Steroids plus antiviral agents are more effective than steroids alone in the treatment of severe Bell's palsy patients over 40 years of age.

OBJECTIVE: The effectiveness of the combination of steroids and antiviral agents in the treatment of Bell's palsy remains unclear. This study evaluated the therapeutic effect of combination therapy in severe Bell's palsy patients and assesses specific conditions under which combination therapy is more effective than steroids alone. METHODS: From January 2005 to December 2019, the records of 1710 Bell's palsy patients who visited Kyung Hee University Hospital were reviewed retrospectively. Of these, 335 (19.6%) patients were diagnosed with severe Bell's palsy, with 162 patients treated with steroids alone and 173 patients treated with combinations of steroids and antiviral agents. The outcomes of treatment were assessed using the House-Brackmann (H-B) grade according to age, sex, hypertension, diabetes, and obesity. RESULTS: The favorable recovery rate was significantly higher in severe Bell's palsy patients who were treated with combinations of steroids and antiviral agents than with steroids alone (78.0% vs. 66.7%, p = 0.020). Subgroup analysis showed that combination therapy resulted in significantly higher recovery rates than steroids alone in patients aged ≥40 years (77.5% vs. 64.1%, p = 0.023) and in those without hypertension (75.8% vs. 63.3%, p = 0.044) and diabetes (79.7% vs. 65.5%, p = 0.007). CONCLUSION: Combination therapy with steroids and antiviral agents resulted in significantly higher favorable recovery rates than steroids alone in severe Bell's palsy patients. Combination therapy was particularly more effective than steroids alone in patients aged ≥40 years and in patients without hypertension and diabetes.

The presence of herpes simplex-1 and varicella zoster viruses is not related with clinical outcome of Bell's Palsy.

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Hematologic Markers of Bell's Palsy: A Meta-analysis.

OBJECTIVE: Bell's palsy (BP) is the most common cause of unilateral peripheral facial paralysis, and inflammation has been proposed as the main pathological cause. The study aim was to investigate the relationship between hematologic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and BP. DATA SOURCES: The following key words were used to search PubMed and Scopus for English language articles: Bell's palsy, facial palsy, facial paresis or facial paralysis, neutrophil, lymphocyte, and platelet. STUDY SELECTION: Articles related to BP with NLR or PLR data. DATA EXTRACTION: The data included patient profiles, House-Brackmann score, treatment modality, NLR, and PLR. DATA SYNTHESIS: Seven articles were selected. A random effect model was used to analyze the aggregated data. Six of these articles that included the NLR and two that included the PLR of BP and control patients were analyzed for the difference between BP and control patients. Three articles that included the NLR of the recovery and nonrecovery groups were analyzed for the relationship between NLR and recovery. CONCLUSIONS: The NLR was significantly higher for the BP patients than for the controls. Furthermore, the NLR was significantly lower for the recovery group than for the nonrecovery group. A high NLR was associated with poor prognosis and related to the severity of facial nerve inflammation. There was no significant difference between the PLRs of the BP patients and controls. The NLR, but not the PLR, was found to be a useful prognostic indicator of BP.

Granulomatosis with polyangiitis and facial palsy: Literature review and insight in the autoimmune pathogenesis.

Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported. Facial nerve palsy is usually reported during the clinical course of the disease but it might appear as the presenting sign of GPA. Necrotizing vasculitis of the facial nerve 'vasa nervorum' is nowadays the most widely accepted etiopathogenetic theory to explain facial damage in GPA patients. A central role for PR3-ANCA in the pathophysiology of vasculitis in GPA patients with oto-neurological manifestation is reported. GPA requires prompt, effective management of the acute and chronic manifestations. Once the diagnosis of GPA has been established, clinicians should devise an appropriate treatment strategy for each individual patient, based on current clinical evidence, treatment guidelines and recommendations.

Neutrophil-lymphocyte ratio: a new predictive and prognostic factor in patients with Bell palsy.

OBJECTIVE: The aim of this study was to investigate whether neutrophil-lymphocyte ratio (NLR) levels are elevated in patients with Bell palsy (BP). Moreover, we aimed to find out whether there is a correlation between NLR levels and the severity and prognosis of BP. MATERIALS AND METHODS: The study group consisted of 25 subjects who presented with BP and 25 control subjects with no evidence of facial nerve pathology. The subjects underwent a general physical examination; an assessment of laboratory blood parameters; and a cranial magnetic resonance imaging, using gadolinium as a contrast medium. RESULTS: The mean (SD) NLR values were 2.16 (0.80) in the patients with BP and 1.36 (0.48) in the control group. The mean NLR values in the patients with BP were significantly higher than in the control group (P = 0.0001). There was a positive correlation between NLR values and grade of facial paralysis (r = 0.661, P = 0.0001). The mean (SD) NLR values in the grades III, IV, V, and VI BP groups were 1.40 (0.54), 1.78 (0.44), 3.00 (0.63), and 2.60 (0.54), respectively. The mean NLR values in the grade V BP group were significantly higher than in the other groups (P = 0.0001). In addition, there was a positive correlation between NLR values and prognosis of facial paralysis (r = 0.239, P = 0.251). CONCLUSIONS: There is no previous study that investigated the association between NLR and BP in the literature. Higher NLR values in patients with BP may be a predictor of worse prognosis.

