Audiovestibular disorders as autoimmune reaction in patients with melanoma.

Melanoma is an aggressive form of cancer derived from neuroectodermal melanocytes. Melanocytes are present in the skin and hair follicles, as well as in the eye (iris and choroids), the leptomeninges, the anal canal and the inner ear. In the inner ear melanocytes are found both in the intermediate layer of the stria vascularis of the cochlea and in the dark cells of the vestibular organs. They are believed to play an important role in the production of endolymphatic potentials and in the maintenance of normal volumes of the inner ear fluids. Recently, audiovestibular dysfunctions have been demonstrated in patients treated with immunotherapy for metastatic melanoma and have been related to an autoimmune attack on the normal melanocytes of the inner ear. Melanoma is an immunogenic tumor type frequently associated with spontaneous autoimmune manifestations which seem to be associated with better prognosis. The melanoma-associated antigens are also expressed in normal melanocytes in the skin, eye and ear. We hypothesize that inner ear melanocytes could be a target of an autoimmune process in patients affected by melanoma. The immune system could produce antibodies that cross-react with both the melanoma cells and the labyrinth melanocytes causing an altered homeostasis of endolymphatic liquids and provoking some labyrinthic disorders such as vertigo, hearing loss, aural fullness and tinnitus resembling or influencing Ménière's disease. In this perspective, audiovestibular disorders could be interpreted as an attempt by the individual immune system to develop anti-tumor response. In patients affected by melanoma an autoimmune genesis has already been advocated for ocular symptoms in melanoma-associated retinopathy, where the cross-reaction happens against retinal cells. A possible role of inner ear melanocytes should be considered as a potential cause of audiovestibular disorders. Further research is needed to demonstrate a connection between melanoma and labyrinth dysfunctions such as in melanoma-associated retinopathy.

Bilateral sudden sensorineural hearing loss and chronic venous cerebrospinal insufficiency: a case report.

OBJECTIVES: We report a case of bilateral sudden sensorineural hearing loss (SSHL) in a patient suffering from chronic venous cerebrospinal insufficiency (CCSVI). METHODS: Audiometric testing confirmed bilateral sensorineural hearing loss with hypoexcitability to caloric stimulation on the left side and echo-colour Doppler examination showed abnormal cerebral venous deficiency. RESULTS: The patient's condition improved after 15 days following medical treatment. CONCLUSIONS: CCSVI may explain the anatomical background which provides a predisposing factor for SSHL although further studies are needed to verify whether this observation is casual or coincidental.

Influence of compact disk recording protocols on reliability and comparability of speech audiometry outcomes: acoustic analysis.

OBJECTIVE: To assess whether different compact disk recording protocols, used to prepare speech test material, affect the reliability and comparability of speech audiometry testing. MATERIAL AND METHODS: We conducted acoustic analysis of compact disks used in clinical practice, to determine whether speech material had been recorded using similar procedures. To assess the impact of different recording procedures on speech test outcomes, normal hearing subjects were tested using differently prepared compact disks, and their psychometric curves compared. RESULTS: Acoustic analysis revealed that speech material had been recorded using different protocols. The major difference was the gain between the levels at which the speech material and the calibration signal had been recorded. Although correct calibration of the audiometer was performed for each compact disk before testing, speech recognition thresholds and maximum intelligibility thresholds differed significantly between compact disks (p < 0.05), and were influenced by the gain between the recording level of the speech material and the calibration signal. CONCLUSION: To ensure the reliability and comparability of speech test outcomes obtained using different compact disks, it is recommended to check for possible differences in the recording gains used to prepare the compact disks, and then to compensate for any differences before testing.

Nickel earlobe dermatitis and clinical non-relevance of the oral exposure.

OBJECTIVE: Nickel is the most common cause of allergic contact dermatitis (ACD). Because nickel restriction is commonly imposed on many patients with the only earlobe ACD to nickel hypersensitivity, the aim of this study was to identify the role of occasional and extended oral nickel exposure in these patients. DESIGN: This is a case-control study. SUBJECTS: Thirty-four outpatients, previously diagnosed as monosensitized to nickel, suffering from earlobe dermatitis were enrolled; 11 of them showed active dermatitis. The control group consisted of six healthy (non-nickel-sensitive) subjects. INTERVENTIONS: High oral nickel challenge (20 mg) and protracted oral challenge (1 mg once a day). Observation period: 6 weeks. RESULTS: Clinical earlobe lesions were not affected by a high oral nickel intake nor by a protracted oral challenge. CONCLUSIONS: Dietary nickel restriction seems to be useless in patients with earlobe ACD due to nickel hypersensitivity.

