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7/26/2019 Viral Causes of Hearing Loss
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Viral Causes of Hearing Loss: A Review for Hearing HealthProfessionalsBrandon E. Cohen,Anne Durstenfeld, and Pamela C. Roehm
Abstract
A number of viral infections can cause hearing loss. Hearing loss induced by these viruses can be
congenital or acquired, unilateral or bilateral. Certain viral infections can directly damage inner
ear structures, others can induce inflammatory responses which then cause this damage, and still
others can increase susceptibility or bacterial or fungal infection, leading to hearing loss.
Typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing
losses can be seen following infection with certain viruses. ccasionally, recovery of hearing
after these infections can occur spontaneously. !ost importantly, some of these viral infections
can be prevented or treated. "or many of these viruses, guidelines for their treatment orprevention have recently been revised. #n this review, we outline many of the viruses that cause
hearing loss, their epidemiology, course, prevention, and treatment.
Keywords: hearing loss, sensorineural hearing loss, sudden sensorineural hearing loss,
cytomegalovirus, lymphocytic choriomeningitis virus, varicella $oster virus, herpes simplex type
%, herpes simplex type &, rubella, measles, rubeola, H#', (est )ile virus, mumps
Introduction
Among the many causes of hearing loss, viruses often are ignored. 'iral infections, in particular
cytomegalovirus *C!'+, cause up to of all congenitally acquired hearing loss. !any
viruses can be the cause of congenital or acquired hearing loss * Table %+. Typically, viruses cause
sensorineural hearing loss */)H0+1 however, a viral etiology has been proposed for otosclerosis.
#nfection with H#' can lead to conductive hearing loss *CH0+ through bacterial and fungal
infections, which become more frequent following the immunosuppression caused by that virus.
Hearing loss caused by viruses can be mild or severe to profound, unilateral or bilateral.
!echanisms involved in the induction of hearing loss by different viruses vary greatly, ranging
from direct damage to inner ear structures, including inner ear hair cells and organ of Corti *as
seen in some of the classically described causes of viral hearing loss such as measles+, to
induction of host immune-mediated damage *Table &+. "ollowing infections with certain viruses,
hearing loss can be reversed or limited by appropriate antiviral therapy. 2ffective vaccines are
available for many of the viruses that cause hearing loss, leading to substantial changes in the
incidence of these infections and to their prevalence as causes of hearing loss. Although it may
http://www.ncbi.nlm.nih.gov/pubmed/?term=Cohen%20BE%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Durstenfeld%20A%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Durstenfeld%20A%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Roehm%20PC%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/table/table1-2331216514541361/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/table/table2-2331216514541361/http://www.ncbi.nlm.nih.gov/pubmed/?term=Durstenfeld%20A%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Roehm%20PC%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/table/table1-2331216514541361/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/table/table2-2331216514541361/http://www.ncbi.nlm.nih.gov/pubmed/?term=Cohen%20BE%5Bauth%5D7/26/2019 Viral Causes of Hearing Loss
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seem a daunting tas3, a wor3ing 3nowledge of the potential viral causes of hearing loss and their
treatment is essential to the recognition of these entities and their appropriate management.
Table 1.'iral Causes of Hearing 0oss.
Virus Type of HL Degree of HL Incidence of
HL
Prevention Treatment Hearing
recovery
Congenital
C!' 4ilateral
progressive
/)H0
/evere 56&7 if
asymptomatic
1 &&658 if
symptomatic
)one 9anciclovir,
valganciclovir
, cidofovir,
foscarnet
nly with
antiviral
therapy
:ubella 4ilateral
/)H0
!ild to severe %&6%; !!: )one )one
0C!' 4ilateral
/)H0
/evere to
profound
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Virus Type of HL Degree of HL Incidence of
HL
Prevention Treatment Hearing
recovery
maximal
H/' @nilateral or
bilateral
/)H0
!oderate to
profound
@p to 77
*congenital+
)one Acyclovir )one
Acquired
!easles 4ilateral
/)H0
>rofound .%67. !!:, #'#g )one )one
'' @nilateral
/)H0
!ild to
moderate
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intravenous immunoglobulin1 !!:measles, mumps, rubella vaccine1 :xtreatment1
/)H0sensorineural hearing loss1 ''varicella $oster virus1 ()'(est )ile virus.
