sensorineural hearing loss / deafness

see also:

• deafness / hearing loss
• presbycusis (deafness of aging)
• drug induced ototoxicity
• endolymphatic hydrops including Meniere's disease

• humans can detect sounds in a frequency range from about 20 Hz to 20 kHz
  • infants can actually hear frequencies slightly higher than 20 kHz, but lose some high-frequency sensitivity as they mature
  • the upper limit in average adults is often closer to 15–17 kHz
  • NB. Middle C on a piano is 256Hz

• fundamental function of this part of the ear is to gather sound energy in a directional manner and deliver it to the eardrum
• resonances of the external ear selectively boost sound pressure with frequency in the range 2–5 kHz
• the vertical asymmetry of the pinna selectively amplifies sounds of higher frequency from high elevation thereby providing spatial information by virtue of its mechanical design
• the ear canal amplifies sounds that are between 3 and 12 kHz.

• plays a crucial role in the auditory process, as it essentially converts pressure variations in air to perturbations in the fluids of the inner ear
• sound waves hit the tympanic membrane (ear drum) which transmits these to the middle ear ossicles
• the three ossicles are arranged in such a manner as to resonate at 700–800 Hz while at the same time protecting the inner ear from excessive energy
• a degree of top-down control is present at the middle ear level primarily through two muscles, the tensor tympani and the stapedius which can restrain the ossicles so as to reduce the amount of energy that is transmitted into the inner ear in loud surroundings.

• ability to detect different sounds intensities and pitches with great sensitivity is mainly due to the inner ear's ability to decode sound waves and amplify individual frequencies.
• sound waves cause movements in the 32,000 inner ear auditory hair cells located within the spiral organ of Corti on the thin basilar membrane in the cochlea of the inner ear:
  • outer hair cells mechanically amplify low-level sound that enters the cochlea
    • the protein prestin (discovered in 2000) is the molecular membrane motor responsible for sound amplification in the inner ear
      • “prestin confers a unique property to auditory sensory outer hair cells (OHCs), termed electromotility (eM), by which the cells rapidly and reversibly contract in response to depolarization of the membrane potential”
      • sound-induced vibrations cause voltage fluctuations across outer hair cells in the inner ear which induce changes to prestin from its compact to its expanded conformation, or vice versa. These conformational changes of prestin trigger length changes of the hair cells and thus vibrations of the sound frequency to be amplified. ¹⁾
      • prestin belongs to the Solute Carrier 26 (SLC26) protein family
      • in addition to evolving into a voltage-dependent membrane motor, mammalian prestin lost the ability to transport solutes
        • the other SLC26 proteins transport ions across the cell membrane using an elevator-transport mechanism, which involves a vertical movement of a mobile transport-domain against a static scaffold-domain
  • inner hair cells transform the sound vibrations in the fluids of the cochlea into electrical signals that are then relayed via the auditory nerve to the auditory brainstem and to the auditory cortex.
    • these hair cells are arranged with tonotopic differences of the basilar membrane due to the different locations of the hair cells.
      • hair cells that have high-frequency resonance are located at the basal end while hair cells that have significantly lower frequency resonance are found at the apical end of the epithelium
    • deflection of the hair-cell stereocilia opens mechanically gated ion channels that allow any small, positively charged ions (primarily potassium and calcium) to enter the cell.
    • the influx of positive ions from the endolymph in the scala media depolarizes the cell, resulting in a receptor potential.
    • this receptor potential opens voltage gated calcium channels, calcium ions then enter the cell and trigger the release of neurotransmitters at the basal end of the cell which diffuse across the narrow space between the hair cell and a nerve terminal, where they then bind to receptors and thus trigger action potentials in the nerve
    • the hair cell is soon repolarized as the perilymph in the scala tympani has a very low concentration of positive ions and this electrochemical gradient makes the positive ions flow through channels to the perilymph.
    • hair cells can also adapt to higher levels of sound:
      • fast adaptation
        • Ca2+ ions that enter a stereocilium through an open MET channel bind rapidly to a site on or near the channel and induce channel closure. When channels close, tension increases in the tip link, pulling the bundle in the opposite direction.
      • slow adaptation - this is mainly in hair cells that sense spatial movement rather than detect auditory signals
• hair cell regeneration:
  • unlike birds and fish, humans and other mammals are generally incapable of regrowing the cells of the inner ear that convert sound into neural signals when those cells are damaged by age or disease
    • the mammalian gene which blocks this regrowth is the Rb1 gene which encodes the retinoblastoma protein, which is a tumor suppressor. Rb stops cells from dividing by encouraging their exit from the cell cycle.
  • TBX2 (T-box transcription factor 2) has been shown to be a master regulator in the differentiation of inner and outer hair cells
  • The cell cycle inhibitor p27kip1 (CDKN1B) has also been found to encourage regrowth of cochlear hair cells in mice following genetic deletion or knock down with siRNA targeting p27