Tinnitus as an alarm bell: stress reaction tinnitus model.

Stress is a significant factor influencing the clinical course of tinnitus. Auditory system is particularly sensitive to the effects of different stress factors (chemical, oxidative, emotional, etc.). Different stages of reaction (alarm, resistance, exhaustion) lead to different characteristics of tinnitus and different therapeutic approaches. Individual characteristics of stress reaction may explain different aspects of tinnitus in various patients with different responses to treatment, despite similar audiological and etiological factors. A model based on individual reactions to stress factors (stress reaction tinnitus model) could explain tinnitus as an alarm signal, just like an 'alarm bell', informing the patient that something potentially dangerous for subject homeostasis is happening. Tinnitus could become a disabling symptom when the subject is chronically exposed to a stress factor and is unable to switch off the alarm. Stress signals, specific for each patient, have to be identified during the 'alarm' phase in order to prevent an evolution toward the 'resistance' and 'exhaustion' phases. In these phases, identification of stressor is no more sufficient, due to the organization of a 'paradoxical auditory memory' and a 'pathologically shifted attention to tinnitus'. Identification of stress reaction phase requires accurate otolaryngology and anamnesis combined with audiological matching tests (Feldman Masking Test, for example) and psychometric questionnaires (Tinnitus Reaction and Tinnitus Cognitive Questionnaires).

Evaluation of head-to-trunk control in whiplash patients using digital CranioCorpoGraphy during a stepping test.

We used digital-CranioCorpoGraphy (dCCG) to document whiplash effects on head-on-trunk stabilization while subjects walked on the spot (Fukuda test). Twenty-five healthy subjects were compared with 33 whiplash patients. Whiplash patients were classified as chronic (more than 6 months after injury) and recent (less than 6 months after injury). Clear differences between healthy subjects and patients were seen and three different strategies were detected. Pattern A appeared similar to normals but quantitative analysis showed significant differences with paradoxical head over-stabilization (collar-effect); pattern B decreased head stability; pattern C decreased head stabilization with reduced displacements of the body. Due to the complexity of the data analyzed for each marker, a coefficient of performance (CP) was calculated to simplify the cut-off between normal and pathological tests. CP clearly identified an abnormal stepping pattern. Our findings indicate that firstly dCCG identified a specific vestibular task in whiplash patients, secondly whiplash did not always provoke vestibular involvement and thirdly dCCG could be a tool to discriminate patients with and without vestibular involvement after whiplash.

Aging and vestibular system: specific tests and role of melatonin in cognitive involvement.

Balance disorders are frequent with aging. They are particularly important because they decrease social autonomy of the aged subjects and they often provoke falls. The cause is always multifactorial. There is evidence that aging affects multiple sensory inputs, as well as the muscoloskeletal system and central nervous system ability to perform sensorimotor integration. For the evaluation of decreased balance skills in elderly, a specific questionnaire has been prepared, in order to identify high risk of falling called falling risk inventory (FRI) questionnaire, and a complex psycho-sensory-motor test has been studied by means of posturography, in order to detect specific vestibular impairment. Regarding ethiopathogenesis of balance disorders in aged subjects, because the decline of behavioral and cognitive performances are due also to decline of biological rhythm control, the role of melatonin (the hormone regulating circadian rhythms, being strictly connected with cerebellar function, and it is well known that cerebellum acts in elderly both at motor and cognitive regulation. The goals of the present paper are: (i) To present a self-administered FRI questionnaire aimed at identifying possible causes of falls and quantifying falling risk in aged. (ii) To validate posturography as a specific test to investigate vestibular involvement in elderly in correlation with FRI. (iii) To present a complex behavioral test (NT) aimed at evaluating both spatial orientation and spatial memory in elderly, factors involved into the genesis of complex dizziness and unsteadiness. (iv) To evaluate the role of melatonin in cognitive involvement in dizzy, old subjects due to the functional correlations between circadian rhythms, cerebellum balance disturbances and cognitive disorders. General conclusions are: FRI correlates with falling risk. Posturography identifies specific vestibular impairments correlated to balance disorders and elderly falls. Spatial orientation is altered in about 40% of dizzy patients but no significant differences are revealed in melatonin rhythm. Spatial memory is highly altered only in subjects with inversion of circadian melatonin rhythm it is possible to hypothesize that the alteration of the normal circadian melatonin rhythm plays some role in the genesis of dizziness in a subpopulation of patients.

Vestibular evoked myogenic potentials in multiple sclerosis: clinical and imaging correlations.

