A. Overview

1. Deafness affects about 0.1% of infants, ~4% of persons <45 years old
2. Reduced hearing affects >20% of persons >65 years old [1]
3. Hearing impairment in developed countries is usually genetic
4. About 15 loci associated with SNHL (non-syndromic) have been identified
5. Acquired (Sudden) SNHL
   1. Incidence is ~20 cases / 100,000 annually
   2. ~30% of sudden SNHL also with vestibular dysfunction
6. Elderly adults should be screened for hearing loss as effective interventions available [10,11]

B. Normal Hearing [2]

1. Anatomy
   1. Outer Ear
   2. Middle Ear
   3. Inner Ear
2. Outer Ear Function
   1. Sound waves impinge on head captured by outer ear (auricle)
   2. Waves then conveyed through external auditory canal (acoustic duct)
   3. These travel to tympanic membrane
3. Middle Ear Function
   1. Tympanic membrane separates outer and middle ear
   2. Vibrations of tympanic membrane are transmitted through middle ear to inner ear via three connected bones called ossicles
   3. These ossicles are (in order from outside to inside): malleus, incus, and stapes
   4. Malleus is attached to the tympanic membrane
   5. Stapes is attached at its base to the oval window of the vestibule
   6. The vestibule contains fluid which receives the sounds waves from base of stapes
4. Inner Ear Function
   1. Inner ear contains two sensory systems: auditory and vestibular (for balance)
   2. Anatomy includes bony and maembranous labyrinths
   3. Bony labyrinth is filled with fluid called perilymph
   4. Bony labyrinth has three main cavities: vestibule, cochlea, and semicircular canals
   5. Semicircular canals include 3 canals, the sacculus and utriculus
   6. The cochlea, a dead end tube, processes auditory signals
   7. The cochear nerve, a branch of cranial nerve VIII (CN VIII), innervates the cochlea
   8. The waves of sound are transmitted from perilymph to endolymph to hair cells
   9. Inner and outer hair cells are found in the Organ of Corti
   10. Hair cell motion is sensed by cochlear neurons
5. Circulation
   1. Blood supply to cochlear system provided by labyrinthic artery (aa)
   2. Labyrinthic aa supplies vestibulocochlearic aa and spiralis modiolic aa
   3. These aa supply the cochlea and vestibular system
   4. Explains why ~30% of patients with sudden SNHL have vestibular dysfunction

C. Causes Of SNHL

1. Infection [1]
   1. Congenital: cytomegalovirus (CMV), rubella, Toxoplasmosis, syphilis, lymphocytic choriomeningitis virus
   2. Acquired Viruses: Epstein-Barr virus, non-polio enteroviruses, measles, mumps, varicella
   3. Acquired Non-Viruses: Borrelia, Haemophilus influenzae, Neisseria meningitidis, malaria (P. falciparum), Streptococcus pneumoniae
2. Drugs
   1. Aminoglycosides
   2. Cisplatin
   3. Salicylates - high dose
   4. Loop diuretics - particularly ethacryinic acid
   5. Streptomycin and other aminoglycosides
3. Trauma: temporal bone fracture, nose exposure
4. Rheumatologic / Inflammatory Disease
   1. Giant cell (Temporal) arteritis
   2. Systemic lupus
   3. Wegener's Granulomatosis and Polyarteritis nodosa [6]
   4. Cogan syndromee
   5. Glucocorticoid responsive SNHL
5. Cerebellopontine Angle Tumors: usually acoustic neuroma
6. Radiation Exposure
7. Idiopathic: Meniere's Disease, presbycusis, others
8. Circulatory
   1. Likely plays major role in many types of SNHL
   2. Circulatory insufficiency would also affect vestibular system in many cases
   3. Vertebrobasilar insufficiency
   4. Thromboembolic disease
9. Genetic Causes (Congenital): ~0.05% of all children in USA
10. Aging [14]
    1. Hearing loss normally occurs with aging, called presbycusis
    2. Multifactorial process, mild to severe
    3. May substantially affect communication
    4. Can contribute to isolateion, depression, possibly dementia
    5. Hearing supplementation is available but underutilized
    6. Cost and appearance of hearing aids is a factor
    7. Primary care patients should screen elderly for hearing problems and refer them
    8. Cochlear implantation is treatment of choice when hearing aids no longer provide benefit
11. Endolymphatic Sac Tumors [16]
    1. Highly vascular, benign, locally aggressive neoplasms
    2. Often destroy surrounding temporal bone
    3. Tinnitus 92%
    4. Vertigo or disequilibrium 62%
    5. Aural fullness 29%
    6. Facial paresis 8%
    7. Commonly found in Von Hippel-Lindau (VHL) syndrome, including bilaterally
    8. Can cause insidious hearing loss consistent with endolymphatic hydrops
    9. Intralabyrinthine hemorrhage (~50% of tumors) can cause acute hearing loss

