Speaker Dr Udaya Chanukya MS ENT Fellow in Skull Base Surgery Consultant ENT Surgeon S.A.I HOSPITALS, AP Agenda 1. Temporal Bone Fractures 2. Otalgia 3. Ear Trauma 4. Ototoxicity

1. Ototoxicity,
Temporal bone fractures
& Otalgia
Dr. Udaya Chanukya
ENT surgeon
Rajahmundry
Andhra Pradesh

2. OTOTOXICITY

3. DEFINITION
• Therapeutically useful drugs, certain
environmental agents such as industrial
solvents that cause damage to the peripheral
end-organs of hearing and balance.
• Exclusions:
Agents which primarily cause damage to the
respective neural pathways and centres

4. PERILYMPH
• Not an ultrafiltrate of Blood plasma or CSF
• Produced and circulated locally
• Blood- perilymph barrier
• Limits the entry of toxins

5. MODES OF ENTRY
 Perilymphatic compartment
– Cochlear aqueduct(Bacterial toxins in meningitis)
– Round window from Middle ear cavity
After gaining access:
Basilar membrane permeability causes free access
to the lateral membranes of hair cells, synaptic ends
and to the nerve fibres

7. Boundaries of endolymph and
perilymph

8. Factors influencing ototoxicity
• Dosing regime
• Malnourishment
• Stress
• Drug interactions
• Liver and renal parameters
• Genetic factors

9. Classification Based on therapeutic usage

10. Classification based on Sites and
modes of action
• Temporary hearing loss(TTS)
– Acute effect on stria vascularis
– Loop diuretics and erythromycin
• Temporary impairment of hair cell
function(TTS)
– Salicylates and Quinine
• Permanent threshold shift(PTS)
– Death of hair cells and vestibular dysfunction
– Aminoglycosides, cisplatin and organic solvents

11. Permanent threshold shift
*** Mammals don’t have the regenerative capacity of
sensory epithelia of Organ of Corti, resulting in
permanent damage of hair cells
**Vestibular epithelium – partial regenration possible

12. AGENTS AFFECTING THE ION-TRANSPORTING
EPITHELIA- LOOP DIURETICS
• primary site of action- Stria vascularis(SV)(ion
transporting epithelium)
• Affecting endolymph composition > affecting
endocochlear potential(EP)
• SV- one of the highest rates of oxidative
metabolism.
• Any oxidative stress on SV, affects strial
activity.

13. • Rapid in onset- within minutes or hours,
persist for some hours
• Usually completely resolved within a day if the
drug is discontinued
• Repeated administartion- NO permanent
deficit
• Dose in conjuction with Aminoglycoside/
cisplatin- Rapid devastatotory hearing loss.

14. • HPE of patients who have died while on
diuretic treatment- extensive oedema and
swelling of the SV(caused by inhibition of ion-
uptake process).
• Mechanism of toxicity- Rapid reversible
decline in the EP.

15. Drugs acting like Loop diuretics
• Potassium cyanide
– inhibition of marginal cell Na+/K+-ATPase.
• Macrolide antibiotics
– rapid, dose-dependent decline in EP

16. AGENTS CAUSING REVERSIBLE
EFFECTS ON HAIR CELLS
• Salicylates and Quinine
• Both enter perilymph readily
• Salicylates
– Threshold shifts across all frequencies
simultaneously, indicating effects along the entire
cochlear spiral.
– Usually develop at high dosage: 2–5 g/day.
– Reversible completely within 3 days.

17. • Salicylates inhibit electrically driven motile
responses of isolated OHCs.(OAEs are
reversibly suppressed)
• Inhibition of the activity that produces signal
amplification in the cochlea.
• EP unaffected on salicylate administration.

18. QUININE
• Entirely reversible threshold shifts at all
frequencies
• Reversible elevation in threshold for the
compound action potential (CAP), which derives
from stimulation of inner hair cells (IHCs)
• IHCs> synaptic transmissions at base of IHCs>
Spiral ganglion neurons> OHCs.
• OHCs are affected at higher concentrations in
quinine toxicity.

19. AGENTS THAT CAUSE PERMANENT HEARING
LOSS AND BALANCE DISORDERS
• Repeated systemic administration
• Aminoglycosides- Most important
• All aminoglycosides are potentially both
cochleotoxic and vestibulotoxic
• Exhibit differences in their toxic potential and
organ preference.