The expression of IL-2 and IL-4 in CD4(+) T cells from mouse lymph nodes and spleen during HSV-1-induced facial palsy.

OBJECTIVE: Herpes simplex virus 1 (HSV-1) is regarded as an important underlying cause of Bell's palsy, but the immunologic mechanism remains unknown. Here, we employed a mouse facial paralysis model to investigate the expressions of CD4(+) T lymphocytes and interleukin (IL)-2 and -4 in the left draining cervical lymph nodes (LCLN) and spleen, as well as the inhibitory effects of glucocorticoids (GCs). METHODS: HSV-1 was inoculated into the surface of the posterior auricle to generate the facial paralysis model. The paralyzed mice were divided into three groups; in one group without any treatment, mice were killed at different time points, and those in the other two groups were injected with methylprednisolone sodium succinate (MPSS) or with a combination of MPSS and GC receptor blocker (RU486). The expression levels of CD4(+) T lymphocytes and CD4(+)-IL-2(+) and CD4(+)-IL-4(+) cells in the LCLN and spleen were detected by fluorescence-activated cell sorting. RESULTS: Expression levels of CD4(+), IL-2, and IL-4 first increased then decreased in LCLN and spleen and peaked 5 and 7 days, respectively, after the manifestation of facial paralysis. All the data at the peak points were significantly different compared with control (p < 0.05), and these effects were inhibited by MPSS. CONCLUSION: Our results suggest that CD4(+), IL-2, and IL-4 participate in the HSV-1-induced facial paralysis immune response. MPSS can effectively attenuate HSV-1-mediated nervous system damage, which is associated with its inhibitory effect on expression of these inflammatory markers.

Bell's palsy and autoimmunity.

OBJECTIVES: To review our current knowledge of the etiopathogenesis of Bell's palsy, including viral infection or autoimmunity, and to discuss disease pathogenesis with respect to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the etiopathogenesis, clinical presentation, diagnosis and histopathology of Bell's palsy from 1975 to 2012 were analysed. RESULTS AND CONCLUSIONS: Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It accounts for 60 to 75% of all cases of unilateral facial paralysis. The annual incidence of Bell's palsy is 15 to 30 per 100,000 people. The peak incidence occurs between the second and fourth decades (15 to 45 years). The aetiology of Bell's palsy is unknown but viral infection or autoimmune disease has been postulated as possible pathomechanisms. Bell's palsy may be caused when latent herpes viruses (herpes simplex, herpes zoster) are reactivated from cranial nerve ganglia. A cell-mediated autoimmune mechanism against a myelin basic protein has been suggested for the pathogenesis of Bell's palsy. Bell's palsy may be an autoimmune demyelinating cranial neuritis, and in most cases, it is a mononeuritic variant of Guillain-Barré syndrome, a neurologic disorder with recognised cell-mediated immunity against peripheral nerve myelin antigens. In Bell's palsy and GBS, a viral infection or the reactivation of a latent virus may provoke an autoimmune reaction against peripheral nerve myelin components, leading to the demyelination of cranial nerves, especially the facial nerve. Given the safety profile of acyclovir, valacyclovir, and short-course oral corticosteroids, patients who present within three days of the onset of symptoms should be offered combination therapy. However it seems logical that in fact, steroids exert their beneficial effect via immunosuppressive action, as is the case in some other autoimmune disorders. It is to be hoped that (monoclonal) antibodies and/or T-cell immunotherapy might provide more specific treatment guidelines in the management of Bell's palsy.

Antiphospholipid antibody-related Bell's palsy in young women.

The present report describes three young women aged 25, 20 and 15 years who presented with Bell's palsy. Two of the patients had a past history of the disease, which responded to steroid treatment. All three patients were positive for antiphospholipid antibody (APLA). In addition, one of the patients tested positive for antinuclear antibodies; however, there was no clinical evidence of systemic lupus erythematosus. All three patients responded well to steroid therapy. We conclude that Bell's palsy may be one of the manifestations of APLA syndrome, and thus, APLA testing should be done in such cases.

Bell's palsy may have relations to bacterial infection.