Table 2. >otential 2tiologies of Hearing 0oss ?ue to ?ifferent 'iral #nfections.
Virus Direct Indirect Unknow
n
Stria
vascuaris
!rgan of
"orti
#eurona
$coc%ear&
centra'
Decreased immunity
and secondary
infection
Host immune
response to vira
antigen
C!' (
0C!' )
H#' ( ( (
H/' (
:ubeola
a
( (
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Virus Direct Indirect Unknow
n
Stria
vascuaris
!rgan of
"orti
#eurona
$coc%ear&
centra'
Decreased immunity
and secondary
infection
Host immune
response to vira
antigen
!umps ( ( (
:ubella ( (
()' )
'' (
Note.C!'cytomegalovirus1 H/'herpes simplex virus1 0C!'lymphocytic
choriomeningitis virus1 ''varicella $oster virus1 ()'(est )ile virus.
a:ubeola is also hypothesi$ed to cause otosclerosis via stimulation of abnormal osteoblastic
activity in endochondral bone of the inner ear.
In this review, we discuss many of the common viral causes of hearing loss and theinterventions available for their prevention and treatment. Viruses causing
congenital hearing losses are discussed rst, followed by those that cause both
congenital and acquired hearing loss, and nally those that exclusively cause
acquired hearing loss. ithin each category, the most common viral causes of
hearing loss are discussed rst, and then infrequent or emerging viruses that have
been shown to cause hearing loss are discussed.
7/26/2019 Viral Causes of Hearing Loss
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Viruses Causing Congenital Hearing Loss
Cto!egalovirus
C!' is an extremely common viral infection with nearly % prevalence. ?espite its high
prevalence, C!' rarely causes symptomatic disease in immunocompetent older infants or
adults. C!' is a member of the herpesvirus family, along with herpes simplex virus *H/'+,
varicella $oster virus *''+, and 2pstein64arr virus. 0i3e all herpesviruses, C!' is a double-
stranded enveloped ?)A virus that can remain latent in the body long after primary infection.
C!' can reactivate and cause disease in immunocompromised hosts. ?uring reactivation, the
virus again begins to ma3e copies of its ?)A and transmission to other people can occur.
C!' is typically acquired early in life and may be acquired in utero. #n the @nited /tates, up to
% of newborns are infected *"owler et al., %;;ass, "owler, 4oppana, 4ritt, D /tagno, &5+. nly 8 to % of infected
neonates will show signs of C!' infection at birth *"owler et al., %;;ass, %;;;+. The average age of diagnosis of hearing impairment in
congenitally infected children is &< to 77 months. Hearing loss may be diagnosed many years
later, and thus C!' may be the cause underlying many cases of idiopathic /)H0 in children
*"owler et al., %;;
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infants have not been identified, and so periodic screening of infected children is necessary
*4arbi, 4inda, Caroppo, D >rimache, &51 "owler et al., %;;;1 /mith et al., &8+. The etiology
of /)H0 resulting from C!' infection is not fully understood. Temporal bone studies
demonstrate inflammation and edema of the cochlea and spiral ganglion, and viral antigens in the
spiral ganglion, organ of Corti, scala media, and :eissnerFs membrane *"owler et al.,%;;
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9anciclovir is the treatment for both early and delayed /)H0 resulting from congenital C!'
infection. 9anciclovir prevents /)H0 progression and sometimes can improve hearing status.
This medication must be administered intravenously and can be associated with neutropenia
*Gimberlin et al., &7+. ther options include valganciclovir *a prodrug of ganciclovir that can
be given orally+, cidofovir, and foscarnet. /tudies are currently underway testing the efficacy andduration of treatment of infected neonates with valganciclovir */hin, Geamy, D /teinberg, &%%+.
9anciclovir is teratogenic in animal studies and so cannot be used to treat pregnant women with
active C!' infection. ther treatment modalities also exist. #n vitro and animal studies support
the use of C!' hyperimmune globulin during pregnancy *Carlson, )orwit$, D /tiller, &%+.
/)H0 that does not respond to antiviral medications can be treated with hearing aids or cochlear
implantation depending on hearing severity. Cochlear implantation can significantly improve
hearing loss due to C!' infection1 however, the extent of improvement in speech and language
s3ills following cochlear implantation may not be as great as in non-C!'-infected children with
severe to profound hearing loss */hin et al., &%%+.