D. Genetic Causes [1]

1. About 50% of congenital cases are hereditary (inherited)
   1. Not associated with well characterized genetic syndromes (Non-Syndromic Causes)
   2. Associated with genetic syndromes (Syndromic Causes)
2. Non-Syndromic Recessive Deafness
   1. Acounts for ~80% of hereditary deafness
   2. Over 20 genes which, when mutated, can cause deafness have been discovered
3. Key Genes in Non-Syndromic Deafness (Table 1, Ref [1])
   1. POU3F4: conductive hearing loss due to stapes fixation mimicking otosclerosis
   2. DIAPH1: Low-frequency loss beginning first decade, then broading across auditory range
   3. KCN4 and GJB3: symmetrical high-frequency SNHL
   4. WFS1: early onset low-frequency SNHL
   5. EYA4: progressive loss beginning age 10
   6. COL11A2: congenital mid-frequency SNHL, age-realted progression
   7. POU4F3: bilateral progressive SNHL beginning age 10
   8. ACTG1: bilateral progressive SNHL beginning age 10
   9. GJB2: most common phenotype, mutation in connexin-26 (see below)
   10. GJB6: similar phenotype to GJB2
   11. SLC26A4: dilatation of vestiibular aquaduct
   12. 12S rRNA (mitochondrial DNA) mutation: varies from mild to profound SNHL, symmetrical
4. Connexin-26 (CX26) [4,7,8]
   1. Gene GJB2, gap junction protein ß2 (connexin 26), chromosome 13q11
   2. Mutations in CX26 are major cause of inherited and sporadic SNHL
   3. Most common mutation is 35delG (85% of mutations)
   4. CX26 mutations found in Ashkenazi Jews with nonsyndromic recessive deafness
   5. In Ashkenazis, 167delT and 30delG mutations are found
   6. In midwestern USA, 35delG mutation is most common (29/41 cases)
   7. Carrier rates (heterozygotes) for mutant GJB2 ~3%
   8. Most CX26 mutations lead to non-progressive deafness
   9. Cochlear implants are effective for children with GJB2 mutations and severe hearing loss [17]
   10. Mutations in the connexin 32 gene cause X-linked Charcot-Marie-Tooth neuropathy
5. Myosin VIIA
   1. Chromosome 11q13
   2. Also linked to hereditory SNHL
6. Syndromic Causes
   1. Alport's Syndrome - renal abnormalities with SNHL
   2. Usher's Syndrome
   3. Pendred's Syndrome - hypothyroidism with SNHL
   4. Jervell and Lange-Nielsen Syndrome - prolonged QTc Syndrome with SNHL [3]
   5. Bjornstad Syndrome - SNHL with pili tori, mutations in gene BCS1L (involved in mitochondrial respiratory complex III) on chr 2q34-36 [15]
7. Usher's Syndrome [12]
   1. Retinitis pigmentosa (vision loss) with SNHL
   2. Autosomal recessive disease
   3. Prevalence ~1 in 25,000
   4. Three clinical subtypes; most severe is type 1
   5. Seven loci for type 1 Usher's have been identified
   6. Mutation of the PCDH15 gene is common cause in Ashkenazi Jews

