Sensorineural Hearing Loss: A Management Analysis

From Stanford University School of Medicine’s Otology and Neurotology Update, 2008

Educational Objectives

The goal of this program is improved diagnosis and management of sensorineural hearing loss (SNHL). After hearing and assimilating this program, the clinician will be better able to:

1.   Describe the cellular mechanisms and genetics of age-related hearing loss (ARHL).

2.   Counsel patients on prevention of ARHL.

3.   List commonly used drugs that can have SNHL as a side effect, and explain the mechanisms by which these agents cause hearing loss (HL).

4.   Define sudden SNHL and describe current research into its treatment.

5.   Explain how magnetic resonance imaging is used in determining underlying structural causes in patients who present with HL.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and plan­ning committee reported nothing to disclose.

Acknowledgements

Drs. Lustig, Monfared, Parnes, and Fischbein were recorded at Otology and Neurotology Update 2008, presented No­vember 6-8, 2008, in San Francisco, CA, and sponsored by the Stanford University School of Medicine. The Audio-Digest Foundation thanks the speakers and the Stanford University School of Medicine for their cooperation in the production of this program.

Age-related Hearing Loss and the Genetics Revolution

Lawrence R. Lustig, MD, Francis A. Sooy, MD, Professor of Otolaryngology and Director, Otology and Neu­rotology, Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, School of Medicine

Prevalence: 1 in 10 people hearing-impaired; prevalence increases with age (40% of those >65 yr of age); 80% of all hearing loss (HL) occurs in elderly; increasing as population ³65 yr of age increases; men have more rapid rate of hearing decline than women in all age groups; higher frequencies more susceptible, so high-frequency HL predom­inant in elderly; rate of change in hearing 0.75 dB/yr to 1.75 dB/yr

Risk factors for age-related hearing loss (ARHL): noise exposure  —  Framingham data show patients with history of noise trauma in youth more likely to lose hearing later on, particularly in higher frequencies, than those without noise exposure; also seen in mice; noise exposure in youth increases susceptibility to ARHL; other risk factors  —  tobacco smoking, short stature, and elevated body mass index (BMI); moderate consumption of alcohol protective

Classic definitions of presbycusis (Schuknecht): sensory HL  —  loss of hair cells in organ of Corti; neural presbycusis  —loss of afferent fibers leading away from organ of Corti; strial atrophy  —  problem in stria vascularis (“battery generator of cochlea”); mixed HL  —  elements of all previous types; seen in most patients; intermediate (conductive) HL  —  patients have evidence of HL but cochlea looks normal

Cellular mechanisms of ARHL: in animal models  —  stria vascularis shows changes in all types of HL; stria creates ionic potential that allows hair cells to fire; Schulte et al  —  disruption of ion transport within stria result of oxida­tive damage to mitochondria, leading to reduction in adenosine triphosphate (ATP) production and secondary cyto­toxic alterations in sodium-potassium ratio in cytosol; end result degeneration of sensory cells of cochlea; 2004 study  —  in mice, ARHL associated with loss of neurons, aggregation of neuronal cell bodies, and vacuolization of supporting cells and pillar cells; C57 mouse  —  best animal model for ARHL; base-to-apex outer hair cell degenera­tion (sensory loss); flat losses of distortion-product otoacoustic emissions (DPOE); strial loss; strial pathology in fi­brocytes in spiral ligament and loss of endocochleal potential (mixed form of ARHL by Schuknecht definition)

Genetics: in C57 mouse, single gene (AH1) causes ARHL; AH1 codes for calcium-binding transmembrane protein (cadherin 23); mutations in mitochondrial DNA can interact with this gene, causing additional forms of HL; cad­herin 23 codes for component of stereocilia tip link; if tip link damaged, stereocilia cannot conduct ions into hair cell, resulting in ARHL; AH1 gene also promotes noise-related HL; several other gene loci track with ARHL; mito­chondrial DNA  —  aging leads to decreased activity of electron transport chain and increased concentration of reac­tive oxygen species, leading to oxidative damage; presbycusis associated with mutations and deletions of mitochondrial DNA; polymorphisms of N-acetyltransferases associated with increased ARHL in humans; rat model  —  strong antioxidants and restricted calorie diet shown to mitigate ARHL; 30% calorie restriction led to least HL over time; transgenic mice  —  have accelerated aging; show loss of spiral ganglion cells and sensory cells, with strong ARHL; criticism of mouse models  —  human genes unlike those of mouse models