20. • Neomycin is the most toxic
• Gentamicin, Kanamycin and Tobramycin - less
• Amikacin and Netilmicin- least toxic.
• Streptomycin and Gentamicin
– more vestibulotoxic than cochleotoxic
• Amikacin and Neomycin
– primarily cochleotoxic

21. • After days or weeks of parenteral treatment.
• Initial affect- high frequencies (hair cell
damage at basal region of cochlea)> low
frequencies (apical region).
• A bilateral loss of 20dB at two or more
adjacent test frequencies is accepted as a
hearing impairment.
• Initial ototoxic effects- detected by high
frequency audiometry.(8kHz- normal
audiometry)

22. LOCATION AND NATURE OF LESIONS
• Hair cells in the basal (high-frequency) coil are
affected first.
• Outer hair cells are more sensitive than inner hair
cells
• Significant progressive loss of spiral ganglion
neurons, the afferent nerves that innervate hair
cells.
• Excess release of the neurotransmitter glutamate
from the IHCs at synapses with afferent
terminals> excitotoxic damage to the nerve.

23. AMINOGLYCOSIDES- VESTIBULAR SYSTEM
• Hair cell loss initially in the central regions of
the epithelia> peripheries.
• Hair cells are specific targets of the
aminoglycosides.
• Susceptibility:
– Cristae> Utricle> Saccule

24. • Aminoglycosides cause death of hair cells by
inducing apoptosis, a programmed cell death
pathway.
– in which particular enzymes called caspases play
the crucial roles.
– generation of reactive free radicals
• free radical scavengers, including n-acetyl
cysteine, salicylate and glutathione, useful in
enhancing the survival of basal coil OHCs.

25. • The death of each hair cell> expansion of the
supporting cells around them >to close the
lesion >effect tissue repair.
• Organ of Corti is replaced by an apparently
simple cuboidal-like epithelium across the
basilar membrane.
• Supporting cells are generally spared.

26. PHARMACOKINETICS
• Linear relationship between serum
concentration of aminoglycoside and the
perilymph concentration
• Clearance from perilymph is delayed and the
drug persists in the inner ear for some time.
• The half-life of aminoglycoside in the inner ear
>30 days

27. PREGNANCY
• Aminoglycoside antibiotics can cross the
placenta
• 18–20w of gestation- ‘critical
period’(sensitivity to the ototoxic agent is
greatest)

28. INTERACTIONS
• LOOP DIURETICS AND AMINOGLYCOSIDES
– Markedly increase the penetration of
aminoglycosides into endolymph, significant
cochlear damage
• NOISE AND AMINOGLYCOSIDES
– In conjunction with aminoglycoside may cause
more extensive damage than with either agent
alone

29. CISPLATIN
• at least 60% of patients, suffer some degree of
hearing impairment.
• progressive loss of hair cells, the extent of
which correlates with the dose of drug
administered.
• Pattern of hair cell damage in the cochlea also
resembles that of the aminoglycosides
• IHCs appear to be relatively resistant

30. INJURIES
– OHCs
– spiral ganglion cells
– Strial atrophy
– Vestibular dysfunction

31. MECHANISMS OF ACTION
• cellular entry of cisplatin.
• Transport proteins
– megalin (LRP2)
– the organic cation transporter OCT2 (also known
as SLC22A2)
– copper uptake transporter Ctr1 (SLC31A1)

32. APOPTOSIS
• Strial marginal cells> Entry into endolymph>
Access to hair cells> cross linking of DNA> inhibit
DNA synthesis> induces cell cycle arrest>
suppress transcription> Apoptosis

33. • Cisplatin binds to sulphhydryl-containing
molecules such as metallothineins and
glutathione that scavenge free radicals and
thereby it negatively affects redox balance.

34. INTERACTIONS
• LOOP DIURETICS AND Cisplatin
– Extensive and quite rapid hearing loss and death
of outer hair cells
• NOISE AND Cisplatin
– Noise above 70dB conjunction with cisplatin may
cause more extensive damage than with either
agent alone.

35. ORGANIC SOLVENTS
• Toluene
• p-xylene
• Ethylbenzene
• n-propylbenzene,
• Styrene
• ά-methylstyrene
• trans-β-methylstyrene
• allylbenzene.
• Trichlroethylene

36. • Entry to the inner ear:
– Vasculature of SV/ spiral prominence> Organ of
Corti
• Features:
– mid-frequency ranges of hearing that are affected
rather than the high frequencies.
– Outermost OHCs> Inner rows of OHCs
– Dieter cells(supporting cells) are affected
– Hensen’s cells (outer ridge of sensory epithelium)
also affected.

