Braz J Otorhinolaryngol.

2018;84(2):135---149

Brazilian Journal of

OTORHINOLARYNGOLOGY
www.bjorl.org

SPECIAL ARTICLE

Tinnitus and sound intolerance: evidence

and experience of a Brazilian group夽
Ektor Tsuneo Onishi a,∗ , Cláudia Couto de Barros Coelho b,c , Jeanne Oiticica d ,
Ricardo Rodrigues Figueiredo e , Rita de Cassia Cassou Guimarães f ,
Tanit Ganz Sanchez d,g , Adriana Lima Gürtler h , Alessandra Ramos Venosa i ,
André Luiz Lopes Sampaio i , Andreia Aparecida Azevedo a,e ,
Anna Paula Batista de Ávila Pires j,k , Bruno Borges de Carvalho Barros a ,
Carlos Augusto Costa Pires de Oliveira i , Clarice Saba l,m , Fernando Kaoru Yonamine a ,
Ítalo Roberto Torres de Medeiros d , Letícia Petersen Schmidt Rosito n ,
Marcelo José Abras Rates o , Márcia Akemi Kii d,g , Mariana Lopes Fávero p ,
Mônica Alcantara de Oliveira Santos q,r , Osmar Clayton Person s ,
Patrícia Ciminelli t,u , Renata de Almeida Marcondes v ,
Ronaldo Kennedy de Paula Moreira w , Sandro de Menezes Santos Torres x

a
Universidade Federal de São Paulo (Unifesp-EPM), Escola Paulista de Medicina, São Paulo, SP, Brazil
b
Universidade do Vale do Taquari (Univates), Lajeado, RS, Brazil
c
University of Iowa, Iowa, USA
d
Universidade de São Paulo (USP), Faculdade de Medicina, São Paulo, SP, Brazil
e
Fundação Educacional D. André Arcoverde (FAA), Faculdade de Medicina de Valença, Valença, RJ, Brazil
f
Universidade Federal do Paraná (UFPR), Hospital de Clínicas, Centro de Zumbido, Curitiba, PR, Brazil
g
Instituto Ganz Sanchez, São Paulo, SP, Brazil
h
Hospital Samaritano São Paulo, Clinica Lima Gürtler, São Paulo, SP, Brazil
i
Universidade de Brasília (UnB), Brasília, DF, Brazil
j
Universidade Federal de Minas Gerais (UFMG), Hospital das Clínicas, Hospital Felício Rocho, Belo Horizonte, MG, Brazil
k
Rede Mater Dei de Saúde, Mater Dei Contorno, Belo Horizonte, MG, Brazil
l
Irmandade Santa Casa de Misericórdia de São Paulo, Hospital Santa Izabel, São Paulo, SP, Brazil
m
Centro de Otorrinolaringologia da Bahia (CEOB), Salvador, BA, Brazil
n
Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
o
Centro de Tratamento e Pesquisa em Zumbido, Belo Horizonte, MG, Brazil
p
Pontifícia Universidade Católica de São Paulo (PUC-SP), Derdic, São Paulo, SP, Brazil
q
Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil
r
Hospital do Servidor Estadual de São Paulo (IAMSPE), São Paulo, SP, Brazil

夽 Please cite this article as: Onishi ET, Coelho CC, Oiticica J, Figueiredo RR, Guimarães RC, Sanchez TG, et al. Tinnitus and sound intolerance:

evidence and experience of a Brazilian group. Braz J Otorhinolaryngol. 2018;84:135---49.

∗ Corresponding author.

E-mail: [email protected] (E.T. Onishi).

Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.

https://doi.org/10.1016/j.bjorl.2017.12.002
1808-8694/© 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open
access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
136 Onishi ET et al.

s
Faculdade de Medicina do ABC, Santo André, SP, Brazil
t
Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
u
Hospital Federal da Lagoa, Rio de Janeiro, RJ, Brazil
v
Faculdade de Medicina de Jundiaí, Jundiaí, SP, Brazil
w
Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
x
Hospital Otorrinos, Feira de Santana, BA, Brazil

Received 3 December 2017; accepted 7 December 2017

Available online 24 December 2017

KEYWORDS Abstract
Tinnitus; Introduction: Tinnitus and sound intolerance are frequent and subjective complaints that may
Hyperacusis; have an impact on a patient’s quality of life.
Hearing loss; Objective: To present a review of the salient points including concepts, pathophysiology, diag-
Hearing aids nosis and approach of the patient with tinnitus and sensitivity to sounds.
Methods: Literature review with bibliographic survey in LILACS, SciELO, Pubmed and MED-
LINE database. Articles and book chapters on tinnitus and sound sensitivity were selected.
The several topics were discussed by a group of Brazilian professionals and the conclusions
were described.
Results: The prevalence of tinnitus has increased over the years, often associated with hearing
loss, metabolic factors and inadequate diet. Medical evaluation should be performed carefully
to guide the request of subsidiary exams. Currently available treatments range from medications
to the use of sounds with specific characteristics and meditation techniques, with variable
results.
Conclusion: A review on tinnitus and auditory sensitivity was presented, allowing the reader
a broad view of the approach to these patients, based on scientific evidence and national
experience.
© 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published
by Elsevier Editora Ltda. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/).

