Maria Chiara Raimondi

Exploring the reasons why melatonin can improve tinnitus

Melatonin has been proposed as a treatment for tinnitus, especially on the basis of its favourable effects on sleep and its vasoactive and antioxidant properties. However, to our knowledge no attempts of interpretation have been advanced through a detailed analysis of the various specific properties of melatonin possibly cooperating in a coincidental way to relieve tinnitus: among these, its modulatory effect on central nervous system resulting in a protective mechanism against an exaggerated sympathetic drive; its capacity to induce a more steady hemodynamic condition, through a multifactorial and multi-organ activity, resulting in a more regular labyrinthine perfusion; a possible action on the skeletal muscle tending to a reduction of the muscular tone, which could relieve tinnitus of muscular origin deriving from tensor tympani tonic contractions; its possible reported antidepressive effect, which could indirectly act on tinnitus; a direct regulation of inner ear immunity as proposed in literature when melatonin was reported to be present in the inner ear. All these observations seem to indicate melatonin as a tool deserving a greater attention than other antioxidants in the attempt of relieving tinnitus, justifying its application from a more precise rationale based on a series of physio-pathological aspects.

Gastric type proton pump of the inner ear: Its possible involvement in labyrinthine disorders

It was recently suggested that the favourable effect of proton pump inhibitors on gastric reflux could threaten the homeostasis of the inner ear in several different ways. Moreover, when it is considered that a gastric type proton pump has been found in the inner ear, it could be hypothesized that this treatment has a direct effect. As ischaemia threatens gastric mucosa even by acid secretion, thus implying resistance of the proton pump to damaging factors, a similar kind of mechanism could be imagined in the inner ear, where it could even cause the osmotic changes possibly involved in Ménières disease hydrops. This hypothesis, if proved, could open new perspectives on some not fully understood phenomena and lead to finding more satisfactory therapeutic options.

Haemodynamic profile of young subjects with transient tinnitus

Abstract Objective: Our objective was to contribute to drawing a haemodynamic profile of healthy subjects prone to labyrinthine disorders of functional origin. The aim was to determine if some haemodynamic aspects could characterize young people with a history of transient tinnitus, considered as an early symptom of cochlear damage possibly derived from hypoperfusion. In one year we studied 60 consecutive subjects (28 ± 5.2, range 18–40 years): 24 who experienced transient tinnitus, and 36 without tinnitus. Exclusion criteria were a history of audiological and otological impairment, ear surgery, and known cardiac abnormalities. A clinical and echographic cardiac evaluation was performed, with assessment of blood pressure, heart rate, and left ventricular structure and function. Results: All results were within the normal range in both groups. The tinnitus group had a slightly lower body mass index (BMI) (p = 0.05) and body surface area (BSA) (p <0.05), while age, blood pressure and heart rate were similar in the two groups. Tinnitus subjects showed reduced diastolic and systolic left ventricular internal dimensions (p = 0.01 and 0.02, respectively) and left ventricular end-diastolic volume (p = 0.02). Left ventricular mass (LVM) related to height 2.7 and observed LVM were reduced in tinnitus subjects (both p = 0.02), while LVM related to BSA had a less marked reduction (p = 0.04), and predicted LVM and appropriate LVM showed only a borderline statistically significant reduction (p = 0.05). Functional systolic left ventricular aspects were similar in the two groups apart from a lower stroke volume in tinnitus subjects compared with the no-tinnitus group (p = 0.03), and no differences were observed in diastolic function indexes between the two groups. Conclusion: Subjects with a history of transient tinnitus, although presenting normal echocardiographic parameters, seem to have smaller somatic and cardiac structural characteristics, which could be less adequate in maintaining peripheral perfusion. In particular, a terminal circle district such as the cochlear one could thus show its stress through tinnitus. This observation indirectly supports the theory of a cochlear origin of tinnitus in a number of cases and is reminiscent of what happens in hypertension and heart failure.

The possible role of proton pump inhibitors of the homeostasis of the inner ear.

The possibility of a benefit in some cases of inner ear sufferance by using proton pump inhibitors has been considered after a casual observation. The hypothesis is advanced considering the adverse effect of reflux on the eustachian tube function, the possible influence of the latter on inner ear symptoms and, from a more general point of view, the trigger effect which a gastric dysfunction requiring proton pump inhibitors could exert on the sympathetic system. These considerations, deserving a further study, seem to be based on logical assessment and therefore in our opinion deserve to be kept in mind in trying to define inner ear disorders of uncertain origin.

Possible influence on heart rate on tinnitus

Assuming the possibility of the inner ear damage due to a hemodynamic imbalance essentially due to an abnormal vasomotor regulatory response, the possibility that heart rate (HR) has a correlation with the onset and/or the enhancement of tinnitus is hypothesized. In fact, recent studies have drawn the influence of other factors than blood pressure, in normotensive subjects, in taking part to the regulation of peripheral resistance, outlining the importance of both cardiac output (CO) - which is a function of heart rate (HR) and stroke volume (SV) and SV itself as a dynamic component to baroreflex control of muscle sympathetic nerve activity (MSNA). From this point of view, it could be possible that a condition of bradycardia can enhance tinnitus regardless of its cause, and conversely that a more elevated HR can be related to a relief of this symptom.

