Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4408_Библиотеки_им_академика_М_И_Перельмана
.pdf
30 Balance andOtitis Media
https://t.me/medicina_free
269
Studies evaluating peripheral vestibular damage secondary to otitis media are very scarce. In fact, the presence of a
potential vestibular lesion secondary to otitis media has been
a matter of great controversy for several reasons. First, the
presence of vestibular symptoms and signs of vestibular dysfunction are much less frequent than auditory symptoms in
otitis media [27, 28]. Second, in most cases, vestibular symptoms in patients with otitis media are frequently associated
with a perilymphatic stula or other causes of dizziness,
such as metabolic diseases or benign paroxysmal vertigo
(Monsanto etal. 2018). Also, Juhn etal. [29] demonstrated
the presence of a blood–labyrinthine barrier, which is a protective mechanism to maintain the ionic balance and homeostasis in the inner ear uids. Several substances and clinical
conditions have been shown to alter the permeability of the
blood–labyrinthine barrier, leading to loss of homeostasis
and cochlear (and possibly vestibular) changes [30, 31].
Although otitis media could be one of these problems affecting the blood–labyrinthine barrier, this has not yet been
explored in experimental studies yet. Nonetheless, growing
evidence indicates a potential vestibular dysfunction secondary to COM: the prevalence of vestibular symptoms in
patients with COM was estimated at 40–60%, and these
symptoms frequently associate with abnormal results in vestibular function tests (caloric tests, cervical vestibular evoked
myogenic potentials (cVEMPs), and rotatory chair)
(Monsanto etal. 2018).
Paparella et al. [32] hypothesized, based on the clinical
observation that many patients with otitis media have uctuating sensorineural hearing loss, tinnitus, and episodic dizziness
or vertigo, that otitis media could be a cause of secondary
endolymphatic hydrops. Based on these observations, the
authors performed an otopathologic study in 194 temporal
bones specimens with otitis media. In these temporal bones,
75 (38.6%) had signs of endolymphatic hydrops. Later, Saito
etal. [33] showed similar ndings: in their temporal bones,
there was a 44.8% prevalence of endolymphatic hydrops.
These histopathological data have been later supported by
clinical studies, observing that some patients with chronic otitis media tend to develop Meniere’s disease over time [34, 35].
Additionally, Zou and Pyykkö [36] demonstrated the presence
of obvious endolymphatic hydrops in a magnetic resonance
imaging of a patient with chronic otitis media. Thus, it is possible that endolymphatic hydrops is one of the potential causes
of vestibular impairment in patients with otitis media.
The rst study to perform an otopathologic evaluation of
the vestibular system in human temporal bones with COM
was Kodama etal. [27]. In this study, the authors demonstrated eosinophilic deposits (suggestive of inammatory
response) in the endolymphatic and perilymphatic compartments, being more concentrated in the saccule. It was also
observed the presence of saccular edema and an abnormal
neuroepithelium, while no signicant abnormalities were
seen in the utricle and semicircular canals. Kodama etal.
[27] also showed that the abnormalities affecting the cochlea
(loss of cochlear hair cells and stria vascularis abnormalities)
were much more frequent than the vestibular changes. After
Kodama’s study, there is a 30-year gap before the subject
was revisited by Monsanto etal. [12], who studied the vestibular neuroepithelium (saccule, utricle, and semicircular
canals) and dark and transitional cells in the crista ampullaris
of the lateral and posterior semicircular canals in temporal
bones with COM. The authors found a signicant loss of
vestibular hair cells type I and II in the saccular and utricular
macula (more intense) and loss of type I cells in the anterior
and posterior semicircular canals (less intense) (Fig.30.2).
Also, the authors found a signicant loss of dark cells in the
COM group as compared with controls. Kaya etal. [37] later
studied vestibular abnormalities in temporal bones of patients
with labyrinthitis (serous, suppurative, and ossicans). The
authors showed that the presence of labyrinthitis caused by
otitis media associated with a high prevalence of endolymphatic hydrops, and a signicant loss of transitional and dark
cells in the semicircular canals, and loss of vestibular hair
cells type I and II in both otolithic organs and semicircular
canals.
In 2017, following the theory of the continuum of otitis
media as described by Paparella etal. [38], investigators at
the University of Minnesota aimed to evaluate potential
routes of progression of the inner ear lesions secondary to
otitis media [10]. In this study, the authors analyzed losses
of cochlear hair cells, stria vascularis, vestibular hair cells,
and vestibular dark and transitional cells in temporal bones
with different types of otitis media and controls. The results
showed that early stages of otitis media associated with
cochlear lesions limited to the basal turn of the cochlea
(loss of outer hair cells and atrophy of the stria vascularis).
As the disease progresses, structures from the middle turn
of the cochlea are affected, and—in more advanced cases
of COM—there is a signicant loss of vestibular hair cells
in the otolithic organs. The authors conclude that the
cochlear damage precedes the vestibular damage secondary
to otitis media, and that the severe and chronicity of the
middle ear inammation seem to directly associate with the
degree of inner ear losses. These ndings are supported by
clinical evidence. Chang etal. [39] demonstrated that the
inner ear decits in patients with COM initiate at the
cochlea, affecting the saccule/utricle and semicircular
canals in a later stage of the disease. Monsanto etal. [28]
also showed a similar pattern, revealing that the hearing
loss in patients with COM initiates at an earlier stage and
affects a signicant higher portion of patients as compared
with vestibular symptoms and abnormalities in the vestibular function tests.