?espite multiple attempts at vaccine development, there is not currently an effective C!'
vaccine. >revention of primary infection in previously uninfected pregnant women is therefore
the mainstay of limiting congenital C!' infection. >regnant women are encouraged to
frequently wash their hands and to avoid contact with saliva or urine of children younger than 5
years, particularly if they are enrolled in daycare. The @./. Centers for ?isease Control and
>revention *C?C+ does not advocate C!' screening due to concerns that C!' #g! testing is
not sufficiently specific and because treatment of C!' during pregnancy is controversial
*Carlson et al., &%+.
Rubella
:ubella, also 3nown as the 9erman measles, is a member of the Togaviridaefamily of viruses.
The genome of this virus is a single-stranded :)A and is enclosed in an icosahedral
nonenveloped capsid. :ubella is most commonly transmitted via contaminated upper respiratory
secretions during coughing, snee$ing, and tal3ing. #n immunocompetent adults, the virus has a
self-limiting course mar3ed by low-grade fever, eye pain with movement, conEunctivitis, sore
throat, malaise, headache, nausea, decreased appetite, transient arthritis, and tender
lymphadenopathy *0ee D 4owden, &1 !c0ean, "iebel3orn, Temte, D (allace, &%7+. #n
contrast, if the virus is acquired during pregnancy it is a potent teratogen and one of the
T:CH/ infections *!c0ean et al., &%7+. Congenital rubella syndrome manifests as hearing
loss, congenital cataracts, microcephaly, mental retardation, thrombocytopenia, cardiac
anomalies, and a characteristic rash *the so-called blueberry muffin spots1>andey, ?udeEa, ?atta,
/ingla, D /aili, &%7+.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr59-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr101-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr15-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr101-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr15-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr64-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr85-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr85-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr85-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr59-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr101-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr15-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr101-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr15-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr64-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr85-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr85-23312165145413617/26/2019 Viral Causes of Hearing Loss
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/)H0 is the most common sequela of congenital rubella infection *8B+ and is most often seen
when maternal rubella infection occurs within the first %5 wee3s of pregnancy. 'estibular
function is spared *(ebster, %;;B+. Hearing loss typically manifests in the first 5 to %& months of
life, although it can present at birth *?ammeyer, &%1?onley, %;;7+. Audiograms often show a
flat, uniform mild to severe /)H0, but isolated high-frequency hearing loss has been reported*?ammeyer, &%1 /heridan, %;5+.
(hile the mechanism of rubella-induced hearing loss has not been fully explained, the virus
causes direct cochlear damage and cell death in the organ of Corti and stria vascularis * 0ee D
4owden, &+. Alterations in the composition of endolymph due to strial damage have also
been described *(ebster, %;;B+. ?epending on the severity of hearing loss, treatment options
include the use of hearing aids and cochlear implantation */mith et al., &8+.
'accination of women prior to or during reproductive age is extremely effective at prevention of
congenital rubella in their offspring *?e 0eenheer et al., &%%+. #n areas without routine rubella
vaccination, congenital rubella remains a common cause of severe to profound bilateral /)H0.
#n a recent 4ra$ilian study, congenital rubella was thought to be the cause of hearing loss in 7&
of patients with deafness *da /ilva, ueiros, D 0ima, &5+. "ollowing the institution of a
Ischool girlJ vaccination program in (estern Australia, the rate of congenital rubella syndrome
dropped to in vaccinated mothers */tanley, /im, (ilson, D (orthington, %;B5+. ?espite
vaccination, however, rare cases of congenital rubella syndrome have been documented,
delivered to previously vaccinated mothers who had received only one dose of the vaccine
*!iller, Cradoc3-(ilson, D >ollac3, %;B&+. There is also one published case of bilateral
profound hearing loss occurring in an adult following measles6rubella vaccination that has beenattributed to rubella infection from the vaccine strain, although this was not confirmed by
isolation of the virus *Hulbert, 0arsen, ?avis, D Holtom, %;;%+.
