Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

Fixed combination of cinnarizine and dimenhydrinate in the prophylactic therapy of vestibular migraine: an observational study.

Vestibular migraine (VM) is one of the most frequent causes of episodic vertigo, with a lifetime prevalence of 0.98%. Prophylactic therapy includes calcium channel blockers, beta-blockers, antiepileptic drugs and antidepressants. We studied the association of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevertan) in a group of 22 patients affected by definite VM. Proposed therapy included one tablet twice a day for 1 month, which was repeated three times with 1 month of interval between drug intake; results were compared with those of a control group of 11 VM patients who asked to observe only lifestyle measures for migraine. The main outcome was the number of vertigo and headache crises in the 6 months before therapy and in the 6 months of follow-up. Subjects performing Arlevertan presented during the 6 months of therapy a decrease of vertigo attacks from 5.3 to 2.1 and of headaches from 4.3 to 1.7 (p < 0.0001); 68% of these subjects reported a decrease of at least 50% of vertigo attacks, while 63% of headaches. Conversely, vertigo attacks decreased from 3.5 to 2.2 and headaches from 2.6 to 2 in patients observing only lifestyle; 18% of these subjects reported a decrease of at least 50% of vertigo crises and 27% of headaches. Our data do not differ from those of previous works assessing efficacy of different prophylactic therapies for VM and reporting consistent reduction of vertigo spells in a rate of patients ranging from 60 and 80%.

Familial clustering and genetic heterogeneity in Meniere's disease.

The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited 1375 patients with definite MD according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs ) and offspring (λo ) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16-48 and 4-12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical.

Transmeatal low-level laser therapy for chronic tinnitus with cochlear dysfunction.

OBJECTIVES: To establish the efficacy of low-level laser therapy for tinnitus. METHODS: We performed a prospective, randomized double-blind study on 60 outpatients with tinnitus presenting sensorineural hearing loss in the affected ear. They were randomly divided into two groups, the first performing active laser therapy 20 min a day for 3 months with a 650-nm, 5-mW soft laser (group L), the second using a dummy device which duplicated all aspects of active laser therapy except for the activation of the laser beam (group C). One subject in both groups dropped out due to an increase in tinnitus loudness. Two more patients in each group ceased to comply with the protocol due to familiar problems. RESULTS: The Tinnitus Handicap Inventory (THI) was considered the main outcome measure; no statistical difference was detected between the 2 groups in the THI total score (p = 0.97), and its functional (p = 0.89), emotional (p = 0.89) and catastrophic (p = 0.89) subscales. Moreover, a visual analog scale for self-perceived loudness of the tinnitus showed no difference between the groups (p = 0.69). Regarding psychoacoustic parameters, the minimum masking level showed no difference (p = 0.42), while loudness expressed in sensation level exhibited lower values in group L (p = 0.0127). Group L subjects also presented a decreased rate of hyperacusis (p = 0.02). No changes were detected in the audiometric threshold in both groups. CONCLUSIONS: Soft laser therapy demonstrated no efficacy as a therapeutic measure for tinnitus.

Simultaneous pleomorphic adenoma of the parapharyngeal space and contralateral submandibular gland. Case report.

Herein the case is reported of a synchronous parapharyngeal space pleomorphic adenoma arising from the pharyngeal prolongation of the parotid gland and the contralateral submandibular gland, diagnosed in a young Caucasian female. Case reports and recent literature are presented. Upon physical examination, asymmetry of the lower part of the right side of the face with overlying intact skin, and a submucosal firm swelling, filling the ipsilateral side of the oropharyngeal wall, involving the right tonsillar bed which was medially displaced was immediately recognizable. The patient did not complain of dysphagia. Palpating the left submandibular region, a painless, mobile, rounded mass, 10 mm in diameter, apparently located in the submandibular gland, was detected. Magnetic resonance imaging showed that both lesions were well-defined and encapsulated. The surgical approach is discussed. Cytological diagnosis was that of a typical pleomorphic adenoma. To the best of our knowledge this is the second case report in the English literature of a concomitant pleomorphic adenoma located both in the parapharyngeal space and the submandibular gland.

Vestibular testing in patients with panic disorder and chronic dizziness.