270
ab
https://t.me/medicina_free
R. da CostaMonsanto et al.
Fig. 30.2 Two representative human temporal bone sections, one from
a healthy donor (a) and other from a donor with chronic otitis media (b)
seen under Nomarsky microscopy (hematoxylin and eosin). In (a), the
Vestibular Symptoms inPatients withOtitis
Media
utricular macula seems normal, with normal number of type I (1) and
type II (2) vestibular hair cells. In (b), the arrows (*) point to areas of
loss of vestibular hair cells in the utricular macula
lead to vestibular dysfunction (such as metabolic diseases,
benign paroxysmal positional vertigo (BPPV), and perilymphatic stula) (Monsanto et al. 2018). However, a 30-year
The association between otitis media and vestibular symptoms has been described in recent studies [40–42]. It is
unclear what exact pathophysiologic mechanisms are
involved with the development of these vestibular symptoms; in fact, no previous study has strongly determined the
presence of a peripheral vestibular lesion secondary to otitis
media. However, growing evidence support the hypothesis
that otitis media does associate with vestibular dysfunction.
A recent systematic review demonstrated that over 30% of
patients with different types of otitis media experience some
sort of symptom attributable to vestibular dysfunction
(Monsanto et al. 2018) (Fig. 30.3). In patients with AOM,
studies estimated that 30–48% of patients complain of dizziness or vertigo in the initial phase of the disease [43–46]. In
OME cases, children were described as “clumsy” and had a
higher tendency to fall as compared with children who did
not have OME [47]. Also, OME associated with worse posturography results as compared with those of healthy children [48]. COM also associates with a high prevalence of
vestibular symptoms, as a meta-analysis estimated the prevalence of dizziness or vertigo in this population at 40–60%
(Monsanto etal. 2018). Despite these evidence, many authors
have disputed the assumption that otitis media leads to a
direct vestibular lesion, hypothesizing that the worse balance
in these patients would be rather due to the active inammation, through a difference in the pressure of the middle ear
caused by the effusion, a direct effect of the hearing loss, or
even due to other diseases or associated issues that could
cohort has demonstrated that the prevalence of self-reported
dizziness in adulthood was signicantly higher among people who had a history of chronic otitis media in the past as
compared with people who did not, showing that otitis media
do lead to permanent (although potentially subclinical)
peripheral vestibular damage [49].
The rst study associating middle ear effusion with disequilibrium was published in 1977 [50]. Nowadays, OME is
acknowledged as the most common cause of dizziness in
childhood—however, the real incidence may be even higher
than reported, as children rarely complain of balancedrelated symptoms. Instead, vestibular symptoms are reported
by caregivers as frequent falls, clumsiness, or bumping into
things [47, 48, 51, 52]. Most studies demonstrated that children with OME have worse results in balance tests, delayed
gross/ne skills acquisition, and abnormal posturography
results. These abnormalities seem to subside after adequate
treatment of the middle ear effusion: the symptoms and signs
of balance disturbances resolved in 96% of the children after
ventilation tube insertion [53]. However, even after the
improvements, these children have lower scores than controls in balance tests as compared with controls [53–55]. A
possible explanation for this is that chronic or repeated
inammation may cause permanent damage to the vestibular
sensory epithelium [56]. Furthermore, adults who had OME
or recurrent AOM during childhood may experience dizziness during their life [49]. Although speculative, it is possible that inammatory mediators or toxins arising from the
30 Balance andOtitis Media
https://t.me/medicina_free
Fig. 30.3 Prevalence of
vestibular symptoms in
patients with different types
of otitis media
271
middle ear inammation may lead to a permanent effect on
the vestibular system [10, 24, 25].
The long-term sequelae due to AOM have been sparsely
studied. Several authors described the presence of vestibular
decits after ear infection, which resolved completely after
treatment [57]. It seems that only patients who develop suppurative labyrinthitis as a consequence of AOM seem to be at
an increased risk of developing a permanent vestibular
sequela [37, 58]. It is possible that future studies in this
regard will shed additional light in this yet pending aspect of
AOM.
The prevalence of vestibular symptoms in patients who
have COM was estimated at 40–60% [41, 59]. It was reported
that the most critical factors associating with the vestibular
symptoms in COM patients are the presence of perilymphatic stulae or exacerbations of the middle ear inammation. The vestibular symptoms in patients with COM are
much less frequent than the auditory [28, 39]. In fact, it was
observed that less than 20% include the vestibular symptoms
as their chief complaints [39]. A possible explanation to that
fact is that the chronic progression of the vestibular impairment caused by COM would allow central compensation for
daily situations [60], or that the vestibular system is more
resistant to inammatory damage as compared with the
cochlea [10].
Vestibular Function Tests
The matter of vestibular testing in patients with otitis media
will be discussed in detail in a different chapter. The different
types of otitis media (OME, AOM, and COM) were evaluated in relation to vestibular impairment with vestibular
function tests (Monsanto etal. 2018), which included electronystagmography (ENG), caloric tests, vestibular evoked
myogenic potentials (VEMP), dynamic and static posturography, sway magnetometry, craniocorpography, and the subjective vertical visual (SVV). Furthermore, scales and
clinical tests were used to evaluate coordination, balance,
and motor skills: Peabody Developmental Motor Scales
(PDMS), Bruininks-Oseretsky Test of Motor Prociency
(BOTMP), Stott Test of Motor Impairment (STMI), and the
Motor Accuracy Test-Revised (MAT-R).
