Tinnitus: Difference between revisions

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==Overview==
==Overview==
[[Tinnitus]] is derived from the Latin word ''tinnire,'' meaning to ring. Tinnitus can be classified as subjective and objective.  This classification not only explains the underlying etiology but also directs the management of tinnitus. In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the [[cochlea]] to the [[auditory cortex]] via [[midbrain]].  Conditions associated with [[Cochlear nucleus|cochlear]] damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model. Common causes of tinnitus include [[Ototoxicity]], [[Presbycusis]], noise induced [[hearing loss]], late onset congenital [[hearing loss]], [[Ménière's disease|meniere's disease]],  and [[Loop diuretics]]. The [[incidence rate]] of tinnitus increases with age and is more prevalent in older people. Tinnitus is more prevalent in men compared to women and [[Smoking|smokers]] compared to non-smokers. If left untreated, patients may progress to functional impairment, [[insomnia]], [[anxiety]], and [[depression]]. TSI is used to rank the patient's based upon their severity. The score ranges from 0-45. Symptoms and history include sounds such as ringing, buzzing, pulsatile, roaring and humming and progressive hearing loss.  An extensive neurological examination may rule out underlying brainstem damage or hearing loss. The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal.  MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed. Initial audiometric tests are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem.  These tests include: pure-tone audiogram, tympanometry, auditory reflex testing, determination of speech discrimination abilities, otoacoustic emissions testing and auditory brainstem response testing (ABR).  Tinnitus is a symptom and not a disease itself.  It is a chronic condition that can be managed by treating the underlying etiology. The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus.  It is usually achieved by identifying the underlying pathology or the associated disease. It is recommended to treat underlying [[insomnia]] and depression (Grade 1B). [[Cochlear implants]] may be considered for tinnitus associated with severe [[sensorineural hearing loss]]. Other therapies include: [[tinnitus retraining therapy]] (TRT) (Grade 1C), [[biofeedback]] (Grade 2C), and  [[Cognitive behavioral therapy|cognitive behavioral therapy (CBT)]] as an adjunct to TRT (Grade 2C). [[Acupuncture]] and electrical stimulation are considered equally effective as placebo, no significant role established so far.
<br />
<br />
==Historical Perspective==
==Historical Perspective==


*In the early 19th century, Frenchman and Jean Marie Gaspard Itard introduced the concept of masking.  They were the first ones to differentiate between subjective and objective tinnitus.
*In the early 19th century, Frenchman and Jean Marie Gaspard Itard introduced the concept of masking.  They were the first ones to differentiate between subjective and objective [[tinnitus]].
*Later in the 19th Century, with the introduction of germ theory and anesthesia, surgical therapy such as incudectomy was established.
*Later in the 19th Century, with the introduction of germ theory and [[anesthesia]], surgical therapy such as incudectomy was established.
*Tinnitus is derived from the Latin word ''tinnire,'' meaning to ring.
*[[Tinnitus]] is derived from the Latin word ''tinnire,'' meaning to ring.
*
*


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===Subjective tinnitus:===
===Subjective tinnitus:===


*It is only experienced by the affected individual in the absence of any auditory stimulation
*It is only experienced by the affected individual in the absence of any [[auditory]] stimulation
*More common, usually described as continuous ringing, high pitch sound
*More common, usually described as continuous ringing, high pitch sound


Line 23: Line 25:


*It is experienced not only by the affected individual but also by anyone else
*It is experienced not only by the affected individual but also by anyone else
*Relative rare, usually described as intermittent venous hum, low pitch sound
*Relative rare, usually described as intermittent [[venous hum]], low pitch sound
*It has an underlying vascular (abnormality of the carotid artery, jugular bulb or jugular vein) or muscular etiology (degenerative conditions such as amyotrophic lateral sclerosis) and usually caused by sound produced in ear, head or neck.<br />
*It has an underlying [[vascular]] (abnormality of the [[carotid artery]], jugular bulb or [[jugular vein]]) or [[muscular]] etiology (degenerative conditions such as [[Amyotrophic lateral sclerosis diagnostic evaluation|amyotrophic lateral sclerosis]]) and usually caused by sound produced in ear, head or neck.<br />


==Pathophysiology==
==Pathophysiology==


In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain.  Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model.
In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the [[cochlea]] to the [[auditory cortex]] via [[midbrain]].<ref name="pmid24744443">{{cite journal |vauthors=Minen MT, Camprodon J, Nehme R, Chemali Z |title=The neuropsychiatry of tinnitus: a circuit-based approach to the causes and treatments available |journal=J. Neurol. Neurosurg. Psychiatry |volume=85 |issue=10 |pages=1138–44 |date=October 2014 |pmid=24744443 |doi=10.1136/jnnp-2013-307339 |url=}}</ref><ref name="pmid10601720">{{cite journal |vauthors=Qiu C, Salvi R, Ding D, Burkard R |title=Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain |journal=Hear. Res. |volume=139 |issue=1-2 |pages=153–71 |date=January 2000 |pmid=10601720 |doi=10.1016/s0378-5955(99)00171-9 |url=}}</ref>  Conditions associated with [[Cochlear nucleus|cochlear]] damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model.<ref name="pmid10669517">{{cite journal |vauthors=Melcher JR, Sigalovsky IS, Guinan JJ, Levine RA |title=Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation |journal=J. Neurophysiol. |volume=83 |issue=2 |pages=1058–72 |date=February 2000 |pmid=10669517 |doi=10.1152/jn.2000.83.2.1058 |url=}}</ref><ref name="pmid9443467">{{cite journal |vauthors=Lockwood AH, Salvi RJ, Coad ML, Towsley ML, Wack DS, Murphy BW |title=The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity |journal=Neurology |volume=50 |issue=1 |pages=114–20 |date=January 1998 |pmid=9443467 |doi=10.1212/wnl.50.1.114 |url=}}</ref>