PALAVRAS-CHAVE Zumbido e intolerância a sons: evidência e experiência de um grupo brasileiro

Zumbido;
Resumo
Hiperacusia;
Introdução: Zumbido e intolerância a sons são queixas frequentes e subjetivas que podem ter
Perda auditiva;
impacto na qualidade de vida do paciente.
Auxiliares de audição
Objetivo: Apresentar uma revisão dos principais pontos incluindo conceitos, fisiopatologia,
diagnóstico e abordagem do paciente com zumbido e sensibilidade a sons.
Método: Revisão da literatura com levantamento bibliográfico na base de dados da LILACS,
SciELO, Pubmed e MEDLINE. Foram selecionados artigos e capítulos de livros sobre zumbido
e sensibilidade a sons. Os diversos tópicos foram discutidos por um grupo de profissionais
brasileiros e as conclusões descritas.
Resultados: A prevalência de zumbido tem aumentado ao longo dos anos, muitas vezes asso-
ciado à perda auditiva, fatores metabólicos e erros alimentares. A avaliação médica deve ser
realizada minuciosamente no sentido de orientar a solicitação de exames subsidiários. Os trata-
mentos disponíveis atualmente variam de medicamentos à utilização de sons com características
específicas e técnicas de meditação, com resultados variáveis.
Conclusão: Foi apresentada uma revisão sobre os temas, permitindo ao leitor uma visão ampla
da abordagem dos pacientes com zumbido e sensibilidade auditiva baseada em evidências
científicas e experiência nacional.
© 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Publicado
por Elsevier Editora Ltda. Este é um artigo Open Access sob uma licença CC BY (http://
creativecommons.org/licenses/by/4.0/).
Tinnitus and sound intolerance: evidence and experience of a Brazilian group 137

Introduction over 60 years of age.1 In a population study carried out in

the city of São Paulo, there was a prevalence of 22%, more
Tinnitus can be defined as a symptom related to the con- common in females (26% in women versus 17% in men) and
scious perception of an auditory sensation in the absence increasely more common with aging. In most cases, tinnitus
of external sound stimuli. It is a prevalent otological is mild and intermittent, and does not prompt the individual
symptom, that can have severe physical and emotional to seek medical assistance.3,7 Hearing loss is associated with
consequences.1---3 tinnitus in approximately 85---96% of cases, and only 8---10%
Tinnitus is often accompanied by some intolerance to of affected individuals have normal hearing.8
external sounds, which may be: There are few studies on hyperacusis prevalence, but it
is estimated to occur between 8---15% in the general popula-
(a) Hyperacusis: clinically, the patient has light to moderate tion, around 3% in children and in 25---40% of those individuals
sensitivity to sounds intensity, with physical discomfort. who have tinnitus.9,10
The Loudness Discomfort Level (LDL) measurement is
below 90---100 dB NA. It is the most frequently studied
type in studies.
(b) Misophonia: clinically, the patient has aversion to spe- Pathophysiology of tinnitus and hyperacusis
cific sounds, usually low and repetitive, which trigger
strong discomfort. It depends on associations of the There are several hypotheses related to the mechanisms of
auditory pathway with the limbic system and on previ- tinnitus generation and hyperacusis. These can be divided
ous negative experience with these sounds, regardless didactically into peripheral and central mechanisms.
of intensity. Although common in practice, it has been
described only recently.
(c) Phonophobia: clinically, the patient is afraid of exposure
to the sounds before they reach the discomfort level.
(d) Recruitment: it is a cochlear phenomenon character- Peripheral mechanisms
ized by injury to outer hair cells (OHCs), of which
auditory sensation is disproportionate to the increase • Spontaneous Otoacoustic Emissions (OAE): weak acous-
in the physical intensity of the sound. Audiometry and tic signal generated by the electromechanical activity
immitanciometry show that there is a reduction in the of the OHCs and captured by microphones in the exter-
auditory dynamic field.4,5 nal acoustic meatus. Controversial mechanism, since
individuals without a complaint of tinnitus may have spon-
taneous OAE.11
Tinnitus classification
• Tectorial membrane detachment: cell injury cause by oto-
toxic agent or acoustic trauma, for instance, affects first
There are several types of classifications,6 and the ones most the OHCs and, later, the inner hair cells (IHCs).2,12 If the
often used are those show in Table 1. lesion affects only the OHCs, there may be loss of the
tectorial membrane support and its direct contact with
Epidemiology the IHCs, which generates sustained depolarization13 that
can be perceived by the Central Nervous System (CNS) as
According to the World Health Organization, 278 million tinnitus.14
people have tinnitus --- approximately 15% of the world’s • Disproportionate OHC lesion: the afferent pathway
population. This prevalence increases to 35% in individuals informs the CNS of the OHC position in relation to the
tectorial membrane, and the efferent path regulates the
length of the OHCs after information processing. As the
Table 1 Tinnitus classification. efferent inhibitory impulse is the result of the summa-
Primary Tinnitus may or may not be associated; tion of afferent impulses, there is a decrease in efferent
(auditory or sensorineural hearing loss (SHL); activity. Since each efferent fiber innervates approxi-
sensorineural) idiopathic (no other cause is observed mately 100 OHCs, this reduction in inhibition can affect
except SHL) areas of the basilar membrane with normal OHCs, causing
Secondary Tinnitus associated with a specific cause them to contract freely; this stimulates the IHCs of these
(para- (other than SHL) or some identifiable regions which could be responsible for the production of
auditory) organic cause tinnitus.15
Acute Symptom onset less than 6 months • Neurotransmitter involvement: glutamate is the main
before excitatory neurotransmitter inside the cochlea, and an
Chronic Symptom for 6 months or more increase in its levels could increase cochlear activity,
Rhythmic It can have vascular origin (synchronous leading to the onset of tinnitus.16 Physical or psycholog-
with heart beat), muscular, auditory ical stress increases dynorphin levels (opioid peptide),
tube and intracranial hypertension which potentiates glutamate action on NMDA (N-methyl-d-
Non-rhythmic Related to the auditory system aspartate) receptors. The peripheral auditory lesion can
Objective Perceived by the examiner lead to neuroplasticity of the auditory cortex, and this
Subjective Perceived only by the patient central reorganization, mediated by serotonin, may be
responsible for the tinnitus.
138 Onishi ET et al.

somatosensory tinnitus.20 Somatic influences on auditory

perception are a fundamental physiological characteristic
inherent to every human being, not limited to patients
with tinnitus. Temporomandibular joint (TMJ) disorders may
affect the auriculotemporal nerve with disinhibition of the
dorsal cochlear nucleus activity, through the serotonergic
somatosensory pathway.