The @./. C?C recommends rubella vaccination at age %& to %8 months of age with a booster at
to 5 years, given as a part of the combined measles, mumps, and rubella *!!:+ vaccine. /ince
the vaccine contains an attenuated live form of rubella, it should not be used to vaccinate during
or % month prior to planned pregnancy *!c0ean et al., &%7+. >ublished cases of accidental
vaccination during pregnancy yielded no cases of congenital rubella syndrome, although .8 of
children had serologic evidence of rubella infection *2rgenoglu et al., &%&1)asiri, Koseffi,
GhaEedaloe, /arafra$ Ka$di, D ?elgoshaei, &;1/ato et al., &%%+. #f a woman not 3nown to be
pregnant is vaccinated, no intervention is currently recommended. Congenital rubella syndrome
has not been reported following birth from mothers who were asymptomatically infected during
pregnancy. ?ue to successful vaccination programs, rubella is currently considered eliminated in
the @nited /tates1 however, cases can still occur due to importation of the infection from other
countries *!c0ean et al., &%7+.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr125-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr22-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr27-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr22-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr100-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr64-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr64-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr125-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr102-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr25-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr23-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr103-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr73-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr50-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr30-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr79-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr79-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr93-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr93-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr125-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr22-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr27-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr22-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr100-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr64-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr64-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr125-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr102-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr25-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr23-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr103-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr73-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr50-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr30-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr79-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr79-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr93-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr72-23312165145413617/26/2019 Viral Causes of Hearing Loss
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L!"hoctic Chorio!eningitis Virus
0ymphocytic choriomeningitis virus *0C!'+ is a single-stranded enveloped :)A virus. 0C!'
is a member of the Arenaviridaefamily and has been identified as an emerging teratogen
*4arton, !ets, D 4eauchamp, &&+. :odents, including the common house mouse, are the
natural hosts and serve as reservoirs of 0C!' *Lamieson, Gourtis, 4ell, D :asmussen, &5+.
#nfection is transmitted to humans through contact with rodent urine, feces, or saliva, and occurs
more commonly in winter months when mice see3 shelter indoors *4onthius, &%&+. The virus is
not typically spread between humans1 however, there have been cases of transmission via organ
transplantation *Lamieson et al., &5+.
#n immunocompetent adults, 0C!' infection is typically either asymptomatic or associated with
upper respiratory tract infection symptoms *fever, headache, nausea, and vomiting+. :arely,
complications such as aseptic meningitis and meningoencephalitis occur. 0C!' infection in
pregnancy greatly increases the ris3 of spontaneous abortion. 0C!' infection can also beteratogenic, especially if the virus is contracted during the first or second trimester, and is
associated with microcephaly, hydrocephalus, ventriculomegaly, pachygyra, cerebellar
hypoplasia, chorioretinitis, periventricular calcification, and hearing loss *Anderson et al.,
&%714onthius, &%&1 Lamieson et al., &51 "igure &+. #n contrast to congenital C!' or rubella,
visual impairment and microcephaly are much more common than hearing loss in congenital
0C!' infection. 0C!' can also be distinguished from these other congenital viral causes of
hearing loss by the lac3 of hepatosplenomegaly *4arton et al., &&+.
"igure &. "etal *&B wee3s gestation+ *a+ and postnatal *wee3 of life %+ *b+ !:# of infant with
congenital 0C!' infection, demonstrating severe ventriculomegaly *asteris3s+.
Note.The patient had severe growth and developmental delays, mild myopia with
chorioretinopathy, profound hearing loss on the left side, and severe loss of hearing on the right.
/ource= !:# images used with permission fromAnderson et al. *&%7+.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr10-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr52-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr11-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr52-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr11-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr11-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr52-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/figure/fig2-2331216514541361/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr10-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr10-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr52-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr11-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr52-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr11-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr52-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/figure/fig2-2331216514541361/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr10-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr5-23312165145413617/26/2019 Viral Causes of Hearing Loss
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2n$yme-lin3ed immunosorbent assay *20#/A+ for 0C!' #g9 and #g! antibodies can establish
the diagnosis of congenital 0C!' infection. Hearing loss in these patients is relatively rare, can
vary in severity between ears, and ranges from severe to profound /)H0 * Anderson et al.,
&%714arton et al., &&+.
:ibavirin, a nucleoside inhibitor used to stop viral :)A synthesis and capping, has been used to
treat 0C!' infection in adults. However, ribavirin efficacy against 0C!' has not been proven
in clinical trials and is associated with significant side effects such as hemolytic anemia.
:ibavirin is a teratogen in many animal models and should not be used to treat pregnant women
*Lamieson et al., &5+. "avipiravir, an antiviral drug that may target :)A-dependent :)A
polymerase and is therefore effective against a wide range of :)A viruses, may be a future
treatment option but at present has only been tested against 0C!' in vitro *4onthius, &%&+.