37. MECHANISM OF ACTION
• supporting cells are involved in the reuptake
of K+ from around the hair cells.
• Failure of reuptake> Excessive accumulation of
K+ around hair cells> programmed death of
hair cells(loss of membrane integrity, cell
swelling and consequential membrane
damage).

38. Other Ototoxic agents
• Vancomycin
• Viomycin
• Polymyxin B
• Desferrioxamine

39. EAR TRAUMA

40. OVERVIEW
• Temporal bone fracture
• Auricular hematoma
• Auricular pseudocyst

41. TEMPORAL BONE TRAUMA
• Blunt trauma to the temporal bone is much
more frequent than penetrating injury
• Incidence:
– RTA- 50%
– Falls- 16–40%
– Assaults (10-37%)
– Gunshot wounds (3–30%).

42. EAR TRAUMA WITH TEMPORAL
BONE FRACTURE
• Classification according to their orientation
relative to the axis of the petrous ridge(Most
commonly used)
– longitudinal 80–90%
– transverse 10–20%
• Fracture lines are often irregular and
sometimes comminuting
• Convenient but clinically not corelating

43. ALTERNATIVE SYSTEM
• Widely being adopted
• Emphasizing the structures involved
• Otic capsule
– violating (more complications- Facial nerve
paralysis, CSF leak and profound hearing loss)
– Sparing
• ANOTHER SIMPLE SYSTEM:
– petrous
– non-petrous fractures.

44. Descriptive strategy
• combining the classifications by describing the
fracture both in terms of its predominant
orientation and whether it involves the
petrous bone, otic capsule and brain
parenchyma

45. TEMPORAL BONE FRACTURES IN CHILDREN
• Longitudinal( 59%)
• Transverse (41%)
• Increase in % of transvere fractures
– non-fused sutures
– different bone density

46. CLINICAL FEATURES
• Hearing loss
– Depending on the trauma intensity
– More commonly Conductive HL (up to 6 weeks)
– SNHL may be present in severe degree of trauma
– 4 kHz and higher frequencies affected
• Vertigo
– 1/3 rd of cases
– Otic capsule violating- resolution upto 12 months(central
adaptation takes over)
– Otic capsule sparing( Vestibular concussion- resolution
within a matter of days)

47. CLINICAL FEATURES
• Sympathetic hearing loss
– Immunologically mediated
– A delayed and progressive loss, without vestibular
symptoms- many months or years following the injury
– Exposure of antigens from traumatized
cochleovestibular membranes is thought to lead to an
immune sensitization, attacking the contralateral ear
– Explanation to the delayed progressive hearing loss
following trauma to the ear

48. CLINICAL EXAMINATION
• Complete neuro-otological examination
• Conscious state assessment (Glasgow Coma Scale)
• Examination of the cranium (evidence of penetrating
injury, lacerations)
• Mastoid bruising (Battle’s sign- indicative of a skull
base fracture)
• Cranial nerve examination- Facial nerve
• TFTs until a formal audiometry is possible

49. CLINICAL EXAMINATION
• Otoscopic examination- cerumen, blood, CSF,
hemotympanum and TM perforation
• Syringing and irrigation methods of cleaning are
contraindicated- ascending infections causing
meningitis
• Soft tissue encountered should be left alone
• Packing the meatus- uncontrolled hemorrage

50. IMAGING
• Sufficient information for the necessary decision-
making.
• High-definition CT scanning is the investigation of
choice.
• Any suspicion of temporal bone fracture- high-
definition temporal bone scan should be obtained
straight away as part of the brain scan evaluation.
• Hearing loss and vertigo in the absence of fracture in
CT scan- MRI may be helpful(T1-weighted MRI may
demonstrate a hyperintense signal in the labyrinth
indicative of haemorrhage)

51. • Targeted imaging
• Specific injured structures
– gadolinium-enhanced MRI of the facial nerve
– angiography for vascular injury

52. HEARING ASSESSMENT
• Clinical speech and whisper tests
• Tuning fork tests
• Early baseline audiometry- to know the progress
• Bilateral temporal bone fracture- urgent hearing
assessment, bedside audiometry
• Formal audiometry- 6 weeks, residual CHL and SNHL
• Tympanometry- middle ear fluid