Medical evaluation

Tinnitus may be the initial manifestation of several systemic

Figure 1 Schematic diagram of the neurophysiological model ear diseases or appear during the course of the latter. The
developed by Pawell Jastreboff. diagnosis and treatment of these diseases can lead to tinn-
itus abolition or amelioration. The patient’s clinical history
should be directed to the complaint:
Central mechanisms
(a) Characterization
• Increased spontaneous neural activity in the auditory - Type of sound: it is noteworthy to ask what type of sound
pathway and in the dorsal cochlear nucleus: the cochlear the patient hears: waterfall, whistle, cicada, etc. Pul-
lesion reduces the afferent stimulus and affects the satile tinnitus can be caused by vascular diseases. In that
autoregulation of the central auditory pathway with case, it is important to evaluate any synchronicity with
increased spontaneous activity, interpreted as tinnitus. the heart beat and variations with the decubitus position,
Autoregulation would lead to exaggerated electrical stim- exercises, stress, etc. The description of sound as fast and
ulation in response to sound, resulting in hyperacusis.2,17 repetitive clicks, although without synchronicity with the
• Cross-talk between the fibers of the VIII cranial nerve: pulsation, suggests a diagnosis of myoclonus.
when loss of the myelin sheath (by tumor compression or - Time of symptom onset: neuroplastic alterations tend to
vascular loop) leads to the formation of atypical neural be greater in more chronic tinnitus.
connections between nerve fibers, the resulting sponta- - Laterality and symmetry: unilateral or asymmetrical tinn-
neous activity can be interpreted by the auditory cortex itus may indicate retrocochlear diseases and should be
as tinnitus.18 investigated in a manner similar to that for an unilateral
• Neural plasticity and alteration in the Tonotopic Map: or asymmetric sensorineural hearing loss.
the reorganization of the tonotopic map in the cochlear - Continuous or intermittent: the tinnitus may be continu-
nuclei, in response to a cochlear lesion, would lead to the ous or intermittent.
activation of certain regions of the auditory cortex, which - Modulation: represents the immediate change of tinnitus
results in the perception of tinnitus and hyperacusis.19 (intensity, frequency or location) in the presence of some
stimulus: head movement, position, muscle contraction,
stress, noise, etc.
Neurophysiological model
(b) Associated symptoms
- Hearing loss: common in patients with tinnitus, it may
The neurophysiological model described by Pawell Jastre-
indicate an underlying otologic disease.
boff in 19902 explains the process that causes an individual
- Vertigo and dizziness: a specific neurotological diagnosis
to be disturbed by tinnitus. It can be divided into three
(dizziness, lightheadedness, decreased visualacuity, faint-
phases: generation, detection and perception (Fig. 1). Gen-
ing sensation, etc.), periodicity (continuous or attacks),
eration occurs mainly in the peripheral auditory pathways
auditory symptoms (aural fullness or hypoacusis, worsen-
(cochlear or auditory nerve dysfunction). Detection occurs
ing of tinnitus, autophony) and other balance complaints
in the subcortical centers and the perception in the auditory
(lateropulsion, oscillopsia, gait changes).
cortex.
- Exposure to noise: it can be occupational or recreational.
Depending on the impact of tinnitus on the affected
The exposure period, frequency and intensity should be
individual, areas of the CNS (limbic system, frontal cortex,
characterized. It is also important to verify the exposure
autonomic nervous system) and areas of negative association
to impact noises such as fireworks, shots and explosions,
that increase patient discomfort, may be activated.13
or barotrauma.
- Otologic history: it should include all otologic symptoms.
Somatosensory Tinnitus In the presence of pain with normal otoscopy, questions
should be asked about dental symptoms: bruxism or den-
The psychoacoustic characteristics of tinnitus (intensity tal tightening, inappropriate habits such as chewing gum,
and frequency) and its location may be altered in some biting pens or pencil, etc.
patients, even temporarily, by different stimuli: forced - General symptoms and personal history: cardiovascular,
contractions of the head, face and neck muscles, pres- metabolic, hormonal, neurological or psychiatric diseases
sure of myofascial trigger points (TP). This characterizes and sleep quality.
Tinnitus and sound intolerance: evidence and experience of a Brazilian group 139