All studies consistently demonstrated that children with
OME had worse performance compared with controls,
regarding the PDMS and BOTMP tests [53, 54, 61–64].
However, the association between low scores in these tests
and presence of vestibular symptoms was inconsistent
among studies. No signicant differences existed in the
results of STMI and MAT-R tests of OME and control groups
[65]. Of ENG tests, rates of abnormalities were signicantly
higher compared with controls in all studies except in the
study of Engel-Yeger etal. [62]. Regarding VEMP testing,
no consistent results were found between OME patients and
controls [64, 66, 67]. VEMP tests using air-conducted stimuli and bone-conducted stimuli varied greatly among studies
(2–30% of absence of responses). The patients subjected to
dynamic or static posturography demonstrated abnormal
results compared with controls in some studies [47, 51, 52,
68]. In contrast, Ben-David etal. did not nd differences in
posturography between OME patients and controls [50].
The studies regarding AOM patients, 93% with AOM had
abnormalities on the ENG and/or caloric tests. Also, caloric
tests demonstrated decreased function in the affected ear in
30.7% of the subjects (Monsanto et al. 2018). Of patients
with COM, ENG tests demonstrated that 56% had spontane-
272
https://t.me/medicina_free
R. da CostaMonsanto et al.
ous nystagmus [40, 69, 70]. Of the caloric tests, 34.3% had
abnormal results in the affected side. However, there were no
signicant relations between the presence of vestibular
symptoms and abnormal caloric responses. Rotatory chair
tests in 60 patients with COM demonstrated a 70% incidence
rate of abnormalities, which was positively associated with
the presence of vertigo [41]. Regarding VEMP tests in
patients with COM, some studies showed worse results in
comparison with controls [39, 41, 59, 71–74]. However, over
again, low correlation between VEMP abnormalities and
clinical symptoms was demonstrated [41, 59]. About posturography, Mostafa etal. [41] did not nd patterns in the
abnormal responses in their 60 subjects, but no control
groups were included by the authors.
Despite many studies using these tests to evaluate possible damage in the inner ear due to otitis media, objective
quantication of vestibular function is hard to achieve with
tests available in daily practice (Monsanto et al. 2018).
Caloric tests, ENG, and VEMPs results are negatively inuenced by the status of the middle ear, and their results should
be interpreted with caution. Further, children’s cooperation
for those tests is often limited [61, 62]. Some vestibular tests
that are not affected by the presence of conductive hearing
loss are viable alternatives to estimate whether the vestibular
system was affected by otitis media or not. Those tests
include clinical bedside tests (gait, static and dynamic postural tests, tests of the vestibule-ocular reexes, cerebellar
function tests, and neurologic evaluation), the video head
impulse test (vHIT), static and dynamic posturography, and
the SVV test [40, 41, 48].
Conclusions
Currently, there is consistent histopathologic and clinical
evidence associating otitis media with peripheral vestibular
system injury, which makes the search for vestibular symptoms and vestibular tests important in the evaluation of
patients with otitis media. However, some aspects regarding
the pathophysiological mechanisms leading to the vestibular
lesion still need further clarication.
References
1. Bluestone CD, Gates GA, Klein JO, Lim DJ, Moji J, Ogra PL, etal.
1. Denitions, terminology and classication of otitis media. Ann
Otol Rhinol Laryngol. 2002;111:8–18.
2. Rosenfeld RM, Shin J, Schwartz SR, Coggins R, Cagnon L,
Hackell JM, et al. Clinical practice guideline: otitis media with
effusion (update). Otolaryngol Head Neck Surg. 2016;154:S1–S41.
3. Lieberthal AS, Carrol AE, Chonmaitree T, Ganiats TG, Hoberman
A, Jackson MA, etal. Clinical practice guideline: the diagnosis and
management of acute otitis media. Pediatrics. 2013;131:e964–99.
4. World Health Organization. Chronic suppurative otitis media:
burden of illness and management options. Geneva: World
Health Organization; 2004. Available at: https://apps.who.int/iris/
handle/10665/42941.
5. Monasta L, Ronfani L, Marchetti F, et al. Burden of disease caused
by otitis media: systematic review and global estimates. PLoS One.
2012;7(4):e36226. https://doi.org/10.1371/journal.pone.0036226.
Epub 2012 Apr 30.
6. Teele DW, Klein JO, Rosner B.Epidemiology of otitis media during the rst seven years of life in children in greater Boston: aprospective, cohort study. J Infect Dis. 1989;160(1):83–94. https://doi.
org/10.1093/infdis/160.1.83.
7. Casselbrant ML, Rubenstein E, Furman JM, Mandel
EM. Effect of otitis media on the vestibular system in children.
Ann Otol Rhinol Laryngol. 1995;104(8):620–4. https://doi.
org/10.1177/000348949510400806.
8. Casselbrant ML, Mandel EM, Kurs-Lasky M, Rockette HE,
Bluestone CD. Otitis media in a population of black American
and white American infants, 0–2 years of age. Int J Pediatr
Otorhinolaryngol. 1995;33(1):1–16. ISSN: 0165-5876. https://doi.
org/10.1016/0165- 5876(95)01184- D.
9. de Oliveira Penido N, Chandrasekhar SS, Borin A, Maranhão AS,
Testa JRG. Complications of otitis media e a potentially lethal
problem still present. Braz J Otorhinolaryngol. 2016;82(3):253–62.
https://doi.org/10.1016/j.bjorl.2015.04.007.
