Presbycusis, deafness of old age

PRESBYCUSIS

INTRODUCTION

• Presbycusis refers to sensorineural hearing impairment in elderly

• Most common otolaryngologic problem of elderly• Involves bilateral high – frequency hearing loss

associated with difficulty in speech discrimination and central auditory processing of information

• Association between advanced age and high tone deafness was first described by Zwaardemaker in 1899

• Occurs in elderly population that relies on special senses to compensate for other age associated disabilities

• elderly patients may rely of hearing to overcome limitations of impaired vision as well as slowed reaction time

• In addition, age associated decline in concentration and memory contribute to difficulty in understanding speech in noisy evn

• Hearing loss may contribute to the isolation of elderly people by restricting their usage of phone, causing them to forfeit social events such as concerts and social gatherings and amplifying their sense of disability

Epidemiology

• No race, sex differences. Increases with age• 25 – 30% of people aged 65 – 75 are estimated to have

impaired hearing• For people aged 75 or older incidence is thought to be

40 – 50%• Westernized countries and primitive civilisations have

very different patterns of hearing loss• Rosen et al study in Sudanese tribe called mabaans

revealed significantly less hearing loss in elderly people than those of urban society

Physiologic property Urged to read and revise from Dr C Favara’s presentation titled:Ultrastructure of the cochlea

• Cochlear duct = coiled duct filled with fluid• Ectodermal origin• Walls are lined with cells that constitute the

membranous labyrinth• Constitutes of hair (sensory cells) and auxiliary

and supportive cells• Membranous labyrinth is surrounded by

additional fluid space filled with perilymph and lined by cells of mesodermal origin

• Role of cochlea is to transduce complex sound waves into electrical activity to transmit to brain via auditory nerve

• Inner hair cells of organ of corti perform the transduction and initiate the depolarisation of spiral ganglion neurons

• Outer hair cells are accessory sensory cells that enhance the sensitivity and selectivity of cochlea

Basic anatomy of cochlea

Endolymph vs perilymph

Endolymph• In scala media• Extracellular fluid• Ionic composition similar to

intracellular fluid• High [K +] , low [Na +]• Electric potential of

endolymph +80mV = endolymphatic potential

perilymph• In scala tympani and scala

vestibuli• Ionic composition similar to

CSF or plasma• Rich in Na and low in K +• Weakly positive electrical

potential• 5 – 7 mV

• Only possible ion communication with spaces beyond scala media is through the ion channels situated in the stereo cilia of the sensory hair cells of the organ of corti

• The stria vascularis generates the end cochlear potential and maintains the ionic composition of the endolymph.

• The mechanical characteristics of the basilar membrane and its related structures further enhance the frequency selectivity of the auditory transduction mechanism.

• The tectorial membrane is an extracellular matrix, which provides mass loading on top of the organ of Corti, facilitating deflection of the stereo cilia.

• Stria vascularis = 3 layers of cells

• Marginal cells• Intermediate cells• Basal cells• Stria vascularis and

spiral ligament are richly supplied by blood vessels

Spiral ligament

• Located between stria vascularis and otic capsule

• Reaches beyond the limits of stria vascularis and perilymphatic spaces of scala vestibuli and scala tympani

• Anchors the lateral aspect of the basilar membrane

• Has prominent capillary bed for the supply and drainage of cochlea

• Essential structure for maintaining the ionic balance in scala media

• K+ absorbed via gap junctions• K+ ion pumps K+ from scala tympani and

organ of corti and reroutes to the basal cells of stria vascularis

• Implicated in presbycusis ( pathological changes of the fibrocytes of spiral ligament)

• Base of cochlea is the region where higher sound frequencies are transduced

• Lower frequencies are transduced at apical end• Range of frequencies is tonotopically distributed

along the cochlear duct from base to apex

the organ of Corti

• Sensorineural end organ of hearing• Contains both sensory and supporting cells• Sensory cells are hair cells which have active

process in their stereocilliar bundles• Receive both afferent and efferent innervation• Coupled with tectorial membrane

• Hair cells are supporting cells are spatially organised in an orderly pattern that extend repetitively for the 2 and half turns of cochlea

• Every sensory cell is surrounded by four supporting cells

• Sensory cells have no contact with each other

• Inner hair cells are true sensory cells, able to send impulses via auditory nerve

• Outer hair cells enhance the performance of the cochlea’s selectivity and sensitivity

• The sensory cells do not reach the basilar membrane, only supporting cells do

• All cells are differentiated, thus no turnover of cells

• If sensory cells are lost, they are irreplacable

• Inner hair cells:– Pear shaped– Central nucleus– Apical tight junction– No desmosomes– At apical surface stereo cilia implanted on cuticular plate– Stereo cilia and reticular lamina are in endolymph, rest

of cell surrounded by perilymph– Base – synaptic connection with afferent nerve

terminals

• Outer hair cells– 3 rows on lateral side – Cylindrical in shape, nucleus in base– Supported by Deiter’s cells– Apical surface part of reticular lamina– Surrounded by and make tight junction at the upper

junction with 4 different deiters cells– Hair bundle is W shaped with multiple rows of stereocilia– Apical surface endolymph, body on all sides except base

by perilymph (space of Nuel)

• Outer hair cells are stiff and motile• Movement modulates distance between

reticular lamina and basilar membrane• Require presence of protein, prestin in cell

membrane to move• Prestin can change it’s conformation at

microseconds rates dependence of changes in electrical voltage

Summary of essential physiology

pathophysiology• Histologic changes associated with aging occur

throughout the auditory system from the hair cells of the cochlea to the auditory cortex in temporal lobe of the brain