- Use of medication and illicit drugs: current use or at the in the fundoscopic examination of the eye assists in the
time of the tinnitus onset, paying special attention to the diagnosis.
use of ototoxic drugs. The evaluation of cranial nerves identifies central eti-
ologies, especially in patients with headache, paresthesia,
(c) Improvement and worsening factors diplopia or dizziness. The study of cranial pairs, cerebellar
Patients with tinnitus usually report worsening in silent tests and the assessment of upper and lower limb muscle
environments. Exposure to noise may be the temporary strength should be included. Tumors of cranial nerves IX,
worsening factor for tinnitus; for instance, in the tonic X, XI may generate pulsatile tinnitus by altering blood flow
tensor tympani syndrome and in the semicircular canal through the jugular bulb inside the jugular foramen.32
dehiscence.21 Studies on foods that interfere with tinnitus
are scarce. Fish consumption one or more times a week TMJ evaluation
and dairy restriction seem to reduce persistent tinnitus.22 When associated with tinnitus, TMJ disorders may also
Hearing loss is an important risk factor, as well as exposure exhibit otalgia, hearing loss, ear fullness, hyperacusis, and
to noise, hyperlipidemia, asthma, osteoarthritis, rheuma- dizziness. Physical examination should be performed with
toid arthritis and thyroid diseases23 and systemic arterial special attention to pain in the TMJ region (spontaneous,
hypertension.24 with chewing and during palpation); crackling of the joint;
Depression and anxiety may be associated, especially difficulty in maximal mouth opening. Forced jaw protrusion
in the most uncomfortable cases.25,26 Among the medica- or lateralization can modulate the tinnitus.
tions implicated in the onset of tinnitus are antibiotics
(aminoglycosides), diuretics (furosemide), chemotherapeu- Nasofibroscopy
tics (cisplatin), as well as nonsteroidal anti-inflammatory Some types of myoclonus can cause tinnitus via contraction
drugs and quinine.27 of the middle ear muscles (tensor tympani and stapedius
muscles)33 or muscles of the palatal region (soft palate
(d) Diet and habits and pharyngeal).34 Palatal myoclonus may be inhibited by
- Smoking: it may have an ototoxic effect.28 opening the mouth; thus, palatal observation through nasofi-
- Alcoholism: it can alter endolymph density, producing broscopy is essential.32 It is possible to observe rhythmic
transient dysfunction of the outer and IHCs. movements in the soft palate region.
- Xanthine consumption: the three main xanthine alkaloids
are caffeine (coffee), theophylline (teas) and theo- Questionnaires
bromine (cocoa), substances present in cola drinks, It is critical to distinguish between tinnitus and tinnitus
analgesic drugs, antihistamines, etc. Although excessive reactions. For that purpose, questionnaires assessing and
consumption of xanthines (above 250 mg/day or 3 cof- quantifying tinnitus and its effects on the patient’s life can
fees/day) is considered an exacerbating factor for tinnitus be used.
and dizziness, this is controversial.29 The most often used are: Tinnitus Questionnaire,35
- Consumption of fast-absorbing sugars and carbohydrates: Tinnitus Handicap Inventory (THI),36 Tinnitus Reaction
it may cause tinnitus or worsen existing tinnitus by Questionnaire37 and Tinnitus Handicap Questionnaire.38 All
hyperinsulinism and alterations in the endocochlear show good reproducibility and internal consistency and,
potential.30,31 therefore, the choice of the tool should be made based
- Prolonged fasting: The Na/K pump mechanism that is on the existence of the adapted version in the country’s
responsible for the endocochlear potential is energy language and familiarity with the questionnaire. The THI,
dependent and the inner ear does not store energy. developed by Newman,36 has been validated in several lan-
Prolonged fasting (over 3 h) is related to energy deficit guages, including Portuguese.39,40 The tool consists of 25
and alteration in the endocochlear potential, which may questions with a score varying from 0 to 100; the higher
worsen tinnitus.31 the score, the greater the effect of tinnitus on the patient’s
life. The Tinnitus Questionnaire is a long questionnaire con-
Physical examination
sisting of 52 questions and has a shorter version, called the
‘‘Mini Tinnitus Questionnaire’’ (or Mini-TQ).41 The Mini-TQ
It should include otoscopy, oroscopy, anterior and posterior has a Portuguese version, with 12 questions that mainly eval-
rhinoscopy. The otoscopy of patients with vascular tinni- uate the annoyance with tinnitus and how it affects the
tus may show a reddish retrotympanic area (paraganglioma, individual’s daily life.42
aberrant internal carotid artery in the middle ear, high and The Visual Analog Scale (VAS) is used to measure subjec-
dehiscent jugular bulb, among others). Periauricular, perior- tive phenomena, and is used widely in pain assessment. It
bital, cervical auscultation and neck palpation can provide provides a simple and quick measurement of intensity and
signs of vascular malformations, arteriovenous fistulas, or degree of annoyance, using numbers from 0 to 10.43
venous ‘‘hum’’ --- a situation in which tinnitus increases with
contralateral cervical rotation and decreases with ipsilat-
eral rotation. In the case of tinnitus related to the patent Complementary assessment
auditory tube, synchrony with respiration is observed and
otoscopy reveals motion of the tympanic membrane during Hearing tests
inspiration and expiration.
Pulsatile tinnitus may be associated with benign Hearing tests help to diagnose hearing loss, as well as to
intracranial hypertension. The presence of papilledema aid in the diagnosis leading to specific treatment. A second
140 Onishi ET et al.

reason to perform these tests is to establish if the patient is - BAEP: changes in the auditory nerve and/or brainstem can
a candidate for hearing aid use. also occur without associated hearing loss.

Audiometry (c) Patient with tinnitus and/or auditory hypersensitivity

Speech and pure-tone audiometry, and immittance testing: and dizziness regardless of hearing loss:
assess auditory acuity, type and degree of hearing loss, thus - Electrocochleography: it is indicated to investigate
directing the medical evaluation. endolymphatic hydrops.
- VEMP or Vestibular Evoked Myogenic Potential: it assesses
- High-frequency audiometry: it evaluates the frequencies the involvement of the otolithic organs and their nerve
of 9000---20,000 Hz, corresponding to the base of the pathways. It evaluates the involvement of otolithic organs
cochlear. There is still no consensus for auditory thresholds and the associated pathways.
at these frequencies.
- Acuphenometry: tinnitus can be measured to demonstrate (2) Examinations requested for scientific research and
to patients that their tinnitus is real, help in patient coun- understanding of pathophysiological mechanisms of
seling, and assist in sound therapy prognosis. tinnitus and/or sound hypersensitivity:
- Tinnitus Matching (TM) attempts to establish the pitch
(frequency) and loudness (intensity) of tinnitus. - BAEP: The increased amplitude ratio of III/I and V/I waves
- Minimum Masking Level (MML) evaluates the lowest sound suggests greater electrical activity in the ventral cochlear
intensity that masks the tinnitus. nucleus and inferior colliculus, while the increase in the
- Residual Inhibition or Suppression Effect: evaluates the latency of the V wave and the III-V interpeak suggest
temporary inhibition of tinnitus, after stimulation with changes in electrical conduction, whether primary or sec-
broadband noise 10 dB above MML, for 60 s. When present, ondary to the tinnitus.45
partial or total inhibition occurs after the end of the stim- - P300: altered latencies may suggest changes in functions
ulus and lasts a brief time until the tinnitus returns to its such as attention and short-term auditory memory.46
previous level.
- LDL: assesses the noise discomfort threshold. Pure or Contralateral suppression of OAE: it evaluates the
pulsating tones are presented, with a gradual increase involvement of the corticofugal auditory efferent system
of 5 in 5 dB, between 500 and 8000 Hz, with 1-second in the origin and maintenance of tinnitus and auditory
inter-stimulus intervals and 1-second duration. The hypersensitivity.47
patient should raise his/her hand when the sound is at
such intensity that he or she does not want to hear it (ini- Laboratory tests
tial discomfort), in order to evaluate the lowest sound
intensity that causes discomfort. Some tests may provide relevant information to the investi-
gation of etiological, predisposing, or coadjuvant factors in
patients with tinnitus.
Electrophysiological and electroacoustic tests
- Fasting glucose and glycated hemoglobin: may be
Electrophysiological and electroacoustic tests help to man- replaced or supplemented by the 3-h glucose tolerance
age the patient with a tinnitus complaint in two ways: test and insulin curve. In this case, the objective is to
by facilitating the investigation of the causal factor and evaluate glucose metabolism and the consequent insulin
the understanding of the pathophysiological mechanisms production, with hyperinsulinemia and reactive hypo-
involved. glycemia being possible suspicions, or also, disaccharidase
alterations (lactose intolerance).31
(1) Tests requested for topographic assessment of tinnitus: - Total cholesterol and fractions and Triglycerides: allow
investigating factors that cause blood hyperviscosity or
(a) Patient with tinnitus and/or auditory hypersensitivity atherosclerotic plaques.48
and sensorineural hearing loss: - Free T4, TSH, anti-peroxidase antibodies and antithy-
- Brainstem Auditory Evoked Potential (BAEP): when the roglobulin antibodies: search for early thyroid
objective is to evaluate the auditory nerve and/or brain- abnormalities.23,49
stem (tumors, demyelination or dyssynchrony).
- Transient/Distortion-Product OAEs: Normal OAEs and Zinc: especially in elderly patients, or in the postopera-
altered audiometric thresholds suggest a noncochlear tive period of bariatric surgery, in which this trace element
cause. In this situation, imaging tests and/or BAEP assess- may be deficient.50
ment should be requested.44 Other tests may be requested, such as the whole blood
count; Magnesium51 ; Vitamin B1252 ; Folic acid53 ; Cortisol54 ;
(b) Patient with tinnitus and/or auditory hypersensitivity Serotonin54 ; Vitamin D; Ferritin.
without hearing loss:
- Transients/Distortion-Product OAE: its alteration suggests Laboratory tests in patients with hyperacusis
that such a cochlear lesion was not sufficient to gener-
ate effects on tonal audiometry, similar to a subclinical To date, laboratory abnormalities related to hyperacusis and
hearing loss. misophonia have not been identified.
Tinnitus and sound intolerance: evidence and experience of a Brazilian group 141

