Betahistine in Ménière's Disease or Syndrome: A Systematic Review.

BACKGROUND: Ménière's disease is characterized by recurrent episodes of vertigo, hearing loss, and tinnitus, often with a feeling of fullness in the ear. Although betahistine is thought to be specifically effective for Ménière's disease, no evidence for a benefit from the use of betahistine exists, despite its widespread use. Reassessment of the effect of betahistine for Ménière's disease is now warranted. SEARCH METHODS: We searched for randomized controlled trials (RCTs) in the Central Register of Controlled Trials (CENTRAL), Ovid Medline, Ovid Embase, CINAHL, Web of Science, Clinicaltrials.gov, ICTRP, and additional sources for published and unpublished trials, in which betahistine was compared to placebo. DATA COLLECTION AND ANALYSIS: Our outcomes involved vertigo, significant adverse effect (upper gastrointestinal discomfort), hearing loss, tinnitus, aural fullness, other adverse effects, and disease-specific health-related quality of life. We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included 10 studies: 5 studies used a crossover design and the remaining 5 were parallel-group RCTs. One study with a low risk of bias found no significant difference between the betahistine groups and placebo with respect to vertigo after a long-term follow-up period. No significant difference in the incidence of upper gastrointestinal discomfort was found in 2 studies (low-certainty evidence). No differences in hearing loss, tinnitus, or well-being and disease-specific health-related quality of life were found (low- to very low-certainty of evidence). Data on aural fullness could not be extracted. No significant difference between the betahistine and the placebo groups (low-certainty evidence) could be demonstrated in the other adverse effect outcome with respect to dull headache. The pooled risk ratio for other adverse effect in the long term demonstrated a lower risk in favor of placebo over betahistine. CONCLUSIONS: High-quality studies evaluating the effect of betahistine on patients with Ménière's disease are lacking. However, one study with low risk of bias found no evidence of a difference in the effect of betahistine on the primary outcome, vertigo, in patients with Ménière's disease when compared to placebo. The main focus of future research should be on the use of comparable outcome measures by means of patient-reported outcome measures.

Rat Model of Ménière's Attack: Intratympanic Injection of Potassium Chloride Produces Direction-Changing Spontaneous Nystagmus and Hearing Fluctuations.

The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks.

Response of the inner ear to lipopolysaccharide introduced directly into scala media.

In an attempt to develop an animal model of immune mediated Meniere's disease, we have injected lipopolysaccharide (LPS) directly into scala media of guinea pigs and monitored functional and morphological changes over a period of 6 weeks. Depending on the concentration of LPS, changes ranged from moderate-to-severe hearing loss and endolymphatic hydrops with minimal cellular infiltrate or fibrosis, to dense cellular infiltration that filled the scalae. Interestingly, higher concentrations of LPS not only induced severe cellular infiltration, hydrops, and hearing loss, but also a substantial enlargement of the endolymphatic duct and sac. Moreover, LPS injections into perilymph failed to induce hydrops, yet still resulted in cellular infiltration and fibrosis in the cochlea. This suggests that chronic hydrops resulting from an immune challenge of the cochlea may not be due to blockage of the endolymphatic duct and sac, restricting fluid absorption. Furthermore, injecting antigen into endolymph may produce chronic immune-mediated hydrops, and provide a more promising animal model of Meniere's, although animals did not display signs of vestibular dysfunction, and the hearing loss was relatively severe.

Espasmo del reflejo de cerca. Tratamiento con toxina botulínica / Spasm of the near reflex. Treatment with botulinum toxin

CASO CLÍNICO: Mujer de 38 años con diplopía y endotropía. Limitación total de la abducción en AO al explorar las versiones, que se normalizan al explorar el reflejo de los ojos de muñeca. Es diagnosticada de espasmo del reflejo de cerca (ERC) y tratada con inyecciones repetidas de Botox en rectos medios, resolviéndose temporalmente el espasmo. DISCUSIÓN: El ERC se caracteriza por miosis, seudomiopía y convergencia que producen diplopía, visión borrosa, cefalea y endotropía variable, progresiva e intermitente. Se puede confundir con una paresia bilateral del vi nervio. El tratamiento con inyecciones repetidas de bótox puede ser efectivo en algunos casos

CLINICAL CASE: A 38-year old female with diplopia and esotropia, with limitation of ocular abduction in both eyes, with full abduction after doll's head rotation also being observed. She was diagnosed with spasm of the near reflex. Treatment with injections of botulinum toxin in both medial rectus has temporally resolved the convergence spasm. DISCUSSION: Near reflex spasm is characterized as miosis, pseudomyopia, and convergent strabismus that lead to diplopia, blurred vision, headache, and variable, progressive, and intermittent esotropia. As the spasm worsens there will be limited ocular versions and ductions simulating a sixth nerve palsy. Botulinum toxin may be effective in some cases

Long-term administration of vasopressin can cause Ménière's disease in mice.