Bell's palsy is the most common acute facial paralysis with its causes still unclear. At present, the most widely accepted causes are viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. Unclear causes lead to unidentified treatments. Most therapeutic methods are simply symptomatic treatment. Fortunately, the pathomechanism of Bell's palsy is relative clear, involving herpes simplex virus (HSV) reactivation within the geniculate ganglion, followed by inflammation and entrapment of the nerve in the bony foramen. This makes symptomatic treatment possible. But the therapeutic effects are not quite satisfactory. Therefore, novel etiological and therapeutic concepts are urgently needed. According to our clinical observation and some facts that do not favor the viral infections theory, we can conclude that all Bell's palsy is not related to viral infections, some even may have relations to bacterial infection. As far as blood routine examination is concerned, though lymphocyte increasing can be seen in most patients with Bell's palsy, there are cases with normal lymphocyte but increased neutrophil. Also, antibiotic treatment in these patients could accelerate recovery to some extent. These results indicate that Bell's palsy in these patients may be caused by bacterial infection.

Reactivation of herpes simplex virus type 1 and varicella-zoster virus and therapeutic effects of combination therapy with prednisolone and valacyclovir in patients with Bell's palsy.

OBJECTIVES: To determine whether reactivation of herpes simplex virus (HSV) type 1 or varicella-zoster virus (VZV) is the main cause of Bell's palsy and whether antiviral drugs bring about recovery from Bell's palsy. STUDY DESIGN: Randomized, multicenter, controlled study. METHODS: One hundred fifty patients with Bell's palsy were enrolled in this study. The patients were randomly assigned to a prednisolone group or a prednisolone-valacyclovir group, in whom virologic examinations for HSV-1 and VZV were performed by simple randomization scheme in sealed envelopes. The recovery rates among various groups were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Reactivation of HSV-1, VZV, and both viruses was detected in 15.3%, 14.7%, and 4.0% of patients, respectively. There was no significant difference in recovery rates between the prednisolone group and the prednisolone-valacyclovir group, although recovery in the patients with HSV-1 reactivation tended to be higher in the prednisolone-valacyclovir group than in the prednisolone group. There was a significant difference in recovery among age groups and between individuals with complete and incomplete paralysis. CONCLUSIONS: Reactivation of HSV-1 or VZV was observed in 34% of the patients with Bell's palsy. The effect of combination therapy with prednisolone and valacyclovir on recovery was not significantly higher than that with prednisolone alone.

[A case of Bell's palsy associated with peginterferon Alfa-2a and ribavirin therapy for chronic hepatitis C virus infection].

Pegylated interferon alfa-2a (PEG-IFN) and ribavirin combination therapy is the first line treatment for chronic HCV infection. There are four reports of Bell's palsy associated with interferon-alpha (IFN-alpha) and ribavirin therapy. We report here a case of Bell's palsy that occurred in a patient with chronic HCV infection during combination PEG-IFN and ribavirin therapy. The patient was 49-year-old man with chronic hepatitis C for 2 years. The liver biopsy showed grade 1 and stage 1. Therapy with PEG-IFN (Pegasys) 180 microgram/week and ribavirin 1200 mg/day was initiated. After 3 weeks of treatment, the patient showed a loss of muscular tone on the left side of his face. A diagnosis of Bell's palsy was made, and the PEG-IFN and ribavirin therapy was stopped. Prednisolone 45 mg/d was given and then tapered for 8 weeks. His palsy improved over 6 weeks.

Bell's palsy associated with IFN-alpha and ribavirin therapy for hepatitis C virus infection.

First-line therapy for hepatitis C virus (HCV) infection comprises interferon-alpha (IFN-alpha) and ribavirin for 6 or 12 months. Mild complications of therapy are common, but more serious complications are rare. Three patients with chronic HCV infection, acquired through injecting drug use, developed idiopathic facial paralysis (Bell's palsy) during therapy, with spontaneous resolution after withdrawal of treatment. Large-scale cohort studies reveal that IFNs are associated rarely with neurologic complications, and only one previous report has linked IFN-alpha therapy and Bell's palsy. We postulate that IFN-alpha therapy led to a breakdown of peripheral tolerance to myelin sheath antigens, leading to neuropathy, just as IFN-alpha therapy can cause autoimmune thyroiditis through breakdown of tolerance to native thyroid antigens.

Lymphocyte subsets in Bell's palsy: immune pathogenesis and outcome prediction.