Treatment of hearing loss in affected children with hearing aids and other assistive listening
devices is indicated when appropriate. Treatment of severe to profound /)H0 in children with
congenital 0C!' may be limited in patients in whom involvement of the vestibulocochlear
nerve is the cause of hearing loss1 however, because severe visual impairment is seen in all
children with congenital 0C!' infection, it should be attempted.
Viruses Causing Congenital and Ac#uired Hearing Loss
Hu!an I!!unodeficienc Virus
H#' is the retrovirus that causes A#?/. H#' is composed of a single-stranded :)A genome,
which is converted to double-stranded ?)A after infection of the host cell. H#' can infect a wide
range of cell types but preferentially infects neurons and immune cells, particularly C?M T-
cells. ver time, death of helper T-cells results in immunosuppression, with resultant
development of opportunistic infections and cancers *>rasad, 4hoEwani, /henoy, D >rasad,
&5+.
/ymptoms of the initial infection are nonspecific and include fever, headache, sore throat, and
myalgias. As the disease progresses and immune deficiency develops, patients developopportunistic infections and other manifestations of H#' in multiple organ systems. Common
symptoms within the temporal bone include hearing loss, tinnitus, chronic otitis media, facial
nerve palsy, and malignancies *>alacios et al., &B1>rasad et al., &51:arey, %;;+.
The prevalence of auditory symptoms in patients with H#' is % to ; * Chandrase3har et al.,
&1!arra et al., %;;
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&%7+. #n a study of & H#'-positive /outh African adults, many patients complained of hearing
loss *&
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ris3 factors for hearing loss, it can be impossible to ethically determine the exact etiology of the
observed hearing losses. Thus, development of an animal model for these studies would
significantly improve understanding of the direct role of H#' in hearing loss.
H#' prevention is predominantly guided by avoidance of contact with infected blood and bodily
secretions. @se of antiretroviral coc3tails reduces H#' transmission from infected mothers to
fetuses and breastfeeding children from &8 to B to % to & */turt, ?o3ubo, D /int, &%+.
Two- or three-drug antiviral regimens initiated as soon as possible *ideally within &675hr+ after
accidental exposure to H#'-infected body fluids also greatly decreases the ris3 of H#' infection
*Tolle D /chwar$wald, &%+. The use of HAA:T has dramatically improved morbidity and
mortality associated with H#' infection. 4y increasing C?M T-cell counts, HAA:T can protect
patients from opportunistic infections that can cause hearing loss. HAA:T use does not
significantly reverse hearing loss, and one study suggested a positive correlation between hearing
loss and use of antiretroviral medications in patients older than 78 years *!arra et al., %;;
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rash that evolves into blisters and then ruptured open lesions, as well as a viral prodrome and
headache. The viruses can latently infect nerve cells innervating the initially infected tissue.
!onths to years later, the viruses can reactivate, leading to recurrent disease. H/' type % is
typically associated with labial herpes and type & with genital herpes, although either virus can
infect and manifest in the otherFs typical territory *(hitley D :oi$man, &%+.
Congenital herpes infection typically arises due to exposure to H/'% or H/'& during delivery.
)eonatal infection is more frequent from women who develop infection late during pregnancy or
who have active herpetic lesions in the birth canal. However, 7 of pregnant women without
prior history of H/'& may be serologically positive and have asymptomatic viral shedding,
which can lead to neonatal infection. !any *5&+ of H/'&-infected mothers are H/'% positive
as well. )eonatal H/'% infection occurs in %N&, to %NB, and H/'& in 8.;N%, live
births *!uller, Lones, D Goelle, &%1(esterberg, Atashband, D Go$a3, &B+. /equelae of
neonatal infection range from eye and mucous membrane involvement to disseminated disease,
encephalitis, hearing loss, mental retardation, microcephaly, and death. !any infected infants
will not have a vesicular rash and so may not be tested for H/' infection *reviewed
in(esterberg et al., &B+.