CONCLUSION: A new murine model of Ménière's disease has been developed, based on long-term administration of vasopressin. Induction of vestibular dysfunction in the present animal model can cause additional stress, by reducing inner ear blood flow. Latanoprost, a selective agonist for the FP prostanoid receptor, may become a new remedy for Ménière's disease. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, with a closer resemblance to the pathophysiological process in Ménière's disease. METHODS: Adult CBA/J or ICR mice were treated by subcutaneous injection of vasopressin for 5 days up to 8 weeks. Morphological analyses were performed of the cochlea, vestibular end organs and endolymphatic sac. The effect of latanoprost on the development of endolymphatic hydrops was also examined. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops, increasing in severity as the vasopressin treatment was prolonged. Animals treated with vasopressin for 8 weeks showed severe endolymphatic hydrops with partial loss of outer hair cells and spiral ganglion cells. These animals also had a reversible vestibular dysfunction following intratympanic injection of epinephrine. Latanoprost inhibited the development of endolymphatic hydrops caused by vasopressin.

Morphological and functional changes in a new animal model of Ménière's disease.

The purpose of this study was to clarify the underlying mechanism of vertiginous attacks in Ménière's disease (MD) while obtaining insight into water homeostasis in the inner ear using a new animal model. We conducted both histopathological and functional assessment of the vestibular system in the guinea-pig. In the first experiment, all animals were maintained 1 or 4 weeks after electrocauterization of the endolymphatic sac of the left ear and were given either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal bones from both ears were harvested and the extent of endolymphatic hydrops was quantitatively assessed. In the second experiment, either 1 or 4 weeks after surgery, animals were assessed for balance disorders and nystagmus after the administration of saline or desmopressin. In the first experiment, the proportion of endolymphatic space in the cochlea and the saccule was significantly greater in ears that survived for 4 weeks after surgery and were given desmopressin compared with other groups. In the second experiment, all animals that underwent surgery and were given desmopressin showed spontaneous nystagmus and balance disorder, whereas all animals that had surgery but without desmopressin administration were asymptomatic. Our animal model induced severe endolymphatic hydrops in the cochlea and the saccule, and showed episodes of balance disorder along with spontaneous nystagmus. These findings suggest that administration of desmopressin can exacerbate endolymphatic hydrops because of acute V2 (vasopressin type 2 receptor)-mediated effects, and, when combined with endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that are similar to the vertiginous attacks in patients with MD.

[Somatoform disorders in neurology visits: history and circumstances: retrospective study of 124 cases]. / Symptômes somatomorphes en consultation de neurologie : expression, soubassement et occasion : étude rétrospective de 124 situations.

We report 124 cases of somatoform disorders, considering psychogenic disorders at the same level as neurological disorders. We noted any psychic, somatic or social condition (history taking) and facilitating circumstances. The patients were aged 16 to 84 years old; 71.7% were women. We observed pain (35.4%), psychogenic headache (25%), sensorimotor loss (27.4%), gait and psychogenic tremor (17.7%), cognitive disorders (11.8%), ocular symptoms (7.2%), and urogenital symptoms (2.4%). Delay to consultation ranged from a few days to 20 years. Psychiatric comorbidity was noted in 30.6% of the cases. In 55.6% of 124 cases, we observed a psychological background. It was a childhood trauma in 15.3% of these cases. In one-third of the 124 situations, we noted an underlying somatic or social condition. Facilitation conditions were frequently mixed. Somatic and/or psychological conditions were noted in one-third of the 124 cases and social conditions in half of them. The neurologist is faced with the challenge of naming the symptom (most often labelled a functional disorder) and of making the decision to stop or limit investigations. Visits by patients with psychogenic disorders make up a significant percentage of neurology speciality appointments. The neurologist should not limit the consultation to differentiating "real" symptoms from psychogenic somatoform disorders, but should also propose a straightforward compassionate approach for effective therapeutic care. By carefully listening to the patient's dialogue, the neurologist can help the patient give meaning to the symptoms, and progress towards improved well-being.

