Lars-Göran Johnsson

Sensory and Neural Degeneration with Aging, as Seen in Microdissections of the Human Inner Ear:

Presbycusis, the gradual loss of hearing that occurs with advancing age, is as subtle and complex as the aging process itself. Schuknecht’has suggested that there are four main types of presbycusis: 1) sensory, with primary loss of the hair cells of Corti’s organ; 2 ) neural, with primary degeneration of neurons of the cochlear nerve and central auditory pathways; 3 ) metabolic, with primary atrophy of the stria vascularis; and 4 ) mechanical, with primary changes in the physical properties of the basilar membrane. To these four might be added vascular presbycusis, characterized by loss of minute vessels supplying the spiral ligament, stria vascularis, and tympanic lip, of which metabolic presbycusis may prove to be a special case. Central presbycusis, with loss of neurons from the cochlear nucleus and other auditory centers of the brain, might also be classified as a distinct type, the term neural presbycusis being reserved for degeneration of first-order neurons of the cochlear nerve. Above all, it should be emphasized that the various types of presbycusis seldom, if ever, occur singly. Any attempt, therefore, to set up an exhaustive classification or a complete list of causative factors in presbycusis at this time is necessarily premature.

Observations on Normal and Degenerating Human Otoconia

Specimens of human otoconia obtained from autopsy material and representing various stages from fetal to advanced old age, were studied by microdissection, scanning electron microscopy, electron microprobe analysis, and x-ray powder diffraction. The typical adult otoconial configuration is a cylindrical, finely serrated body with pointed ends; crystallographically, it corresponds to a single crystal of calcite. Other, less numerous types include joined otoconia, pure rhombohedrons and multifaceted, presumably immature forms. Many otoconia achieve the adult configuration during fetal development. The multifaceted otoconia are most numerous, and the rhombohedrons proliferate, during childhood in the utricle. Crystals from both end organs are virtually identical in composition in the young adult, but saccular otoconia are the larger. In middle and advanced age the otoconia decrease in number, especially in the saccule. Saccular otoconia degenerate progressively in a posteroanterior direction across the macula; they assume a specific, fibrous, hollowed-out appearance, which is not duplicated by either chemical etching or autolysis. Neogenesis and growth of otoconia appear to occur postnatally, with different characteristic growth potentials for those of the saccule and the utricle. Age-related saccular otoconial degeneration appears to involve the organic material, which disappears either before or simultaneously with the mineral substance.

Vascular Changes in the Human Inner Ear Associated with Aging

This study is conccrned with the condition of the minute vessels of the inner car as seen in a collection of temporal bones obtained at autopsy from patients of widely varying ages. Its purpose is to examine the microvascular pathology that occurs with aging and to consider its possible relation to presbycusis. Because of the difficulty of setting up any standards of normal vascularization, the approach is qualitative and descriptive rather than quantitative and statistical.

Sequence of Degeneration of Corti's Organ and its First-Order Neurons

In our temporal bone material, sensory and neural degeneration do not occur independently. Usually there is a good correlation between the extent and severity of hair cell loss and the nerve degeneration in the osseous spiral lamina. Sensorineural degeneration in ototoxicity and after sound exposure is mostly sensory in nature in the initial phase of the process. Presence of supporting elements effectively delays secondary nerve degeneration. Degeneration of Cortis organ can often be complete, but the corresponding nerve degeneration is usually only severe to subtotal, never complete. Sensorineural degeneration which is predominantly neural (without parallel hair cell loss) is rare and occurred in less than 5% of our material. Severe subtotal nerve degeneration with hair cells still remaining was found only in one single temporal bone. Furthermore, Spoendlins experiments in the cat suggest that in man also a portion of the first-order cochlear neuron could have an unusual degeneration behavior and may not degenerate in the case of compression or transection. The fact that sensory and neural degeneration rarely occur in reasonably “pure” forms may explain why it is often difficult to distinguish between them by means of audiological tests alone.

