Ales Hahn

Long-term prophylactic treatment of attacks of vertigo in Meniere's disease--comparison of a high with a low dosage of betahistine in an open trial

Conclusion. Despite the considerable limitations of an open, non-masked trial, particularly in Menières disease (MD), a higher dosage of betahistine-dihydrochloride and a long-term treatment seems to be more effective than a low dosage and short-term treatment. Objective. To evaluate the prophylactic effects of a low versus high dosage long-term treatment with betahistine-dihydrochloride on the number of attacks in MD. Patients and methods. We performed an open, non-masked trial, in which patients with MD received either a low dosage of betahistine-dihydrochloride (16 or 24 mg tid) or a higher dosage of 48 mg tid for at least 12 months. The outcome measure was the number of attacks per month during a 3-month period. Non-parametric tests and a random effects model were used for statistical analysis. Results. A total of 112 patients were included in the analysis: 50 received betahistine-dihydrochloride in a low dosage (16 mg tid, n=21, 24 mg, n=29) and 62 received 48 mg tid. Follow-up examination every 3 months showed that the number of attacks per month decreased in both groups over time. For instance, after 12 months the mean (median) number of attacks dropped from 7.6 (4.5) to 4.4 (2.0) (p<0.0001) in the low-dosage group, and from 8.8 (5.5) to 1.0 (0.0) (p<0.0001) in the high dosage group. The number of attacks after 12 months was significantly lower in the high dosage group than in the low dosage group (p12M=0.0002). The treatment was well tolerated in both groups.

Comparison of 10-mg doses of 4-aminopyridine and 3,4-diaminopyridine for the treatment of downbeat nystagmus.

Objective Animal experiments have demonstrated that aminopyridines increase Purkinje cell excitability, and in clinical studies, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) improved downbeat nystagmus. In this double-blind, prospective, crossover study, the effects of equivalent doses of 4-AP and 3,4-DAP on the slow-phase velocity (SPV) of downbeat nystagmus were compared. Methods Eight patients with downbeat nystagmus due to different etiologies (cerebellar degeneration [n = 1], bilateral vestibulopathy [n = 1], bilateral vestibulopathy and cerebellar degeneration [n = 1], Arnold-Chiari I malformation and cerebellar ataxia [n = 1], cryptogenic cerebellar ataxia [n = 4]) were included. They were randomly assigned to receiving a single capsule of 10 mg of 3,4-DAP or 4-AP followed by 6 days with no medication. One week later, the treatment was switched, that is, 1 single capsule (10 mg) of the other agent. Recordings with 3-dimensional video-oculography were performed before and 45 and 90 minutes after drug administration. Results Both medications had a significant effect throughout time (pre vs post 45 vs post 90) (F(2,14) = 8.876; P < 0.01). Following the administration of 3,4-DAP, mean slow velocity decreased from −5.68°/s (pre) to −3.29°/s (post 45) to −2.96°/s (post 90) (pre vs post 45/post 90 P < 0.01). In 4-AP, the mean SPV decreased from −6.04°/s (pre) to −1.58°/s (post 45) to −1.21°/s (post 90) (pre vs post 45/post 90 P < 0.00001). Both after 45 and after 90, the mean SPVs were significantly lower for 4-AP than for 3,4-DAP (P < 0.05). None of the patients reported serious side effects. Conclusion Based on these results, 10-mg doses of 4-AP lead to a more pronounced decrease of the SPV of downbeat nystagmus than do equivalent doses of 3,4-DAP.

Quality of life in patients with chronic rhinosinusitis: a validation of the Czech version of SNOT-22 questionnaire

