Tinnitus is Modulated by Migraine

Abstract

Tinnitus refers to perceiving sound without any external source. It is a subjective phenomenon that can be described as ringing, buzzing, hissing, or other similar sounds. Clinically, tinnitus is commonly reported, but there is still a lack of standardized objective diagnostic tests, making patient self-reporting the primary method of assessment. A nationwide survey in the United States revealed that 50 million individuals aged 20 or older experienced tinnitus in the past year, with 16 million having daily occurrences.1 Tinnitus poses a significant socioeconomic burden, being the most common disability among veterans, with over 1.5 million veterans receiving disability benefits amounting to $1.3 billion annually.2www.shutterstock.com. Tinnitus, migraine, headache, treatment.Figure 1: Schematic diagram of the migraine mechanisms leading to tinnitus perception. Tinnitus, migraine, headache, treatment.Figure 2: Integrative neurosensory rehabilitation algorithm for treatment of tinnitus. Tinnitus, migraine, headache, treatment.Table 1: Summary of Dietary and Physiologic Migraine Triggers.Tinnitus is caused by damage to the hair cells in the cochlea or loss of synapses between hair cells and auditory nerves and the resulting loss of auditory input to the central nervous system.3 Specifically, in the most common types of hearing loss, damage to hair cells in the high-frequency region of the cochlea leads to detectable hearing loss and a rearrangement in the tonotopic organization of the auditory cortex.4,5 It has been thought that this reorganization causes cortical neurons to respond to frequencies from less affected cochlear cells, resulting in the perception of tinnitus due to their spontaneous firing.5 EPIDEMIOLOGICAL ASSOCIATION BETWEEN TINNITUS AND MIGRAINE Research shows a higher prevalence of migraine in individuals with tinnitus and subjective hearing loss. In a study of the National Health and Nutrition Examination Survey (NHANES) database, we have found that migraine rates were 36.6% and 24.5% among patients with tinnitus and subjective hearing loss, respectively.6 Multivariate logistic regression indicated that patients with tinnitus were more likely to have migraine, and migraine patients were more likely to have tinnitus and subjective hearing loss.6 Additionally, a cohort study in Taiwan revealed a significant association between a history of migraine headaches and cochlear symptoms like tinnitus, hearing loss, and sudden deafness.7 Further analysis of questionnaire data from tinnitus patients showed that 44.6% of subjects suffered from migraine headaches.8 These findings suggest a potential mechanistic link between migraine and altered attention to the dysregulation of the central auditory pathway in a subset of tinnitus patients. PATHOPHYSIOLOGICAL CONCEPTS RELATING TINNITUS TO MIGRAINE The pathophysiology of tinnitus involves the auditory pathway, which is modulated by the central nervous system. This connection implies a potential pathophysiological link between migraine and tinnitus, possibly related to changes in central hypersensitivity involving the trigeminal nerve, which might exacerbate tinnitus. While not all migraine patients experience tinnitus, many of them report auditory symptoms in association with migraine headaches, with tinnitus being one of the most common auditory manifestations. In patients with fluctuating tinnitus (louder at times, quieter at other times), their louder tinnitus appears to be linked to migraine. This association is most likely pathophysiologically linked to the central nervous system, particularly the activation of the trigeminal ganglion, altered blood flow to the inner ear, and likely increased attention and sensitivity of the brain during migraine activation.9 The presence of migraine does not mean the patient is having a headache, as many patients with active migraine do not develop headaches (e.g., ocular migraine, vestibular migraine, cochlear migraine, abdominal migraine, etc.). Migraine is a state of sensitivity of the brain which is brought on by electrophysiologic changes in the brain, sometimes termed central or brain sensitivity disorder. When the migraine process is active in the brain, the patient may have sensitivity to sound, light, motion, heat, smells, atmospheric changes, etc. One of these sensitivities is the increased perception of tinnitus seen in cochlear migraine. Vestibular migraine is a type of migraine that is more widely recognized, characterized by recurrent vertigo symptoms.10 Studies have shown that patients with vestibular migraine have significantly higher rates of tinnitus compared to those without the condition.11 In 2018, the concept of “cochlear migraine” was introduced, which involves migraine symptoms along with