====Lesion projection zone (LPZ):====
====Lesion projection zone (LPZ):====
This zone is defined as the area in the auditory cortex that represents the damaged cochlear input.  The neurons in the LPZ zone show 2 main changes:
This zone is defined as the area in the [[auditory cortex]] that represents the damaged [[Cochlear nerve|cochlear]] input.  The [[neurons]] in the LPZ zone show 2 main changes:


*Accelerated spontaneous firing rate
*Accelerated spontaneous firing rate
*Increased representation of neurons that represent the damaged cochlear region also known as lesion edge frequencies in the LPZ
*Increased representation of [[neurons]] that represent the damaged [[Cochlear nerve|cochlear]] region also known as lesion edge frequencies in the LPZ


===Tinnitus model:===
===Tinnitus model:===
This model explains 2 major phenomena in the auditory cortex caused by lack of sensory peripheral auditory input (cochlea)
This model explains 2 major phenomena in the [[auditory cortex]] caused by lack of [[sensory]] [[Peripheral Nervous System|peripheral]] auditory input ([[cochlea]])


*Hyperactivity in the lesion projections zone (LPZ)
*Hyperactivity in the lesion projections zone (LPZ)
*Increased cortical representation of the lesion-edge frequencies in the LPZ
*Increased [[Cortical area|cortical]] representation of the lesion-edge frequencies in the LPZ


==Causes of subjective tinnitus==
==Causes of subjective tinnitus==
===Common Causes===
====Sensorineural hearing loss:====
====Sensorineural hearing loss:====


*Ototoxicity
*[[Ototoxicity]]
*Presbycusis
*[[Presbycusis]]
*Noise induced hearing loss
*Noise induced [[hearing loss]]
*Late onset congenital hearing loss
*Late onset congenital [[hearing loss]]
*Idiopathic
*[[Idiopathic]]


====Cochlear injury:====
====Cochlear injury:====


*Ménière disease
*[[Ménière's disease|Meniere's disease]]
*Loop diuretics
*[[Loop diuretics]]
*Platinum based chemotherapy
*Platinum based [[chemotherapy]]
*Antibiotics
*[[Antibiotics]]
*Salicylate
*[[Salicylate]]
*Trauma
*[[Trauma]]


====Vascular causes:====
====Vascular causes:====


*Systemic hypertension
*[[Systemic hypertension]]
*Sickle cell anemia
*[[Sickle cell anemia]]
*Small vessel disease
*[[Small-sized vessel vasculitis|Small vessel disease]]<ref name="pmid9927967">{{cite journal |vauthors=Fortune DS, Haynes DS, Hall JW |title=Tinnitus. Current evaluation and management |journal=Med. Clin. North Am. |volume=83 |issue=1 |pages=153–62, x |date=January 1999 |pmid=9927967 |doi=10.1016/s0025-7125(05)70094-8 |url=}}</ref><ref name="pmid10609479">{{cite journal |vauthors=Levine RA |title=Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis |journal=Am J Otolaryngol |volume=20 |issue=6 |pages=351–62 |date=1999 |pmid=10609479 |doi=10.1016/s0196-0709(99)90074-1 |url=}}</ref>
*Hypercholesterolemia
*[[Hypercholesterolemia]]
*Hypercoagulable state
*[[Hypercoagulable state]]
*Diabetic vasculopathy
*[[Diabetic vascular disease|Diabetic vasculopathy]]


====CNS causes:====
====CNS causes:====


*Pseudotumor cerebri
*[[Pseudotumor cerebri]]
*Stroke
*[[Stroke]]
*Vascular malformations
*[[Vascular malformations]]
*Tumor
*[[Tumor]]
*Sarcoid
*[[Sarcoid]]
*Multiple sclerosis
*[[Multiple sclerosis]]


====Infections:====
====Infections:====


*Rubella
*[[Rubella]]
*Cytomegalovirus
*[[Cytomegalovirus]]
*Chronic otitis media
*[[Chronic otitis media]]
*Neurosyphilis
*[[Neurosyphilis]]
*Measles
*[[Measles]]
*Lyme disease
*[[Lyme disease]]
*Meningitis
*[[Meningitis]]


====Bone disease:====
====Bone disease:====


*Otosclerosis
*[[Otosclerosis]]
*Fibrous dysplasia
*[[Fibrous dysplasia]]
*Osteogenesis imperfecta
*[[Osteogenesis imperfecta]]
*Paget disease
*[[Paget's disease]]