Imaging diagnosis angiography. It helps to investigate pulsatile tinnitus,

palatal or stapedius myoclonus, as there may be associ-
(1) Imaging tests in non-rhythmic tinnitus ated neurological lesions. It also helps in the diagnosis
- Cervical X-ray: allows the diagnosis of cervical diseases of benign intracranial hypertension, which usually affects
such as compression of vessels by the alar process of the middle-aged, Caucasian, obese women with complaints of
vertebrae. headache, visual blurring, double vision and/or pain on
- Temporal bone tomography: this test allows the identi- ocular movement.58
fication of middle and inner ear diseases that may be - Angiography: it allows the diagnosis of small arteriove-
associated with non-rhythmic tinnitus.30,55 nous fistulas, but it should be the last option due to its
- Magnetic resonance imaging of the inner ear with gadolin- risks. It also becomes important in patients with glomus
ium: it helps in the identification of neurologic diseases tumor to assess the vascular supply and the possibility for
and is essential to rule out retrocochlear disease in embolization.59
patients with unilateral or asymmetrical tinnitus, with or
without hearing loss.30,55 Fig. 2 shows a suggested investigation flowchart for pul-
satile tinnitus.
(2) Imaging tests in patients with rhythmic tinnitus
- Temporal bone CT with contrast: it may clarify possi-
ble retrotympanic pulsatile lesions identified at otoscopy: Treatment and rehabilitation
aberrant carotid artery, high jugular bulb and glomus
tumor.56 Counseling is a principal component of two important ther-
- Doppler ultrasound of carotid, vertebral and subclavian apies for hyperacusis. In Hyperacusis Activities Treatment,
arteries: it investigates atherosclerotic disease that can guidelines on thinking, emotions, hearing, concentration
change laminar blood flow. These patients usually have and sleep are proposed, in addition to the acoustic ther-
hypercholesterolemia, hypertension, diabetes mellitus, apy that will be discussed below. This counseling is directed
angina and smoking habit.56 by a specific questionnaire to recognize the areas most
- Transcranial Doppler ultrasound: it evaluates atheroscle- affected.60 In Tinnitus Retraining Therapy (TRT), the coun-
rosis in the intracranial carotid system, in addition to arte- seling is also directed toward auditory hypersensitivity ---
rial malformations and other vascular abnormalities.56 hyperacusis and misophonia. In the latter, results exceed 76%
- Angiotomography: it is considered the gold standard in for isolated hyperacusis or 83% for isolated misophonia.61
pulsatile tinnitus. It shows the association of the vessels Ear protective devices can increase a person’s hear-
with the bony structures of the temporal bone.57 ing sensitivity and we often see patients with hyperacusis
- Magnetic resonance angiography: the arterial phase is wearing them. They should be encouraged to avoid such
important in the diagnosis of carotid artery dissection. protection because it reinforces an association between
The venous phase allows the diagnosis of fistulas and arte- auditory signals and distress and potentiates existing fear
riovenous malformations, but with less sensitivity than and underlying anxiety.62

Pulsatile tinnitus

Otoscopy
Retrotympanic Tu Normal

TB CT/MRI Normal Auscultation/

SAH/anemia/ compression and
hyperthyroidism ipsilateral cervical torsion
Tinnitus decreases Tinnitus does not change
High jugular
Glomus
bulb/ arterial
Venous
Aberrant
carotid
CT/angiography venous CT/angiography MRI
MRI/transcranial US or CT/transcranial US

Normal Arthrosclerosis
Changed fundoscopy Normal fundoscopy Jugular bulb abnormality /AVF/AVM
or sigmoid sinus /
BIH Venous HUM hydrocephalus Idiopathic

Figure 2 Flowchart of pulsatile tinnitus investigation. Tu, tumor; CT, computed tomography; TB, temporal bones; SAH; systemic
arterial hypertension; MRI; magnetic resonance imaging; US, ultrasound; BIH, benign intracranial hypertension; AVF, arteriovenous
fistula; AVM, arteriovenous malformation.
142 Onishi ET et al.