non-vestibular ear-related symptoms.7,12 During migraine attacks, there is an increase in sensory sensitivity, making individuals more sensitive to visual, auditory, and olfactory stimuli. This heightened sensitivity of the brain to sound during migraine activation may enhance the perception of tinnitus and hyperacusis, which often co-occur in patients. As the trigeminal nerve directly innervates the inner ear blood supply and cause neurogenic inflammation, its activation in migraine attacks may cause hearing loss or increase central sensitivity or attention to the tinnitus percept in the auditory cortex.13 The main proposed mechanism for migraine is spreading cortical depression or altered electrical activity across the cortex. This leads to inflammation in the intracranial meninges and activation of trigeminal meningeal nociceptors.12 This inflammatory state releases neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) from the trigeminal ganglion, causing secondary vasodilation, capillary leakage, and edema, contributing to the variety of symptoms including headache experienced during migraine activation (Figure 1).12 Some patients with migraine never develop a headache and just develop atypical migraine symptoms (such as increased perception of tinnitus, neck stiffness, hyperacusis, etc.). SIMILAR TRIGGERS FOR TINNITUS AND MIGRAINE In our experience, treating thousands of patients with tinnitus, we have observed shared triggering factors between tinnitus and migraine (Table 1), including sleep disturbances, stress, diet, and weather changes. High sodium foods, which often contain preservatives like glutamate or byproducts of protein breakdown like tyramine, are common triggers for migraine headaches.14 Consuming sodium-containing foods (which causes a relative dehydration) along with dehydration can trigger migraine. Tyramine is also found in fermented products, alcoholic beverages like wine and beer, and aged cheese. A reduced sodium diet is commonly recommended as a first-line treatment for patients with inner ear symptoms, as it is believed to help increase plasma aldosterone levels, affecting endolymph regulation in the inner ear. However, the link between dietary sodium intake and tinnitus can only be hypothesized based on clinical observations due to a lack of randomized controlled trials.15 We have found that sodium intake on its own is not what causes increased migraine/tinnitus but rather the dehydration that a high sodium intake creates is the issue. Increased water intake can overcome the increased intake of sodium. However, many high-sodium foods contain other trigger molecules primarily tyramine and glutamate (e.g., soy sauce, canned/frozen foods, potato/corn chips, etc.), which increased water cannot overcome. Caffeine overuse or withdrawal has also been identified as a trigger for migraine headaches. Caffeine blocks adenosine receptors which is important in modulating neuronal activity, particularly neurotransmitter release. We have found caffeine to be the worst dietary trigger of migraine/tinnitus and gradual elimination is strongly recommended. After caffeine, we have found fermented alcohols (wine/beer) to be the next most common dietary trigger. Stress, a well-known trigger for tinnitus, has also been reported most commonly as a trigger by individuals experiencing migraine headaches.16 Meteorological changes, such as weather and atmospheric pressure fluctuations, have been proposed as migraine triggers.17 A retrospective review found that 26% of patients with vestibular migraine reported weather changes as a trigger.18 In clinical settings, we often encounter patients who report that their tinnitus can be triggered by weather changes, primarily low atmospheric pressure. Low atmospheric pressure generally occurs prior to rain or snow storms, in windy weather, overcast weather, or travel to the mountains or by airplane. Low atmospheric pressure has also been associated with exacerbating symptoms of Meniere’s disease (another migraine-related disorder), including tinnitus.19 Finally, both migraine and tinnitus can be triggered by loud sounds. Patients will often describe a temporary increase in tinnitus as a result of loud (but non-toxic) noise exposure (e.g., restaurant, high frequency sounds, ambulance siren, etc.). This increase in the perception of tinnitus is most likely due to a temporary increase in migraine (brain sensitivity) that is triggered by the loud or high frequency sound. While the patient cannot be isolated from loud sounds at all times, it provides further evidence that the tinnitus can likely be improved with the control of the underlying migraine process. TREATMENT OF TINNITUS AS A MANIFESTATION OF MIGRAINE Conventional treatments for tinnitus fall into categories like dietary and lifestyle