53. VESTIBULAR ASSESSMENT
• Head injury of any type- dizziness is
predominant
• Presence of nystagmus- evidence of vestibular
involvement
– horizontal nystagmus- fast phase directed away
from the side with the failed labyrinth.
Gait testing, Romberg and Unterberger tests-
depends on the general state of the patient

54. Treatment- Acute stage
• Antibiotics
– 2% of patients face meningitis complication.
Prophylactic use of antibiotics- no proven benefit.
• Steroids
– Large randomized controlled studies have
demonstrated no benefits with the use of steroids
in overall outcome when used in the acute setting,
even finding a very significant increase in
mortality in more serious cases of traumatic brain
injury

55. Treatment- medium and long term
• Conductive hearing loss- Ossiculoplasty
• Bilateral otic capsule fractures
– Bilateral cochlear implantation
• Unilateral profound losses
– may benefit from a CROS or bone-anchored hearing
aid(Counter shadowing affect). D.irectional
discrimination is disappointing.
– Cochlear implant provides best results- funding being
the crippling point.(Regular monitoring is important as
an obliterative labyrinthine process may compromise
successful implantation in the future)

56. Complications
• FACIAL PALSY
– About 7% of temporal bone fractures
– Penetrating trauma> blunt trauma
– Type:
• 10–25% of longitudinal fractures
• 38–50% of transverse
• more common otic capsule violating fractures
– Location:
• 60% geniculate ganglion
• 20% 2nd genu
• 8% tympanic portion
• 6% mastoid portion

57. Clinical issues:
• Onset:
– Immediate- direct damage to nerve(transection/
impingement)
– Delayed (presence of neural continuity)
• Involvement:
– Partial
– complete.
• Prognosis: excellent recovery in cases of
partial or delayed facial nerve palsy

58. Investigation
• Elecrophysiological testing
– immediate complete palsy
– complete paralysis, with an uncertain history, that
were thought to have been of delayed onset but
have failed to improve.
• Electroneuronography- 10 days post injury- practical
issues
• Electromyography- Good recovery is expected if the
decline of CAP doesn’t reach 90%.

59. Investigation
• HRCT temporal bones
• MRI scan
– Cases of complete facial palsy
– location of injury

60. Treatment
• Steroids:
– Systemic administration is usual for both delayed
and immediate cases of facial palsy despite there
being no controlled studies.
– Dosing regimen is 1 mg per kg per day of
prednisolone, or equivalent, for 1–3 weeks, with a
taper for longer courses.

61. Surgical treatment
• The role and timing of surgery remains
controversial.
• Immediate palsies showing the requisite 90%
degeneration on electroneuronography within
2 weeks of injury are considered for surgery.
• Early identification and repair of a transacted
nerve, and decompression of a clearly
impinged nerve, are appropriate

62. Complications:
• Other cranial nerve palsies:
– 6th CN- petrus apex fracture
– Lower CN palsies- Jugular foramen hematoma
• CEREBROSPINAL FLUID LEAK:
– vary widely between 11% and 33%
– Most (81%) resolve spontaneously within 5 days
and 95% within 14 days
– Larger defects- less likely for spontaneous healing

63. • Management:
– Bed rest with head elevation and avoidance of
straining and lifting.
– If the leak has not stopped within 10 days, insertion of
a lumbar drain is a sensible intervention.
• Pre-operative MRI: location of leak/ herniation
• Peri-operative CT- cysternography
• Surgery: Multilayered closure
– autologous cartilage, temporalis fascia, fascia lata, and
porcine- and bovine-derived artificial dura have been
used.

64. AURICULAR HAEMATOMA

65. • Definition:
– collection of blood occurring in the subperichondrial
layer or an intracartilagenous space of the pinna.
• Painful swelling
• Seen frequently in wrestling, boxing and rugby
players
• Folding the helix into concha- Hematoma
• Usually – Lateral surface of pinna, firmly attached
skin and perichondrium. Shearing of
perichondrium>rupture of vessels> collection of
blood underneath.

66. Management
• Early evacuation results in good resolution
with minimal cosmetic deficit.
• Hematoma> chondroblast invasion>
granulation tissue> new cartilage formation
• Separated perichondrium on the anterior
surface> new cartilage formation at the areas
of breeches> cartilage buckling over and over>
typical irregular appearance-’Cauliflower ear’

67. AURICULAR PSEUDOCYST
• Definition:
– Intracartilaginous cystic collection, devoid of any
epithelial lining, containing viscous, straw-colored,
sterile fluid
– Due to repeated minor trauma
– Usually painless

68. MANAGEMENT
• evacuate the hematoma
– Aspiration(high recurrence)
– Anterior approach
– Posterior appraoch
• remove granulation tissue
• compress or obliterate the dead space to
prevent re- accumulation.