10. Monsanto RDC, Schachern P, Paparella MM, Cureoglu S, de
Oliveira Penido N.Progression of changes in the sensorial elements
of the cochlear and peripheral vestibular systems: the otitis media
continuum. Hear Res. 2017;351:2–10. ISSN: 0378-5955. https://
doi.org/10.1016/j.heares.2017.05.003.
11. Paparella MM, Oda M, Hiraide F, et al. Pathology of sensorineural hearing loss in otitis media. Ann Otol Rhinol Laryngol.
1972;81:632–47. https://doi.org/10.1177/000348947208100503.
12. Monsanto RDC, Erdil M, Pauna HF, etal. Pathologic changes of
the peripheral vestibular system secondary to chronic otitis media.
Otolaryngol Head Neck Surg. 2016;155:494–500. https://doi.
org/10.1177/0194599816646359.
13. Paparella MM. Interactive inner-ear/middle-ear disease,including
perilymphatic stula. Acta OtolaryngolSuppl. 1991;485:36–45.
14. Anon. Politzer’s text-book of the diseases of the ear for students
and practitioners. Indian Med Gaz. 1927;62:410–1.
15. Mackenzie GW. LXXXIX. Suppurative labyrinthitis with report
of cases. Ann Otol Rhinol Laryngol. 1927;36:1019–77. https://doi.
org/10.1177/000348942703600412.
16. Turner AL, Fraser JS.Labyrinthitis, a complication of middle-ear
suppuration: aclinical and pathological study. J Laryngol Otol.
1928;43:609–44. https://doi.org/10.1017/S0022215100032485.
17. Druss JG. Pathways of infection in labyrinthitis: report of three
different types. Arch Otolaryngol. 1929;9:392–403. https://doi.
org/10.1001/archotol.1929.00620030414004.
18. Arslan M. Modications of the osmotic pressure of perilymph
and endolymph. An hypothesis on the pathogenesis of Menière’s
disease. Acta Otolaryngol (Stockh). 1969;67:360–77. https://doi.
org/10.3109/00016486909125463.
19. Cureoglu S, Schachern PA, Rinaldo A, et al. Round window
membrane and labyrinthine pathological changes: an overview. Acta Otolaryngol (Stockh). 2005;125:9–15. https://doi.
org/10.1080/00016480410022534.
20. Goycoolea MV, Paparella MM, Goldberg B, etal. Permeability of
the middle ear to staphylococcal pyrogenic exotoxin in otitis media.
Int J Pediatr Otorhinolaryngol. 1980;1:301–8.
21. Goycoolea MV, Lundman L. Round window membrane.
Structure function and permeability: a review. Microsc
Res Tech. 1997;36:201–11. https://doi.org/10.1002/
(SICI)1097- 0029(19970201)36:3<201::AID- JEMT8>3.0.
CO;2- R.
30 Balance andOtitis Media
https://t.me/medicina_free
273
22. Schachern PA, Paparella MM, Goycoolea MV, et al. The permeability of the round window membrane during otitis media. Arch
Otolaryngol Head Neck Surg. 1987;113:625–9.
23. Ghaheri BA, Kempton JB, Pillers D-AM, et al. Cochlear cytokine gene expression in murine chronic otitis media. Otolaryngol
Head Neck Surg. 2007;137:332–7. https://doi.org/10.1016/j.
otohns.2007.03.020.
24. MacArthur CJ, Pillers D-AM, Pang J, etal. Altered expression of
middle and inner ear cytokines in mouse otitis media. Laryngoscope.
2011;121:365–71. https://doi.org/10.1002/lary.21349.
25. MacArthur CJ, Hausman F, Kempton JB, et al. Otitis media
impacts hundreds of mouse middle and inner ear genes. PLoS One.
2013;8:e75213. https://doi.org/10.1371/journal.pone.0075213.
26. Trune DR, Kempton B, Hausman FA, et al. Correlative mRNA
and protein expression of middle and inner ear inammatory cytokines during mouse acute otitis media. Hear Res. 2015;326:49–58.
https://doi.org/10.1016/j.heares.2015.04.006.
27. Kodama A, Ishii T, Oka Y, etal. Histopathology of the inner ear in
chronic otitis media. Equilib Res. 1988;47:94–100.
28. Monsanto RDC, Kasemodel ALP, Tomaz A, Elias TGA, Paparella
MM, Penido NO.Evaluation of vestibular symptoms and postural
balance control in patients with chronic otitis media. J Vestib Res.
2020;30(1):35–45. https://doi.org/10.3233/VES- 200691.
29. Juhn SK, Meyerhoff WL, Paparella MM. Clinical application of
middle ear effusion analyses. Laryngoscope. 1981 Jun;91(6):1012-
1015. https://doi.org/10.1288/00005537-198106000-00023.
30. Ishiyama G, Lopez IA, Ishiyama P, etal. The blood labyrinthine
barrier in the human normal and Meniere’s disease macula utricle.
Sci Rep. 2017;7:253. https://doi.org/10.1038/s41598- 017- 00330- 5.
31. Ishiyama G, Wester J, Lopez IA, Beltran-Parrazal L, Ishiyama
A.Oxidative stress in the blood labyrinthine barrier in the macula
utricle of Meniere’s disease patients. Front Physiol. 2018;9:1068.
https://doi.org/10.3389/fphys.2018.01068.