The aim of this prospective study is to define the prognostic significance of lymphocyte subset analysis in children with Bell's palsy. Lymphocyte subgroup analysis in peripheral blood was performed in 17 children with Bell's palsy by using flow cytometry. Before a standard protocol of corticosteroid treatment, patients were categorized into two groups for facial nerve impairment on the basis of the clinical findings: Group 1 (mild to moderate impairment), 7 patients; and Group 2 (severe impairment), 10 patients. Outcome of the patients was evaluated at the end of 3 months follow-up and categorized as satisfactory recovery (n = 12) or unsatisfactory recovery (n = 5). Decreased percentages of B cells (CD19) and T helper/inducer (CD4) subsets were measured in patients with Bell's palsy compared with age-matched healthy control patients. Patients with severe impairment had significantly lower percentages of CD4 and CD19 subsets, whereas patients with mild to moderate impairment had only decreased percentage of CD19 subsets. There was no statistically significant difference in the percentage of lymphocyte subsets between the patients with satisfactory and unsatisfactory recovery. These results provide additional support for cell-mediated immunopathogenesis in patients with Bell's palsy, without any prognostic significance for the outcome.

CSF and serum levels of soluble fractalkine (CX3CL1) in inflammatory diseases of the nervous system.

The new CX(3)C-chemokine fractalkine (CX(3)CL1) was measured by Western blot in the cerebrospinal fluid (CSF) and serum of patients with inflammatory diseases of the peripheral and central nervous system (Bell's palsy, BP; Guillain-Barré Syndrome, GBS; multiple sclerosis, MS; viral meningitis, VM; bacterial meningitis, BM) and patients with noninflammatory neurological diseases (controls). In controls, fractalkine was detectable at low concentrations in the CSF and, at much higher levels, in serum. In all inflammatory neurological diseases under study, CSF fractalkine levels were significantly (p<0.01) increased vs. controls (BM>>GBS>VM>MS>BP>controls). In serum, fractalkine levels were significantly increased only in MS patients. The fractalkine CSF/serum ratios (a measure of the chemotactic gradient) were significantly elevated in BM, VM and GBS; furthermore, they tended to be increased in BP and to be decreased in MS. The elevated fractalkine CSF/serum ratios in diseases without CSF pleocytosis (GBS, BP) and a lack of correlation between fractalkine levels and CSF leukocyte counts suggested that soluble fractalkine is not a major chemokine in the CSF. There was no evidence of significant intrathecal production of fractalkine as the mean fractalkine indices (fractalkine CSF/serum ratio:albumin CSF/serum ratio) were <1 in all inflammatory diseases and not significantly elevated vs. controls.

Serum cytokine levels in Bell's palsy.

OBJECTIVE: To assess the significance of the serum levels of the cytokines (interleukine (IL-6, IL-8, IL-1b, IL-2r, and tumor necrosis factor alpha (TNF - alpha)) in the patients with Bell's palsy. STUDY DESIGN: A clinical and laboratory study in which serum cytokine levels were compared between the patients who had Bell's palsy and healthy controls. METHODS: Twenty-three patients with Bell's palsy and 30 healthy volunteers were included in the study. The blood samples of the patients and controls were obtained, and serum IL-1b, IL-2r, IL-6, IL-8, and TNF- alpha levels determined with chemiluminescence enzyme immunometric assay on an Immulite Immunoassay. The serum of the patients was taken between 2 days and 1 month after the disease. The assay was not in vitro lymphocyte stimulation. RESULTS: The IL-6, IL-8 and TNF- alpha levels were significantly higher in Bell's palsy than in controls (p < 0.05). The IL-1b and IL-2r levels were similar in both groups (p > 0.05). The levels of cytokine IL-6, IL-8, TNF- alpha, IL-1b, IL-2r did not correlate with the degree of recovery (p > 0.05). CONCLUSION: An alteration in the concentration of the cytokines is expected not only in many inflammatory and infectious diseases but also in Bell's palsy. Cytokines are not stored or preformed within cells. Therefore, high cytokine levels (IL-6 and IL-8, and TNF- alpha) should represent their production in response to underlying pathology in Bell's palsy, or these cytokines may be pathogenetic factors in Bell's palsy. However, serum levels of these cytokines do not help determine the prognosis in Bell's palsy as far as the results of this study are concerned.

[Aetiopathogenesis of Bell's idiopathic peripheral facial palsy]. / Etiopatogenia de la parálisis facial periférica idiopática o de Bell.

INTRODUCTION: Bell's facial palsy is a common condition with an incidence varying between 11.5 and 40.2 cases per 100,000 persons per year. However, some aspects of its aetiopathogenesis are still not clear. DEVELOPMENT: Over the years four theories have been suggested to explain the disorder: vascular, immunological, compressive and viral. The vascular theory (the oldest) has been ruled out by various studies. Subsequently, the immunological and compressive theories were described almost simultaneously. The former established the mechanisms generating a neural inflammatory response, and the second the morphological basis which made the nerve sensitive to these mechanisms. Both theories suggested, amongst other agents, a virus as the agent triggering the process. Recently a virus of the herpes simplex family has been identified as the cause of the disease. CONCLUSION: At present there is broad general agreement that Bell s facial palsy is caused by reactivation of a latent infected with human herpes simplex virus, localized to the facial nerve.