Patients with multiple sclerosis (MS) frequently report symptoms related to vestibular disorders in the course of their disease. At present, the fundamental tests assessing vestibulospinal involvement are posturography and vestibular evoked myogenic potentials (VEMPs). While posturography cannot be performed in every subject requiring minimal stance control, VEMPs do not require any specific skill on the part of the subjects and they may be investigated in all patients able to sit. VEMPs were recorded for 40 patients (17 men, 23 women; mean age 38 years, range 17-71 years) fulfilling diagnostic criteria of clinically defined MS, by means of rarefaction clicks, recording modulation of sterno-cleido-mastoideus tonic contraction saccule-mediated modulation. VEMPs were found to be abnormal in 28 of 40 patients. In 18 of the cases the VEMPs were asymmetric, i.e., had a prolonged latency on one side. In six cases latency was increased on both sides (mean delay 4.1 ms). In four subjects VEMPs were absent on one side. Concordance with clinical findings of presence/absence of brainstem involvement was found in 55% and with MRI findings in 65% of the cases. Abnormal VEMPs indicated brainstem dysfunction in four patients (10%) with normal MRI and no specific clinical signs.

The treatment of acute vertigo.

Vertigo and dizziness are very common symptoms in the general population. The aim of this paper is to describe the physical and pharmacological treatment of symptoms characterized by sudden onset of rotatory vertigo. Acute vertigo can be subdivided into two main groups: (1) spontaneous vertigo and (2) provoked vertigo, usually by postural changes, generally called paroxysmal positional vertigo (PPV). Sudden onset of acute vertigo is usually due to acute spontaneous unilateral vestibular failure. It can be also fluctuant as, e.g., in recurrent attacks of Ménière's disease. Pharmacotherapy of acute spontaneous vertigo includes Levo-sulpiride i.v., 50 mg in 250 physiologic solution, once or twice a day, methoclopramide i.m., 10 mg once or twice a day, or triethilperazine rectally, once or twice a day, to reduce neurovegetative symptoms; diazepam i.m., 10 mg once or twice a day, to decrease internuclear inhibition, sulfate magnesium i.v., two ampoules in 500 cc physiological solution, twice a day, or piracetam i.v., one ampoule in 500 cc physiological solution, twice a day, to decrease vestibular damage. At the onset of the acute symptoms, patients must lie on their healthy side with the head and trunk raised 20 degrees. The room must be quiet but not darkened. If the patient is able to swallow without vomiting, it is important to reduce nystagmus and stabilize the visual field with gabapentine, per os, 300 mg twice or three times a day. The first step of the physical therapy of acute vertigo is vestibular electrical stimulation, that is to say, a superficial paravertebral electrical stimulation of neck muscles, aimed to reduce antigravitary failure and to increase proprioceptive cervical sensory substitution. PPV is a common complaint and represents one of the most common entities in peripheral vestibular pathology. While the clinical picture is well known and widely described, the etiopathogenesis of PPV is still a matter of debate. Despite the different interpretation of PPV etiopathogenesis, the maneuvers described by Semont, Epley, or Lempert and their modifications are undoubtedly effective. For this reason the first therapeutic approach in acute provoked vertigo must be by means of one of these kinds of treatments.

Falls in the elderly: the development of a risk questionnaire and posturographic findings.

In elderly people, owing to a perturbation at several levels, including the motor, sensory and cognitive levels, a condition of dizziness and unsteadiness complicated by frequent falls often appears. In this article, we review the most recent information about clinical and instrumental tools available for preventing mobility-related accidents and report the results of a comparative study of postural control, carried out through tetraataxiometry (by Tetrax, Tel Aviv, Israel), in two samples of elderly women belonging to two different populations: 24 Italian women (11 reporting falls and 13 without falls) having a mean age of 73.1 years, and 37 Israeli women (12 with falls and 25 without falls) having a mean age of 72.5 years. The posturographic findings show that the falling subjects, to maintain postural control, are highly dependent on somatosensory inputs and have a weaker "systeme postural fin" (fine postural system), according to Gagey. They also show that an elderly subpopulation exists that, for unknown reasons, is immune to destabilization and falls.

Vertigo and multiple sclerosis: aspects of differential diagnosis.