====Metabolic disorders:====
====Metabolic disorders:====


*Hyperparathyroidism
*[[Hyperparathyroidism]]
*Chronic renal failure
*[[Chronic renal failure]]
*Diabetes mellitus
*[[Diabetes mellitus]]
*Thyroid disease
*[[Thyroid diseases|Thyroid disease]]


====Autoimmune diseases:====
====Autoimmune diseases:====


*Autoimmune inner ear disease
*[[Autoimmune disease|Autoimmune]] inner ear disease
*SLE
*[[SLE]]
*Rheumatoid arthritis
*[[Rheumatoid arthritis]]


====Medications:====
====Medications:====


*ACE inhibitors
*[[ACE inhibitor|ACE inhibitors]]
*Antimalarial medications
*[[Antimalarial medication|Antimalarial]] medications
*Aminoglycosides
*[[Aminoglycosides]]
*Dapsone
*[[Dapsone]]
*Doxazosin
*[[Doxazosin]]
*Calcium channel blockers
*[[Calcium channel blockers]]
*Benzodiazepines
*[[Benzodiazepines]]
*Cisplatin
*[[Cisplatin]]
*Clarithromycin
*[[Clarithromycin]]
*COX-2 inhibitors
*[[COX-2 inhibitor|COX-2 inhibitors]]
*Loop diuretics
*[[Loop diuretics]]
*Tricyclic antidepressant<br />
*[[Tricyclic antidepressant]]<br />


==Differential Diagnosis of Tinnitus==
==Differential Diagnosis of Tinnitus==
<br />
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Diseases
| colspan="5" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Clinical manifestations'''
! colspan="2" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para-clinical findings
| colspan="1" rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Gold standard'''
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Additional findings
|-
| colspan="4" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Symptoms'''
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical examination
|-
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acute onset
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Recurrency
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Nystagmus
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hearing problems, tinnitus
|-
| colspan="10" style="background: #7d7d7d; color: #FFFFFF; text-align: center;" |'''Peripheral'''
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Ramsay Hunt syndrome type II|HSV oticus]]<br>
 
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px;" |
*loss of tastein the front two-thirds of the [[tongue]]
*[[Acute facial nerve paralysis]]
*[[Vesicles]] in the [[ear canal]], the [[tongue]], and/or [[hard palate]]
 
| style="background: #F5F5F5; padding: 5px; text-align: center;" | + [[Varicella zoster virus|VZV]] antibody titres
| style="background: #F5F5F5; padding: 5px;" |
*[[Magnetic resonance imaging|MRI]] with [[gadolinium]] contrast may show enhancement of the [[facial nerve]] and [[vestibulocochlear nerve]]
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]
| style="background: #F5F5F5; padding: 5px;" |
*May be associated with [[otalgia]], [[dry mouth]] and [[dry eyes]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Ménière's disease|Meniere disease]]<br>
 
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | + (Progressive)
| style="background: #F5F5F5; padding: 5px;" |
*[[Sensorineural hearing loss]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] may show small or invisible [[vestibular aqueduct]]
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]
*Ruling out other CNS and ear pathologies.
| style="background: #F5F5F5; padding: 5px;" |
*May be associated with [[Nausea and vomiting|nausea]], [[Nausea and vomiting|vomiting]], and [[tinnitus]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Labyrinthine concussion<br>
 
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;" |
*[[high frequency hearing loss]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] may show evidence of [[head trauma]] or [[temporal bone]] [[fracture]]
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]
| style="background: #F5F5F5; padding: 5px;" |
*Follows blunt [[head trauma]]
*May be associated with [[dizziness]] or [[tinnitus]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Perilymphatic fistula]]<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;" |
*[[Tullio phenomenon]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] may show fluid around the round window recess
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]/[[Imaging]]
| style="background: #F5F5F5; padding: 5px;" |
*Complication of  [[stapedectomy]], [[head injury]], or heavy lifting
*It may be provoked by activities such as [[Sneeze|sneezing]], lifting, straining, [[Cough|coughing]], and loud sounds.        (Tullio phenomenon)
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Semicircular canal
dehiscence syndrome<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
 