H/'% infection is much more frequently associated with encephalitis and hearing loss following
infection in neonates compared with H/'& *al !uhaimeed D a3$ou3, %;;
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Animal studies have confirmed that herpes simplex infections can cause hearing loss and
vestibular symptoms. "ollowing infection with H/'% or H/'&, fibrosis of the scala tympani and
vestibule, loss of outer hair cells, and atrophy of the stria vascularis and tectorial membrane were
found in these animals. 'iral antigens were located throughout the cochlea, and viral capsids
were found within cochlear nerve fibers, including both afferent and efferent nerve endings.These findings were similar to those found in human temporal bone studies of patients with
deafness following 3nown viral infection with measles or rubella *)omura, Gurata, D /aito,
%;B8+. (hen treated with acyclovir and steroids, animals infected with H/' had less severe
hearing loss and decreased damage to intracochlear structures than untreated, infected animals
*/to3roos, Albers, D /chirm, %;;;+. #n all of these animal studies, temporal bone changes
induced by H/' infection were similar to those seen in humans with sudden /)H0
*//)H012sa3i et al., &%%1)omura et al., %;B81 /to3roos et al., %;;;+.
H/'% and H/'& have been associated with //)H0 in some, but not all, human studies in which
testing for these viruses following onset of hearing loss has been performed *9arcia 4errocal,
:amire$-Camacho, >ortero, D 'argas, &1Goide, Kanagita, Hondo, D Gurata, %;BB1 /ugiura
et al., &1 'eltri, (ilson, /prin3le, :odman, D Gavesh, %;B%1 (ilson, %;B51 Koshida,
Kamauchi, /hin3awa, Horiuchi, D /a3ai, %;;5+. Additionally, H/'% has been suggested as the
etiologic agent in !eniereFs disease, although not all studies support this association *Arnold D
)iedermeyer, %;;yy33o, &81 Ta3ahash et al., &%1 'rabec, &71 (elling, !iles, (estern, D >rior,
%;;
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meningitis and hearing loss, therapy for H/'% meningitis may be adequate *86%mgN3g
acyclovir T#? or valacyclovir %,mg T#?1 /tudahl et al., &%7+. Hearing loss that does not
recover following treatment with steroids and antiherpetic agents can be remediated with hearing
aids or cochlear implantation, depending on the severity of loss.
Viruses Causing Ac#uired Hearing Loss
&easles 'Rubeola(
The measles virus *rubeola+ is an enveloped single-stranded :)A virus in the paramyxovirus
family. #t is very easily transmitted through contact with respiratory secretions from patients with
measles. /ymptoms include fever, cough, nasal congestion, erythematous maculopapular rash,
conEunctivitis, and pathognomonic Gopli3 spots on the buccal mucosa. Hearing loss is a commoncomplication of measles infection1 prior to widespread vaccination, measles accounted for 8 to
% of cases of profound hearing loss in the @nited /tates *!cGenna, %;;
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twenties is indicated for prevention of mumps+. >rior to the development of widespread
vaccination, measles would infect O; of susceptible children in epidemics. Compilation of
infection data from multiple countries shows
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with otosclerosis can be treated with either hearing amplification or stapedotomy for their
conductive loss and with hearing aids for /)H0. "or patients with severe /)H0 from
otosclerosis, cochlear implantation or stapedotomy for far advanced otosclerosis plus a
postoperative hearing aid can rehabilitate hearing */emaan et al., &%&+.
Varicella )oster Virus
'' is a double-stranded enveloped ?)A virus of the Herpesviridaefamily. '' is a highly
contagious virus that is transmitted either by droplets from coughing or snee$ing of actively
infected individuals or by direct contact with fluid from herpetic vesicles. ''-infected patients
are infectious from & days prior to appearance of the viral rash until after all the vesicles have
crusted. '' first causes a primary infection that, when symptomatic, manifests with fever, an
erythematous macular rash, and pustules *chic3enpox+. #n some individuals, the primary
infection is asymptomatic. The virus can subsequently remain latent in neurons in various parts
of the body for an extended period, reactivating years later. /ymptoms of '' reactivation *e.g.,$oster or shingles+ include both systematic symptoms *fever and malaise+ as well as local
symptoms *severe pain and a vesicular rash+ that are limited to the area innervated by the
neurons in which the virus reactivated. :is3 factors for viral reactivation include age O8 years,
pregnancyNpostpartum states, and immunocompromise *Gansu D Kilma$, &%&1 /weeney D
9ilden, &%+.
:eactivation of latent '' within the geniculate ganglion causes :amsay Hunt syndrome or
H through the development of geniculate ganglionitis and inflammation of the facial nerve.