Equilibrium disorders caused by involvement of brainstem and cerebellar structures are common in patients with multiple sclerosis (MS), but peripheral conditions such as benign paroxysmal positional vertigo (BPPV) can be sometimes confused with those of a central origin. Therefore, an accurate otoneurologic investigation paying attention to differential diagnosis aspects should be performed in these subjects. Among available diagnostic tools, electro-oculography, posturography and vestibular evoked myogenic potentials (VEMPs) are especially suited to assess vestibulo-oculomotor and vestibulospinal systems. This paper briefly describes the most recent otoneurologic diagnostic strategies for MS patients and the results of initial clinical experiences, and finally provides suggestions for differentiating MS-related vestibular disorders from other common otoneurological conditions.

Grading brainstem involvement in multiple sclerosis - by means of electro-oculography.

One of the most frequent disorders of the brainstem in multiple sclerosis (MS) is internuclear opthalmoplegia (INO). The aim of this study is to show how it is possible to monitor the course of MS grading INO on the basis of electro-oculographic findings. We selected 130 patients with a diagnosis of clinically defined multiple sclerosis (78 males and 52 females, mean age 43.5 years) from a population of 354 MS patients. Both saccadic eye movements and spontaneous, vestibular (VOR), visuo-vestibular (VVOR) and optokinetich nystagmus (OKN) were assessed. Slowing of the adducting eye was considered as a sign of lesion of the interocular pathways. Statistical analyses showed that the most sensitive test was VVOR, the least sensitive being randomised saccades. An impairment of random saccades was always associated with abnormal results on all other tests. It seems thus possible to grade the involvement of the medial longitudinal fasciculi (MLF) in MS from an abnormality limited to the VVOR test up to an impairment of randomised saccadic movements. Grading brainstem involvement in MS is particularly important in therapeutic trials and during rehabilitation.

Short form of the Dizziness Handicap Inventory: construction and validation through Rasch analysis.

A new item response scale is presented, which measures the severity of self-reported balance deficits. The scale, DHIsf, is a short form of the Dizziness Handicap Inventory. The scale was constructed and validated by Rasch analysis. Rasch analysis was applied to rescore or remove any items misfitting, redundant, or off-target, until an optimal instrument was obtained. The 25-item, 3-level Dizziness Handicap Inventory was, thus, reduced to the 13-item, 2-level DHIsf. The retained items explore the domains of eye/head movements, full body activities, and mood alterations. Data were collected from 55 outpatients (63 +/- 13 yr; 43 females) attending otoneurological rehabilitation referral at a general hospital because of complaints of dizziness or imbalance. They were fully independent in ambulation and showed no evidence of major neurological or orthopedic diseases. Objective tests included brain computed tomography, sovraaorctic Doppler sonography, craniocorpography, static posturography, and nystagmography. The findings were categorized as pathologic, borderline, or normal. At least one examination was borderline or abnormal in 42 patients. The DHIsf was well targeted on this sample, with a mean score of 5.7/13 (standard deviation, 2.8; median, 5; range, 1-13). The Rasch statistics showed that the 13 items evenly fitted a hierarchy of difficulty within a homogeneous construct. A moderate but significant variance explanation of DHIsf measures was provided by a two-way analysis of variance model, with craniocorpography and nystagmography as independent categorical variables (r2 = 0.15; P = 0.018). When the clinical tests were individually taken into account, their outcome (dichotomized as abnormal v borderline or normal) could not be predicted by either of the DHIsf measures or raw scores (logistic regression). The DHIsf compares favorably with the original Dizziness Handicap Inventory, shows some consistency with the instrumental findings, and provides original information on the severity of imbalance syndromes, as it is seen from the patient's perspective.

Melatonin influences human balance.

In order to evaluate a possible correlation between melatonin, the cerebellum and, consequently, human balance, a double-blind pilot study was performed in 5 subjects with random administration of different doses of melatonin. Before and 1 h after a single administration, a complete otoneurological examination was performed. This first pilot study revealed that melatonin had effects on human equilibrium although these effects were not dosage related and were different in individual subjects. On the basis of these results, a second study was performed. Fourteen healthy volunteers were investigated before and 1 h after administration of a single dose of 10 mg melatonin. The otoneurological examination was restricted to the evaluation of: horizontal saccades, horizontal sinusoidal smooth pursuit, eyes open, eyes closed and head retroflexed static posturography. All subjects showed a decrease in posturographic performances, especially in the simplest test (eyes open) and half of them (6 out of 13) showed also impairment of eye movements. These results confirm the role of melatonin in the control of sensorimotor performances, and the cerebellar receptors might be correlated with the control of human balance.

Virtual environments in the diagnosis, prevention, and intervention of age-related diseases: a review of VR scenarios proposed in the EC VETERAN Project.