Time course changes of vasopressin-induced enlargement of the rat intrastrial space and the effects of a vasopressin type 2 antagonist.

CONCLUSION: The intrastrial space was enlarged remarkably at 20 min after vasopressin (VP) injection, and this enlargement of the intrastrial space was reduced by administration of OPC-31260 before VP injection. These results suggest that VP increases the influx of water from the perlymph to the basal cells via aquaporin (AQP) 2 and causes the formation of endolymphatic hydrops. OBJECTIVES: To investigate a time course of changes of the stria vascularis after VP injection and the influence of OPC-31260 on experimentally induced enlargement of the intrastrial space caused by VP injection. MATERIALS AND METHODS: In the time course study, Wistar rats were injected with 50 microg/kg of VP subcutaneously. The stria vascularis specimens were harvested at 10, 20, 30, and 60 min after VP injection. For OPC-31260 administration, animals were administered 100 mg/kg of OPC-31260 orally 1 h before receiving 50 microg/kg of VP subcutaneously. The specimens were harvested 20 min after VP injection. These specimens were observed using transmission electron microscopy. RESULTS: In the time course study, the incidence of intrastrial space enlargement was 50%, 100%, 25%, and 0% for 10, 20, 30, and 60 min, respectively. In the study with OPC-31260 administration, the stria vascularis showed no morphological changes.

Effect of inner ear blood flow changes in Ménière's model mice.

CONCLUSIONS: The endolymphatic sac (ES) is important for inner ear fluid homeostasis. A dysfunctional ES can cause vertigo attacks following additional stress such as a sudden change in endolymphatic volume and/or pressure, or restricted inner ear blood flow. OBJECTIVE: The purpose of this study was to elucidate the mechanism of vertigo attacks in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were given an intratympanic injection of lipopolysaccharide and an intraperitoneal injection of aldosterone. These 'model' animals had epinephrine or sodium nitroprusside (SNP) instilled into the middle ear cavity. Cochleae, vestibules, and endolymphatic sacs were studied morphologically by light microscopy. RESULTS: The injection of epinephrine into the model animals reduced the endolymphatic hydrops in the cochlea, but also produced mild hydrops in the vestibule, which was never observed in untreated (control) animals. The ES did not react to epinephrine in the normal way. Injection of SNP did not cause any changes.

Vestibulotoxicity as a consequence of systemically administered tobramycin in cystic fibrosis patients.

CONCLUSION: The reported prevalence of vestibulotoxicity (30.4%) in cystic fibrosis (CF) patients supports vestibulotoxicity screening in CF patients during or after tobramycin exposure. Prospective longitudinal investigation is required for a more specific evidence-based proposal. OBJECTIVE: To investigate the prevalence of tobramycin-induced vestibulotoxicity in CF patients, as it had not been investigated before. PATIENTS AND METHODS: In this observational cohort study, 23 CF patient volunteers from the Haga Teaching Hospital Adult CF centre who had been exposed to at least one treatment with systemically administered tobramycin were included. Subjective feelings of dizziness were measured using validated questionnaires and vestibular symptoms were assessed by physical examination. Electronystagmography (ENG) with caloric irrigation was used as the gold standard. RESULTS: Peripheral vestibular loss was found in seven patients (7/23 = 30.4%). Central vestibular loss was found in one patient. Analysis of the 19 completed questionnaires showed that 12 patients (12/19 = 63.2%) did not experience dizziness and 3 patients (3/19 = 15/8%) experienced specific vestibular symptoms. The results of the questionnaire could not predict the results of ENG with caloric irrigation. Physical examination showed no abnormalities in any patients. No age- or dose-related predictive factors were found.

Comparisons of cochleotoxicity among three gentamicin compounds following intratympanic application.

