Mervi Kanerva

Prednisolone and valaciclovir in Bell's palsy: a randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND Previous trials of corticosteroid or antiviral treatments for Bells palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients. METHODS In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263. FINDINGS Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1.40, 95% CI 1.18 to 1.64; p<0.0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1.01, 0.85 to 1.19; p=0.90). The number of patients with adverse events was similar in all treatment arms. INTERPRETATION Prednisolone shortened the time to complete recovery in patients with Bells palsy, whereas valaciclovir did not affect facial recovery.

Sunnybrook and House-Brackmann Facial Grading Systems: Intrarater repeatability and interrater agreement

OBJECTIVE: To assess repeatability and agreement of the House-Brackmann (H-B FGS) and the Sunnybrook (SFGS) Facial Grading Systems. STUDY DESIGN AND SETTING: Eight video-recorded facial palsy patients were graded in 2 sittings by 28 doctors. Repeatability and agreement for SFGS were measured by intraclass correlation coefficient (ICC) and coefficient of repeatability (CR), and for H-B FGS by agreement percentage and kappa coefficients. RESULTS: Repeatability for SFGS was from good to excellent and for H-B FGS from fair to good. Agreement between doctors for SFGS was moderate by CR and nearly perfect by ICC. For H-B FGS, the agreement percentage was 50%, and generalized kappa indicated only fair agreement. CONCLUSIONS: SFGS was at least as good in repeatability as H-B FGS and showed more reliable results in agreement between doctors. SIGNIFICANCE: While waiting for an ideal scale for facial grading, the usage of SFGS can be encouraged over H-B FGS.

Bell's palsy - the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial.

Clin. Otolaryngol. 2012, 37, 283–290

Melkersson-Rosenthal syndrome:

OBJECTIVES: To study characteristics of Melkersson-Rosenthal syndrome (MRS) patients with facial palsy (FP) and differences in patients treated at the Departments of Otorhinolaryngology and Dermatology. METHODS: Clinical picture of MRS was studied from patient charts at two departments. Patients with FP received a questionnaire and were examined. Tissue biopsies were searched for non-necrotizing granulomatous infiltrations typical of MRS and blood DNA for UNC-93B1 gene mutations predisposing to herpesvirus infection. RESULTS: At the Department of Otorhinolaryngology, all 18 MRS patients had FP, 9 the triad form. Two patients revealed non-necrotizing granulomatous infiltrations during acute edema episodes; another two had association with uveitis. Edema was rarely persistent and did not dominate the clinical picture. No UNC-93B1 mutations were found. At the Department of Dermatology, 2 patients had triad MRS and 15 had monosymptomatic granulomatous cheilitis with persistent edema and typical MRS histology. CONCLUSION: The clinical picture of MRS with FP differed from the current knowledge of edema-dominated MRS. More studies focusing on MRS with FP would broaden our understanding of the syndrome.

Prednisolone in Bell's Palsy Related to Treatment Start and Age.

Objective: To evaluate if treatment start and age are related to the outcome in Bells palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients Data were collected from the Scandinavian Bells palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered. Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone (p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone.

The Effect of Prednisolone on Sequelae in Bell's Palsy

OBJECTIVE To study whether prednisolone reduces sequelae in Bells palsy. DESIGN Prospective, randomized, double-blind, placebo-controlled, multicenter trial with 12 months of follow-up. SETTING Seventeen referral centers. PATIENTS In all, 829 patients aged 18 to 75 years. INTERVENTIONS Randomization within 72 hours in a factorial fashion to placebo plus placebo (n = 206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n = 210); valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n = 207); or prednisolone plus valacyclovir (n = 206). MAIN OUTCOME MEASURES Facial function at 12 months assessed with the Sunnybrook and House-Brackmann grading systems. RESULTS In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P < .001). In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P < .001). The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P < .001 and P = .01, respectively). No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P = .10) or House-Brackmann grades higher than III (P = .80). Synkinesis was assessed with the Sunnybrook score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P = .001). Sixty patients had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P = .005). CONCLUSION Prednisolone significantly reduces mild and moderate sequelae in Bells palsy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00510263.

Sunnybrook and House-Brackmann Systems in 5397 Facial Gradings

Objectives. To study the correlation between Sunnybrook and House-Brackmann facial grading systems at different time points during the course of peripheral facial palsy. Study Design. Prospective multicenter trial. Setting. Seventeen otorhinolaryngological centers. Subjects and Methods. Data are part of the Scandinavian Bell’s palsy study. The facial function of 1920 patients with peripheral facial palsy was assessed 5397 times with both Sunnybrook and House-Brackmann (H-B) facial grading systems. Grading was done at initial visit, at days 11 to 17 of palsy onset, and at 1 month, 2 months, 3 months, 6 months, and 12 months. Statistical evaluation was by Spearman correlation coefficient and box plot analysis. Results. Spearman correlation coefficient varied from −0.81 to −0.96, with the weakest correlation found at initial visit. Box plot analysis for all assessments revealed that Sunnybrook scores were widely spread over different H-B grades. With 50% of the results closest to the median, Sunnybrook composite scores varied in H-B grades as follows: H-B I, 100; H-B II, 71 to 90; H-B III, 43 to 62; H-B IV, 26 to 43; H-B V, 13 to 25; and H-B VI, 5 to 14. Conclusion. Gradings correlated better in follow-up assessments than at initial visit. As shown by the wide overlap of the grading results, subjective grading systems are only approximate. However, a conversion table for Sunnybrook and H-B gradings was obtained and is included in the article. It can be used for further development of facial grading systems.