In order to investigate the relationship between chronic dizziness and vestibular function in patients with panic disorder, in the present study neurotologic findings in 15 patients with panic disorder and chronic dizziness were compared with those in 15 patients with chronic dizziness, without panic disorder. All underwent neurotologic screening for spontaneous, positional and positioning nystagmus with head-shaking and head-thrust tests, an audiometric examination and electronystagmography with bithermal stimulation according to Freyss. A significantly higher number of patients with panic disorder and chronic dizziness showed pathological neurotologic findings in comparison to subjects with chronic dizziness only (9 and 2 patients, respectively; p < 0.05). Most patients with panic disorder showed signs of peripheral vestibular disorders. These results suggest that the complaint of dizziness in patients with panic disorder may be linked to a malfunction of the vestibular system and vestibular disorders may play a role in the pathophysiology of panic disorder. Possible mechanisms underlying this finding are discussed. In patients with panic disorder and chronic dizziness between panic attacks, a careful neurotologic examination is warranted.

Vestibular function in HIV patients: preliminary report.

Main purpose of this study was to evaluate vestibular function, focusing attention on percentage of peripheral damage in 30 HIV positive patients (23 male, 7 female), age range 26-68 years, belonging to Categories A-C of CDC classification of infection, underwent electronystagmography with bithermic stimulation according to Freyss (125 cc of water at 30 degrees C and 44 degrees C in 30 sec). The angular velocity of slow phase was considered as the main value of labirinthine functionality. Peripheral vestibular damage has been found in 35.7% of Class A patients; a similar percentage of peripheral signs was found in Classes B and C, where, on the contrary, increased central vestibular signs were observed. In order to evaluate equilibrium in these patients, a Dynamic Gait Index (DGI) test was performed. Scores were >21 points in 85.7% of Class A patients and decreased in Classes B and C.

Point prevalence of vertigo and dizziness in a sample of 2672 subjects and correlation with headaches.

Vertigo and dizziness are common symptoms in the general population, with an estimated prevalence between 20% and 56%. The aim of our work was to assess the point prevalence of these symptoms in a population of 2672 subjects. Patients were asked to answer a questionnaire; in the first part they were asked about demographic data and previous vertigo and or dizziness. Mean age of the sample was 48.3 ± 15 years, and 46.7% were males. A total of 1077 (40.3%) subjects referred vertigo/dizziness during their lifetime, and the mean age of the first vertigo attack was 39.2 ± 15.4 years; in the second part they were asked about the characteristics of vertigo (age of first episode, rotational vertigo, relapsing episodes, positional exacerbation, presence of cochlear symptoms) and lifetime presence of moderate to severe headache and its clinical features (hemicranial, pulsatile, associated with phono and photophobia, worse on effort). An age and sex effect was demonstrated, with symptoms 4.4 times more elevated in females and 1.8 times in people over 50 years. In the total sample of 2672 responders, 13.7% referred a sensation of spinning, 26.3% relapsing episodes, 12.9% positional exacerbation and 4.8% cochlear symptoms; 34.8% referred headache during their lifetime. Subjects suffering from headache presented an increased rate of relapsing episodes, positional exacerbation, cochlear symptoms and a lower age of occurrence of the first vertigo/dizziness episode. In the discussion, our data are compared with those of previous studies, and we underline the relationship between vertigo/dizziness from one side and headache with migrainous features on the other.

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study.

OBJECTIVE: To better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. METHODS: 17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6 ± 9.8 y.o, disease duration 22 ± 35 months) underwent a 29-channel resting-state electroencephalography (EEG - 5 min opened-eyes, 5 min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs - N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7 ± 15.1 y.o). RESULTS: Eyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers' clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. CONCLUSIONS: We showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. SIGNIFICANCE: This might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach.

Association of cinnarizine and betahistine in prophylactic therapy for Ménière's disease with and without migraine.

Prophylactic therapy of Ménière's disease (MD) includes betahistine and calcium-blockers (the latter also useful for migraine prevention). The aim of our work was to assess the efficacy of combined therapy with cinnarizine and betahistine in MD subjects both with and without migraine and poorly responsive to betahistine alone. Fifty-two MD subjects were included who were poorly responsive to betahistine during 6 months of follow-up; 29 were migraineurs. Combined therapy was administered with betahistine 48 mg/day and cinnarizine 20 mg BID for 1 month, 20 mg/day for 2 weeks and 20 mg every 2 days for 2 more weeks, and then repeated. Results were collected over 6 months of follow-up. MD subjects with and without migraine demonstrated a decrease in both vertigo spells and migrainous attacks during combined therapy (from 9.4 to 3.8 and from 6.8 to 5.9 in 6 months, respectively, for vertigo spells, while migraine decreased from 3.8 to 1 in 6 months, respectively). A correlation was seen between decrease of vertigo spells and headaches in the sample of MD subjects with migraine. Our data support a proactive role for cinnarizine in preventing vertigo spells, especially in MD patients with migraine.