(air-bone gaps on audiometry)
| style="background: #F5F5F5; padding: 5px;" |
*[[Tullio phenomenon]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] may show defect in the arcuate eminence of the [[superior semicircular canal]]
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]/[[Imaging]]
| style="background: #F5F5F5; padding: 5px;" |
*It may be provoked by [[Valsalva maneuver]], [[Cough|coughing]], and [[Sneeze|sneezing]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Cogan syndrome]]<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;" |
*[[Interstitial keratitis]]
*[[Oscillopsia]]
*Absent [[vestibular function]] on [[Caloric reflex test|caloric test]]
*[[Systemic vasculitis]] ([[Aortitis]])
| style="background: #F5F5F5; padding: 5px; text-align: center;" |Increased [[ESR]] and  [[cryoglobulins]]
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] may show  [[calcification]] or soft tissue attenuation obliterating the intralabyrinthine fluid spaces
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]
| style="background: #F5F5F5; padding: 5px;" |
*It may cause [[Ménière's disease|Ménière]]-like attacks
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Vestibular schwannoma]]<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;" |
*[[Sensorineural hearing loss]]
*+ [[Rinne test]]
*Lateralization of [[Weber test]] to the normal [[ear]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] we may show  erosion, and widening of the [[Internal auditory meatus|internal acoustic meatus]]
*T1-weighted [[MRI]] may show a hypointense mass lesion where as T-2 weighted MRI  shows a hyperintense [[mass]] lesion
| style="background: #F5F5F5; padding: 5px;" |
*[[Imaging]]
| style="background: #F5F5F5; padding: 5px;" |
*[[Gadolinium]]-enhanced [[MRI]] scan is the definitive diagnostic test for  [[Vestibular schwannoma|acoutic neuroma]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Otitis media]]<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px;" |
*Fever
*Presence of effusion in the [[middle ear]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |Increased [[Acute phase reactant|acute phase reactants]]
| style="background: #F5F5F5; padding: 5px;" |
*Opacification of the [[middle ear]]
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]
| style="background: #F5F5F5; padding: 5px;" |
*Patient may show other [[signs]] and [[symptoms]] of [[upper respiratory infection]] such as [[cough]], [[nasal discharge]], and [[fever]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Aminoglycoside toxicity<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;" |
*[[Oscillopsia]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History/ Physical exam]]
| style="background: #F5F5F5; padding: 5px;" |
*May be associated with [[nausea]], [[vomiting]], and [[ataxia]]
*possibly irreversible
*[[Gentamicin]] is the most common one
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! colspan="10" style="background: #7d7d7d; color: #FFFFFF; text-align: center;" |Central
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Vestibular migraine<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" |–
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px;" |
*History of [[migraine headaches]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*[[MRI]] may show [[White matter|white-matter]] hyper-intensities (WMHs)
| style="background: #F5F5F5; padding: 5px;" |
*ICHD-3 criteria
| style="background: #F5F5F5; padding: 5px;" |
*It may be associated with [[anxiety]] and [[depression]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Multiple sclerosis]]<br>
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px;" |
*[[Lhermitte's sign]]
*[[Spasticity]]
*[[Hyperreflexia]]
*[[Internuclear ophthalmoplegia]]
*[[Optic neuritis]]
*[[Gait disturbance]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |Elevated concentration of [[CSF]] [[oligoclonal bands]]
| style="background: #F5F5F5; padding: 5px;" |
*[[CT scan]] shows brain atrophy and contrast enhanced demyelinating plaques
*[[MRI scan|MRI]] showing cerebral plaques disseminating in time and space.
| style="background: #F5F5F5; padding: 5px;" |
*[[History and Physical examination|History and physical examination]]
*[[Imaging]]
*[[CSF analysis]]
| style="background: #F5F5F5; padding: 5px;" |
*[[MS]] is twice as prevalent in women as compared to men
*The onset of [[symptoms]] is mostly between the age of fifteen to forty years and  rarely before the  age of fifteen or after the age of sixty years
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Brain tumor|Brain tumors]]<br>
 
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;" |
*[[Papilledema]]
*[[Focal neurological deficits]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |Cerebral spinal fluid ([[CSF]]) may show cancerous cells
| style="background: #F5F5F5; padding: 5px;" |
*On [[CT scan]] most of the [[brain tumors]] appears as a hypodense mass lesions
*On T1- weighted [[MRI scan|MRI]] most of the [[brain tumors]] appears as a hypointense or Isointense whereas on T2-weighted [[MRI contrast agent|MRI]] they  appear as hyperintense lesions
| style="background: #F5F5F5; padding: 5px;" |
*[[Imaging]]
 
*[[Biopsy forceps|Biopsy]]
| style="background: #F5F5F5; padding: 5px;" |
*May experience  [[headache]], [[seizures]], [[Visual disturbance|visual changes]] and changes in [[personality]], [[mood]] and [[concentration]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Cerebellar infarction]]/hemorrhage
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | ++/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px;" |
*[[Limb]] [[ataxia]]
*[[Gait abnormality|Gait disturbance]]
*[[Dysarthria]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*Based on the time interval lapsed  between the onset of  [[stroke]] and [[imaging]] performed there may be different presentations
| style="background: #F5F5F5; padding: 5px;" |
*[[Imaging]]
| style="background: #F5F5F5; padding: 5px;" |
*[[Posterior inferior cerebellar artery]] is the most common artery that causes [[vertigo]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Brain stem ischemia
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/−
| style="background: #F5F5F5; padding: 5px;" |
*Contralateral body [[Muscle weakness|weakness]]
*[[Visual field]] deficits
*[[Oculomotor nerve|Oculomotor]] abnormalities
*[[Bulbar]] findings
| style="background: #F5F5F5; padding: 5px; text-align: center;" |−
| style="background: #F5F5F5; padding: 5px;" |
*Based on the time interval lapsed  between the onset of  [[stroke]] and [[imaging]] performed there may be different presentations
*For more information [[Ischemic stroke CT|click here]]
 
| style="background: #F5F5F5; padding: 5px;" |
*[[Imaging]]
| style="background: #F5F5F5; padding: 5px;" |
*It may be associated with [[subclavian steal syndrome]]
|}
'''ABBREVIATIONS'''
 