2ighth nerve involvement results from transfer of the virus from the nearby geniculate ganglionor directly from the facial nerve within the internal auditory canal. /ymptoms include facial
nerve paralysis, herpetic vesicles, severe otalgia, /)H0 *& of affected patients+, tinnitus
*B+, and vertigo *71 /weeney D 9ilden, &%1 "igure 7+. Additional symptoms such as
ipsilateral loss of lacrimation and impaired sense of taste in the ipsilateral two thirds of the
tongue result from damage to the facial nerve. 2rythematous vesicles that ultimately erupt and
crust can typically be seen on the pinna, external auditory canal, tympanic membrane, hard
palate, and tongue *Gansu D Kilma$, &%&+. :arely, patients can present with all of the signs and
symptoms of H without a herpetiform rash *$oster sine herpete1/weeney D 9ilden, &%+.
Although the facial, trigeminal, and vestibular nerves are most commonly affected, cases have
been reported involving the glossopharyngeal and vagus nerves with resulting dysphagia and
hoarseness *0in, Gao, D (ang, &%%+.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr98-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr57-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/figure/fig3-2331216514541361/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr57-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr65-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr98-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr57-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/figure/fig3-2331216514541361/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr57-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr112-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr65-23312165145413617/26/2019 Viral Causes of Hearing Loss
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"igure 7. Herpes $oster oticus, with crusted vesicles on the face in the left '& distribution and
vesicles and swelling of the left tongue.
/ource= Clinical photograph used with permission from 4raverman @ri, and 9reenberg *&+.
/)H0 is unilateral and can range from a mild, high frequency loss to profound1 however, it isusually mild to moderate. ccasionally, /)H0 can occur suddenly as the first manifestation of
H, and so must be included in the differential diagnosis of //)H0 *(ayman, >ham, 4yl, D
Adour, %;;+. >atients with H have been found to have A4: changes consistent with both
cochlear and retrocochlear dysfunction *Abramovich D >rasher, %;B5+.
The diagnosis of H is usually made based on history and physical examination. 2nhancement
of the seventh and eighth cranial nerves on gadolinium-enhanced, T%-weighted !:# can be
observed *9ant$, :edleaf, >erry, D 9ubbels, &%+. Hemorrhage of the cochlear nerve and
destruction of the apex of the organ of Corti have been reported. Temporal bone studies of
affected individuals have shown loss of geniculate ganglion cells with neuronal swelling and
chromatolysis, perivascular lymphocytic infiltrates, neural demyelination, and axonal loss
*Ale3sic, 4ud$ilovich, D 0ieberman, %;
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)egative prognostic factors for hearing recovery in H include older age, male gender, the
presence of vertigo, and hearing impairment within speech frequencies *(ayman et al., %;;+.
High-frequency /)H0 indicates a better prognosis for complete recovery. The severity of facial
nerve paralysis does not necessarily correlate with the severity or prognosis of auditory and
vestibular symptoms *9ant$ et al., &%+.
Control of primary varicella infection may decrease the incidence of H. >rior to the advent of
vaccination for varicella, chic3enpox was an extremely common childhood disease with an
annual incidence of %8 to %5 per %, population. The @./. C?C recommends vaccination of
children using one of two licensed vaccines. 'A:#'AQ, a single-antigen live-attenuated
varicella vaccine, has been available in the @nited /tates since %;;8 for use in healthy patients
aged %& months and older. A second vaccine, >rouad *!!:'+, includes the live-attenuated
antivaricella vaccine as well as the !!: vaccine. These vaccines are thought to reduce the
incidence of primary '' infection by up to ;5. :ecommendations include two doses of the
vaccine, the first at %& to %8 months of age and the second at age to 5 years. "or teens without
evidence of immunity, the recommendations include two doses of 'A:#'AQ separated by to B
wee3s between doses. 4ecause the vaccines include live-attenuated virus, they should not be
administered to patients with decreased humoral immunity or to pregnant women. However,
these vaccines can be administered to patients with H#' and breastfeeding mothers *!arin,
9uris, Chaves, /chmid, D /eward, &revention of '' reactivation is also possible via immuni$ation with ostavax, a live-
attenuated antivaricella vaccine that currently is recommended in the @nited /tates for patients
aged 8 years and older *C?C, &%%+. This vaccine utili$es the same attenuated strain as the
'A:#'AQ and !!:' vaccines but at a higher potency. "ifteen percent to 7 of individuals
who were infected with '' experience reactivation later in life *up to .& per %, @./.
population+1 ostavax decreases this incidence by 8 *Harpa$, rtega-/anche$, D /eward,
&B+. (hile the direct impact of varicella immuni$ation on H has not been measured,
presumably the incidence of these cases will also decrease.