Voice disorders in primary school teachers.

Previous reports focusing on the high prevalence of voice disorders in teachers have suggested that vocal loading might be the main causal factor. The aim of our study was to assess the prevalence of voice disorders in a sample of primary school teachers and evaluate possible cofactors. Our sample was composed of 157 teachers (155 females, mean age 46 years). Participants were asked to complete two selfadministrated questionnaires: one with clinical data, and the second an Italian validated translation of VHI (voice handicap index). On the same day they also underwent a laryngostroboscopic exam and logopedic evaluation. The results were compared with those of a control group composed of accompanying individuals. Teachers presented a higher rate of abnormalities at laryngostroboscopic examination than the control group (51.6% vs. 16%, respectively). Among these, 7.1% presented nodules. In our sample, vocal fold disorders were not correlated with years of teaching, smoking, coffee consumption, or levels of anxiety. Our findings are in agreement with previous reports on the prevalence of pathologic disorders among teachers; nonetheless, the prevalence of nodules was lower than in previous investigations, and voice loading was not correlated with laryngostroboscopic findings. Current Italian law does not include any guidance regarding voice education and screening in subjects with high vocal loading. Our work stresses the need for such legislation.

Vestibular assessment in patients with vestibular schwannomas: what really matters?

Vestibular function is often underdiagnosed in vestibular schwannomas (VS). To evaluate it in a selected group of patients harbouring vestibular schwannomas, 64 patients were included in this study, recruited between March 2008 and June 2011 at our institution. All patients underwent Gd-enhanced MRI and complete neurotological evaluation before gamma knife surgery. Morphological measurements included Koos Classification and quantification of internal acoustic canal filling in length and diameter. Cochlear and vestibular functions were assessed considering pure tone and speech audiometry, bedside examination and caloric test by videonystagmography. A statistical analysis was performed to find possible correlations between morphological and cochleovestibular data. Patients with a higher intracanalicular length (ICL, mean value 8.59 and median 8.8 mm) of the tumour presented a higher value of UW than the subgroup with a lower length (51.9 ± 24.3% and 38.8 ± 18.1% respectively, p = 0.04), while no difference was detected for pure tone audiometry (PTA) values (50.9 ± 22.3 db and 51.1 ± 28.9 db respectively). Patients with a higher ICL also presented a higher rate of positive HIT (88% and 60% respectively, p = 0.006). Patients with a higher value of intracanalicular diameter (ICD, mean value 5.22 and median 5.15 mm) demonstrated higher values of UW (50.2 ± 29.1% and 39.3 ± 21% respectively, p = 0.03), but not different PTA (50.2 ± 29.1 db and 51.9 ± 29.9 db respectively). Finally, patients with a positive head impulse test (HIT) demonstrated significantly higher values of unilateral weakness (UW) (p = 0.001). Vestibular disorders are probably underdiagnosed in patients with VS. ICL and ICD seem to be the main parameters that correlate with vestibular function. Also, in case of small intracanalar T1 VS a slight increase of these variables can result in significant vestibular impairment. The data reported in the present study are not inconsistent with the possibility of proactive treatment of patients with VS.

Postural control in patients after a recent vestibular neuritis with hyperhomocysteinemia.

To assess the possible role of hyperhomocysteinemia (HyHcy) in delaying recovery after acute vestibular neuritis. In our retrospective study, 90 subjects were evaluated within 7 days from the beginning of an acute vertigo. All subjects had high plasma levels of homocysteine (Hcy). 46 patients were treated with homocysteine lowering therapy and betahistine for 1 month, while 44 subjects received only betahistine. Subjective symptoms were evaluated with the Dizziness Handicap Inventory (DHI) questionnaire, administered 7 days after the beginning of vertigo and again after 1 month. Moreover, postural control performed at 1 month' control was studied with static stabilometry in a subgroup of 21 non-treated and 20 treated patients. DHI total score decreased significantly more in the subgroup of subjects treated with homocysteine lowering therapy. Moreover, posturographic data were significantly increased in non-treated compared with treated subjects. Our data support the possibility of a role of HyHcy in preventing recovery after a recent vestibular neuritis. A microvascular disorder or the neurotoxic effect of HyHcy have been considered as possible causal factors. Although not conclusive, our data are not inconsistent with the hypothesis of a poorer adaptation in patients with untreated HyHcy.