32. Paparella MM.Middle ear effusions: denitions and terminology
Ann. Otol. Rhinol. Laryngol., 85 (2 Suppl. 25 Pt 2) (1976 Mar-Apr),
pp. 8–11.
33. Saito H, Kitahara M, Kitajima K, Takeda T, Yazawa D, Matsubara
H, Kitano J.Distended Reissner’s membrane and otitis media (in
Japanese). Pract Otol (Kyoto). 1981;74(Suppl 5):2413–8.
34. Paparella MM, Morizono T, Le CT, et al. Sensorineural hearing
loss in otitis media. Ann Otol Rhinol Laryngol. 1984;93(6):623–9.
https://doi.org/10.1177/000348948409300616.
35. Yamamoto E, Mizukami C. Endolymphatic hydrops induced
by chronic otitis media. In: Kitahara M, editor. Ménière’s disease. Tokyo: Springer; 1990. https://doi.org/10.1007/978- 4- 431-
68111- 3_25.
36. Zou J, Pyykkö I. Endolymphatic hydrops in Meniere’s disease secondary to otitis media and visualized by gadoliniumenhanced magnetic resonance imaging. World J Otorhinolaryngol.
2013;3(1):22–5.
37. Kaya S, Schachern PA, Tsuprun V, etal. Deterioration of vestibular
cells in labyrinthitis. Ann Otol Rhinol Laryngol. 2017;126:89–95.
38. Paparella MM, Abdelhammid MM, Schachern PA, Sahni R, Yoon
TH, da Costa SS.Otopathologiccorrelates of the continuum of otitis media. Ann Otol Rhinol Laryngol. 1990;99(6_Suppl):17–22.
https://doi.org/10.1177/00034894900990S606.
39. Chang C-W, Cheng P-W, Young Y-H. Inner ear decits after
chronic otitis media. Eur Arch Otorhinolaryngol. 2014;271:2165–
70. https://doi.org/10.1007/s00405- 013- 2714- 7.
40. Lee JS, Lee SK, Shin IH, etal. Vestibular evoked myogenic potential according to middle ear condition in chronic otitis media with
tympanic membrane perforation. Acta Otolaryngol. 2014;134:
34–40.
41. Mostafa BE, Shak AG, El Makhzangy AMN, etal. Evaluation
of vestibular function in patients with chronic suppurative otitis
media. ORL J Otorhinolaryngol Relat Spec. 2013;75:357–60.
42. Paparella MM.Interactive inner-ear/middle-ear disease, including
perilymphatic stula. Acta Otolaryngol. 1991;485:36–45.
43. Eliashar R, Gross M, Saah D, etal. Vestibular involvement in myringitis bullosa. Acta Otolaryngol. 2004;124:249–52.
44. Kim CH, Yang YS, Im D, etal. Nystagmus in patients with unilateral acute otitis media complicated by serous labyrinthitis. Acta
Otolaryngol. 2016;136:559–63.
45. Nishimura M, Doi K, Kubo T, etal. Inner ear damage in acute otitis
media. Pract Otorhinolaryngol. 2000;93:455–9.
46. Yamaguchi J, Yagi T, Baba S, etal. Inner ear damage in acute otitis
media. OtolJpn. 1992;2:259–63.
47. Casselbrant ML, Furman JM, Rubenstein E, et al. Effect of oti-
tis media on the vestibular system in chil-dren. Ann Otol Rhinol
Laryngol. 1995;104:620–4.
48. Casselbrant ML, Furman JM, Mandel EM, et al. Past history of
otitis media and balance in four-year-old children. Laryngoscope.
2000;110:773–8.
49. Aarhus L, Tambs K, Hoffman HJ, etal. Childhood otitis media is
associated with dizziness in adulthood: the HUNT cohort study.
Eur Arch Otorhinolaryngol. 2016;273:2047–54.
50. Ben-David J, Podoshin L, Fradis M, et al. Is the vestibular system affected by middle ear effusion? Otolaryngol Head Neck Surg.
1993;109:421–6.
51. Casselbrant ML, Redfern MS, Furman JM, et al. Visualinduced
postural sway in children with and without otitis media. Ann Otol
Rhinol Laryngol. 1998;107:401–5.
52. Gawron W, Pospiech L, Orendorz-Fraczkowska K. An evaluation of postural stability and the effects of middle-ear drainage on
vestibulo-spinal reexes of children with chronic otitis media with
effusion. Int J Pediatr Otorhinolaryngol. 2004;68:1175–9.
53. Golz A, Netzer A, Angel-Yeger B, etal. Effects of middle ear effusion on the vestibular system in children. Otolaryngol Head Neck
Surg. 1998;119:695–9.
54. Orlin MN, Effgen SK, Handler SD.Effect of otitis media with effusion on gross motor ability in preschool-aged children: preliminary
ndings. Pediatrics. 1997;99:334–7.
55. Wang M-C, Lee G-S.Vestibular evoked myogenic potentials in
middle ear effusion. Acta Otolaryngol. 2007;127:700–4.
56. Joglekar S, Morita N, Cureoglu S, et al. Cochlear pathology
in human temporal bones with otitis media. Acta Otolaryngol.
2010;130:472–6.
57. Balatsouras DG, Kaberos A, Assimakopoulos D, etal. Etiology of
vertigo in children. Int J Pediatr Otorhinolaryngol. 2007;71:487–94.