Tinnitus as a warning for preventing vasovagal syncope

It has been widely outlined by our group the possibility that a sufferance of the inner ear can take place as a consequence of hemodynamic imbalance which could affect young and healthy people and recognize a merely functional origin. As reported in previous papers, an altered reaction of the autonomic nervous system could actually jeopardize the labyrinthine perfusion even in absence of other damages. From this standpoint, the hypothesis that a hyperactivity of the vagal response to an acute sympathetic drive may result in an inner ear sufferance deserves to be explored. A mechanism which appears to fit to this model is represented by the Bezold-Jarisch reflex (BJR), which is considered to be responsible for vasovagal syncope and is characterized by a dynamic reasonably compatible with our findings. According to these premises, especially considering that the inner ear has a less active protective mechanism against ischemia as compared to brain, in predisposed subjects tinnitus, when considered as an initial symptom of inner ear hypoperfusion, can represent a warning able to prevent the lack of consciousness related to the syncope.

The possible role of Vicorder® apparatus in the diagnostic protocol of inner ear diseases

Abstract Objective: Cardiovascular risk factors are widely reputed to be a possible cause for hearing impairment, and the role of arterial stiffness as a cardiovascular risk predictor has been recently emphasized. For these reasons pulse wave velocity (PWV) could represent a useful parameter in order to rapidly assess or rule out the existence of an underlying overall deteriorating circulatory condition in cases of inner ear impairment. Method: In order to assess the real significance of PWV for audiological purposes, a study was carried out comparing this parameter in subjects with normal hearing and those with symmetrical sensorineural hearing loss. Results: The results suggested an apparent lack of correlation between arterial stiffness and hearing deterioration. Conclusion: The findings appear to indicate that the relationship between systemic circulation and inner ear function, when excluding acute and/or well identifiable impairment factors, is not as linear as expected.

Angiogenesis: Possible analogies between the eye and the inner ear

Angiogenesis is a phenomenon concerning both physiological conditions linked to development and pathological conditions; in the latter it is aimed at providing an enhancement in blood supply to tumours, on one hand, and to restore the circulation in peripheral arterial and ischemic diseases, on the other hand, thus resulting in a controversial effect depending on the circumstances. When occurring in the eye, angiogenesis clearly proved to represent a threaten, whereas an univocal interpretation of the action of angiogenesis on the inner ear homeostasis is still lacking despite the morphologic and functional analogies between eye and labyrinth. These analogies can raise same doubt on the supposed role of angiogenesis in terms of preserving the function of a threatened inner ear: even this organ could be further damaged by microvascular disorders and/or mechanical changes able to jeopardize its architecture and consequently its function. If a parallelism between ear and eye is extendable to this aspect, this could open new perspectives in the treatment of certain affections of the inner ear by borrowing therapeutic strategies that have given appreciable and consolidate responses in the treatment of degenerative retinopathy.

Proton pump inhibitors: A possible effect on Ménière's disease?

Background: The model of explanation for the pathogenesis of Ménières disease (MD) proposed by our group postulates a crucial role for the maintained activity of the labyrinthine gastric-type proton pump under ischaemic conditions. Thus, the administration of the common proton pump inhibitors (PPI) could exert a favourable influence on MD symptoms. Method: In order to help assess the validity of this hypothesis a questionnaire was administered to a selected population of sufferers from MD; the aim was to verify the percentage of PPI users and the incidence of MD symptoms among users and non-users. Results: These showed a higher prevalence of PPI users in the selected sample compared to an unselected large series in the literature; the difference was statistically significant in all cases. In contrast, no statistically significant differences between users and non-users were found regarding the incidence of symptoms in the previous six months, even though the group of PPI users had a slightly better performance. Conclusion: Despite these inconclusive findings and the consequent need for further studies to eventually propose PPI as a therapy for MD, some physiological and pharmacological aspects seem to support a possible positive influence of this category of drugs on the inner ear.

Meniere's disease and the use of proton pump inhibitors.

PRINCIPLES On the basis of previous observations we examined the possibility of a favourable effect of proton pump inhibitors (PPI) on Menieres disease (MD). A preliminary step was made by retrospectively analysing the number of menieric crisis in group of patients suffering from MD and using PPI for other reasons as compared to a group of menieric subjects who had never used PPI. METHODS Between January 2001 and December 2006, 42 patients affected by MD were examined in the tertiary referral centre at the University Hospital of Bologna, Italy and in the private office of an ENT specialist in Cassino, Italy. Within the study group, 18 patients had used PPI for various reasons for at least 12 consecutive months, whilst 24 patients had never been prescribed them. We recorded the number of menieric crises reported in the observation period. The mean follow-up period was 21.9 months. Statistical analysis was performed by means of the x2 test and significance was defined when p<0.05. RESULTS Most of MD patients (72%) using PPI suffered less than one episode of menieric crisis/year. On the other hand patients who had never used a PPI, experienced considerably more episodes only 16.7% having less than one crisis per year. This difference was statistically significant (p<0, 001). CONCLUSIONS Even taking the limitations of this retrospective study into account the reported data nevertheless strongly suggest a possible role for proton pumps in the pathogenesis of MD. This could lead to interesting developments and contribute to a better definition of MD and the therapeutic possibilities.