Per Hanner

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.

HEARING IMPAIRMENT IN PATIENTS WITH ANTIBODY PRODUCTION AGAINST BORRELIA BURGDORFERI ANTIGEN

This study aimed to evaluate the extent to which hearing disorders may be a result of tick-borne Borrelia burgdorferi infection. 98 patients with different patterns of hearing dysfunction were studied. The patients had a history of sudden hearing loss, disorders similar to Menières disease, or hearing loss in combination with acute facial palsy or with vertigo. Serum antibodies against the B burgdorferi antigen were determined during the acute and convalescent periods. 17 patients (17%) showed serological evidence of borreliosis (reciprocal titre of 320 or above). All but 3 of these patients also had vertigo and 3 subjects had peripheral facial palsy. All the 17 patients were treated with high doses of intravenous benzylpenicillin. The hearing of 5 patients improved on treatment. Although the specificity of antibody production against borrelia antigen has not been completely clarified, it is concluded that repeated serological examinations are worthwhile in patients with unexplained hearing disorders.

Borrelia infection and vertigo.

73 patients with vertigo were studied regarding serum antibodies to Borrelia spirochete antigen, using an indirect immunofluorescence method. Ten patients (14%) had serological evidence of Borrelia infection. All 10 patients had severe, incapacitating vertigo. Four of the Borrelia patients had positional vertigo and all 10 had positional nystagmus when tested using ENG. Five of them had unilateral caloric weakness. Five patients had abnormal oculomotor tests. Borrelia infection is an etiological factor which should be considered in patients suffering from vertigo especially if positional nystagmus is present.

Elevated Levels of Myelin Basic Protein in CSF in Relation to Auditory Brainstem Responses in Bell's Palsy

Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was quantified from 28 patients with acute facial palsy. The mean value of MBP in CSF in the study group was 3.4±0.22 μg/1 (mean±SEM), which was significantly higher than the found in 37 healthy subjects (2.4±0.13 μg/1). Using a 95% confidence interval, 10 patients demonstrated significantly increased CSF concentrations of MBP (>3.95 μg/I). Auditory brainstem response (ABR) test showed that 5 patients had abnormal brainstem responses. No significant correlation was observed between elevated MBP in CSF and either pathologic auditory brainstem responses or the clinical degree of the palsy. These results suggest that a brainstem involvement may occur in patients with Bells palsy. Furthermore, our data accord with previous reports suggesting Bells palsy to be part of a polyneuropathy.

Trigeminal dysfunction in patients with Bell's palsy.

The trigeminal function was investigated in 30 consecutive patients with acute unilateral peripheral facial palsy. The patients were tested with electrophysiological methods within 5 weeks after onset of the disease. Trigeminus-evoked potential test (TEP) disclosed trigeminal dysfunction in 47%, while the blink reflex test (BR) showed trigeminal pathology in 60% of the patients. A topographical analysis of the trigeminal system showed that 24% of the patients had BR patterns that were consistent with brainstem involvement. In 2 cases (7%), TEP was pathological though the BR test proved normal. These findings suggest a more central trigeminal affection and may demonstrate multifocal lesions. This was further underlined by the investigation of the auditory brainstem response (ABR) which indicated brainstem involvement in 28%. It is concluded that acute facial palsy is frequently a symptom of a central nervous affection.

Increased antisecretory factor reduces vertigo in patients with Ménière's disease: a pilot study.

It has been hypothesized that the symptoms of vertigo in patients with Ménières disease somehow are related to impaired production and/or transport of endolymph. Antisecretory factor (AF) is a protein known to affect transport processes in the intestine and it has been shown that intake of specially processed cereals (SPC) can increase endogenous AF synthesis. In a prospective open pilot study, 24 patients with severe Ménières disease (functional level scale 5-6 according to the criteria of AAO-HNS) received SPC for 14-30 days. AF levels in plasma increased by 83% in 20 of the 24 patients studied. The attacks of rotatory vertigo were reduced, to final AAO-HNS functional level scale 1-3, in 12 patients and in three of these hearing was normalized. Twelve patients had no or minor effects of the treatment. The correlation between AF activity after treatment and the final AAO-HNS functional level scale was -0.65, P<0.001. Studies in rats using immunohistochemistry methods showed that AF was localized to the cochlea and the vestibule of the inner ear. The present results suggest that AF might be a new regulator of the endolymph.

Antisecretory factor-inducing therapy improves the clinical outcome in patients with Ménière's disease.

Abstract Conclusion: Intake of antisecretory factor (AF)-inducing SPC-flakes® significantly reduced vertigo in patients suffering from Ménières disease (MD). The positive effect may be due to a modulation of the transport of water and ions in the endolymphatic space. Objective: To evaluate the effects of a 3-month treatment period with SPC-flakes® in patients suffering from MD. Patients and methods: A prospective, double-blind, placebo-controlled study was performed. A total of 51 adult patients with MD were included in the study: 27 subjects treated with SPC-flakes® and 24 subjects with control cereals. The patients received SPC-flakes® or control cereals (1 g per kg body weight per 24 h in two servings) for 3 months. Otoneurological examinations were carried out before and after this period. Results: The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) grading system. Fourteen of the 27 patients randomized to intake of the AF-inducing SPC-flakes® reported decreased vertigo, compared with 2 of 24 in the control group (p < 0.001). No consistent change in the otoneurological examinations could be demonstrated in any of the groups of patients.

Scandinavian Bellʼs Palsy Study: A Multicentre Placebo-controlled Evaluation of Prednisolone and/or Valaciclovir for the Treatment of Bellʼs Palsy

Conclusions Recent studies indicate that herpesvirus and an inflammatory reaction may be responsible for the nerve injury in Bell’s palsy. Despite several studies with steroids and some with antiviral therapy, the treatment effect of such drugs has still not been convincingly demonstrated. In order to get further knowledge on the treatment of Bell’s palsy, a multicentre placebo-controlled study with prednisolone and/or valaciclovir is to start in Scandinavia. The rationale and outlines for this study will be presented.