58. Igarashi M, O-Uchi T, Isago H, etal. Utricular and saccular volumetry in human temporal bones. Acta Otolaryngol. 1983;95:75–80.
59. Ho K-Y, Chien C-Y, Tsai S-M, etal. Clinical signicance of vestibular function with caloric and vestibular evoked myogenic potential
testing for patients with simple chronic otitis media. J Int Adv Otol.
2012;8:447–52.
60. Lacour M, Helmchen C, Vidal P-P.Vestibular compensation: the
neuro-otologist’s best friend. J Neurol. 2016;263:54–64.
61. Cohen H, Friedman EM, Lai D, et al. Balance in children with
otitis media with effusion. Int J Pediatr Otorhinolaryngol.
1997;42:10107–15.
62. Engel-Yeger B, Golz A, Parush S.Impact of middle ear effusion on
balance performance in children. Disabil Rehabil. 2004;26:97–102.
63. Hart MC, Nichols DS, Butler EM, et al. Childhood imbalance
and chronic otitis media with effusion: effect of tympanostomy
tube insertion on standardized tests of balance and locomotion.
Laryngoscope. 1998;108:665–70.
64. Said EA, Ahmed MK, Mohamed ES.Role of vestibular testing in
deciding treatment strategies for children with otitis media with
effusion. Egypt J Ear Nose Throat Allied Sci. 2015;16:151–9.
65. Von T, Deitz JC, McLaughlin J, et al. The effects ofchronic otitis
media on motor performance in 5- and 6-year-old children. Am J
Occup Ther. 1988; 42:421–426.400R.
274
https://t.me/medicina_free
R. da CostaMonsanto et al.
66. Wang M-C, Lee G-S.Vestibular evoked myogenicpotentials in middle ear effusion. Acta Otolaryngol. 2007;127:700–4.
67. Kolkaila EA, Emara AA, Gabr TA.Vestibular evaluation in chil-
dren with otitis media with effusion. J Laryngol Otol. 2015;129:
326–36.
68. Jones NS, Prichard AJN, Radomskij P, etal. Imbalance and chronic
secretory otitis media in children: effect of myringotomy and insertion of ventilation tubes on body sway. Ann Otol Rhinol Laryngol.
1990;99:477–81.
69. Kanaya T, Shirato M, Unno T.Equilibrium ndings of chronic otitis
media. Pract Otorhinolaryngol. 1982;75:2392–8.
70. Kanoh Y, Yagi T, Yoshimoto Y, et al. A study on preoperative
electronystagmography in chronic otitis media. Equilib Res.
1980;39:43–8.
71. Seo T, Miyamoto A, Saka N, etal. Vestibular evoked myogenic
potential induced by bone-conducted stimuli in patients with conductive hearing loss. Acta Otolaryngol. 2008;128:639–43.
72. Wang M-C, Liu C-Y, Yu EC-H, etal. Vestibular evoked myogenic
potentials in chronic otitis media before and after surgery. Acta
Otolaryngol. 2009;129:1206–11.
73. Yang T-L, Young Y-H.Comparison of tone burst and tapping evocation of myogenic potentials in patients with chronic otitis media.
Ear Hear. 2003;24:191–4.
74. Zhou G, Poe D, Gopen Q.Clinical use of vestibular evoked myogenic potentials in the evaluation of patients with air-bone gaps.
Otol Neurotol. 2012;33:1368–74.
The Use ofTopical Treatment
https://t.me/medicina_free
andMiddle–Inner Ear Interaction
MarcosV.Goycoolea, LeandroRodríguez,
andPilarEpprecht
31
Introduction
The use of otologic drops as topical treatment for external
otitis, for some forms of otitis media, in otologic surgery and
for mastoid cavities is well established. Potential ototoxicity
involves the concept that under specic circumstances, some
of the components of these preparations (ototoxic components) can reach the inner ear and cause sensory damage.
Until 1995 [1], there were at least nine reports totaling
165 documented patients who developed sensorineural hearing loss owing to the use of ear drops for otitis media. In a
survey composed of 2235 otolaryngologists, 3.4% reported
having seen cochlear damage owing to otologic drops [2, 3].
If each of these otolaryngologists would have seen at least
one case, this would represent 76 additional cases. Moreover,
if 3.4% of otolaryngologists worldwide (ear drops are used
universally) would see, at the very least, one case (a very
conservative estimate), ototoxicity to otologic drops would
constitute a signicant problem. To our knowledge, no new
reviews documenting groups of publications describing
patients who developed sensorineural hearing loss owing to
the use of ear drops have been available. However, isolated
case reports keep appearing in the literature. Moreover, in
our daily otologic practice, we occasionally receive patients
who are referred because they developed sensorineural hearing loss after using ear drops with ototoxic components. In
brief, ototoxicity due to components of ear drops is a reality
to be addressed and with awareness it can be signicantly
diminished. Therefore, to avoid this complication while ben-
M. V. Goycoolea (*)
Department of Otolaryngology, Clínica Universidad de Los Andes,
Santiago, Chile
L. Rodríguez
Department of Otolaryngology, Clínica Universidad de Los Andes,
and Hospital del Salvador, Santiago, Chile
P. Epprecht
Department of Otolaryngology, Clínica Universidad de Los Andes
and Exequiel González Cortés Hospital, Santiago, Chile
eting from the use of these preparations, it is important to
review the potential routes of passage of these components to
the inner ear, the pathogenesis of these events, and the experimental and clinical evidence available. With this information in hand, safer means of using drops can be developed.