>ermanent hearing impairment occurs in about 8 of cases of H *!ura3ami et al.,
%;;rasher, %;B51Gaberos, 4alatsouras, Gorres,
Gandiloros, D 2conomou, &&+. )onpharmacological treatment is focused on the use of hearing
aids to remediate mild to moderately severe /)H0.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr124-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr38-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr67-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr67-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr46-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr46-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr77-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr77-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr124-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr124-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr1-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr54-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr54-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr54-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr124-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr38-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr67-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr67-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr46-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr46-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr77-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr77-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr124-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr1-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr54-2331216514541361http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222184/#bibr54-23312165145413617/26/2019 Viral Causes of Hearing Loss
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&u!"s
The mumps virus is an enveloped single-stranded :)A virus that belongs to the paramyxovirus
family, which also includes measles. !umps is transmitted through infected respiratory
secretions and is highly contagious *9upta, 4est, D !ac!ahon, &8+. (hile mumps is one of
the most common causes of acquired /)H0, its incidence varies greatly between studies.
2stimates of the incidence of hearing loss following mumps infection range from % per %, to
% per 7, to as high as 7 per % in the %;B #sraeli epidemic * Hashimoto, "uEio3a, D
Ginuma3i, &;1Ganra et al., &&+. ?ifferences in vaccination practices between nations may
underlie this variance in /)H0. "or instance,Hashimoto et al. *&;+have reported an incidence
of .% in Lapan, where measles6rubella vaccine was more commonly administered than the
!!:.
#nitially, mumps presents with symptoms of a flu-li3e illness, followed by bilateral swelling of
the parotid glands *2lliman, /engupta, 2l 4ashir, D 4edford, &
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The ris3 of /)H0 following mumps infection is not correlated with severity of the infection or
presence of parotitis *Hall D :ichards, %;B
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that initial outbrea3, instances of ()' have been reported throughout the 2ast Coast and the
midwestern @nited /tates *Hayes, Gomar, et al., &8+.
nly & of ()' infections are symptomatic, and most commonly present with a flu-li3e
illness *Hayes, /eEvar, et al., &8+. However, neurological complications, such as meningitis,
encephalitis, and acute flaccid paralysis, occur in less than % of cases. These manifestations are
more common in elderly or immunocompromised patients. #n most cases, the severe neurologic
complications eventually resolve with only supportive treatment, although some patients may
suffer from persistent flaccid paralysis */eEvar et al., &7+.
Hearing loss resulting from ()' infection is extremely rare. /imilar to other neurologic
symptoms, hearing loss is also reported more frequently in immunocompromised patients and
often recovers spontaneously *Lamison, !ichaels, :atard, /weet, D ?eboisblanc,
&
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thers cause hearing loss as a result of infection in childhood or adulthood. Hearing loss
following viral infection is often sensorineural, although it may be mixed *C!', measles+ or
conductive *measles+. Auditory system damage is typically intracochlear1 however, some viruses
can affect the auditory brainstem as well. !echanisms of inEury to the peripheral auditory system
can include direct viral damage to the organ of Corti, stria vascularis, or spiral ganglion1 damagemediated by the patientFs immune system against virally expressed proteins *C!'+1 and
immunocompromise leading to secondary bacterial infection of the ear *H#', measles+. Hearing
loss due to H or C!' infection can be treated medically with stabili$ation or improvement in
hearing thresholds. Common childhood vaccines can prevent several of the viral infections
discussed within this review and should be recommended to patients and parents. The incidence
of hearing loss following vaccination with live-attenuated virus vaccines, such as the !!: and
!!:', is extremely rare. :ehabilitation of hearing loss due to other viruses typically involves
hearing aids, with cochlear implantation for patients with severe to profound hearing loss.
,eclaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship,
andNor publication of this article.
-unding
The authors disclosed receipt of the following financial support for the research, authorship,
andNor publication of this article= This wor3 was supported by the )ational #nstitutes of
HealthN)ational #nstitute of ?eafness and ther Common ?isorders 9rant GB ?C;&BB.
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