Prevention and treatment: calorie restriction; antioxidants and vitamins (long-term studies needed in humans); noise protection probably best preventive measure; smoking cessation; low alcohol intake; cochlear implants; elec­troacoustic stimulation; inner ear drug delivery; gene therapy

Ototoxicity

Ashkan Monfared, MD, Neurotology Fellow and Instructor, Department of Otolaryngology, Stanford Univer­sity, School of Medicine, Palo Alto, CA

Aspirin: at high doses, causes reversible ototoxicity and tinnitus; ototoxicity dose-dependent and resolves in 1 to 3 days after aspirin stopped; pathophysiology  —  decrease in otoacoustic (OA) emissions as soon as drug enters blood; levels highest in serum, followed by perilymph, followed by cerebrospinal fluid (CSF); changes microanatomy of inner ear, eg, vesiculation of outer hair cells; causes permeability to potassium, decreases cochlear blood flow, and changes prostaglandin (PG) levels in inner ear; clinical pearls  —  causes bilateral mild to moderate sensorineural HL (SNHL); level of tonal tinnitus not directly correlated with level of aspirin in blood; no synergy with loud noise exposure; lowers level of ototoxicity from gentamicin

Nonsteroidal anti-inflammatory drugs (NSAIDs): naproxen  —  2 case reports of SNHL; ibuprofen  —  no reports; no evidence in animal studies

Loop diuretics: eg, furosemide (Lasix)  —  high risk for SNHL in patients with renal insufficiency, young patients, and those on aminoglycosides; HL may be temporary or permanent; mechanism decreased cochlear potentials resulting from electrical abnormalities in stria vascularis; can cause morphologic changes in stria; toxicity related to high dosage and high rate of infusion

Aminoglycosides: ototoxicity worse with single daily dose; toxicity may be unilateral; site of action  —  gentamicin and tobramycin cause mostly vestibular toxicity; neomycin, kanamycin, and amikacin cause mostly cochlear toxic­ity; streptomycin causes vestibular and cochlear toxicity; risk factors  —  17% of population has genetic propensity for ototoxicity from gentamicin; linked to duration of therapy and dosage, previous HL, poor renal function, and liver problems

Macrolides: ototoxicity mostly reversible but sometimes permanent; higher doses and poor renal or hepatic function increase susceptibility; several case reports of SNHL from azithromycin at low oral doses; mechanism unknown

Chemotherapeutic agents: »50% of patients have ototoxicity from cisplatin; later generation agents, ie, carboplatin and oxaliplatin, less ototoxic; mechanism  —  DNA crosslinking; sodium-potassium ATP pump; amino acid trans­port; types of damage  —high-frequency HL (>8000 Hz); detected on auditory brainstem response (ABR) measure­ments and DPOE; HL bilateral and often permanent; can cause tinnitus; risk factors  —  cumulative dose >200 mg; patient age; renal insufficiency; concomitant radiation therapy; other chemotherapeutic agents; aminoglycosides; loop diuretics; noise exposure; preexisting HL; damage  —outer hair cells; spiral ganglion; stria vascularis; superox­ide radicals created; at low dose, stereocilia damaged; at high doses, hair cells damaged; 60% of patients have tin­nitus (not related to level of HL); vestibular toxicity thought to result from neurotoxicity; second-generation agents  —  ototoxicity in 33% of patients given high doses, 1% with low doses; ototoxicity of carboplatin linked to inner hair cells

Topical agents: almost all topical antibiotics damage mucosa of middle ear and cause inflammation; penicillin least inflammatory, ticarcillin most; topical aminoglycosides known to cause HL since 1950s; in animals, medication placed in ear detected in serum; topical aminoglycosides  —  almost all case reports of human toxicity involve long-term use by patients without active infection; in patients with dry ear, rate of development of SNHL or vestibular damage from aminoglycoside greatly reduced; tobramycin with dexamethasone (eg, TobraDex) not as cochleotoxic as other aminoglycosides; informed consent  —  recommended when medications containing aminoglycosides pre­scribed

Corticosteroids: hydrocortisone, neomycin and polymyxin B (eg, Cortisporin) causes severe middle and inner ear toxicity in animals; inner ear toxicity due mostly to polymyxin, middle ear toxicity from inactive ingredient

Fluoroquinolones: ofloxacin causes moderate middle ear inflammation in animal models; no reports of SNHL or vestibular toxicity from ofloxacin or other fluoroquinolones