Does Ménière's Disease in the Elderly Present Some Peculiar Features?

Object. Aim of our study was to establish some peculiar features of Ménière's Disease (MD) in a group of elderly MD patients, in which the first vertigo spell happened when over 65 years old. Material and Methods. We analyzed a group of 73 younger than 65-years-old and a group of 30 elderly MD patients. All patients underwent a neurotological evaluation, an anamnestic evaluation including a lifetime history of migraine, and blood withdrawal for autoantibody screening. Results. Some differences were found between elderly and younger MD patients. Elderly MD patients presented a higher prevalence of Tumarkin attacks and a lower prevalence of lifetime history of migraine; moreover, they presented a faster develop of hearing loss and vertigo spells than a subgroup of 32 younger patients matched for the duration of illness. Conclusions. Some clinical features of MD in elderly have been pointed out. Particularly, the lower rate of migrainous history and positivity for autoantibodies often associated with MD, in our opinion, support the hypothesis of a vascular disorder acting as a predisposing factor for MD in elderly.

Case reports on two patients with episodic vertigo, fluctuating hearing loss and migraine responding to prophylactic drugs for migraine. Menière's disease or migraine-associated vertigo?

Recent reports have focused on a possible association between migraine and Menière's disease; patients suffering from Menière's disease present a higher rate of migraine. In some cases, the clinical features of migraine-associated vertigo may mimic the presentation of Menière's disease. The present report focuses on two cases of females with recurrent episodes of rotational vertigo, fluctuating hearing loss and tinnitus lasting from a few minutes to several hours; both cases also presented migrainous attacks. As a result of repeated cochleovestibular attacks, both patients presented a permanent low frequency sensorineural hearing loss. Preventive therapies for Menière's disease did not reduce vertigo attacks, while topiramate and acetylsalicylic acid treatment resulted in a significant reduction of both migraine and vertigo. Both the diagnosis of Menière's disease and of migraine-associated vertigo rely on clinical history and both disorders lack a specific diagnostic test. In the early stages, differential diagnosis between Menière's disease and migraine-associated vertigo is often very difficult; previous investigations focused on the possibility that subjects with migraine may experience all symptoms of Menière's disease, including sensorineural fluctuating hearing loss. In conclusion, a trial with prophylactic drug treatment for migraine might be suggested in patients with clear symptoms of migraine and recurrent cochleovestibular disorders.

Dizziness, migrainous vertigo and psychiatric disorders.

OBJECTIVES: This study sought to establish the prevalence of vestibular disorders, migraine and definite migrainous vertigo in patients with psychiatric disorders who were referred for treatment of dizziness, without a lifetime history of vertigo. STUDY DESIGN: Retrospective study. SETTING: Out-patients in a university hospital. MATERIALS AND METHODS: Fifty-two dizzy patients with panic disorders and agoraphobia, 30 with panic disorders without agoraphobia, and 20 with depressive disorders underwent otoneurological screening with bithermal caloric stimulation. The prevalence of migraine and migrainous vertigo was assessed. The level of dizziness was evaluated using the Dizziness Handicap Inventory. RESULTS: Dizzy patients with panic disorders and agoraphobia had a significantly p = 0.05 regarding the prevalence of peripheral vestibular abnormalities in the group of subjects with PD and agoraphobia and in those with depressive disorders. Migraine was equally represented in the three groups, but panic disorder patients had a higher prevalence of migrainous vertigo definite migrainous vertigo. Almost all patients with a peripheral vestibular disorder had a final diagnosis of definite migrainous vertigo according to Neuhauser criteria. These patients had higher Dizziness Handicap Inventory scores. The Dizziness Handicap Inventory total score was higher in the subgroup of patients with panic disorders with agoraphobia also presenting unilateral reduced caloric responses or definite migrainous vertigo, compared with the subgroup of remaining subjects with panic disorders with agoraphobia (p < 0.001). CONCLUSIONS: Our data support the hypothesis that, in patients with panic disorders (and especially those with additional agoraphobia), dizziness may be linked to malfunction of the vestibular system. However, the data are not inconsistent with the hypothesis that migrainous vertigo is the most common pathophysiological mechanism for vestibular disorders.