[[VZV]]= [[Varicella zoster virus]], [[MRI]]= [[Magnetic resonance imaging]], [[ESR]]= [[Erythrocyte sedimentation rate]], [[EEG]]= [[Electroencephalogram]], [[CSF]]= [[Cerebrospinal fluid]], GPe= [[Globus pallidus|Globus pallidus externa]], ICHD=  International Classification of Headache Disorders
 
==Epidemiology and Demographics==
==Epidemiology and Demographics==


* Tinnitus affects 10 to 15% of the population.
*[[Tinnitus]] affects 10 to 15% of the population.
* 85% of the population presenting with ear symptoms/disorders report tinnitus as an associated symptom.
*85% of the population presenting with ear symptoms/disorders report tinnitus as an associated [[symptom]].<ref name="pmid20670725">{{cite journal |vauthors=Shargorodsky J, Curhan GC, Farwell WR |title=Prevalence and characteristics of tinnitus among US adults |journal=Am. J. Med. |volume=123 |issue=8 |pages=711–8 |date=August 2010 |pmid=20670725 |doi=10.1016/j.amjmed.2010.02.015 |url=}}</ref>
* The incidence rate of tinnitus increases with age and is more prevalent in older people.
*The [[incidence rate]] of tinnitus increases with age and is more prevalent in older people.<ref name="pmid20371585">{{cite journal |vauthors=Shetye A, Kennedy V |title=Tinnitus in children: an uncommon symptom? |journal=Arch. Dis. Child. |volume=95 |issue=8 |pages=645–8 |date=August 2010 |pmid=20371585 |doi=10.1136/adc.2009.168252 |url=}}</ref>
*Tinnitus is more prevalent in men compared to women and [[Smoking|smokers]] compared to non-smokers.<ref name="pmid15782448">{{cite journal |vauthors=Adams PF, Hendershot GE, Marano MA |title=Current estimates from the National Health Interview Survey, 1996 |journal=Vital Health Stat 10 |volume= |issue=200 |pages=1–203 |date=October 1999 |pmid=15782448 |doi= |url=}}</ref><ref name="pmid15040757">{{cite journal |vauthors=Ahmad N, Seidman M |title=Tinnitus in the older adult: epidemiology, pathophysiology and treatment options |journal=Drugs Aging |volume=21 |issue=5 |pages=297–305 |date=2004 |pmid=15040757 |doi=10.2165/00002512-200421050-00002 |url=}}</ref>


==Risk Factors==
==Risk Factors==
 
Common risk factors of tinnitus include
* Age
*Age
* Sensorineural hearing loss
*[[Sensorineural hearing loss]]
*Loud noise exposure
*[[Vestibular schwannoma]]
*[[Ototoxic|Ototoxic medication]]
*History of [[anxiety]] and [[depression]]
*History of [[head trauma]]
*History of [[multiple sclerosis]]


==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==


*Early clinical features include  
*Early clinical features may include ear fullness, huming or ringing sensations in the ear
*If left untreated, patients may progress to
*If left untreated, patients may progress to functional impairment, [[insomnia]], [[anxiety]], and [[depression]].<ref name="pmid2381186">{{cite journal |vauthors=Stouffer JL, Tyler RS |title=Characterization of tinnitus by tinnitus patients |journal=J Speech Hear Disord |volume=55 |issue=3 |pages=439–53 |date=August 1990 |pmid=2381186 |doi=10.1044/jshd.5503.439 |url=}}</ref>
*Common complications of


==Diagnosis==
==Diagnosis==
===Diagnostic criteria:===
====Tinnitus severity index (TSI)====
*TSI is used to rank the patient's based upon their severity
*The score ranges from 0-45
====Tinnitus handicap questionnaire:====
*This questionnaire includes 27 questions and is used to estimate the social, physical and emotional handicap severity
====Tinnitus handicap inventory:====
*This questionnaire has 4 categories to classify severity
*None, mild,  moderate, and severe.
===History and Symptoms:===
===History and Symptoms:===


* Sounds such as ringing, buzzing, pulsatile, roaring and humming
*Sounds such as ringing, buzzing, pulsatile, roaring and humming
* Progressive hearing loss
*Progressive hearing loss
* Recent exposure to excessive or loud noise or head trauma
*Recent exposure to excessive or loud noise or head trauma
* Poor hygiene leading to cerumen impaction
*Poor hygiene leading to cerumen impaction
* Ear pain
*Ear pain
* History of certain medication exposure
*History of certain medication exposure


===Physical Examination:===
===Physical Examination:===


* The ear examination may show signs of cerumen impaction, underlying infection or tympanic membrane perforation.
*The ear examination may show signs of cerumen impaction, underlying infection or tympanic membrane perforation.
* Auscultation of neck, orbits and periauricular areas as helpful in establishing the diagnosis of vascular causes
*Auscultation of neck, orbits and periauricular areas as helpful in establishing the diagnosis of vascular causes
* An extensive neurological examination may rule out underlying brainstem damage or hearing loss
*An extensive neurological examination may rule out underlying brainstem damage or hearing loss
* The Weber and Rinne test are done to establish sensorineural or conductive hearing loss
*The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal.


===Laboratory Findings:===
===Laboratory Findings:===


* There are no specific lab findings associated with tinnitis.
*There are no specific lab findings associated with tinnitis.