Dear Sir, Quality of life (QoL) is defined as the difference between expectations and experience [1]. A part of the overall QoL is health-related quality of life (HRQoL), which is influenced by the health of patients and can be changed through treatment. Since the 1990s, there have been increased efforts to evaluate QoL of patients in all medical fields. Tools used to evaluate QoL are either generic health instruments for assessing general conditions or diseasespecific questionnaires focused on symptoms of a disease. Chronic rhinosinusitis (CRS) is a disease characterized by a high prevalence and significant reduction in QoL. Although today there are many diagnostic methods for evaluating sinonasal disease, it cannot be said that the results clearly correlate with QoL, as it is perceived by patients [2]. Until now, there has been no validated Czech version of the questionnaire for evaluating QoL in patients with CRS. We used sinonasal outcome test (SNOT-22) questionnaire [3], which is based on the SNOT-20 questionnaire [4]. The difference between the two assessment tools is the addition of two questions relating to the evaluation of (i) nasal obstruction and (ii) smell and taste, which can be regarded as important indicators of QoL. SNOT-22 is recommended as one of the best tools for assessing QoL in patients with CRS [5]. A group of 52 patients (31 men, 21 women; mean age 50.5 years) with CRS, either with or without nasal polyps (NP) who were scheduled to undergo endoscopic sinus surgery (ESS) were enrolled in the study. All the patients filled a SNOT-22 questionnaire (Czech version) preoperatively (T0), 3 months (T1), and 6 months (T2) after surgery. There were two control groups: group 1 consisted of 50 patients admitted to the ENT clinic with non-sinonasal disease (24 men, 26 women; mean age 44.9 years); group 2 consisted of 50 healthy students of the Faculty of Medicine (22 men, 28 women; mean age 24.1 years). Both control groups also completed the SNOT-22 questionnaire. The study was approved by local Ethics Committee and each patient signed an informed consent. Properties of the questionnaire were tested by determining reliability, validity, and sensitivity. Reliability (internal consistency) was tested using Cronbach’s a and test–retest reliability determination. For the latter (determination of the stability of the questionnaire over time), 10 patients completed the questionnaire for a second time—3 weeks after completing the questionnaire in time T1. Discriminate validity (the ability of the questionnaire to distinguish between those who suffer from disease and other populations) was tested by comparing the patients with the two control groups. The groups were then compared with analysis of variance (ANOVA) and Tukey– Kramer HSD test. Sensitivity (responsiveness) was assessed using the standardized mean response (SRM) coefficient. Results of Cronbach’s a were 0.852, 0.904, and 0.877 in T0, T1, and T2, respectively. Values approaching 1.0 indicate excellent internal consistency. Also, the value of test–retest reliability, expressed as Pearson’s coefficient, of 0.86 indicates a high correlation between the two questionnaires completed by the same patient 3 weeks apart. ANOVA and the Tukey–Kramer HSD test showed significant differences between patients with CRS and the two control groups (Table 1). P. Schalek (&) L. Otruba A. Hahn Department of ENT, Third Faculty of Medicine, Charles University, Srobarova 50, 100 34 Praha 10, Czech republic e-mail: schalekp@hotmail.com

Postural control in subjects with visual impairment.

Purpose TO investigate the effect of long-term, not experimentally induced visual impairment on balance, and to clarify which means are used to compensate for this sensory deficit. Methods Posturography was examined in 50 visually impaired subjects (11 with congenital blindness and 39 with acquired visual impairment) and 50 healthy controls. Examination was performed in 4 testing conditions: while standing on firm surface or foam pads (which decreases the somatosensory input) and with open or closed eyes (manipulating visual input). Results Subjects with acquired visual impairment were significantly less stable than controls when tested with open eyes, especially when standing on foam pads, but equal to controls when eyes were closed. Congenitally blind subjects performed equally to normal controls in all test conditions when tested with eyes open, and performed significantly better than controls with eyes closed. In comparison to subjects with acquired visual impairment, the congenitally blind were significantly more stable in all test conditions. Fourier analysis revealed that the visually impaired subjects showed decreased intensity values within the lowest frequency range of 0.1 Hz and below, a range believed to be sensitive to the function of the visual system. Conclusions We have found that vision impairment influenced postural control, especially if acquired and not congenital. The somatosensory and vestibular systems serve as compensatory mechanisms, which is utilized most effectively by the congenitally blind.

Combined Laser- EGb 761 Tinnitus Therapy

The treatment of patients with chronic tinnitus is very problematic and therefore otologists are trying to discover more suitable courses of therapy. In this study we wanted to evaluate the outcome of using a combination of EGb 761 and soft laser therapy. We examined 120 patients with an average duration of tinnitus of 10 years. The patients underwent pure-tone audiometry, speech audiometry and objective audiometry tests. The intensity and frequency of tinnitus was also determined. EGb 761 was administered 3 weeks before starting soft laser therapy. Patients underwent 10 sessions of laser therapy, each lasting for 10 min. An improvement in tinnitus was audiometrically confirmed in 50.8% of patients: 10 dB in 18; 20 dB in 22; 30 dB in 10; 40 dB in 6; and 50 dB in 5.The treatment of patients with chronic tinnitus is very problematic and therefore otologists are trying to discover more suitable courses of therapy. In this study we wanted to evaluate the outcome of using a combination of EGb 761 and soft laser therapy. We examined 120 patients with an average duration of tinnitus of 10 years. The patients underwent pure-tone audiometry, speech audiometry and objective audiometry tests. The intensity and frequency of tinnitus was also determined. EGb 761 was administered 3 weeks before starting soft laser therapy. Patients underwent 10 sessions of laser therapy, each lasting for 10 min. An improvement in tinnitus was audiometrically confirmed in 50.8% of patients: 10 dB in 18; 20 dB in 22; 30 dB in 10; 40 dB in 6; and 50 dB in 5.

