The research described above suggested that the place coding of frequency would be best achieved with electrodes placed inside the scala tympani. However, initial studies on patients by some groups were primarily with electrodes outside the cochlea, as the cochlea was considered by some to be too delicate for surgical implantation (Legouix (1957)
cited by Simmons (1966)
Research commencing in 1972 (Clark et al. 1975b
) showed that when multiple electrodes were inserted into the scala tympani of the cochlea, through a number of holes drilled in the overlying bone, there was marked damage of all structures, and associated loss of the auditory nerve fibres (Clark et al. 1975b
). However, it was found (Clark et al. 1975b
; Clark 1977
) that a free-fitting electrode carrier could be passed through the round window and along the scala tympani with only mild histopathological changes in the cochleae. The study also emphasized that the cochlea needed to be protected from middle ear infection extending around the electrode, which could also lead to meningitis.
The studies to determine how to achieve an adequate insertion depth and the stiffness and extensibility of the materials required were undertaken on human temporal bones and moulds of the cochleae (Clark et al. 1975a
). The electrode carriers were found to pass only 10
mm upwards into the tightening spiral of scala tympani of the basal turn, but as with the experimental animal, they passed downwards easily into the widening spiral of the cochlea. It was also demonstrated that an electrode bundle inserted upwards along the scala tympani would lie at the periphery of the spiral, and that its upward progress in the basal turn was impeded through frictional forces against the outer wall (Clark et al. 1975a
). However, it was discovered in 1977 that an appropriate insertion depth could be achieved if the electrode bundle became increasingly stiff towards its proximal end, as well as having a flexible tip (Clark 2003
). This was made possible by the incremental addition of electrode wires that progressively stiffened the array from the tip to the base. This electrode with increasing stiffness could be passed around the basal turn to lie opposite the speech frequency region, as shown in .
Figure 8 A banded, free-fitting, smooth, tapered, electrode array with graded stiffness that has passed into the scala tympani of the basal turn of the human cochlea. M, modiolus; RW, round window or entry point to the basal turn of the cochlea; BT, basal turn (more ...)
In the late 1970s and early 1980s, a series of studies was undertaken to ensure that the materials for the electrode array, as well as the receiver–stimulator package, were biocompatible and non-toxic before they were used in a clinical trial for the FDA (Clark et al. 1983
; Clark 1987
). The procedures were appropriate modifications of those outlined in the US Pharmacopeia (1980)
and exceeded the recommendations. An initial report (Clark et al. 1983
) and a more detailed study (Clark 1987
) established that Silastic MDX-4-4210, Silastic medical adhesive type A, and platinum were biocompatible and produced little fibrous tissue reaction in the subcutaneous and muscle tissue in the rat and cat, and Silastic MDX-4-4210 and FEP (fluoroethylene propylene) produced little reaction in the cat cochlea. Candidate materials were further tested for the FDA for cytopathic effects against embryonic cells, for systemic toxicity by intravenous and intraperitoneal injection in mice, intracutaneous irritation in rabbits, and for tissue reactions to subcutaneous and intramuscular implantation after 90 days. The assembled units were evaluated by implanting them intramuscularly for four weeks and examining the tissue response, as the manufacturing process and working of materials could change their biocompatibility.
It was found that circumferential platinum band electrodes had the required smooth surface to facilitate the insertion of a free-fitting array with graded stiffness (Clark et al. 1979a
) (). The bands lay flush with the surface of the array to minimize resistance when inserted. The wires passed centrally along the tube to emerge through openings where they were welded to the bands. The outside diameter of the array varied from 0.56 to 0.64
mm, to ensure that it would fit freely into the scala tympani, and the electrodes had a width of 0.3
mm and inter-electrode spacing of 0.45
mm. This enabled 20 electrodes to lie along the first 15
mm of the array where they would be opposite the speech frequencies if the whole array were inserted 20–25
mm. With the circumferential electrodes, the array was tolerant of lateral displacement or rotation as a result of the insertion.
To ensure the array did not lead to significant trauma, investigations were carried out on human temporal bones (Shepherd et al. 1985
). A localized tear of the basilar membrane and fracture of the spiral lamina were seen in two of nine bones when the insertion had continued beyond the point of first resistance. This would have led to a restricted loss of neurons (Simmons 1967
; Axelsson & Hallen 1973
Furthermore, the research by Clark et al. (1987c)
in the experimental animal indicated that the banded electrode array was not held tightly by a fibrous tissue sheath after long-term implantation, and could be easily removed and another one reinserted at a later stage if replacement was required. This meant that the future implantable receiver–stimulators did not require a connector, and this made them smaller and able to be implanted in young children.