Potential Routes fromMiddle toInner Ear
Potential routes include round and oval windows, bony stulae, micro-ssures, and blood and/or lymph vessels. Bony
stulae, micro-ssures, and the oval window do not seem to
play a signicant role, and lymphatics which are abundant in
the round window membrane seem to participate in a peripheral rather than in a central direction. This is because the inner
ear is of neurectodermal origin; therefore, it should not have
lymphatics [3]. Blood vessels are an important route to consider because of the abundant vascular connections between
the middle and inner ear in the round window [3–5].
The predominant pathway—and the most evaluated—
seems to be the round window membrane. This membrane is
the only soft tissue barrier between the middle and the inner
ear. It is located inferiorly in the medial wall of the middle
ear and lies in a niche, being therefore susceptible to exposure to uids in the middle ear cavity.
Ultrastructural studies of the round window membrane of
humans, monkeys, felines, and rodents have disclosed three
basic layers: an outer epithelium, a middle core of connective tissue, and an inner ear epithelium. Despite being formed
by three layers, experimental evidence has suggested that it
behaves like a semipermeable membrane. Such evidence
suggests that the layers of the round window participate in
resorption and secretion of substances to and from the inner
ear. Different substances, including antibiotics and tracers,
when placed in the middle ear, traverse the membrane.
Permeability is selective. Factors affecting permeability
include size, concentration, electrical charge, thickness of
the membrane, and facilitating agents [6, 7].
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
M. V. Goycoolea et al. (eds.), Textbook of Otitis Media, https://doi.org/10.1007/978-3-031-40949-3_31
275
276
https://t.me/medicina_free
M. V. Goycoolea et al.
Available evidence of ototoxicity and/or passage of the
components of commonly used ear drops that can be detected
directly or indirectly in the inner ear after placing them in
experimental animals in the round window niche are
described in Table31.1. Those detected when placed in the
middle ear of humans are described in Table31.2.
Table 31.1 Components of commonly used ear drops that can be
detected directly or indirectly in the inner ear after placing them in
experimental animals in the round window niche
Antibiotics
Chloramphenicol
Gentamicin
Neomycin
Polymyxin B
Antiseptics
Acetic acid
Ethanol
Local anesthetics
Lidocaine
Solvents
Propylene glycol
Corticosteroids (benecial)
Hydrocortisone
Betamethasone
Table 31.2
detected directly or indirectly in the inner ear after placing them in the
middle ear of humans
Antibiotics
Chloramphenicol
Gentamicin
Neomycin
Polymyxin B
Local anesthetics
Lidocaine
Corticosteroids (benecial)
Dexamethasone
Components of commonly used ear drops that can be
Inner Ear Eects ofEar Drop Components
Chloramphenicol, neomycin, polymyxin B, and gentamicin
have been shown to cause hair cell damage [3, 8, 9]. Propylen
gycol is ototoxic and in addition causes inammatory reactions in the middle ear mucosa[10]. On the other hand, ciprooxacin [11], dexamethasone, and methyl prednisolone [12,
13] traverse the round window membrane and are safe to use.
Permeability oftheRound Window
Membrane inOtitis Media
The question that comes up is what happens to the permeability of otologic drop components in middle ears with otitis
media. The round window membrane in otitis media undergoes the same histopathologic changes that the mucoperiosteum of the middle ear does (it is part of it). These changes
suggest that in early stages (the rst 3–5 days of active
inammation), there may be an increase in permeability but
that, as the inammatory process develops (1 week of
inammation and thereafter), the membrane becomes
thicker and develops protective mechanisms in terms of
decreased permeability. As the active inammatory process
decreases (and the membrane regains its normality), so does
the thickness and the protective mechanisms of the membrane decrease. Experimental evidence in cats, chinchillas,
and guinea pigs using tracers and neomycin has conrmed
this suggestion [6, 8].
There is an apparent discrepancy between experimental
studies and clinical impressions in terms of ototoxicity of ear
drops. As mentioned, animal studies have shown that during
an established active inammatory process (draining ears),
round window membrane permeability drastically decreases
31 The Use ofTopical Treatment andMiddle–Inner Ear Interaction
https://t.me/medicina_free
277
owing to an increase in the thickness of the membrane to
defensive mechanisms in the membrane [14] and dilution
effects by the middle effusion. In my opinion, this is what
happens in clinical cases because the physician uses otologic
drops once the inammatory process is already established.
Therefore, in light of the available experimental evidence, it
comes as no surprise that in these cases, ototoxic drugs traverse the membrane less readily and are less likely to cause
inner ear damage, leading to an “apparent discrepancy.”
However, once the active inammatory process decreases or
subsides, the defensive mechanisms decrease, and the membrane becomes more permeable. Moreover, if one reviews
the documented cases of patients who have developed sensorineural hearing loss owing to the use of otologic drops for
otitis media [1], these tend to coincide with this explanation.
Most of the reported cases are related to prolonged use of
drops and/or in patients who continued their use once the
drainage had subsided. That is to say, ototoxicity occurred
once the active inammatory process had subsided, the
defensive mechanisms had decreased, and the membrane
had become more permeable.
Although the subject of discussion of this chapter is ototoxicity, there are two aspects to be mentioned as complications in the use of ear drops. The relatively high incidence of
allergic reactions to the neomycin contained in ototopical
drops, and the signicant vertigo that develops when drops
containing lidocaine enter the middle ear cavity.