adjustments, medications, cognitive behavioral therapy (CBT), and music or sound therapy. However, there is currently no FDA-approved medication specifically for tinnitus treatment. Medications prescribed for tinnitus are often aimed at managing the psychological impact of chronic tinnitus, such as depression and anxiety. Interestingly, treatments commonly used for migraine show promise as alternative approaches for addressing tinnitus and other inner ear conditions. Antidepressants like nortriptyline have been prescribed previously to treat tinnitus, acting through serotonergic and antimuscarinic mechanisms.20 They may be more effective for patients with severe phenotypes who are already experiencing anxiety or depression. Both depression and anxiety are more common in tinnitus than the general population.21 Selective serotonin reuptake inhibitors (SSRIs) in some patients may be better tolerated than tricyclic antidepressants.22 In a recent network meta-analysis of 36 randomized controlled trials with 2,761 participants, Chen, et al. reported that pharmacological interventions targeting the brain (such as amitriptyline, acamprosate, and gabapentin) and those with anti-inflammatory effects (steroids and melatonin) significantly reduced tinnitus severity and response rate compared with placebo or waiting-list control groups.23 Interestingly, steroids are one of the best migraine abortives and melatonin has shown efficacy in the treatment of migraine. In our clinical practice, we have observed improvements in tinnitus fluctuations and reduced loud tinnitus in patients treated with the migraine regimen and the management of migraine triggers. Treatment of the underlying migraine process appears to significantly reduce the fluctuations (loud bothersome periods) in patients with tinnitus. The constant low-level tinnitus is not affected by migraine treatment, as it is caused by the baseline cochlear damage. However, loud and fluctuating tinnitus can often be improved with migraine therapy. Non-pharmacological interventions, including CBT to reduce stress and music therapy typically used for migraine headaches, may also help alleviate tinnitus. A meta-analysis found that the pooled odds ratios of clinically significant improvement post-CBT treatment and 3-month follow-up in children and adolescents showed significant improvement with CBT compared to placebo only.24 In a proof-of-concept study, we demonstrated that undergoing an 8-week course of internet-based CBT (iCBT) modules (consisting of behavioral coaching, stress and sleep management, meditation and breathing exercises, migraine dietary recommendations, etc.) and personalized sound therapy (using frequency-matched sounds mixed with music) led to enhanced tinnitus-specific quality of life measures.25 This improvement was more than a mixed music with customized sound therapy trial alone we previously performed.26 The iCBT for tinnitus is now commercially available. We have recently introduced the term “otologic migraine” to encompass migraine-induced symptoms affecting the ear, including the auricular (ear pressure/pain), cochlear (hearing loss/tinnitus), and vestibular symptoms. In other words, otologic migraine, representing the impact of migraine on the ear, may play a part in the association between tinnitus and migraine. Additionally, we adopt an “integrative neurosensory rehabilitation” approach to migraine treatment, incorporating broad lifestyle modifications (improvement in stress/sleep), dietary changes (increased hydration, avoidance of hunger, and elimination of dietary triggers), and supplements (magnesium and riboflavin), along with pharmacological treatment if necessary. This algorithmic approach for treating tinnitus as a migraine phenomenon is outlined in Figure 2. We have found significant improvement in the perception of tinnitus in patients with loud, bothersome tinnitus or those with fluctuating tinnitus with the control of the underlying migraine etiology. While this regimen does not “cure” the tinnitus, it significantly reduces the impact of the tinnitus. We recently concluded a randomized clinical trial of two novel migraine prophylactic medications versus placebo for the treatment of bothersome or fluctuating tinnitus. The full clinical trial’s results will be reported in the near future. Disclosures: Dr. Hamid R. Djalilian is an advisor to NeuroMed Care LLC (telemedicine platform for the medical treatment of tinnitus and vertigo). He also holds equity in Elinava Technologies (xtinnitus.com, an internet-based cognitive behavioral therapy for tinnitus), Cactus Medical LLC (otitis media diagnosis device), and is an advisor to NXT Biomedical LLC (direct drive hearing aid). Dr. Djalilian also has pending patents related to tinnitus treatment. Dr. Mehdi Abouzari has no relevant disclosures.