Malou Hultcrantz

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.

Estrogen and hearing: a summary of recent investigations

Is the female sex steroid estrogen the key to preserved hearing in the aging human? This question remains unanswered, but hearing loss is more profound in elderly males than females. There are also well-known sex differences in the auditory brainstem response (ABR), i.e. women have shorter latencies than men. Moreover, menopausal women who are administered hormone replacement therapy have slightly better hearing than those who are not, and women with Turners syndrome (45,X), who are biologically estrogen-deficient, show longer ABR latencies and early presbyacusis. These findings are also supported by animal experiments. When boosted with estrogen or testosterone the non-reproductive female midshipman fish alters its inner ear auditory mechanism so that it can hear the males hum-like call. If estrogen receptor β is knocked out in mice, severe progressive hearing loss occurs, leading to early deafness. In apparent contradiction to these findings, there have been case reports suggesting that hormone replacement therapy and oral contraceptive use can lead to hearing loss, but of another type, namely acute sudden deafness. Such contradictory aspects of the action of estrogen are commonly found and may spring from the fact that there are two estrogen receptors, α and β, both of which are present in the inner ear of mice, rats and humans. Knowing how sex steroids can alter hearing ability may give important clues as to how estrogen can preserve hearing in humans. In this review we present a summary of current knowledge about hearing and estrogen.

Estrogen receptors in the normal adult and developing human inner ear and in Turner's syndrome

The influence of estrogens, the female sex hormone, on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The presence of estrogen receptors alpha and beta has earlier been shown in the inner ear of mice and rats. The aim of this study was to map possible estrogen receptors in the human inner ear. Inner ear tissue from human adults, aborted human normal fetuses and fetuses with Turners syndrome were collected. Paraffin embedded sections of adult and fetal inner ears were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptor alpha containing cells were found in the adult human inner ear only in the spiral ganglion, and estrogen receptor beta in the stria vascularis solely. The human fetal inner ear tissue from both normal and Turner fetuses showed a very weak staining of estrogen receptor alpha in the spiral ganglion cells, but no specific labeling of the Köllikers organ of Corti at 13, 14 and 18 weeks of age. No staining of estrogen receptor beta was seen in the fetal inner ear.

Mapping of estrogen receptors α and β in the inner ear of mouse and rat

Abstract The sex hormone estrogen is classically known to influence growth, differentiation and function of peripheral tissues of both the female and male reproductive tract, mediated through the estrogen receptors alpha and beta. The influence of estrogens on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The aim of this study was to map eventual estrogen receptors in the inner ear in mouse and rat. Paraffin embedded sections of mouse and rat inner ear were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptors alpha and beta containing cells were found in the inner ear, showing a unique distribution pattern, both in the auditory pathways and in the water/ion regulating areas. The presence of estrogen receptors indicates that estrogens may have an effect on the inner ear and hearing functions.

Ear and hearing problems in 44 middle-aged women with Turner's syndrome

The present study has investigated ear and hearing problems in 44 women with Turners syndrome (median age 45.5 years). Social hearing problems were common after the age of 40 and 27% were fitted with hearing aids. Audiograms revealed a hearing loss > 20 dB hearing level (HL) in 91% leading to clinically significant hearing problems in 60%. A distinct dip in the 1.5 kHz frequency range, with a mean value of 46 dB was found in 30 women. The occurrence of the dip was correlated to the karyotype. All women with the karyotype 45,X and 45,X/46,X,i(Xq) demonstrated this dip while in the 45,X/46,XX group it was found in 31%. No dips were found among 45,X/46,XY and 45,X/46,XX/47,XXX women. With increasing age a progressive high frequency hearing loss was added to the dip leading to severe hearing problems earlier in the Turner women than age-matched controls. This might be due to a genetic defect leading to premature ageing of their hearing organ. These data emphasize the importance of providing early information to Turner girls of their predisposition to hearing impairment. Patient awareness of importance of audiological evaluations and the benefit of hearing aids should be stressed.

Otological problems in children with Turner's syndrome

Ear and hearing disorders are common problems among girls and women with Turners syndrome. During infancy and childhood the girls often suffer from repeated attacks of acute otitis media and later in life the women frequently complain of a rapid onset of social hearing problems due to sensorineural hearing impairment. A study of 56 girls aged 4-15 years with Turners syndrome was performed to investigate the prevalence of eardrum pathology and hearing impairment in young children and teenagers with Turners syndrome. A possible relation to karyotype was also investigated. A high prevalence (61%) of recurrent acute otitis media was found in the study group and 32% had been treated with ventilation tubes. Fifty-seven percent showed eardrum pathology, such as effusion, myringosclerosis, atrophic scars, retraction pockets and perforations. Auricular anomalies were noted in 23% of the cases, most commonly in the 45, X group. The audiometric analysis showed conductive hearing loss (air-bone gap > 10 dB HL) in 43% and the typical sensorineural dip in the middle frequencies was found in 58% of the girls, of whom the youngest was 6 years old. Four percent were using hearing aids. The data of this study further confirm that the dip is progressive over time and may be detectable as early as at the age of 6, giving a chance to predict a future hearing loss. The findings emphasize the importance of regular otological examinations and audiological evaluations of all girls with Turners syndrome early in life.