===Imaging:===
===Imaging:===
Line 169: Line 469:
*MRA and CTA are the gold standard diagnostic tests for arteriovenous fistula related tinnitus.
*MRA and CTA are the gold standard diagnostic tests for arteriovenous fistula related tinnitus.
*MRI with contrast is the initial preferred diagnostic test of choice for suspected vascular tinnitus.
*MRI with contrast is the initial preferred diagnostic test of choice for suspected vascular tinnitus.
*MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed.
*MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed.<ref name="pmid8059655">{{cite journal |vauthors=Dietz RR, Davis WL, Harnsberger HR, Jacobs JM, Blatter DD |title=MR imaging and MR angiography in the evaluation of pulsatile tinnitus |journal=AJNR Am J Neuroradiol |volume=15 |issue=5 |pages=879–89 |date=May 1994 |pmid=8059655 |doi= |url=}}</ref>


===Other Diagnostic Testing:===
===Other Diagnostic Testing:===


*Initial audiometric tests are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem.  These tests include:
*Initial audiometric tests<ref name="pmid25274374">{{cite journal |vauthors=Tunkel DE, Bauer CA, Sun GH, Rosenfeld RM, Chandrasekhar SS, Cunningham ER, Archer SM, Blakley BW, Carter JM, Granieri EC, Henry JA, Hollingsworth D, Khan FA, Mitchell S, Monfared A, Newman CW, Omole FS, Phillips CD, Robinson SK, Taw MB, Tyler RS, Waguespack R, Whamond EJ |title=Clinical practice guideline: tinnitus executive summary |journal=Otolaryngol Head Neck Surg |volume=151 |issue=4 |pages=533–41 |date=October 2014 |pmid=25274374 |doi=10.1177/0194599814547475 |url=}}</ref> are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem.  These tests include:
**Pure-tone audiogram
**Pure-tone audiogram
**Tympanometry
**Tympanometry
Line 182: Line 482:


==Treatment==
==Treatment==
Tinnitus is a symptom and not a disease itself.  It is a chronic condition that can be managed by treating the underlying etiology.
 
*Tinnitus is a symptom and not a disease itself.  It is a chronic condition that can be managed by treating the underlying etiology.
*The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus.  It is usually achieved by identifying the underlying pathology or the associated disease.
*It is recommended to treat underlying [[insomnia]] and depression. (Grade 1B)


===Medical Therapy===
===Medical Therapy===
Following medications have minimal to modest role in relieving tinnitus.
*[[Misoprostol]]
*[[Lidocaine]] (intratympanic or intravenous)
*[[Benzodiazepine]] (alprazolam)
*[[Steroids]] such as [[dexamethasone]] (intratympanic)
*[[Carbamazepine]]
Following medications have been studied for tinnitus but are not found to be effective and have no role in the treatment of tinnitus
*[[Anticonvulsants]]
*[[Melatonin]]
*[[Ginkgo biloba]]
*[[Niacin]]


===Surgery===
===Surgery===
*[[Cochlear implants]] may be considered for tinnitus associated with severe [[sensorineural hearing loss]].
===Other therapies:===
*[[Tinnitus retraining therapy]] (TRT) (Grade 1C)
*[[Biofeedback]] (Grade 2C)
*[[Cognitive behavioral therapy|Cognitive behavioral therapy (CBT)]] as  an adjunct to TRT (Grade 2C)
*[[Acupuncture]] and electrical stimulation are considered equally effective as placebo, no significant role established so far.


===Prevention===
===Prevention===
*Tinnitus may be been prevented by limiting the exposure to loud noise.


==References==
==References==

Latest revision as of 17:57, 6 October 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2] Sabeeh Islam, MBBS[3]

Overview

Tinnitus is derived from the Latin word tinnire, meaning to ring. Tinnitus can be classified as subjective and objective.  This classification not only explains the underlying etiology but also directs the management of tinnitus. In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain.  Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model. Common causes of tinnitus include Ototoxicity, Presbycusis, noise induced hearing loss, late onset congenital hearing loss, meniere's disease, and Loop diuretics. The incidence rate of tinnitus increases with age and is more prevalent in older people. Tinnitus is more prevalent in men compared to women and smokers compared to non-smokers. If left untreated, patients may progress to functional impairment, insomnia, anxiety, and depression. TSI is used to rank the patient's based upon their severity. The score ranges from 0-45. Symptoms and history include sounds such as ringing, buzzing, pulsatile, roaring and humming and progressive hearing loss. An extensive neurological examination may rule out underlying brainstem damage or hearing loss. The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal. MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed. Initial audiometric tests are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem.  These tests include: pure-tone audiogram, tympanometry, auditory reflex testing, determination of speech discrimination abilities, otoacoustic emissions testing and auditory brainstem response testing (ABR). Tinnitus is a symptom and not a disease itself.  It is a chronic condition that can be managed by treating the underlying etiology. The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus.  It is usually achieved by identifying the underlying pathology or the associated disease. It is recommended to treat underlying insomnia and depression (Grade 1B). Cochlear implants may be considered for tinnitus associated with severe sensorineural hearing loss. Other therapies include: tinnitus retraining therapy (TRT) (Grade 1C), biofeedback (Grade 2C), and cognitive behavioral therapy (CBT) as an adjunct to TRT (Grade 2C). Acupuncture and electrical stimulation are considered equally effective as placebo, no significant role established so far.