Rehabilitation after acute vestibular disorders.

OBJECTIVES: To assess the efficacy of rehabilitation for dizzy patients after recent acute vestibular disturbance. METHODS: Forty patients recently hospitalised for an acute episode of rotational vertigo which lasted days were randomly divided into two groups. The first group (20 patients; group R) underwent active rehabilitation, while the second group (20 patients; group C) were told only to 'perform their daily activities'. Group R subjects underwent a total of 10 sessions of rehabilitation, including exercises on a stabilometric platform, point de mire and a series of five exercises repeated five times daily. All patients performed static stabilometry (posturography), undertook the dynamic gait index test, and completed a dizziness handicap questionnaire and a visual analogue scale for anxiety, at baseline and on completion. RESULTS: At 25 days, the rehabilitated patients obtained better results for all recorded outcomes, compared with the control group. The greatest difference in the rehabilitated subjects, compared with the control group, was for the dynamic gait index test; however, this difference was not statistically significant. The visual analogue scale anxiety score was statistically significantly more reduced in rehabilitated patients compared with control patients. Control patients maintained a higher visual dependence for postural control. CONCLUSIONS: These results would appear to support the effectiveness of a supervised exercise programme for patients following acute onset of vestibular disturbance. A correlation was found in both groups between dynamic gait index results and anxiety. In our experience, a rehabilitation programme seems to reduce dependence on visual cues for postural control.

Efficacy of low-level laser therapy in Ménière's disease: a pilot study of 10 patients.

OBJECTIVE: To assess the efficacy of low-level laser therapy (LLLT) for Ménière's disease (MD). MATERIALS AND METHODS: Twenty patients with unilateral MD were included in the study; all presented with uncontrolled vertigo. The patients were randomly divided into two groups: group 1 patients received LLLT 20 min a day with a 5-mW soft laser for 6 mo, while group 2 received betahistine 16 mg twice a day for 6 mo. According to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines, the main outcome for vertigo control was considered to be the number of spells per month in the 6 mo before treatment compared with the same parameter in the 6 mo of therapy. The duration of spells expressed in minutes was also considered. Moreover, a hearing test was performed before and after therapy and results were reported as the pure tone average of 500-, 1000-, 2000-, and 3000-Hz frequencies. All results were valued at baseline, and after 3 and 6 mo of therapy. RESULTS: Compared to baseline, the number and duration of spells were significantly reduced in both groups; statistical significance was detected for the 3-mo control in both groups (p 0.05 with the multiple pair comparison test). Betahistine seems to have a faster action in spell reduction (p 0.05 comparing the 3-mo results between the two groups). Audiometric examination did not show a statistically significant difference between the two groups. CONCLUSIONS: In our experience, LLLT seems to prevent vertigo spells in MD, although results indicate that it has a slower action than betahistine. Dose-dependent therapeutic effects could explain the last result. In our opinion, increased blood flow in the inner ear is the main mechanism leading to the therapeutic results.

Stiff-person syndrome with acute recurrent peripheral vertigo: possible evidence of gamma aminobutyric acid as a neurotransmitter in the vestibular periphery.

OBJECTIVE: We report a case of a 58-year-old man suffering from stiff-person syndrome and recurrent peripheral vertigo. METHOD: A case report and a review of the recent literature on stiff-person syndrome are presented. RESULTS: The patient presented with recurrent episodes of vertigo with a pure peripheral pattern and with concomitant episodes of burning muscle pain, muscle twitching, weight gain and fatigue, worsening with tension or stress that also occurred in periods without vertigo. Cochlear examinations only showed presbyacusis-like hearing loss. The diagnosis of stiff-person syndrome was made with electromyographic examination and from findings in the blood and cerebrospinal fluid of high titres of anti-glutamic acid decarboxylase (GAD67) autoantibodies. In a two-year follow-up period, therapy for stiff-person syndrome abolished episodes of both stiffness and vertigo. CONCLUSION: As far as we know, no other clinical case of acute vestibular damage with a possible correlation with anti-glutamic acid decarboxylase antibodies has been described. Peripheral vertigo possibly related to a lack of gamma aminobutyric acid underlines a possible role of gamma aminobutyric acid as a neurotransmitter in the peripheral vestibular system.