The Course of Pain in Bell's Palsy: Treatment With Prednisolone and Valacyclovir.

Objective: To evaluate the effect of prednisolone and valacyclovir on ipsilateral pain around the ear and in the face or neck in Bells palsy. The incidence and intensity of pain during the first 2 months of palsy and its prognostic value were also assessed. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen tertiary referral centers in Sweden and 1 in Finland. Patients: Data are part of the Scandinavian Bells palsy study; 829 patients aged 18 to 75 years with onset of palsy within 72 hours were included. Follow-up time was 12 months. Intervention: Patients were assigned to 1 of 4 treatment arms in a factorial fashion: placebo plus placebo; prednisolone 60 mg daily for 5 days, then tapering for 5 days, plus placebo; valacyclovir 1,000 mg 3 times daily for 7 days plus placebo; or prednisolone plus valacyclovir. Main Outcome Measures: Pain was registered on a visual analog scale within 72 hours, at Days 11 to 17, 1 month, and 2 months. Facial function was assessed with the Sunnybrook and House-Brackmann systems. Results: Prednisolone and/or valacyclovir did not significantly affect the incidence or intensity of pain during the first 2 months. Pain was registered in 542 (65%) of 829 patients. At 2 months, 53 (8%) of 637 patients still reported pain. Subjects with pain at Days 11 to 17 had lower facial recovery rates at 12 months than those with no pain (p < 0.0001). Conclusion: Prednisolone and/or valacyclovir did not affect the incidence or intensity of ipsilateral pain in Bells palsy. The incidence of pain was similar during the first 2 weeks and then decreased. Presence of pain at Days 11 to 17 indicated a worse prognosis for facial recovery.

Search for Herpesviruses in cerebrospinal fluid of facial palsy patients by PCR.

Conclusions: Herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) DNA were not detected in the cerebrospinal fluid (CSF) of patients with acute idiopathic peripheral facial palsy (Bells palsy). Our results indicate either the absence of these viruses or the presence of technical shortcomings. The role of human herpesvirus 6 (HHV-6) in this disorder and the significance of a positive HHV-6 DNA finding in the central nervous system need further investigation. Objective: Our goal was to determine whether DNA of HSV-1, VZV, or HHV-6 can be found by polymerase chain reaction (PCR) in the CSF of peripheral facial palsy patients. Materials and methods: We used PCR to detect the presence of HSV-1, VZV, and HHV-6 DNA in CSF. This was a retrospective case control study with 33 peripheral facial palsy patients (34 CSF samples) in the study group (26 with Bells palsy, 5 with simultaneously diagnosed herpesvirus infection, 1 with puerperal facial palsy, 1 with Melkersson-Rosenthal syndrome). The control group included 36 patients, most with diagnosed or suspected Borreliosis and facial palsy or sudden deafness. Results: One patient with Bells palsy had HHV-6 DNA in CSF. Neither HSV-1 nor VZV DNA was detected in patients or controls.

Microbiologic findings in acute facial palsy in children.

Objective Microbiologic causes of facial palsy in children were investigated. Study Design Prospective clinical study. Setting Tertiary referral center. Patients Forty-six children aged 0 to 16 years with peripheral facial palsy. Interventions Paired serum samples and cerebrospinal fluid were tested to find indications of microbes associated with facial palsy. The microbes tested were herpes simplex virus 1 and 2, varicella-zoster virus, human herpesvirus-6, Mycoplasma pneumoniae, Borrelia burgdorferi, influenza A and B virus, picorna, cytomegalovirus, parainfluenza virus, respiratory syncytial virus, coxsackie B5 virus, adenovirus, and enterovirus, Chlamydia psittaci, and Toxoplasma gondii. Besides the routine tests in clinical practice, serum and cerebrospinal fluid samples were tested with a highly sensitive microarray assay for DNA of herpes simplex virus 1 and 2; human herpes virus 6A, 6B, and 7; Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. Results Incidence for facial palsy was 8.6/100,000/children/year. Cause was highly plausible in 67% and probable in an additional 11% of cases. Borrelia burgdorferi caused facial palsy in 14 patients (30%), varicella zoster virus in 5 (11%) (one with concomitant adenovirus), influenza A in 3 (6%), herpes simplex virus 1 in 2 (4%) (one with concomitant enterovirus), otitis media in 2 (4%), and human herpesvirus 6 in 2 (4%). Mycoplasma pneumoniae, neurofibromatosis, and neonatal age facial palsy affected 1 child (2%) each. Conclusion Microbiologic etiology association of pediatric facial palsy could frequently be confirmed. Borreliosis was the single most common cause; hence, cerebrospinal fluid sampling is recommended for all pediatric cases in endemic areas. Varicella zoster virus accounted for 11% of the cases, being the second most common factor.