Historical Perspective

  • In the early 19th century, Frenchman and Jean Marie Gaspard Itard introduced the concept of masking.  They were the first ones to differentiate between subjective and objective tinnitus.
  • Later in the 19th Century, with the introduction of germ theory and anesthesia, surgical therapy such as incudectomy was established.
  • Tinnitus is derived from the Latin word tinnire, meaning to ring.

Classification

Tinnitus can be classified as subjective and objective.  This classification not only explains the underlying etiology but also directs the management of tinnitus.

Subjective tinnitus:

  • It is only experienced by the affected individual in the absence of any auditory stimulation
  • More common, usually described as continuous ringing, high pitch sound

Objective tinnitus:

Pathophysiology

In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain.[1][2]  Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model.[3][4]

Lesion projection zone (LPZ):

This zone is defined as the area in the auditory cortex that represents the damaged cochlear input.  The neurons in the LPZ zone show 2 main changes:

  • Accelerated spontaneous firing rate
  • Increased representation of neurons that represent the damaged cochlear region also known as lesion edge frequencies in the LPZ

Tinnitus model:

This model explains 2 major phenomena in the auditory cortex caused by lack of sensory peripheral auditory input (cochlea)

  • Hyperactivity in the lesion projections zone (LPZ)
  • Increased cortical representation of the lesion-edge frequencies in the LPZ

Causes of subjective tinnitus

Sensorineural hearing loss:

Cochlear injury:

Vascular causes:

CNS causes:

Infections:

Bone disease:

Metabolic disorders:

Autoimmune diseases:

Medications:

Differential Diagnosis of Tinnitus

Diseases Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging
Acute onset Recurrency Nystagmus Hearing problems, tinnitus
Peripheral
HSV oticus
+ +/− +/− + VZV antibody titres
Meniere disease
+/− + +/− + (Progressive)
Labyrinthine concussion
+ +
Perilymphatic fistula
+/− + +
  • CT scan may show fluid around the round window recess
Semicircular canal

dehiscence syndrome

+/− + +

(air-bone gaps on audiometry)

Cogan syndrome
+ +/− + Increased ESR and cryoglobulins
  • CT scan may show calcification or soft tissue attenuation obliterating the intralabyrinthine fluid spaces
Vestibular schwannoma
+ +/− +
Otitis media
+ +/− Increased acute phase reactants
Aminoglycoside toxicity
+ +
Central
Vestibular migraine
+ +/− +/−
  • ICHD-3 criteria
Multiple sclerosis
+ +/− +/− Elevated concentration of CSF oligoclonal bands
  • CT scan shows brain atrophy and contrast enhanced demyelinating plaques
  • MRI showing cerebral plaques disseminating in time and space.
  • MS is twice as prevalent in women as compared to men
  • The onset of symptoms is mostly between the age of fifteen to forty years and rarely before the age of fifteen or after the age of sixty years
Brain tumors
+/− + + + Cerebral spinal fluid (CSF) may show cancerous cells
  • On CT scan most of the brain tumors appears as a hypodense mass lesions
  • On T1- weighted MRI most of the brain tumors appears as a hypointense or Isointense whereas on T2-weighted MRI they appear as hyperintense lesions
Cerebellar infarction/hemorrhage + ++/− +/−
  • Based on the time interval lapsed between the onset of stroke and imaging performed there may be different presentations
Brain stem ischemia + +/− +/−
  • Based on the time interval lapsed between the onset of stroke and imaging performed there may be different presentations
  • For more information click here

ABBREVIATIONS

VZV= Varicella zoster virus, MRI= Magnetic resonance imaging, ESR= Erythrocyte sedimentation rate, EEG= Electroencephalogram, CSF= Cerebrospinal fluid, GPe= Globus pallidus externa, ICHD= International Classification of Headache Disorders

Epidemiology and Demographics

  • Tinnitus affects 10 to 15% of the population.
  • 85% of the population presenting with ear symptoms/disorders report tinnitus as an associated symptom.[7]
  • The incidence rate of tinnitus increases with age and is more prevalent in older people.[8]
  • Tinnitus is more prevalent in men compared to women and smokers compared to non-smokers.[9][10]

Risk Factors

Common risk factors of tinnitus include

Natural History, Complications and Prognosis

  • Early clinical features may include ear fullness, huming or ringing sensations in the ear
  • If left untreated, patients may progress to functional impairment, insomnia, anxiety, and depression.[11]

Diagnosis

Diagnostic criteria:

Tinnitus severity index (TSI)

  • TSI is used to rank the patient's based upon their severity
  • The score ranges from 0-45

Tinnitus handicap questionnaire:

  • This questionnaire includes 27 questions and is used to estimate the social, physical and emotional handicap severity

Tinnitus handicap inventory:

  • This questionnaire has 4 categories to classify severity
  • None, mild,  moderate, and severe.