Which Drops Are Safe toUse?
Based on the available evidence, our indications and rationale for the use of otologic drops are as follows:
In chronic otitis media (chronic draining ears), topical treat-
ment is our main modality. In our Clinical Department,
we consider it safe to use quinolones as a rst line of
treatment, based on their safety prole. It is also possible
that shorter courses of other drops could be safe and
reasonable, should quinolones be either unavailable or
contraindicated (e.g., allergy) or that the bacteria are
resistant to them, assuming that the round window mem-
brane has an established inammatory process, and its
permeability is drastically reduced.
In recently draining ears, we consider it safe to use quino-
lones and, if needed, other types of otologic drops while
drainage persists, assuming that the round window membrane has an inammatory process and that patients are
closely monitored, and as soon as the drainage decreases,
if needed, we switch to quinolone drops (e.g., ciprooxacin), assuming that the membrane becomes more
permeable.
In ears without drainage (e.g., placement of ventilation tubes
in patients with “cloudy” effusion), we use only quinolone drops.
Future Trends
In terms of future trends or alternatives, some of our experimental approaches include the following:
Developing slow-release biodegradable membranes that
could release substances over time in the middle ear [15],
because otologic drops achieve adequate local levels but
only for very short periods of time. Another experimental
approach that has been described is the use of a sustainedrelease ciprooxacin hydrogel that could be used as a
single administration [16].
Developing spheres of a size that would not traverse the
round window membrane or be absorbed by the middle
ear mucosa, to which ototoxic drugs could be attached
(provided that they would stay attached and remain effective) [3].
Developing means of dening the stage of reactivity of the
middle ear mucosa and of permeability of the round window to use ototoxic drugs safely. The stage of reactivity
should eventually be determined by evaluating middle ear
effusions, since they are a reection of the stage of reactivity of the middle ear mucosa [17].
Better dening the “defense” mechanisms of the round win-
dow membrane (round window membrane defense system) [3].
Developing research protocols that would evaluate not only
passage but also mechanisms, routes, and distribution in
the inner ear. This would also allow the eventual development of therapeutic approaches.
278
https://t.me/medicina_free
M. V. Goycoolea et al.
References
1. Linder TE, Zwuky S, Brandle P.Ototoxicity of ear drops: a clinical
perspective. Am J Otol. 1995;16:653–7.
2. Lundy LB, Graham MD.Ototoxicity and ototopical medications: a
survey of otolaryngologists. Am J Otol. 1993;14:141–6.
3. Goycoolea MV, Jung TK. Complications of suppurative otitis
media. In: Paparella MM, Shumrick DA, Gluckman JL, Meyerhoff
WI, editors. Otolaryngology, vol. 2. Philadelphia: W.B.Saunders;
1991. p.1381–403.
4. Axelsson A.The vascular anatomy of the cochlea in the guinea pig
and man. Acta Otolaryngol (Stockh). 1968;243:1–30.
5. Nakashima T, Ito A. Blood ow of the round window. Arch
Otorhinolaryngol. 1981;230:57–9.
6. Goycoolea MV. Clinical aspects of round window membrane
permeability under normal and pathological conditions. Acta
Otolaryngol (Stockh). 2001;121:437–47.
7. Goycoolea MV, Muchow D, Schachern PA. Experimental studies
on round window membrane structure function and permeability.
Laryngoscope. 1988;98(Suppl 44):1–20.
8. Palomar GV, Palomar AV.Are some ear drops ototoxic or potentially ototoxic? Acta Otolaryngol (Stockh). 2001;121:565–8.
9. Smith BM, Myers MG. The penetration of gentamicin and neomycin into perilymph across the round window membrane.
Otolaryngol Head Neck Surg. 1979;87:888–91.
10. Wright CG, Meyerhoff WL.Ototoxicity of otic drops applied to
the middle ear in the chinchilla. Am J Otolaryngol. 1984;5:166–76.
11. Bagger-Sjoback D, Lundman L, Nilsson-Ehle I.Ciprooxacin and
the inner ear: a morphological and round window membrane permeability study. ORL J Otorhinolaryngol Relat Spec. 1992;54:5–9.
12. Itoh A, Sakata E. Treatment of vestibular disorders. Acta
Otolaryngol Suppl (Stockh). 1991;481:617–23.
13. Parnes LS, Sun AH, Freeman DJ.Corticosteroid pharmokinetics in
the inner ear uids: an animal study followed by clinical application. Laryngoscope. 1999;109(Suppl 91):1–17.
14. Goycoolea MV, Lundman L.Round window membrane. A review.
Microsc Res Tech. 1997;36:201–11.
15. Goycoolea MV, Muchow D, Sirvio L, Winandy RM. In search
of missing links in otology. Part II. Development of an implantable middle ear drug delivery system: initial studies of sustained
ampicillin release for the treatment of otitis media. Laryngoscope.
1991;101:727–32.
16. Wang X, Fernández R, Tsivkovskaia N, Harrop-Jones A, et al.
Nonclinical assessment of a sustained-release ciprooxacin hydrogel for the treatment of otitis media. Otol Neurotol.
2014;35(3):459–69.
17. Goycoolea MV, Paparella MM, Juhn SK, Carpenter AM.A longitudinal study of cellular changes in otitis media. Otolaryngol Head
Neck Surg. 1979;87:685–700.
Соседние файлы в папке Библиотека им академика М.И. Перельмана