A group of worldwide virtual reality and health-care researchers have decided to combine their efforts in a multidisciplinary project titled VETERAN-virtual environments in the diagnosis, prevention and intervention of age-related diseases. The main goal of the VETERAN project is the tuning and testing of different virtual environments, designed to address the cognitive/functional impairments that may occur due to the aging process and age-related disorders. In particular the developed modules will address the problems commonly found in the following pathologies that have a strong impact on the elderly health care policy: Alzheimer's disease and other senile dementias; stroke and unilateral spatial neglect; mobility-related accidents within specific environments (e.g., falls, shocks). The project will focus on research into clinical aspects of age-related diseases and disorders of high morbidity and specifically target goals of prevention, treatment, or delay in onset. Another goal of the VETERAN project is to define and develop new protocols and tools to be used for general rehabilitation purposes. These tools will aim to provide systematic restorative training within the context of functionally relevant, ecologically valid simulated environments. This approach is hoped to optimise the degree of transfer of training and/or generalisation of learning to the person's real world environment.

Ginkgo biloba (EGb 761) in the treatment of equilibrium disorders.

In an open, controlled study, 44 patients complaining of vertigo, dizziness, or both, caused by vascular vestibular disorders were randomly treated with extract of Ginkgo biloba (EGb 761) 80 mg twice daily or with betahistine dihydrochloride (BI) 16 mg twice daily for 3 months. A complete neuro-otologic and equilibrimetric examination was performed at baseline and after 3 months of treatment, with evaluation of clinical findings. In the first month of therapy, vertigo and dizziness improved in 64.7% of patients treated with BI and in 65% of those who received EGb 761. Compared to baseline, no statistically significant changes were observed in cranial scans for patients with a "central" cranial pattern. Likewise, no changes versus baseline were observed in both groups for the equilibrium score. The comprehensive test battery showed the following findings: EGb 761 induced a slight decrease of saccadic delay and considerably increased saccadic velocities; BI improved saccadic accuracy but did not modify delay; EGb 761 improved smooth pursuit gain at 0.4 Hz 40 degrees/s three times more than BI; both drugs asymmetrically reduced nystagmus maximum velocity at 40 degrees/s; both drugs asymmetrically improved the sinusoidal vestibulo-ocular reflex; BI considerably reduced--whereas EGb 761 considerably improved--visuovestibular ocular reflex. No side effects were recorded during the trial except for transient mild headache and gastric upset in 2 patients receiving EGb 761 and transient cyanosis of nails and lips in 1 patient given BI. These results suggest that EGb 761 and BI operate at different equilibrium receptor sites and show that EGb 761 can considerably improve oculomotor and visuovestibular function.

Value of otoneurological tests in the staging of multiple sclerosis.

We looked for correlations between otoneurological findings and neurological signs in multiple sclerosis (MS). 41 patients were tested for: spontaneous and caloric nystagmus, horizontal pursuit eye tracking, full-field optokinetic nystagmus and eye movements. The findings were compared with the course of the disease (progressive or remitting), age at onset of MS and disability, in order to test the predictive value of this type of test. The correlation between otoneurological abnormalities and lesion site is very high for brainstem lesions. Subclinical brainstem lesions were detected in 66% of patients with optic neuritis only and in 42% of those with spinal cord involvement only. Eye movement disorders are more frequent (p less than 0.1) in disease of long duration. The vestibular examination was altered in 100% of patients with clinically definite and probable MS, in 91% of those with possible and in 80% of those with suspected MS. No specific otoneurological pattern was identified. No significant correlation with age at onset or with disability was found.

Allergic and disergic children rhinopathy.

Authors studied 42 children affected with obstructive rhinopathy. They complained nose obstruction with mono or bilateral difficult nasal breathing, permanent (rarely seasonal) symptoms, hypertrophic adenoids, nasal hypersecretion, hearing loss and recurrent otitis media. Two groups of tests were performed: 1) to document the entity of nasal stenosis and the correlated otologic diseases: rhinomanometry by Mercury NR1 rhinomanometer; tympanogram, classified according to Jerger; tubotympanogram, according to Honjo, Morimitsu and Cocchini. 2) To formulate etiologic hypothesis: Prick skin tests; immunoenzymatic specific and total IgE assay; nasal smear; secretory IgA assay. In 8 children anamnesis showed an environmental allergy while familiar anamnesis was positive in 26 cases. Skin tests and/or IgE assay were positive in 14. Neutrophilia in nasal smear was noted in 30, lymphocytosis in 2 and eosinophilia in 5. Secretory IgA were decreased in 39. Children were divided into three classes: A: no documented atopic component; B: disergic children; C: allergic children.