Charge density, charge per phase, total charge, and direct current (DC) lead to neuronal damage through their effects on the ability of cellular metabolism to maintain homeostasis (McCreery & Agnew 1983
). Electrical current can also produce an electrolytic reaction at the electrode–tissue interface with the release of toxic platinum ions (Agnew et al. 1977
Safe current and charge densities for stimulating the auditory nerves were determined for the bands. Long-term stimulation in the experimental animal was undertaken with these banded arrays using current levels and charge densities at the top of the range required to produce maximum loudness in the first patients. The pulses were biphasic with a negative and positive phase. The charge per phase was balanced so there was no residual charge to produce a build up of damaging DC.
An initial (Shepherd et al. 1982
) and more detailed study (Shepherd et al. 1983
) showed that charge densities less than 32
geom./phase and DC levels less than 0.3
μA had no adverse effects on neurons in the cochlea, and did not produce new bone growth when stimulation was carried out continuously for up to 2000
h. Charge density is measured either for the real reactive or just the geometric area. This became the upper allowable charge density for use in patients.
Scanning electron microscopy also demonstrated no corrosion of the banded electrodes taken from the experimental animals (Shepherd et al. 1984
), although corrosion was seen for electrodes in saline with the same charge densities. This confirmed the protective effect of protein.
The response of the human cochlea and brainstem to implantation and electrical stimulation with the banded array was subsequently studied (Clark et al. 1988
). This analysis enabled the response of the cochlea to be compared with that of the experimental animal. Stimulation for 10
h in the human did not lead to any observed effect on the auditory spiral ganglion cells in the cochlea or the higher brain centres.
The same stimulus parameters were also considered safe for children aged 2 years and above. But prior to implanting children under 2 years, studies were undertaken in the experimental animal to ensure the parameters had no adverse effect on the immature cochlea or central nervous system (Ni et al. 1992
; Burton et al. 1996
As high stimulus rates (800–2000
) were later shown to improve speech processing, their effect on neuronal survival was examined in the experimental animal. Long-term stimulation at rates up to 2000
and DC levels below 0.3
μA produced no significant loss of auditory ganglion cells (Tykocinski et al. 1995
; Xu et al. 1997
). Thus, high rates of stimulation were safe if the above parameters were used.
Initially, it was shown in the experimental animal (Clark et al. 1975b
; Clark 1977
; Shepherd et al. 1983
) that spontaneous middle ear infection could spread around the electrode at its entry to the cochlea, and result in severe infection with marked loss of the auditory neurons (spiral ganglion cells) with the risk of device-related meningitis. With these electrode insertions there had been no attempt to facilitate a seal. As a result, in 1977 further studies were commenced to determine how to seal the entry point (Clark et al. 1984
Firstly, foreign material was glued as discs or sleeves around the electrode at the opening into the cochlea to encourage the ingrowth of fibrous tissue into the material, and so increase the path length for bacteria (Clark et al. 1984
). The materials were tested in the presence of experimentally induced Staphylococcus aureus
and Streptococcus pyogenes
infections of the middle ear. To compare the findings, an effective system was developed for classifying cochlear infection. This was based on the severity of the acute inflammation, the degree of healing, and the extent of the spread within the cochlea (Clark et al. 1984
It was found that a muscle autograft around the electrode or a Teflon felt disc, prevented a Staphylococcus aureus infection in the middle ear extending to the cochlea. In addition, a fascial graft around the array prevented Streptococcus pyogenes, a more invasive organism, spreading to the basal turn of the cochlea. On the other hand, Dacron mesh with an overlying fascial graft was associated with a strong inflammatory response. This facilitated the spread of infection to the basal turn of the cochlea and along the cochlear aqueduct towards the meninges. It was thus not recommended as a round window seal for patients.
Studies were undertaken to find out how the tissue around the electrode entry healed, to understand how to prevent the extension of infection to the cochlea. Research (Franz et al. 1984
) on the penetration of horseradish peroxidase into tissues showed an increased permeability of the surrounding tissue and round window membrane over a period of approximately 2 weeks. Thereafter the round window membrane barrier returned to normal in a further two weeks. Healing could thus be a vulnerable stage for the spread of infection and the development of meningitis.