Pharmacological and surgical treatment of Ginkgo Biloba shows diverse results in systematic
hyperacusis reviews. A recent study assessing 1543 patients, concluded
that there is limited evidence to demonstrate its efficacy in
Successful treatments have already been described tinnitus treatment.67
in patients with hyperacusis using alprazolam,63 A single study analyzed the efficacy of vinpocetine
carbamazepine,21 fluoxetine and fluvoxamine64 and demonstrating some positive results in tinnitus associated
citalopram.17 with acoustic trauma.68
Regarding the surgical treatment of hypersensitiv- Betahistine may be effective when tinnitus is associated
ity, isolated reports in the literature range from fascia with dizziness.69
reinforcement placed on the oval and round windows,
obliteration of semicircular canal dehiscence and even Ion channels
labyrinthectomy.65,66
There have been studies on drugs that act on the sodium,
Pharmacological treatment of tinnitus potassium and calcium channels.

Although to date there is no drug approved by the F.D.A. Sodium channels

(Food and Drug Administration) with a specific indication
for tinnitus treatment, there is no reason to believe that The prototype of this approach was the verification of the
tinnitus cannot be pharmacologically treated. immediate effects of intravenous lidocaine on tinnitus.70
There is no consensus regarding the duration of treat- However, because of the administration route and possible
ment, as it should be individualized. In most studies, the side effects, there is no clinical application for lidocaine
treatment is carried out for 2---3 months. in tinnitus treatment. A systematic review of the use of
Didactically, one can classify drugs for tinnitus treatment anticonvulsants (including carbamazepine and lamotrigine)
in three large groups (Table 2): concluded that there is no evidence that anticonvulsants
have a significant positive effect on tinnitus treatment.71
- Drugs that improve vascular supply and inner ear
metabolism;
- Drugs that act on ion channels; Potassium channels
- Drugs that act on neurotransmitters.
There is only experimental evidence of the effect of this
type of drug on tinnitus, including the flindokalner.72
Vascular and metabolic supply of the inner ear

The indication for the use of trimetazidine, which pre-

Calcium channels
sumably acts on cochlear metabolism, has recently been
withdrawn for treatment of dizziness and tinnitus. Although the mechanism of action for gabapentin is not fully
understood, it is believed that calcium channel blocking is
the main mechanism. A recent systematic review concluded
that there is not enough clinical evidence to recommend the
Table 2 Classification of medications for tinnitus
use of gabapentin for the treatment of tinnitus.73
treatment.
A single open-label study evaluated the effects of
Mechanism of action Medications nimodipine with a poor outcome.74
Improves vascular supply and Trimetazidine
internal ear metabolism Ginkgo biloba extract Neurotransmitters
Vinpocetine
Betahistine Glutamate
Effect on ion channels Carbamazepine
Gabapentin This is the main excitatory neurotransmitter and the
Nimodipine effects of excitotoxicity have been well experimentally
documented.16 Caroverine blocks AMPA and NMDA receptors,
Effect on Neurotransmitters Caroverine
but the promising initial results were not replicated.75 It is
Memantine
not commercially available in Brazil. Memantine is an NMDA
Acamprosate
blocker that has shown promising results in experimental
Clonazepam
studies,76 but not in a clinical trial.77 Acamprosate is an
Baclofen
NMDA blocker that also has GABAergic activity. The results
Sertraline
were positive in two studies,78,79 but the drug is not available
Trazodone
in Brazil. The clinical trial of the NMDA blocker esketamine
Cyclobenzaprine
(AM-101) for the treatment of tinnitus for up to 3 months
Pramipexole
in duration, using intratympanic injections, is currently in
Sulpiride
phase 3, with very promising phase 2 results.80
Tinnitus and sound intolerance: evidence and experience of a Brazilian group 143

GABA - Vitamin B12: Vitamin B12 deficiency may cause tinni-

tus and cyanocobalamin replacement may improve the
A recent systematic review of the benzodiazepines used symptom.52
in the treatment of tinnitus has concluded that there is - Melatonin (N-acetyl-5-methoxitriptamine): is a hormone
evidence, albeit not robust, of positive effects of clon- secreted by the pineal gland. It acts on sleep control, has
azepam, a GABA-A receptor agonist, but not of alprazolam neuromodulatory action and antioxidant properties.94 The
or diazepam.81 In a randomized cross-over study against use of melatonin improves sleep, particularly in elderly
Ginkgo biloba, the efficacy of clonazepam in tinnitus relief patients with insomnia. It is inexpensive and safe, and
was demonstrated.82 The risk of dependence and side has few adverse effects. Preliminary studies suggest that
effects (drowsiness, urinary retention, increased eye pres- melatonin has a positive effect on sleep disturbances
sure) require caution for its use. caused by tinnitus.95
Experimental evidence for efficacy of the GABA-B agonist - Zinc: this element plays an essential role in function of
baclofen a has not been replicated in clinical trials.83 the cochlear and auditory pathways. Zinc replacement
therapy may benefit patients with tinnitus,96 especially
in subjects with zinc deficiency.
Serotonin