69. Anterior approach

70. Posterior approach
• Better cosmesis
• Incision over the hematoma> flap raised>
5mm window in the cartilage> granulation
curetted> flap repositioned.

71. NON-SURGICAL METHODS
• Compression suture methods with
absorbable, or non-absorbable, through and
through mattress sutures are most commonly
used over bolsters and are probably the most
effective

72. Pseudocyst
• Same as hematoma, but granulation is not
present here.

73. OTALGIA

74. Introduction
• Origin:
– within the ear (primary otalgia)
– Disease processes elsewhere (secondary or
referred otalgia).
• Distribution:
– Children otalgia is much more frequently otogenic
– Adults referred otalgia is the more common cause

75. ANATOMY
• The sensory supply of the ear is highly
complex and not fully determined.
• 4 CN and 2 Cervical nerves- Sensory supply
• Cranial surface of pinna& Lateral skin below
EA meatus
– greater auricular nerve
– lesser occipital nerve

76. • The auriculotemporal nerve(branch of the mandibular
division of the trigeminal nerve)supplies the lateral
surface of the tympanic membrane, EAM, lateral skin
of the pinna above the level of the external meatus
• The auricular branch of the vagus (Arnold’s nerve)
supplies the posteroinferior quadrant of the tympanic
membrane, posteroinferior meatal skin and an area of
the concha.
• Extent of facial nerve distribution matches to that of X
CN, but relatively sparse
• The middle ear is supplied by the tympanic branch of
the glossopharyngeal nerve (Jacobson’s nerve).

77. • The trigeminal nerve is probably the most common
pathway of origin of referred pain to the ear.
• Mandibular division of the trigeminal nerve:
– anterior two-thirds of the tongue, floor of the
mouth, palate, lower teeth, major salivary glands,
temporomandibular joint (TMJ) and mandible.
• Referred pain arising from structures in these
areas tends to be perceived in the ear canal.

78. • Facial nerve:
– sensory divisions including the nervus intermedius of
Wrisberg and the greater superficial petrosal nerve
– Sensation from posterior nasal cavity and sphenoid
sinus
• The glossopharyngeal nerve:
– receives sensory input from the posterior third of the
tongue, palatine tonsils, nasopharynx, hypopharynx
and parapharyngeal and retropharyngeal spaces.
– Pain referred from these structures tends to be
perceived as a deep intense otalgia.

79. • The vagus nerve:
– valleculae, supraglottis, thyroid gland and more
distant sites within the thorax including the
tracheobronchial tree and oesophagus.
• The upper cervical nerves (C2 and C3):
– innervate the muscles and facet joints of the
cervical Spine.

80. PRIMARY OTALGIA

81. REFERRED OTALGIA
• MALIGNANCY
• CERVICAL
• DENTAL
• NEURALGIA
• MISCELLANEOUS

82. MALIGNANCY
• Referred otalgia may be part of a symptom complex, or
perhaps more importantly, can be the sole presenting
symptom.
• A full examination of the oral cavity and flexible nasal
endoscopy to examine the pharynx and larynx are
therefore an essential part of the assessment of a
patient with otalgia in the absence of local pathology
within the ear.
• Otalgia and odynophagia are often presenting
symptoms of hypopharyngeal malignancy
• Otalgia is a cardinal symptom of laryngeal malignancy.

83. DENTAL
• Most common cause
• Teeth, periodontal tissues or the TMJ.
• Pulpitis- most common problem causing otalgia.
• TMJ-
– diffuse pain felt in or around the joint, crepitus and
trismus. Almost always accompanied by otalgia
– The most reliable diagnostic clinical finding in TMJ
dysfunction is tenderness of the masticatory muscles

84. • CERVICAL:
– Cervical spine degenerative disease (CSDD) must
be considered as an increasingly common cause of
referred otalgia.
• NEURALGIA
– Otalgia can present as one of the features of
various cranial neuralgias. Trigeminal neuralgia
and post-herpetic neuralgia
– Glossopharyngeal neuralgia
– Geniculate neuralgia
– Stylohyoid syndrome

85. MISCELLANEOUS
• Vestibular schwannoma (VS)
• Cholesterol granuloma
• Nasal/sinus disease
• Laryngopharyngeal reflux

86. • Thank you