In the presence of middle ear infection, the round window membrane demonstrated a more marked proliferation of the connective tissue and the formation of protuberances of the mucous membrane, as well as mucous cell proliferation around the electrode. This was part of the body's first line of defence against bacteria, as mucus is bacteriostatic. In these round windows, although the permeability was increased, the penetration of horseradish peroxidase into the scala tympani was limited. Horseradish peroxidase always passed through the gap between the membrane and the prosthesis. However, particles were taken up by a connective tissue envelope that formed around the prosthesis after about one week. These data emphasized that, in the early healing phase, infection could extend to the inner ear, but they also demonstrated the importance of an early development of a connective tissue sheath around the electrode array. This sheath provided an effective barrier against the spread of infection (), by also allowing the second and third lines of defence to operate. With the formation of a sheath, capillaries brought the phagocytic white cells to the tissue surrounding the electrode and the space between the electrode and sheath, to engulf the bacteria (second line of defence). The same mechanism allowed lymphocytes to penetrate the tissue and space next to the electrode, and provide antibodies against the invading organisms (third line of defence) (Cranswick et al. 1987
Figure 9 A photomicrograph of an implanted cat cochlea. M, infection in the middle ear with proliferation of the mucous membrane; R, thickened round window extending into a well-formed electrode sheath. There is no extension of the infection to the cochlea. Reprinted (more ...)
Additional evidence for the importance of a sheath around the electrode was obtained from the study by Cranswick et al. (1987)
. The entry point through the round window was not sealed with tissue, and it was found there were two types of histological response in the cochlea, one with loose connective tissue in the basal turn, and another with an extensive sheath around the electrode array. There was a trend for infection to extend into the cochlea when there was localized loose fibrous tissue rather than a complete sheath.
These studies thus stressed that infection could more easily spread to the cochlea in the postoperative period, and emphasized the need for strict aseptic measures before, during and after surgery.
Later, when it was discovered that cochlear implants should be best carried out on children under two years of age, research was undertaken to ensure that middle ear infections with Streptococcus pneumoniae, very common in this age group, could be prevented from extending to the inner ear and thus leading to meningitis. Would sealing the electrode entry point with a fascial graft also be effective against Streptococcus pneumoniae, which has a different pathogenicity from the other organisms tested?
As a preliminary study (Berkowitz et al. 1987
) indicated that sealing to prevent the ingress of pneumococcal infection would be important, research was undertaken on 21 kittens to compare different sealing techniques following the induction of pneumococcal otitis media (Dahm et al. 1994
). The results indicated that cochlear implantation did not increase the risk of labyrinthitis following pneumococcal otitis media, but there was a reduced incidence of infection when the entry point was grafted. Therefore, for safety, it is important to place a fascial graft around the electrode where it enters the cochlea.
The response of the human cochlea to implantation and a fascial graft was studied by Clark et al. (1988)
and Dahm et al. (2000)
. There was a good seal around the electrode at the entry through the round window and a well developed fibrous sheath. Both would have been an effective barrier against the spread of infection from the middle ear.
The above experimental results only apply to a single-component free-fitting array, but not a two-component array. A space between two components is a conduit for infection, a home to allow pathogens to multiply, as well as a site to increase the pathogenicity of the organisms and reduce the ingress of antibodies and antibiotics (Clark 2003
A detailed analysis of the growth of different parts of human temporal bones from birth to adulthood was made to determine the growth changes (Dahm et al. 1993
). Key findings were that: (i) the distance between the sino-dural angle (the site for the implant) and the round window (near the site for the electrode insertion into the cochlea) increased on average by 12
mm from birth to adulthood with a standard deviation of 5
mm. Therefore, a paediatric cochlear implant should allow up to 25
mm of lead wire lengthening. This was consistent with the conclusions of O'Donoghue et al. (1986)
from radiographic studies. In addition, as there was no increase in the distance between the round window and the fossa incudis (floor of the mastoid antrum) with age, this indicated that fixation of the lead wire to the fossa would be desirable, as any growth changes would be transmitted to this point rather than pulling the electrode from the round window (Dahm et al. 1993
). Studies also showed that a redundant loop for the lead wires could lengthen even if surrounded with fibrous tissue, and furthermore it would not need a protective sleeve (Burton et al. 1994