Selective serotonin reuptake inhibitors (SSRIs) are widely Sound therapy

used as antidepressants in the associations between tinnitus,
anxiety, and depression. A recent systematic review con- Personal Sound Amplifier (PSA) and sound
cluded that there is insufficient evidence of a direct effect generator
of antidepressants on tinnitus.84 However, they may be help-
ful in relieving depression and anxiety associated with it. It There is an association between tinnitus and hearing loss
is worth adding that there are reports about the onset or in approximately 85---96% of cases.2 The decrease in the
worsening of tinnitus with the use of antidepressants, espe- sound entry into the cochlea results in a decrease in affer-
cially the tricyclic ones. A single clinical trial demonstrated ent activity to the auditory nerve and the auditory pathways,
the benefits of sertraline, an SSRI, in tinnitus relief.85 Tra- resulting in changes in all pathways that are responsible for
zodone, a serotonin modulator, on the other hand, showed the appearance of tinnitus.97 Several studies have shown a
no beneficial effects.86 reduction of tinnitus annoyance with the use of a hearing
Cyclobenzaprine has several mechanisms of action, aid and/or sound generator.98,99 In the American Academy
including 5 HT-2 receptor antagonism. Clinical studies of Otorhinolaryngology guidelines, the use of hearing aids
showed a positive effect in some patients at the dose of is recommended for patients with hearing loss and tinnitus
30 mg a day.87 discomfort, although prospective studies are of low qual-
ity and limited by methodological problems (bias, small
Dopamine sample, short time of treatment and with associated treat-
ments, such as sound therapy and counseling). The literature
Agonists (piribedil88 and pramipexole89 ) and antagonists contains some studies that showed improvement in tinni-
(sulpiride90 ) have shown beneficial effects in clinical tri- tus discomfort with the use of the hearing aid after one
als, but need confirmation by randomized trials with larger to three months of treatment.99,100 Therefore, we suggest
samples. Pyribedil was commercially discontinued in Brazil that a test with PSA, with or without a sound generator,
approximately 2 years ago. should be performed for a period equal to or greater than 30
days. The tinnitus improvement occurs in approximately 82%
of patients who used an open-fit BTE (Behind-the-Ear) PSA
Other mechanisms of action
with relief ventilation, and there was no difference between
the two groups. However, the preference for open-fit occurs
Several drugs have already been assessed in clinical studies in 66% of the patients.100 In clinical practice, we observed
without meaningful results, such as melatonin, furosemide, that patients who receive both a hearing aid and a sound
atorvastatin, misoprostol, vardenafil. The drugs described generator show tinnitus improvement during the prosthesis
for use in tinnitus cases of muscular origin include clon- adaptation period and often choose the device without a
azepam, thiocolchicoside and sumatriptan.91 There are sound generator, since the hearing aid helps to mask exter-
clinical reports on the relief of tinnitus of vascular origin nal noise. Sound amplification improves patient quality of
with propranolol.92 life by favoring hearing and masking tinnitus. Advice and/or
guidance regarding tinnitus is essential during the adapta-
Use of supplements in the treatment of tion to hearing aids, aiming to inform the patient about the
tinnitus reason for choosing this treatment to improve both hearing
and tinnitus.
Dietary supplements may contain vitamins, minerals, herbs
or nutritional substances. Considered as ‘‘natural’’ prod- Sound generator
ucts, they are inexpensive and can be sold without a It can be used in several ways: mixing point --- TRT, total
prescription, but that does not necessarily mean they are and partial sound masking. Or, the lowest intensity capa-
safe and effective.93 The most often used in the treatment ble of promoting tinnitus relief --- TAT (Tinnitus Activities
of tinnitus are: Treatment).101 Any therapeutic approach applying sound
144 Onishi ET et al.

therapy for tinnitus is improved when it is associated with of the notched sound to reduce the excitability of hyperac-
counseling/guidance. tive auditory neurons, which would occur as a result of the
In patients with reduced sound tolerance, it is essential strengthening of inhibitory networks, previously weakened
to avoid sound deprivation with the use of an ear protector, in the critical frequency band of tinnitus.
which can increase central auditory gain and exacerbate the
symptoms of hyperacusis.4 In these cases, it is advisable to Tones for central neural auditory desynchronization
carry out sound desensitization with the use of a sound gen- Acoustic Coordinated Reset Neuromodulation aims to reduce
erator and hearing aid, gradually introducing the sound for abnormal levels of synchronous neural activity in the cere-
the time that is tolerated by the patient. The adaptation bral auditory cortex, a condition in which a large population
must be slow and progressive, depending on the patient’s of neurons repeatedly and spontaneously fires impulses at
tolerance. Initially, it is recommended to use the hearing the same time. The Neuromodulator CR emits a sequence
aid in quiet environments and, subsequently, in noisy envi- of low intensity tones, obtained through a mathemati-
ronments. In severe cases of reduced sound tolerance, it cal algorithm in which the used tones coincide with the
may be necessary to initially apply the sound generator to frequency bands adjacent to the tinnitus frequency, individ-
improve sound tolerance and a later adaptation with a hear- ually adjusted for each person. The objective is to stop the
ing aid.102 Currently, the use of digital technology devices increase of the abnormal synchronic firing in brain auditory
has facilitated the programming of these treatments com- neurons, responsible for the tinnitus perception.106
bined with a hearing aid and a sound generator. The use of
hearing aids may be valid in patients suffering from tinnitus,
Habituation therapy or TRT
even with mild hearing loss.
TRT or Habituation Therapy aims to change the most acti-
Music therapy in tinnitus treatment vated neural networks in patients with tinnitus annoyance,
which are limbic system (hippocampal segment) and the
Customized sounds for tinnitus pitch autonomic nervous system, regardless of the source of the
Customized acoustic stimuli are adapted according to the tinnitus.2 The TRT is based on three pillars:
patient’s hearing and tinnitus pitch. Two types of sounds
are offered: relaxing soft music of variable amplitude and a - Demystification: includes all measures used to reduce or
broadband noise similar to white noise. At different phases, eliminate the negative connotation and activation of the
the white noise is added or may be removed to help mask limbic and autonomic nervous systems.
the tinnitus. Between 80 and 90% of patients experienced a - Counseling: covers all anti-tinnitus measures. The removal
significant reduction in tinnitus, even when they were not of negative associations related to tinnitus, through coun-
using the device.103 seling sessions in which the patient understands the
hearing function and the mechanisms of tinnitus percep-
Fractal tones tion, may be sufficient to promote the habituation of the
Based on the fractal analysis of sounds, five patterns of semi- reaction, that is, the patient can still perceive the tinni-
random tones, similar to bell tunes, were created along with tus, but ceases to be bothered by it.
broadband white noise. The proposal is the presentation of - Habituation: physiological process characterized by the
melodic tones with a slower time (60---70 beats per minute, progressive decline of responses to the same stimulus. The
similar to resting heart rate), less repetition and without concomitant use of sound therapy may be necessary, for
emotional content, which promotes relaxation. A study on it promotes the constant input of sounds, either through
the effectiveness of music therapy with fractal tones showed sound generators, hearing aid amplification prostheses or
that it does not depend on the nature of the hearing loss or environmental sounds. Habituation occurs if the stimulus
tinnitus characteristics.104 is neutral, that is, free of associations and/or connotations
with negative emotional states. Patients with hyperacu-
S-Tones with modulated amplitude and frequency sis, associated or not with tinnitus, are also candidates
S-Tones, with modulated frequency and amplitude, produce for treatment with TRT. Table 3 summarizes the propo-
a robust and synchronized neuronal activity in the audi- sals and modalities of TRT treatment according to patient
tory cortex. Very slow sounds produce explosions of neural groups. The efficacy of habituation therapy is around
activity, and very fast sounds do not show synchroniza- 84---86%, and may vary according to patient adherence to
tion, but if presented within a specific interval, the neurons treatment.107,108
synchronously fire in response to the sound stimulus. Sup-
pression is a physiological process where sounds modulate Transcranial magnetic stimulation (TMS)
the activity of the auditory cortex and interrupt tinnitus
generation.105 It is a noninvasive technique of neurostimulation and cor-
tical neuromodulation. The procedure generates repetitive
Spectral notched music pulses of short duration (100---300 microseconds) and high
The notched music, tailor-made with the removal of sounds power (1.5---2.0 Tesla) magnetic field.109 Modern TMS systems
that have the same frequency as the tinnitus, can reduce its apply a rapidly changing magnetic field over a specific neu-
volume. The results indicate that the short-term, intensive ral region, inducing electrical activity in the target cortical
Tailor-Made Notched Sound Therapy seems to be effective in region. This is typically characterized by disruption of the
patients with tinnitus frequencies ≤8 kHz due to the ability stimulated target area activity and potential for change in
Tinnitus and sound intolerance: evidence and experience of a Brazilian group 145