E. Evaluation

1. Screening in Elderly [11,15]
   1. Elderly persons who acknowledge hearing impairment require audiometry
   2. Elderly persons who reply no should be screened with "whispered voice" test
   3. Weber and Rinne tests should not be used for general screening
2. Early evaluation of all infants and children should be performed if SNHL is possible
3. Patients with asymmetric SNHL should be referred to otolaryngologist for evaluation
4. Audiometry to assess severity, rule out conductive hearing loss
5. Auditory evoked response testing for cases of asymmetry
6. MRI with Gadolinium
   1. Especially in cases of asymmetry, to rule out cerebellopontine angle tumors
   2. Most commonly acoustic neuroma (vestibular schwannoma)
7. Serum testing in cases of rheumatologic diseases
8. All cases of sudden SNHL should be referred immediately to otolaryngologist

F. Treatment [11]

1. Unfortunately, little treatment is available for congenital SNHL
2. Rheumatologic Diseases
   1. Glucocorticoids in high doses intially (prednisone 60mg qd initially)
   2. Cyclosporine may be added if glucocorticoids cannot be tapered
3. Sudden SNHL [9,13]
   1. Glucocorticoids may be of some benefit
   2. Prednisone 60mg po qd initially for at least 1 month (~50% response)
   3. Taper prednisone to 40mg po qd x 1 month, then slow taper
   4. Methotrexate of no benefit for maintenance after prednisone taper [13]
   5. Single fibrinogen / LDL apheresis for 2 hours improves blood flow
   6. Reduction in fibrinogen and LDL does not affect plasma volume
   7. Dextran for plasma expansion shows mild but slow benefit
   8. Fibrinogen / LDL apheresis has more rapid onset of action than standard plasma expansion
   9. Pentoxifylline (Trental®) of marginal benefit
4. Acoustic Neuromas
   1. Most common cerebellopontine angle tumors
   2. Tumors of schwann cells
   3. Microsurgical resection or stereotactic radiosurgery
   4. Radiosurgery preserves neurological function in >70% of persons [5]
   5. Damage to the facial or trigeninal nerves are most common complications
5. Most cases of reduced hearing are treated with hearing aids, assisted listening devices [1]
6. Cochlear implantation for cases of severe to profound bilateral deafness is promising
7. Cohclear implants have been effective even in persons beyond age 80 [14]

G. Conductive Hearing Loss

1. Cerumen Impaction
2. Foreign Body
3. Otitis externa
4. Otitis media
5. Cholesteatoma
6. Otosclerosis
7. Trauma with tympanic membrane perforation or hemorrhage
8. Middle ear masses

References

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2. Jackler RK. 2003. JAMA. 289(12);1557
3. Splawski I, Timothy KW, Vincent GM, et al. 1997. NEJM. 336(22):1562
4. Estivill X, Fortina P, Surrey S, et al. 1998. Lancet. 351(9100):394
5. Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC. 1998. NEJM. 339(20):1423
6. Seo P and Stone JH. 2004. Am J Med. 117(1):39
7. Denoyelle F, Marlin S, Weil D, et al. 1999. Lancet. 353(9161):1298
8. Green GE, Scott DA, McDonald JM, et al. 1999. JAMA. 281(23):2211
9. Suckfull M et al. 2002. Lancet. 360(9348):1811
10. Yueh B, Shapiro N, MacLean CH, Shekelle PG. 2003. JAMA. 289(15):1976
11. Bogardus ST Jr, Yueh B, Shekelle PG. 2003. JAMA. 289(15):1986
12. Ben-Yosef T, Neww SL, Madeo ACE, et al. 2003. NEJM. 348(17):1664
13. Harris JP, Weisman MH, Derebery JM, et al. 2003. JAMA. 290(14):1875
14. Gates GA and Mills JH. 2005. Lancet. 366(9491):1111
15. Bagai A, Thavendiranathan P, Detsky AS. 2006. 295(4):416
16. Butman JA, Kim HJ, Baggenstos M, et al. 2007. JAMA. 298(1):41
17. Papsin BC and Gordon KA. 2007. NEJM. 357(23):2380