Melanocytes of the Vestibular Labyrinth and Their Relationship to the Microvasculature

The melanocytes of the vestibular labyrinth as seen in colored guinea pigs show a characteristic pattern of distribution in the wall of the utricle and in the ampullae, but they are not present in the wall of the saccule. They are found mainly in well-vascularized regions of apparent secretory or metabolic importance, including the “dark cell” areas. Their dendrite-like processes are often in intimate contact with the capillaries, although no pinocytotic vesicles or other indications of transfer of substances between the melanocytes and the capillary endothelium are seen under the electron microscope. In the human ear, the apparent density of the melanocytes varies with skin color. They are numerous in the cochlea, especially in the bony wall of the modiolus and on the osseous spiral lamina, and they occur also in Reissners membrane and in the stria vascularis. In the vestibular system they are found in the wall of the saccule as well as in the utricle, the crus commune, and the ampullae, but not in the semicircular canals. They tend to be diffusely scattered, rather than to form the well-defined, intensely pigmented areas that are characteristic of the guinea pig. Close contacts with capillaries are seen mainly in the tympanic portion of the spiral ligament. The significance of melanin and the melanocytes in the labyrinth is unknown, but both the anatomical relation of certain melanocytes to capillaries, and the biochemical relation of melanin to the catecholamines support the hypothesis that they may have a vasomotor function. Other evidence, including the not infrequent association of sensorineural deafness with hereditary disorders of pigmentation also suggests that the melanocytes may play a role of some biological consequence in the inner ear.

Incorporation Of Radioactive Calcium Into Otolithic Membranes And Middle Ear Ossicles Of The Gerbil

45CaCl2 was injected into gerbils in single or multiple doses, and the resulting radioactivity in serum, otoconial CaCO3, bone samples, and selected labyrinthine epithelium was determined by liquid scintillation spectrometry. Incorporation into both utricular and saccular otoconia occurred at the rate of 0.06-0.07 nmole Ca++ per day, corresponding to a fractional rate of uptake of 0.1%. The retention of radioactivity had a half-life of approximately 11 days. The rate of incorporation of calcium for the middle ear ossicles was 5-7 times that for otoconia and was similar to that for otic capsule and skeletal bone. The level of 45Ca++ was higher in the pigmented regions of the utricular membranous wall than in the non-pigmented areas of the utricular and ampullary wall and in the stria vascularis.

Cochlear microvasculature in normal and damaged ears.

The minute vessels of the cochlea were examined post mortem in normal guinea pigs and in others exposed to intense noise or treated with the ototoxic drugs gentamicin and quinine. The benzidine stain was used to display the capillary networks, and osmic acid for surface preparations, “thick” sections, and ultrathin sections for electron microscopic examination.

Degeneration patterns in human ears exposed to noise.

Various forms of sensorineural degeneration patterns related to noise exposure are illustrated in six pairs of temporal bones selected from a group of 33 male patients with histories of noise exposure. For the entire group the commonest form of lesion, associated with a 4-kHz dip in the audiogram, was a relatively diffuse degeneration in the second quadrant of the basal turn, in the 9–13 mm area. An advanced form of this lesion had a wide gap of more or less complete sensorineural degeneration affecting the entire second quadrant and displaying various degrees of extension toward the apex and base. The pattern associated with an “abrupt high-tone loss,” with more or less complete hair cell and nerve degeneration in both the second and first quadrants and extending to the basal end of the cochlea, was rare. In one case this pattern appeared to have evolved from the first type of lesion as the remaining nerve fibers in the first quadrant had degenerated. The protective effect of the acoustic shadow of the head for the right ear, in shooting from the right shoulder, is demonstrated for the higher frequencies. Two almost identical cases of sharply-circumscribed single areas of degeneration in the first quadrant and one case with two such areas represent the third type of lesion. In one of these cases there was a history of firearm usage. It is postulated that this type of lesion is caused by impulse noise. In most of the material the degeneration pattern differed markedly from the diffuse degeneration seen with presbycusis. Degeneration patterns with knife-sharp transitions between completely degenerated and apparently undamaged areas appear to be characteristic of noise-induced injuries.

Hearing Loss and Cochlear Pathology in Monkeys After Noise Exposure

Old World monkeys were exposed to octaveband noise from 0.5 to 8 kHz at 120 dB SPL, 8 hours daily for 20 days. Restricted permanent threshold shifts and localized loss of outer hair cells were produced, which were reasonably well correlated with the exposure frequencies. There was also a loss of both inner and outer hair cells at the extreme basal end of Cortis organ, regardless of the exposure frequency. Implications for human inner ear pathology are discussed.

Otolithic Membranes of the Saccule and Utricle in Man

The otolithic membranes of the human saccule and utricle can be prepared as whole mounts or surface specimens for microscopic examination. They are not simple, homogeneous, gelatinous structures as heretofore described. Instead, each shows a definite and characteristic fibrillar design, which appears to be correlated with the known cytoarchitectural pattern of the underlying neuroepithelium.