Table 3 Categorization of tinnitus patients for TRT.

Category Tinnitus Hypoacusis Hyperacusis Exacerbation Therapy
with sound
0 Low impact Absent Absent Absent Counseling
1 High impact Absent Absent Absent Sound generator at the mixing point
2 High impact Present Absent Absent PSA + Sound enrichment
3 High impact Absent Present Absent Sound generator close to auditory threshold
4 High impact Absent Present Present Sound generator close to auditory threshold

the function of the interrupted area. Therefore, there is Physical therapy in the treatment of chronic
neuroplasticity modulation in cortical and thalamic-cortical tinnitus
areas in the same way. TMS is a safe and effective proce-
dure for tinnitus control, but it requires studies with a longer There are anatomical and functional associations between
follow-up period.110 the ears and the mandible, face, nape and neck. Somatosen-
sory tinnitus may be divided according to the topography
Cognitive-behavioral therapy (CBT) of symptoms as (1) Craniofacial Dysfunction (CFD), and (2)
Craniocervical Dysfunction (CCD).
Therapeutic approaches typically involve relaxation training
to reduce alertness, creating methods to ignore the tinnitus- CFD
related information. CBT aims to identify and change the
emotional significance of tinnitus. According to McKenna
They represent TMJ, masticatory system muscles and/or
et al.,111 regardless of the symptom’s initial cause, the cog-
neuromuscular attachment dysfunctions. In 2003, Tuz et al.
nitive behavioral process contributes to its severity through
evaluated the prevalence of 4 otologic symptoms (otalgia,
intrusive negative thoughts, selective attention, hypervigi-
tinnitus, vertigo and hearing loss) in 200 patients with tem-
lance, misconceptions, counterproductive behaviors and a
poromandibular dysfunction and compared them with an
distorted perception of tinnitus. CBT is structured, for a
asymptomatic control group.117 Tinnitus is at least 2 times
limited time, as an objective to help the patient face certain
more prevalent in patients with CFD. The following are asso-
difficulties, constructing positive thoughts. A 15-year follow-
ciated factors: dental malocclusion associated with stress
up study demonstrated stability in the improvement,112
and muscular tension, inadequate masticatory power and/or
constituting a good therapeutic option for patients with tinn-
muscular overload during the masticatory process, bruxism,
itus, alone or associated with other types of treatment.
anxiety disorders, systemic diseases that alter bone struc-
tures, postural disorders, sleep deprivation. The otologic
Acupuncture symptomatology is due to the fact that the ears and the TMJ
and its attachments share common innervations (mainly the
Acupuncture has been used in the treatment of tinni- V and VII cranial nerves) and have neural networks crossed
tus, similar to the treatment of painful conditions. The at the level of the brainstem that are able to modulate
needle stimulation causes an electrical discharge that trigg- each other. The cranio-cervical-facial system (mouth, face,
ers action potentials and influences the activity of the head and neck) can modulate the onset and/or perception of
olivocochlear nucleus or the modulation of ascending audi- tinnitus twice as frequently in tinnitus patients than in the
tory pathway connections with the limbic system and the ones without this symptom.118 The long-term effects of TMJ
amygdala.6 In the studies that showed positive results of treatment have been described in 73 tinnitus patients and
acupuncture on tinnitus, the time and degree of improve- in 50 patients with tinnitus and TMJ dysfunction.119 In the
ment were very variable.113---115 Acupuncture is a safe treatment group, 43% of the patients had tinnitus improve-
treatment option with no adverse effects, but more studies ment, 39% had unaltered tinnitus, and 18% had symptom
are required to evaluate its effect on tinnitus. worsening.

Mindfulness CCD
Mindfulness has its origin in Eastern meditative practices. It A recent study showed that among treated patients with
is defined as a specific form of concentration at the present non-pulsatile tinnitus, 43% were diagnosed with somatosen-
time, intentionally and without judgment. The practices sory tinnitus.120 CCD may be related to inadequate posture
encompass several techniques, such as breathing exercises, of the body. The patient has pain and physiological move-
experiencing everyday situations in a conscious way and ment limitation, neck stiffness, sensitivity and/or pain
attention to the sense organs. Studies have shown benefits at cervical muscle palpation, radiated pains, headaches
over tinnitus, reducing annoyance, improving depressive and and joint dysfunction. Cervical proprioception dysfunction
anxious states and facilitating the acceptance of tinnitus by may cause tinnitus and other neurotological symptoms.
the patient in up to 87.5%.116 The patient should be referred early for multidisciplinary
146 Onishi ET et al.

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