History and Symptoms:

  • Sounds such as ringing, buzzing, pulsatile, roaring and humming
  • Progressive hearing loss
  • Recent exposure to excessive or loud noise or head trauma
  • Poor hygiene leading to cerumen impaction
  • Ear pain
  • History of certain medication exposure

Physical Examination:

  • The ear examination may show signs of cerumen impaction, underlying infection or tympanic membrane perforation.
  • Auscultation of neck, orbits and periauricular areas as helpful in establishing the diagnosis of vascular causes
  • An extensive neurological examination may rule out underlying brainstem damage or hearing loss
  • The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal.

Laboratory Findings:

  • There are no specific lab findings associated with tinnitis.

Imaging:

  • MRA and CTA are the gold standard diagnostic tests for arteriovenous fistula related tinnitus.
  • MRI with contrast is the initial preferred diagnostic test of choice for suspected vascular tinnitus.
  • MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed.[12]

Other Diagnostic Testing:

  • Initial audiometric tests[13] are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem.  These tests include:
    • Pure-tone audiogram
    • Tympanometry
    • Auditory reflex testing
    • Determination of speech discrimination abilities
    • Otoacoustic emissions testing
    • Auditory brainstem response testing (ABR)

Treatment

  • Tinnitus is a symptom and not a disease itself.  It is a chronic condition that can be managed by treating the underlying etiology.
  • The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus.  It is usually achieved by identifying the underlying pathology or the associated disease.
  • It is recommended to treat underlying insomnia and depression. (Grade 1B)

Medical Therapy

Following medications have minimal to modest role in relieving tinnitus.

Following medications have been studied for tinnitus but are not found to be effective and have no role in the treatment of tinnitus

Surgery

Other therapies:

Prevention

  • Tinnitus may be been prevented by limiting the exposure to loud noise.

References

  1. Minen MT, Camprodon J, Nehme R, Chemali Z (October 2014). "The neuropsychiatry of tinnitus: a circuit-based approach to the causes and treatments available". J. Neurol. Neurosurg. Psychiatry. 85 (10): 1138–44. doi:10.1136/jnnp-2013-307339. PMID 24744443.
  2. Qiu C, Salvi R, Ding D, Burkard R (January 2000). "Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain". Hear. Res. 139 (1–2): 153–71. doi:10.1016/s0378-5955(99)00171-9. PMID 10601720.
  3. Melcher JR, Sigalovsky IS, Guinan JJ, Levine RA (February 2000). "Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation". J. Neurophysiol. 83 (2): 1058–72. doi:10.1152/jn.2000.83.2.1058. PMID 10669517.
  4. Lockwood AH, Salvi RJ, Coad ML, Towsley ML, Wack DS, Murphy BW (January 1998). "The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity". Neurology. 50 (1): 114–20. doi:10.1212/wnl.50.1.114. PMID 9443467.
  5. Fortune DS, Haynes DS, Hall JW (January 1999). "Tinnitus. Current evaluation and management". Med. Clin. North Am. 83 (1): 153–62, x. doi:10.1016/s0025-7125(05)70094-8. PMID 9927967.
  6. Levine RA (1999). "Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis". Am J Otolaryngol. 20 (6): 351–62. doi:10.1016/s0196-0709(99)90074-1. PMID 10609479.
  7. Shargorodsky J, Curhan GC, Farwell WR (August 2010). "Prevalence and characteristics of tinnitus among US adults". Am. J. Med. 123 (8): 711–8. doi:10.1016/j.amjmed.2010.02.015. PMID 20670725.
  8. Shetye A, Kennedy V (August 2010). "Tinnitus in children: an uncommon symptom?". Arch. Dis. Child. 95 (8): 645–8. doi:10.1136/adc.2009.168252. PMID 20371585.
  9. Adams PF, Hendershot GE, Marano MA (October 1999). "Current estimates from the National Health Interview Survey, 1996". Vital Health Stat 10 (200): 1–203. PMID 15782448.
  10. Ahmad N, Seidman M (2004). "Tinnitus in the older adult: epidemiology, pathophysiology and treatment options". Drugs Aging. 21 (5): 297–305. doi:10.2165/00002512-200421050-00002. PMID 15040757.
  11. Stouffer JL, Tyler RS (August 1990). "Characterization of tinnitus by tinnitus patients". J Speech Hear Disord. 55 (3): 439–53. doi:10.1044/jshd.5503.439. PMID 2381186.
  12. Dietz RR, Davis WL, Harnsberger HR, Jacobs JM, Blatter DD (May 1994). "MR imaging and MR angiography in the evaluation of pulsatile tinnitus". AJNR Am J Neuroradiol. 15 (5): 879–89. PMID 8059655.
  13. Tunkel DE, Bauer CA, Sun GH, Rosenfeld RM, Chandrasekhar SS, Cunningham ER, Archer SM, Blakley BW, Carter JM, Granieri EC, Henry JA, Hollingsworth D, Khan FA, Mitchell S, Monfared A, Newman CW, Omole FS, Phillips CD, Robinson SK, Taw MB, Tyler RS, Waguespack R, Whamond EJ (October 2014). "Clinical practice guideline: tinnitus executive summary". Otolaryngol Head Neck Surg. 151 (4): 533–41. doi:10.1177/0194599814547475. PMID 25274374.

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