• the cochlear nerve (AKA auditory nerve or acoustic nerve) is one of two parts of the vestibulocochlear nerve, a cranial nerve present in amniotes, the other part being the vestibular nerve.
• 90-95% of the neurons are thick, myelinated, bipolar type I neurons and innervate the inner hair cells
• the remainder of the neurons are thin, unmyelinated, unipolar type II neurons which innervate the outer hair cells
• the cell bodies of the cochlear nerve lie within the cochlea and collectively form the spiral ganglion
• the peripheral axons of the 30,000 auditory nerve fibers form synaptic connections with the hair cells of the cochlea via ribbon synapses using the neurotransmitter glutamate.
• the central axons form synaptic connections with cells in the ipsilateral cochlear nucleus complex of the brainstem
• after exiting the cochlear at its base, the nerve passes with the vestibular nerve through the internal auditory canal to the brainstem

• there are three major components of the cochlear nuclear complex:
  • dorsal cochlear nucleus (DCN)
  • anteroventral cochlear nucleus (AVCN)
  • posteroventral cochlear nucleus (PVCN)
• each of the three cochlear nuclei are tonotopically organized
• even with loss of both auditory cortical centres causing cortical perceptual deafness, brainstem processing allows reflexive responses to sound
• signal pathways in brainstem:
  • superior olivary complex (SOC) of mid pons
    • 14 nuclei
      • the first convergence of the left and right cochlear pulses
      • MSO determines the angle the sound came from by measuring time differences in left and right info
      • LSO normalizes sound levels between the ears and uses the sound intensities to help determine sound angle and then innervates the IHC
      • VNTB innervate OHC
      • MNTB inhibit LSO via glycine
      • LNTB are glycine-immune, used for fast signalling
      • DPO are high-frequency and tonotopical
      • DLPO are low-frequency and tonotopical
      • VLPO have the same function as DPO, but act in a different area.
      • PVO, CPO, RPO, VMPO, ALPO and SPON (inhibited by glycine) are various signalling and inhibiting nuclei
    • trapezoid body:
      • most of the cochlear nucleus (CN) fibers decussate in the trapezoid body and this crossing aids in sound localization
      • ⇒ cochlear nucleus:
        • ventral (VCN) region of cochlear nucleus
        • dorsal (DCN) region of cochlear nucleus
        • ⇒ lateral lemniscus of pons-midbrain junction
          • dorsal nuclei respond best to bilateral input and have complexity tuned responses
          • intermediate nuclei have broad tuning responses
          • ventral nuclei have broad and moderately complex tuning curves
            • help the inferior colliculus (IC) decode amplitude modulated sounds by giving both phasic and tonic responses (short and long notes, respectively)
          • ⇒ inferior colliculus caudal midbrain
            • appears to be responsible for the 'startle response' and ocular reflexes
            • responds to specific amplitude modulation frequencies, allowing for the detection of pitch
            • determines time differences in binaural hearing
            • receives inputs including:
              • visual areas (pretectal area: moves eyes to sound. superior colliculus: orientation and behavior toward objects, as well as eye movements (saccade))
              • pons (superior cerebellar peduncle: thalamus to cerebellum connection/hear sound and learn behavioral response)
              • spinal cord (periaqueductal grey: hear sound and instinctually move)
              • thalamus
            • ⇒ medial geniculate complex of thalamus / rostral midbrain
              • ventral part
                • relay and relay-inhibitory cells: frequency, intensity, and binaural info topographically relayed
              • dorsal part
                • broad and complex tuned nuclei: connection to somatosensory info
              • medial part
                • broad, complex, and narrow tuned nuclei: relay intensity and sound duration
              • ⇒ primary auditory cortex

• auditory cortex
  • upper part of both temporal lobes
  • takes part in the spectrotemporal (time and frequency) analysis of the inputs passed on from the ear
  • development of this part is also dependent upon:
    • presence of sound inputs in early life
    • testosterone influences causing sexual dimorphism of the auditory cortex
      • males have a larger planum temporale volume on average
  • unilateral destruction of the auditory pathway above the brainstem cochlear nucleus, results in slight hearing loss, whereas bilateral destruction results in cortical deafness.
  • 3 main parts:
    • the core (which includes primary auditory cortex, A1)
      • structure preserves tonotopy
      • receives direct input from the medial geniculate nucleus of the thalamus and thus is thought to identify the fundamental elements of music, such as pitch and loudness.
    • the belt (secondary auditory cortex, A2)
    • the parabelt (tertiary auditory cortex, A3)
  • final sound processing is then performed by the parietal and frontal lobes
    • due to the contralateral nature of the auditory system, the right ear is connected to Wernicke's speech area, located within the posterior section of the superior temporal gyrus in the left cerebral hemisphere.
    • the rostromedial prefrontal cortex (RMPFC) also represents tonality and projects to many diverse areas including the amygdala, and is thought to aid in the inhibition of negative emotion
  • see https://en.wikipedia.org/wiki/Auditory_cortex

• prolonged acute exposure to loud noise results in transient reduced hearing
• this may be due to depletion of calcium stores within the tectorial membrane of the cochlear which appears to regulate hearing by release calcium ions ²⁾