• Elucidation of pathophysiology of presbycusis is still incomplete

• Crowe and associates• Saxen and Gacke and Schuknecht – Studied histologic changes in cochlea of human

ears with presbycusis– Identified 4 sites of aging in cochlea and divided

presbycusis into 4 types based on these sites– Histologic changes correlated approximately with

symptoms and auditory test results

Sensory presbycusis

• Epithelial atrophy with loss of sensory hair cells as well as supporting cells in the organ of corti

• Originates in basal turn of cochlea and slowly progress towards the apex

• sharp drop in high frequency threshold, begins after middle age

• Abrupt downward slope of audiogram begins above speech frequency, speech discrimination is preserved

• Histologically atrophy may be limited to only the first few millimetres of basal end of cochlea

• Process is slowly progressive over time• ? Due to accumulation of lipofuscin pigment

granules at the basal end of cochlea

Neural presbycusis

• Atrophy of nerve cells in the cochlea and central neural pathways– Schuknecht estimated that 2100/35000 neurons are

lost every decade. Loss begins early in life and may be genetically predetermined

– Effects not noticeable until old age because PTA not affected until 90% of neurons are gone

• Atrophy occurs throughout the cochlea• Basilar region slightly more predisposed than the

remainder of cochlea

• No precipitous drop in high frequency threshold observed

• A disproportionally severe decrease in speech discrimination is a clinical correlate of neural presbycusis

• May be observed before hearing loss is noted because fewer neurons are required to maintain speech thresholds than speech discrimination

Metabolic (strial)

• Results as atrophy of stria vascularis• Normally maintains the chemical and bioelectrical

balance and metabolic health of cochlea• Hearing is represented by a flat hearing curve

because entire cochlea is affected• Speech discrimination is preserved• Process in younger population (30 – 60 years)

with slow progression and may be familial

Mechanical (i.e. cochlear conductive)

• Results from thickening and secondary stiffening of the basilar membrane of the cochlea

• Thickening is more severe in the basal turn of the cochlea where the basilar membrane is narrow

• Correlates with gradually sloping high frequency sensorineural hearing loss that is slowly progressive

• Speech discrimination is average for the given PTA

• Changes associated with presbycusis is rarely found exclusively at one site

• Development typically involves simultaneous changes at multiple sites

• Explained by the difficulty of associating specific clinical symptoms or signs with specific anatomical location

• Large volume of current research is being conducted to determine the exact underlying cause of presbycusis

• Much of the research focuses on finding underlying genetic abnormalities that may cause, contribute to or predispose to presbycusis

• Genetic mutation of mitochondrial DNA– Reduced perfusion of the cochlea

associated with age may contribute to the formation of reactive oxygen metabolites

– Affect the inner ear neural structures and cause damage to mitochondrial DNA

– Damaged mitochondrial DNA = reduced oxidative phosphorylation = disruption in ATP production = disruption of K+ channels = neural dysfunction

• Damaged mitochondrial DNA may lead to anatomic changes of the inner ear– Narrowing of the vaso nervorum In the auditory meatus in

temporal bone (Dai et al 2006)– Greater rates of apoptosis of supporting cells in inner ear

(pickles et al 2004)• 2 specific deletions– mtDNA4834 and mtDNA4977 have been linked to age related

hearing loss in rodents– Han et al and Dai et al have demonstrated mtDNA4977

deletion with archived human temporal bones from patients with presbycusis

Other causes

• Nutritional and anatomic– Berner et al investigated the relation between

vitamin B12 and Folate - not significant relationship

– Martin Villares et al found positive relation ship between high cholesterol levels and hearing loss

– Statin users had no improvement in rate of presbycusis

The Patient….

• Presentation varies• Patients typically have more difficulty

understanding rapidly spoken language, vocabulary that is less familiar or more complex as well as speech within a noisy, distracting environment

• Localising sound is difficult for patient

aetiology

• Arteriosclerosis– Cause diminished perfusion and oxygenation of

cochlea• Diet and metabolism– DM accelerates process of arteriosclerosis– Diffuse proliferation and hypertrophy of intimal

endothelium which may also interfere with perfusion of cochlea

– Brainstem neuropathy in DM

• Accumulated exposure to noise• Drug and environmental chemical exposure• Genetics• stress

workup

• Blood tests for autoimmune• Audiology with PTA and speech discrimination– Need for additional testing can be determined

from the audiometric plus physical examination of the patient

treatment

• Presbycusis is not curable – Effects of disease on patients lives can be

managed– Amplification devices – properly fitted hearing aids– Older patients with arthritis and visual difficulties

need extra help on learning to use hearing aids– Patients using hearing aids may still experience

difficulties with speech discrimination in noisy situations

• Lip reading – May help patients with diminished speech

discrimination and hearing aid users who have difficulty in noisy evns

– Assistive listening devices• Range from amplification of telephone signal to sound

transmitters

– Cochlear implants • Patients with cochlear changes and intact spiral ganglia

and central candidates are best candidates

Future of treatment…• Researchers proposing

treatments that address underlying genetic cause

• Medications that block production of reactive oxygen metabolites (carnitine) may treat presbycusis at molecular level

• Stem cell transplant into the cochlea to attempt to regenerate sensory cells….