A fixed combination of cinnarizine/dimenhydrinate for the treatment of patients with acute vertigo due to vestibular disorders : a randomized, reference-controlled clinical study.

AbstractBackground and objective: Vestibular dysfunction commonly leads to — often severe — vertigo symptoms. The objective of this study was to compare the antivertiginous efficacy and tolerability of a fixed combination of cinnarizine/dimenhydrinate with those of betahistine in patients with acute vertigo due to vestibular disorders. Methods: Sixty-six patients experiencing acute vertigo attacks participated in this prospective, double-blind, three-centre, comparative study. Patients who assessed at least one vertigo symptom as being of medium intensity (≥2) on a 5-point visual analogue scale (VAS; from 0 = no symptoms to 4 = very severe symptoms) were randomly allocated to treatment with the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg three times daily or betahistine 12 mg three times daily for 4 weeks. The primary efficacy endpoint was change in mean vertigo score, as determined by patients’ assessments of 12 individual vertigo symptoms on the 5-point VAS after 4 weeks of treatment. Results: Treatment with the fixed combination led to significantly greater improvements in mean vertigo scores than the reference therapy betahistine after 4 weeks of therapy (p = 0.013). The differences were clinically relevant, based on the Mann-Whitney estimator. Furthermore, the incidence of vertigo-associated vegetative symptoms was significantly reduced after 1 (p = 0.004) and 4 weeks (p = 0.023) in the fixed-combination group relative to the betahistine group. Three patients, all of them in the betahistine group, reported adverse events, none of which was considered serious. Almost all patients (n = 62) rated the tolerabilities of both medications as very good or good. Conclusion: The fixed combination of cinnarizine/dimenhydrinate was shown to be an effective and very well tolerated treatment option for patients with acute vertigo due to vestibular disorders. The combination proved to be significantly more efficient in reducing vertigo and associated vegetative symptoms than betahistine in such patients.

Comparison of Cinnarizine/Dimenhydrinate Fixed Combination with the Respective Monotherapies for Vertigo of Various Origins

AbstractBackground and Objective: Vertigo may arise from dysfunction in the peripheral and/or the central vestibular system. Simultaneous activity of a medication at both sites will serve to improve the efficacy of antivertigo treatment. The aim of this study was to compare the efficacy and tolerability of a fixed combination of the peripherally acting cinnarizine (20 mg) plus the centrally acting dimenhydrinate (40 mg) with those of equally dosed monotherapies in the treatment of vertigo of various origins. Methods: This prospective, randomized, double-blind, active-controlled, multicentre study included patients who assessed at least one vertigo symptom as being of at least medium intensity (≥2) on a 5-point visual analogue scale (VAS; ranging from 0 = not present to 4 = very strong) and who had pathological vestibulospinal movement patterns and/or nystagmus reactions. Patients were randomly assigned to receive either cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination, cinnarizine 20 mg as monotherapy or dimenhydrinate 40 mg as monotherapy, each three times daily for 4 weeks. Patients were examined at baseline (t0), and after 1 week (t1w) and 4 weeks (t4w) of treatment. The primary efficacy endpoint was the decrease in mean vertigo score (MVS) at t4w, which was calculated by averaging the total score for 12 individual vertigo symptoms, each assessed using the 5-point VAS. Results: The study included 182 patients, of whom 177 were evaluable for efficacy. The mean ± SD reduction in MVS after 4 weeks of treatment with the fixed combination (−1.44 ± 0.56) was significantly greater than the reductions with each of the active treatments alone (cinnarizine −1.04 ± 0.53; dimenhydrinate −1.06 ± 0.56; p = 0.0001, both comparisons). Cinnarizine 20mg/dimenhydrinate 40 mg as a fixed combination was associated with a significantly higher responder rate (78% of patients with MVS ≤0.5 at t4w) than the monotherapies. The odds ratios for MVS ≤0.5 at t4w in the cinnarizine or dimenhydrinate groups versus the fixed combination group were 0.345 and 0.214, respectively. The fixed combination reduced concomitant vegetative symptoms significantly more effectively than cinnarizine at both t1w (p < 0.05) and t4w (p<0.01). Nine patients reported 15 adverse events (AEs) [three AEs for the fixed combination, six AEs each for cinnarizine and dimenhydrinate]. At t4w the tolerability of the treatments was rated as very good or good by almost all patients in all groups (fixed combination and dimenhydrinate 96.6% each; cinnarizine 98.3%). Conclusion: The fixed combination of cinnarizine 20 mg/dimenhydrinate 40 mg was an effective and well tolerated treatment for patients with vestibular vertigo of central and/or peripheral origin. The efficacy of the fixed combination exceeded that of each of the equally dosed active substances given as monotherapy, leading to higher responder rates, and showed a very good and comparable tolerability with a similar or even smaller rate of adverse events than the active substances given alone.

