering from headache and idiopathic epilepsy visiting for the first time. The headache patients who had used antiheadache drugs other than routine tranquilizers were not entered into the study. Those controls with a recent history of using corticosteroids or long-term corticosteroid usage were excluded. Based on current medical service delivery and medical consult behaviors, headache and Bells palsy have similar referral levels. The source populations for controls and cases were considered reasonably similar. A current stroke or corresponding medical history was the exclusion criterion for the control group too. Blood pressure was measured using a standard method by a standard sphygmomanometer. Hypertensive patients were considered those with a blood pressure equal or more than 140/90 mm Hg or a positive history of hypertension currently treated by antihypertensive drugs. The blood pressure of those patients who lacked any of these criteria for hypertension but had a blood pressure above 130/90 mm Hg at the first visit was measured again

after 1 month, and the mean blood pressure was calculated. Fasting blood sugar and if needed 2-hour postprandial blood sugar were measured for all case and control group patients. Based on these data, diabetic patients were distinguished. Also those patients who declared being diabetic and those who received antidiabetic treatment were considered as being diabetic. Others who had fasting blood sugar above 126 mg/dl and postprandial sugar above 200 mg/dl were diagnosed as diabetic, but if they were using corticosteroids, the tests were repeated 1 month after withdrawing them. Data were entered into the computer and analyzed using the Stata 8 statistical software package. To compare the means and proportions, t and 2 tests were used, and odds ratios were calculated along with 95% confidence intervals (CI). The statistical significance level was considered at 0.05. To detect the independent effect of exposure variables, a multiple logistic regression test was used. The dependent variable (having a diagnosis of Bells palsy) as well as independent variables (being diabetic or hypertensive) were coded as 0 for lacking disease and 1 for having it. The maximum likelihood approach was used to estimate weights of logistic parameters. Those variables that perfectly predicted the outcome were omitted from the model as well as variables with no statistical or trivial statistical but no clinical significance.

Results

Basic Information about Control and Case Groups The mean age 8 SD in the control group was 40 8 17.8 years. That of patients in the case group was 42.9 8 21.1 years (fig. 1). Further details of demographic characSavadi-Oskouei/Abedi/ Sadeghi-Bazargani

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Table 1. Demographic characteristics of study participants

Patients

Mean age 8 SD years Diabetic Nondiabetic 51.6819.9 39.31820.6 63.7816.6 39.6817.5 41.5819.6

Sex frequency male: 31 female: 28 male: 79 female: 63 male: 1 female: 3 male: 86 female: 111 male: 197 female: 205 percent 52.5 47.5 55.6 44.4 25 75 43.6 56.3 49 51

Job frequency farmers: 17 others: 42 farmers: 49 others: 93 farmers: 1 others: 3 farmers: 57 others: 140 farmers: 124 others: 278 percent 28.8 71.18 34.5 65.49 25 75 28.93 71.06 30.84 69.15

Cases

Controls

Diabetic Nondiabetic

Total

teristics are given in table 1. 84.6% of controls were headache patients. The medical history and current medical investigations of the controls did not confirm any comorbidity of importance related to Bells palsy other than hypertension or diabetes. The distribution of Bells palsy occurring in different months of the year is given in figure 2. There was a history of facial palsy in 21.9% of the patients. None of the cases or controls used drugs which could be related to Bells palsy. Determinants of Bells Palsy Bivariate analysis showed an increased risk of developing Bells palsy for patients having diabetes or hypertension. 37.3% of Bells palsy patients had hypertension compared to 14.9% of controls, and 29% of Bells palsy patients had diabetes compared to 2% of the controls. Logistic regression results stratified for patients younger than 40 years of age and others showed that diabetes was the independent predictor of Bells palsy in both age groups. At ages below 40 years, due to perfect prediction diabetes was omitted from the model, and for the second age group the odds ratio of diabetics developing Bells palsy was calculated to be 15.9 (95% CI: 5.446.8). As for hypertensive patients, logistic regression results showed that hypertension could not independently predict the occurrence of Bells palsy in patients younger than 40 years but for older ones the odds ratio of hypertensive patients developing Bells palsy was calculated to be 4.5 (95% CI: 2.58.1).

35 30 Occurrence (n) 25 20 15 10 5 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Fig. 2. Occurrences of Bells palsy over the year.