Outcome of the bone-anchored hearing aid procedure without skin thinning: a prospective clinical trial.

Objective: To evaluate the outcome of Bone-Anchored Hearing Aid surgery without skin thinning, a test group with direct implantation without such thinning was compared with a control group that underwent the traditional procedure. Study Design: This was a single-center, prospective clinical trial designed to evaluate a novel approach to Bone-Anchored Hearing Aid implantation. Eligible patients were enrolled consecutively in the test group or selected to be age-matched controls. Setting: University Hospital. Patients: Eighteen adult patients, suffering from hearing loss, suitable for implantable hearing aid. Methods: Single-step surgery was performed on 18 patients under local anesthesia. In 9 of these, a linear incision was made, a hole was punched through the skin above the bone-anchored implant, and a longer abutment (8.5-12 mm) was introduced, whereas the other 9 were subjected to the standard protocol, using a dermatome and skin thinning. All of the patients were followed for 12 months. Results: The test group exhibited good preservation of the tissue, no increasing skin reactions and no adverse events. The time required for this surgery was reduced, as was their healing time. These patients also experienced less numbness and pain in the surrounding area and had an improved cosmetic outcome. Main Outcome and Conclusion: This clinical trial indicates that introduction of the abutment to the osseointegrated screw directly through the skin, without skin thinning, could be beneficial. This approach had fewer negative effects than the conventional procedure during the 12- month follow-up period.

Turner's syndrome and hearing disorders in women aged 16-34.

Forty women with Turners syndrome aged 16-34 years were tested clinically and audiometrically according to their ear problems and hearing. A high incidence of middle-ear infections was demonstrated. A mid-frequency sensorineural hearing loss was frequently diagnosed and could be correlated to the karyotype. The dip showed a progression with age. Middle-ear problems were more common among women with a dip. An early high-frequency hearing loss could be noted in the present group among the older women. In some cases this had already led to social hearing problems and use of hearing aids. When comparing these women with a group of elderly Turner women the dip was not as deep, the maximum peak was seen in the 2 kHz region and social hearing problems and hearing aids were not as frequent. If no dip was found no major hearing problems could be detected or expected in future life. The data emphasize the importance of early audiological evaluation and information about predisposition to hearing impairment in Turners syndrome.

Hearing in women at menopause. Prevalence of hearing loss, audiometric configuration and relation to hormone replacement therapy

Conclusion. Hormone replacement therapy (HRT) may have a protective effect on hearing impairment in postmenopausal women. New guidelines for classification of audiometric configuration in age-related hearing loss are suggested. Objectives. To describe prevalence of hearing loss and audiometric configuration in a group of middle-aged women with respect to menopausal stage and HRT. Subjects and methods. A total of 143 women around menopause were sampled through the Swedish population register. The mean hearing threshold levels were compared according to menopausal status. The audiograms in the 57 women with hearing loss were classified according to audiometric configuration. Results. In all, 57 women (40%) had any kind of hearing loss; 42 had very minute hearing loss; 15 had a 4FA (average of thresholds at 0.5, 1, 2, and 4 kHz) of at least 20–39 dB HL in at least one ear. Two of these had a 4FA of 40–69 dB HL in at least one ear. The most common configurations were: gently sloping (47%), steeply sloping (14%), and high-frequency U-shaped (14%). The postmenopausal women who were not on HRT had poorer hearing mainly at 2 and 3 kHz, compared with pre- and perimenopausal women, and postmenopausal women on HRT.

Na,K-ATPase α- and β-isoforms in the developing cochlea of the mouse

Abstract Immunohistochemistry was used to investigate the presence of Na,K-ATPase α- and β-subunits isoforms (α1, (α2, α3 β1and β2) in the cochlea of the mouse at different ages between embryological day (E) 19 and postnatal day (P)+30. α1 was mainly found in the stria vascularis and in the spiral ligament; it increased steadily from p+4. These data correlates well with the morphological and electrophysiological maturation of the cochlea. α3 predominated in the spiral ganglia and the cochlear nerve. This finding is well in accordance with reports that α3 seems to be associated with the nervous system. The β-subunit was found mainly in those tissues where staining of the α-subunit also was seen. Both subunits were localized in tissue regions where fluid regulation is expected to play an important role. For some isoforms, the expression pattern of Na,K-ATPase during development in the mouse is different from that in the rat. The expression of Na,K-ATPase and that of glucocorticoid receptors during development in the inner ear of the mouse show a similar pattern, which may indicate that glucocorticoid receptors could be involved in regulating the expression of Na,K-ATPase.