Other agents: alcohol ototoxic in animals; acetic acid preparations (eg, VoSoL) ototoxic in animals because of pro­pylene glycol; gentian violet (10% alcohol); clotrimazole, topiramate, and nystatin show no adverse effects in ani­mals; dexamethasone has adverse effects on healing of tympanic membrane; hydrocortisone causes mucosal thickening and inflammation of round window; chlorhexidine (case reports of middle ear toxicity); iodine (use paint, not scrub, in patients with perforation of ear drum, since solvent in scrub toxic to middle and inner ear; ben­zalkonium ototoxic in animals; caveat  —  chlorhexidine should not be used in patients with ear drum perforations (complete HL reported at certain concentrations)

Treatment of Sudden Sensorineural Hearing Loss: An Evidence-based Analysis

Lorne S. Parnes, MD, Professor, Department of Otolaryngology, University of Western Ontario Schulich School of Medicine and Dentistry, London, ON

Overview: definition  —  SNHL considered sudden if 30-dB HL in 3 contiguous test frequencies occurs in <72 hr; mostly idiopathic (cause known in 10%-15% of cases); theoretic causes  —intralabyrinthine membrane rupture, vas­cular event (eg, mini-stroke) viral infection, immune-mediated phenomena; best prognosis  —  mild HL; upsloping audiogram; absence of vertigo; early start of recovery

Treatment: includes volume expanders, calcium antagonists, vasodilators, diuretics, antiviral agents, and anti-in­flammatory immunologic agents, (eg, oral steroids; treatment of choice); speaker’s study  —  first part systematic lit­erature review of all randomized controlled trials (RCTs) from 1966 to 2004; only 16 RCTs met inclusion criteria for meta-analysis, and only 2 of these compared steroids to placebo; 4 looked at antivirals and steroids; Wilson study (1980) found some hearing recovery with steroids vs placebo, but study design problematic; no effect of ste­roids plus antivirals; Cochrane review  —  also found steroids not effective

Intratympanic (IT) steroid therapy: 1996 study found 25% improvement; in speaker’s experience with 13 patients, 46% improved, including several with severe-to-profound HL and poor prognosis; recent literature  —  no consis­tency in steroid used (eg, dexamethasone, methyl prednisolone), concentration of steroid, or method of delivery (eg, microcatheter, direct injection); criteria for improvement also vary; speaker’s study  —retrospective review of 26 pa­tients in whom IT steroids used as sole initial treatment; injection of dexamethasone or methyl prednisolone twice weekly for 2 consecutive weeks; 7 of 26 also had vertigo; 50% presented within 10 days of onset of HL and other 50% after 10 days; HL severe (only 4 of 26 had serviceable hearing); after treatment, speech perception threshold improved from 82 dB to 55 dB, word recognition score improved, and number of patients with serviceable hearing increased to 15; 7 patients with vertigo had slight improvement but not statistically significant; early vs late treatment  —no significant differences between groups before treatment; after treatment, patients treated early had better results

RCT with standardized protocol: ongoing (need 254 participants); noninferiority trial of efficacy and side effects; comparing oral to IT steroids; details at www.suddendeafness.org

Imaging of Sensorineural Hearing Loss and Vertigo

Nancy J. Fischbein, MD, Associate Professor of Radiology and Otolaryngology–Head and Neck Surgery, Stan­ford University School of Medicine, Palo Alto

Whole brain: includes sagittal T1_, and axial T2, diffusion-weighted imaging, and post-gadolinium scan of whole brain; posterior fossa targeted with Fast Imaging Employing Steady sTate Acquisition (FIESTA) sequence, which includes pre-gadolinium T1 and post-gadolinium T1 with fat saturation (FAT SAT) in axial and coronal planes; in some cases, computed tomography (CT) complementary and needed

Starting point: T1 weighted image in sagittal plane serves as localizer for technologist to set up slices through poste­rior fossa and whole brain; allows viewing of ventricles, brainstem, cerebellar tonsils, sella turcica, and clivus; pa­tient with intracranial hypotension may have low-lying tonsils and brain sag such that diencephalon and mesencephalon have descended in posterior fossa; HL and vertigo may be initial manifestation of intracranial hy­potension; assess clivus and central skull base for tumor; consider skull base osteomyelitis; in patient with tinnitus, look at patency of venous sinuses

Axial fast-spin echo T2 weighted image of whole brain: used to assess supra- and infratentorial structures; in me­dium-resolution sequence, slices 5 mm thick; goes through posterior fossa; enables viewing of brainstem, vessels, fluid in Meckel’s cave, and internal auditory canal (IAC); allows detection of intra- or extra-axial mass; can detect large eighth nerve schwannoma with associated cysts or area of hemorrhage; can detect white matter disease and brainstem pathology; different sequences used to characterize lesions