CONCLUSION: Among the three main gentamicin (GM) compounds following intratympanic application, the cochleotoxicity of C2 was the most severe, whereas that of C1a was the weakest. Understanding of the different cochleotoxicity characteristics of each compound may be of use in future custom-made intratympanic therapy for Ménière's disease. OBJECTIVE: To investigate differences in cochleotoxicity among three major GM compounds following intratympanic application. MATERIALS AND METHODS: Three GM compounds (C1, C2, and C1a) were isolated. Sprague-Dawley rats were treated every 2 days for 2 weeks with intratympanic application of saline, GM complex, C1, C2, and C1a. The cochleotoxicity of each compound was assessed by measuring auditory brainstem response (ABR) and through morphological analyses using scanning electron microscopy. RESULTS: The ABR threshold of the C2 group was found to be more impaired than those of the other groups. The C1a group showed the mildest elevation of the ABR thresholds. Morphological analyses revealed that the proportion of remaining outer hair cells (OHCs) was the lowest in animals treated with C2. Morphologically, the C1 and C1a groups showed the least damage to OHCs.

A new animal model for Ménière's disease.

CONCLUSION: A new murine model for the study of Ménière's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine.

[Ototoxicity of aminoglycoside antibiotics]. / Ototoxizität von Aminoglykosidantibiotika.

In gram-negative infections aminoglycosides still remain to present a first-line antibiotic. Their use is limited by the high risk for side effects and especially nephrotoxicity and ototoxicity. The more recently developed members of this group, although purporting to be less ototoxic, are also capable of producing inner ear damage in sufficiently high doses. This paper reviews the morphological, histochemical, and electrophysiological evidence concerning the mode of action of aminoglycosides on the auditory and vestibular systems and discusses the available methods for the detection of possible clinical ototoxicity. With recent advances in aminoglycoside monitoring techniques, the risk of toxicity has been greatly reduced. Guidelines are proposed about the prevention of ototoxicity and the management of patients with established auditory or vestibular dysfunction.

Acute cochleovestibular toxicity due to topical application of potassium iodide.

We present a case report of a patient who suffered from an acute cochleovestibular deficit after topical application of potassium iodide solution into the left ear. Although the vestibular symptoms progressively disappeared, severe sensorineural hearing loss persisted after treatment with hyperbaric oxygen therapy and intravenous administration of corticosteroids and vasodilating agents. The mechanisms of ototoxicity after topical application of solutions are discussed with emphasis on the particular features of the present case: a patulous Eustachian tube syndrome and the presence of a tympanostomy tube in the left ear.

[Bilateral malfunction of peripheral vestibular organs. Observations of 20 cases of Dandy syndrome]. / Beidseitiger Funktionsverlust der peripheren Gleichgewichtsorgane. Beobachtungen zu 20 Fällen von Dandy-Syndrom.

BACKGROUND: Dandy's Syndrome initially provokes dizziness and vertigo. Later on patients suffer from motion unsteadiness especially in dark surroundings and from oscillopsies. Gentamicin is ototoxic mostly for the vestibular part of the inner ear, and it is nephrotoxic. It may cause transitory renal dysfunction. Chronic or acute renal insufficiencies inhibit gentamicin clearance. PATIENTS: Among 20 cases we found 15 who had previously been treated with aminoglycosides (13 with gentamicin and two with streptomycin). Ten of our patients showed symptoms of preexistant chronic nephrosis or of transitory renal insufficiency caused by gentamicin therapy. In all 13 cases, peripheral vestibular function was destroyed or severely damaged by antibiotic. The same patients had no hearing loss. CONCLUSIONS: The different reactions of the cochlear and the vestibular end organs support the theoretical basis for transtympanic gentamicin treatment of Menière's disease.--Other reasons for Dandy's Syndrome were bilateral Menière's disease, skull fractures, and bilateral vestibular disorders.

Carbamazepine-induced sensorineural hearing loss.

Carbamazepine is a commonly prescribed anticonvulsant medication that affects various levels of the nervous system. We report a case of temporary sensorineural hearing loss in a patient after overdosing with 36 g of carbamazepine. Six days after the overdose, the patient complained of bilateral hearing loss and tinnitus. Audiograms revealed a 30- to 40-dB sensorineural hearing loss bilaterally. Another audiogram 2 weeks later showed a complete recovery in both ears accompanied by a clinical resolution in audiovestibular symptoms. Carbamazepine is used to treat partial and generalized seizures, trigeminal neuralgia, and bipolar illness. Adverse effects are not common but most frequently include dizziness, drowziness, nausea, and skin rashes; rare complications are agranulocytosis, bradycardia, and heart block. Documented hearing loss as a side effect of carbamazepine has not been reported, to our knowledge.