• usually effects high frequencies primarily, particularly around 4000Hz, although later all frequencies become affected
• ~20% of adolescents in Western cultures have noise-induced deafness
• OH&S recommended levels:
  • hearing protection if exposed to > 85dBA
  • < 8hrs at 85dBA (eg. power lawn mower)
  • < 4hrs at 88dBA
  • < 2hrs at 91dBA
• recommended portable device volume levels listening to music using earphones based upon NIOSH standards:
  • < 4.6hrs / day at 70% maximum level
  • < 1.2hrs / day at 80% maximum level
  • less if other risk factors such as ototoxic drugs
• a short blast of loud noise also can cause severe to profound SNHL

• see drug induced ototoxicity

• see presbycusis (deafness of aging)
• usually effects high frequencies primarily

• see endolymphatic hydrops including Meniere's disease
• usually effects low frequencies primarily +/- high frequencies with relative sparing of mid-frequencies

• migraine may cause vasospastic micro-vascular ischaemic damage to the inner ear, hearing loss, and susceptibility to developing endolymphatic hydrops including Meniere's disease

• meningitis
• head injury
• acoustic neuroma
• meningioma
• leukaemia

• acute unexplained sensorineural hearing loss of at least 30 dB over at least three test frequencies occurring over less than a 72hr period
• >90% are unilateral
• many present with a sensation of a blocked or full ear
• 90% have tinnitus
• 20-60% have vertigo
• most are idiopathic ?role of Herpes simplex virus (HSV) as with Bell's palsy
• recovery is often spontaneous
• can occur at any age but peak is around 50yrs
• incidence 2 to 20 per 100,000 people per year
• associations:
  • increased serum levels of fibrinogen and homocysteine
  • genes related to prothrombotic states (particularly MTHFR polymorphisms)
  • bilateral SSNHL:
    • cardiovascular disease in older patients
    • positive anti-nuclear antibodies (ANA)
• Ix and Mx:
  • otoscopy to exclude local causes
  • audiometry
  • MRI scan with gadolinium to exclude other causes of unilateral hearing loss, such as acoustic neuroma, perilymphatic fistula, Meniere disease, vascular insufficiency, multiple sclerosis, or other conditions involving the central nervous system, although MRI is likely to be normal in over 90%
    • of those with only mid-frequency loss, 1/3rd may have a retrocochlear tumor
    • stroke (CVA) involving anterior inferior cerebellar artery (AICA) which feeds the internal auditory artery, may cause sudden hearing loss with ipsilateral Horner syndrome, diplopia, nystagmus, facial weakness, limb clumsiness, ataxia, and contralateral loss of pain or temperature sensation.
  • 10-14 days high dose corticosteroids is often tried but efficacy is unproven
  • antiviral agents are generally not used as do not appear to be useful
  • oral magnesium and zinc may have a role but very small studies
• prognosis:
  • 2/3rds will have some recovery although only 25% of those with profound hearing loss will have some recovery
  • those who have not improved within three months will generally not recover significantly

• hyperthyroidism
• hypothyroidism
• congenital viral infections (eg. rubella, CMV, toxoplasmosis, syphilis)
  • hearing loss is often delayed and progressive
• congenital malformations of the inner ear
  • Michel / Mondini / Scheibe / Alexander
• viral cochleitis
• surgery
• barotrauma
• penetrating trauma
• autoimmune diseases
• multiple sclerosis (MS)
• stroke (CVA)
• complication of Kawasaki disease
• prematurity especially birth weight < 1500g (incidence 1 in 200)
• neonatal jaundice

• 1 in 2000 children have hereditary sensorineural hearing loss (SNHL)
• genetic causes account for almost half of children with SNHL
• 1/3rd of these are associated with syndromes
• 80% are autosomal recessive such as:
  • Usher syndrome
  • Pendred syndrome
  • Alport syndrome - mainly in the 2000 to 8000 Hz range
  • Jervell-Lange-Nielsen syndrome (long QT syndrome with deafness)
  • > 80 distinct loci have been linked with non-syndromic recessive hearing loss (ARNSHL) which accounts for 77% of non-syndromic genetic deafness
• 15% are autosomal dominant including:
  • Waardenburg syndrome types I and II
  • neurofibromatosis I and II
  • branchio-oto-renal syndrome
  • velocardiofacial syndromes
  • Williams-Beuren syndrome (WBS) - mild to moderate high-frequency sensorineural hearing loss in adulthood
  • > 60 loci have been mapped and over 25 genes have been implicated in non-syndromic AD hearing loss (ADNSHL) which accounts for 22% of non-syndromic genetic deaafness
• 2% are X-linked
  • Hunter syndrome (mucopolysaccharidosis 2)
  • Alport syndrome
  • X-linked congenital SNHL
  • early onset progressive sensorineural hearing loss
• 1% are mitochondrial
• adult onset deafness:
  • c.1696_1707 del RIPOR2 variant present in some 1 in 1000³⁾