Diffusion-weighted imaging (DWI): whole-brain image sensitive to microscopic motion of water; used in diagnosis of acute stroke; impact on otology involves ability to make specific diagnosis of epidermoids and cholesteatomas, since both have highly organized structures that restrict motion of water and have very bright signal intensity on DWI; DWI useful for determining completeness of resection after cholesteatoma surgery

FIESTA sequence: 3-dimensional (3-D) gradient echo sequence that allows heavily T2-weighted images with very thin sections (£0.5 mm); decreased sensitivity to flow and motion reduces CSF pulsation artifact and provides ex­cellent edge definition; used to define cisternal segments of cranial nerves and fluid spaces of labyrinth; 3-D acqui­sition allows viewing of multiplanar reformations and projections; now routine for IAC studies, neurovascular compression in patients with hemifacial spasm or trigeminal neuralgia; used for stereotactic radiosurgical targeting

Gadolinium: contraindicated in patients with elevated creatinine or known renal insufficiency (association with nephrogenic systemic fibrosis); used in IAC protocol (small focus of enhancement often from intracochlear schwannoma; pre-gadolinium T1 weighted image used to identify intrinsically bright pathologies (eg, fat, blood, protein); normal fluid dark, and soft tissue masses usually intermediate; follow axial postgadolinium image with coronal plane image to distinguish artifacts, clarify lesion morphology, and assess anatomic relationships; example of patient with glomus jugulare tumor invading IAC

Whole-brain assessment: done after gadolinium to look for additional lesions; FLuid Attenuation Inversion Recov­ery (FLAIR) sequence  —  T2-weighted image with CSF suppression excellent for detecting multiple sclerosis

Additional Information

Current information on upcoming Stanford University continuing medical education  activities can be obtained at:

http://med.stanford.edu/seminars/.

Suggested Reading

Asplund MS et al: Protective effect of edaravon against tobramycin-induced ototoxicity. Acta Otolaryngol 129:8, 2009; Conlin AE, Parnes LS: Treatment of sudden sensorineural hearing loss: II. A Meta-analysis. Arch Otolaryngol Head Neck Surg 133:582, 2007; Conlin AE, Parnes LS: Treatment of sudden sensorineural hearing loss: I. A systematic review. Arch Otolaryngol Head Neck Surg 133:573-81, 2007; Dallan I et al: Transtympanic steroids in refractory sudden hearing loss. Personal experience. Acta Otorhinolaryngol Ital. 26:14, 2006; Kujawa SG, Liberman MC: Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth. J Neurosci 26:2115, 2006; Lorito G et al: Different strat­egies in treating noise induced hearing loss with N-acetylcysteine. Med Sci Monit. 2008 Aug;14:BR159, 2008; Low WK et al: L-N-Acetylcysteine protects against radiation-induced apoptosis in a cochlear cell line. Acta Otolaryngol 128:440, 2008; Miller JM et al: Interactive effects of aging with noise induced hearing loss. Scand Audiol Suppl 48:53, 1998; Mills JH et al: Gender-specific effects of drugs on hearing levels of older persons. Ann N Y Acad Sci. 884:381, 1999; Patel AM et al: Functional magnetic resonance imaging of hearing-impaired children under sedation before cochlear implantation. Arch Oto­laryngol Head Neck Surg 133:677, 2007; Schuknecht HF, Gacek MR: Cochlear pathology in presbycusis. Ann Otol Rhinol Laryngol 102(1 Pt 2):1, 1993; Schulte BA: Immunohistochemical localization of intracellular Ca-ATPase in outer hair cells, neurons, and fibrocytes in the adult and developing inner ear. Hear Res 65:262 1993; Shone G et al: The effect of noise ex­posure on the aging ear. Hear Res 56:173, 1991; Spicer SS, Schulte BA: Pathologic changes of presbycusis begin in second­ary processes and spread to primary processes of strial marginal cells. Hear Res 205:225-40, 2005; Takemura K et al: Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig. Hear Res 196:58, 2004; Takumida M, Anniko M: Radical scavengers for elderly patients with age-related hearing loss. Acta Otolaryngol 129:36, 2009; Wilson WR et al: The efficacy of steroids in the treatment of idiopathic sudden hearing loss. A double-blind clinical study. Arch Oto­laryngol 106:772, 1980.