Mastoiditis complicated with Gradenigo syndrome and a hypertrophic pachymeningitis with consequent communicating hydrocephalus

We present the clinical, radiological and pathological features of a case of a cranial hypertrophic pachymeningitis that developed in the course of mastoiditis and petrous apex inflammation and responded to immunosuppressive therapy only. Documented by the development of clinical findings, magnetic resonance imaging, cerebrospinal fluid changes, histopathology findings, by otosurgical intervention and finally by the insertion of a ventriculo-peritoneal shunt, the case illustrates a gradual development of pachymeningitis with consequent hydrocephalus and intracranial hypertension. We consider this disease development an example of immune-induced proliferative fibrotic changes in meninges.

Cogan's syndrome: a case report.

Cogans syndrome is a rare autoimmune disorder connecting ophthalmologic and audiovestibular signs. A case of a young patient is reported, describing the evolution of her illness, and diagnostic and therapeutic measures performed. Response to treatment, including glucocorticoid therapy and hyperbaric oxygenation, is discussed. A synoptic review of knowledge of this rare disorder is incorporated.

Visuo-vestibular biofeedback in patients with peripheral vestibular disorders.

It is well known that diseases of the vestibular system can be compensated by increased spontaneous activity of other systems engaged in maintaining equilibrium, i.e. proprioceptive and visual systems. A complex approach using multisensory stimulation is the optimal way to achieve vestibular compensation. The aim of our study was to determine the effect of vestibular rehabilitation therapy as measured by posturography in a group of 72 patients suffering from vestibular disorders: Ménières disease ( n = 31), neuritis vestibularis ( n = 21) and vertebrobasilar insufficiency ( n = 20). Patients underwent the following examinations: electronystagmography; caloric, rotatory and optokinetic tests; computed posturography; craniocorpography; pure-tone audiometry; speech audiometry; and tinnitometry (tinnitus loudness, pitch). The instability in patients with Ménières disease decreased 3 weeks after starting the therapy; nevertheless, the decrease in area (the surface formed by the movement of the patients equilibrium point during a defined time) was transitory because of the increase in area values obtained between the 3rd and 6th weeks when measured with closed eyes. In the vestibular neuronitis patients, the measured values of area and the velocity of the patients movement decreased continuously. The values measured in the patients suffering from vertebrobasilar insufficiency decreased continuously, the absolute values remaining pathological.It is well known that diseases of the vestibular system can be compensated by increased spontaneous activity of other systems engaged in maintaining equilibrium, i.e. proprioceptive and visual systems. A complex approach using multisensory stimulation is the optimal way to achieve vestibular compensation. The aim of our study was to determine the effect of vestibular rehabilitation therapy as measured by posturography in a group of 72 patients suffering from vestibular disorders: Ménières disease (n = 31), neuritis vestibularis (n = 21) and vertebrobasilar insufficiency (n = 20). Patients underwent the following examinations: electronystagmography; caloric, rotatory and optokinetic tests; computed posturography; craniocorpography; pure-tone audiometry; speech audiometry; and tinnitometry (tinnitus loudness, pitch). The instability in patients with Ménières disease decreased 3 weeks after starting the therapy; nevertheless, the decrease in area (the surface formed by the movement of the patients equilibrium point during a defined time) was transitory because of the increase in area values obtained between the 3rd and 6th weeks when measured with closed eyes. In the vestibular neuronitis patients, the measured values of area and the velocity of the patients movement decreased continuously. The values measured in the patients suffering from vertebrobasilar insufficiency decreased continuously, the absolute values remaining pathological.