Discussion

In our study, 29% of Bells palsy patients were diabetic while in another case-control study it was reported to be 24.8% [5]. The frequency of diabetes mellitus reported in subjects affected by Bells palsy varies widely. Many studies have discussed diabetes as a risk factor or predisposing factor of Bells palsy or stated an association between diabetes and Bells palsy. However, because of methodological limitations, conclusions drawn in some of these studies do not seem to be quite rational. Most of these studies are simple descriptive or even case studies [518]. Even considering case-control studies, an independent
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role of suspected risk factors was not evaluated properly, and no published cohort study was found in the Medline database [5, 14]. Our study showed that diabetes has an independent role in increasing the risk of Bells palsy for both age groups. Contrary to the available literature and our findings, some studies have not found any difference in the prevalence of diabetes between Bells palsy patients and the general population [19]. It is a controversy also if facial nerve degeneration is associated with diabetes and if diabetic patients are more vulnerable to treatment failure [1924]. Considering the fact that taste involvement is uncommon in Bells palsy among diabetic patients in older studies, a vascular rather than metabolic mechanism has been suggested for facial nerve palsy in diabetics [5, 17, 25]. Although it is accepted that diabetes increases the risk of Bells palsy, there is some doubt whether recombinant human insulin-like growth factor 1 used along with insulin may give rise to Bells palsy or not [26, 27]. Facial paralysis in a hypertensive patient was first described more than 100 years ago. We did not find any independent role for hypertension to cause Bells palsy among patients younger than 40 years, but hypertension had an association although not a very strong one with Bells palsy among older patients. Contrary to diabetes there is less evidence in the literature for hypertension to cause or predispose to Bells palsy in the general population [57, 1215, 2830]. There has been more attention on hypertension in Bells palsy among children and pregnant women [3137]. The incidence of Bells palsy is significantly higher during the last trimester of pregnancy and the puerperium. Suggested explanations for this association include fluid retention, hypertension, compromise of the vasa nervorum, infection (particularly with herpes simplex virus) and an autoimmune process [33]. Aynaci and Sen [35] stated that as hypertension is one of the rare causes of peripheral facial paralysis in children, the nonawareness of this association at presentation may cause serious medical errors and result in delays in the diagnosis of hypertension which may worsen with corticosteroid therapy given for Bells palsy. Our findings were consistent with those of a study in Nigeria which stated that hypertension was associated with Bells palsy in patients above 50 years of age [38]. However, that was only a cross-sectional study, and no other case-control or prospective study was found to strongly defend the role of hypertension in causing Bells palsy. This shortage of evidence may be caused by overlooking an interaction between age and hypertension in
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studies conducted without age limitations or by not using multivariate analysis; as well, in some studies the effect size and strength of observed association were not considered as focus of analysis. A variety of physiological theories to explain the relationship between facial paralysis and hypertension have been published. Although the true etiology remains unknown, there seems to be an adequate explanation to support a probable association between hypertension and Bells palsy as well as its dependence on age. Small hemorrhages into the facial canal and neural partial necrosis may be a possible explanation, and there is evidence for the first mechanism in 2 autopsies reported in the literature. To discuss the role of age in the association of hypertension and Bells palsy, there may be the following considerations: (1) hypertension has a cumulative and long-term effect predisposing to Bells palsy; (2) increased vascular pathology at higher ages explains the association present at higher ages; (3) a severe uncontrolled hypertension which is common at higher ages may lead to Bells palsy; (4) a pathological and even idiopathic hypertension (which is more common in hypertensive children) can lead to Bells palsy, and (5) the higher physiological susceptibility in children and pregnant women may be the cause of an association between hypertension and Bells palsy. Any of the explanations mentioned above or other unknown mechanisms may explain the effect of age on the association of hypertension and Bells palsy. Although based on our design, methods and findings we may not accept or reject any and further research is needed, regarding the first 3 mechanisms we tend to focus more on the second. Most of the child cases go to the pediatric clinics instead of a neurology clinic in our area. So our opinion on the fourth and fifth mechanisms is mainly based on reports in the literature.

Conclusion

Hypertension may increase the risk of Bells palsy among those aged above 40 years. More specifically designed case-control or prospective studies are needed to clearly investigate the association between hypertension and Bells palsy. Researchers should be very cautious when declaring an independent role of hypertension in the etiology of Bells palsy. As for the limitations and strengths of the study, like in other case-control studies, unknown confounding factors may possibly modify effects. Unlike some other caseSavadi-Oskouei/Abedi/ Sadeghi-Bazargani

control studies, based on the definition and natural progress of Bells palsy, its association with hypertension and diabetes is not much affected by reverse causality and temporality problems. A future cohort study with cardiology researchers as coinvestigators or at least a largerscale age-stratified case-control study is suggested to further clarify the observed associations.
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Acknowledgements
We are thankful to Ardabil University of Medical Sciences which supported this research project as well as Alavi University Hospital physicians and nurses who helped in conducting the study.

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