|Fig1. Adapted from KidsHealth.Org..An overall model of a CI inserted in the cochlea|
Since the discovery of cochlear implantation (CI) in1957 by Djourno and Eyriès, CI has become a very common yet invasive procedure for people with severe to profound sensorineural hearing loss (having a threshold of hearing between 71 and 90 dB HL). This type of deafness is due to a congenital or trauma induced inner hair cells damage. Since these hair cells are missing/damaged and interfering with the connections of ear to the central nervous system (both afferent and efferent inputs), CI is used with general anesthesia to bypass these hair cells and directly stimulate the ganglion cells of auditory nerve and thus, reactivating inputs to the CNS. Current research on optimized multichannel 18mm electrodes and safe surgical approaches for the insertion of implant has evolved from the successful insertion of 220,000 cochlear implants worldwide. It has been found that the scala tympani, a fluid filled chamber running along the long axis of cochlea, is the best place to insert the prosthesis while insertion in scala vestibular (SV), another tube in the cochlea, creates more trauma induced hair cell apoptosis. Every CI consists of the following parts (Fig.1): 1) a microphone 2) a speech processor 3) a transmitter magnet located on the skin and a receiver implanted on the skull 4) an electrode array that is inserted into the cochlear by two different surgical approaches (the traditional cochleostomy approach and a newer round window approach). Along with the major surgery there are also two minor procedures before the insertion of implants: mastoidectomy (removal of mastoid cells) and tympanatomy (opening of the eardrum). Overall, CI has been very effective in recovering hearing loss and improving the quality of life of patients.
Table of Contents
1.1 Cochlear Implant
1.1.a Electrode features, optimization, anatomic situation
To stimulate the ganglion cells of the auditory nerve, an array of electrodes is placed in the scala tympany (ST) of the cochlea. Since the lumen of ST decreases from base to apex and it has a curved structure, the insertion of electrodes is limited and cannot go further than 30 mm (while the size of total lumen of cochlea is 34 mm). Usually, arrays are 18-26 mm in length and stimulate different types of neurons. Cochlea has a tonotopic map and thus, cochlear implant imitates this map by stimulating electrodes placed more on the basal site for higher frequency sounds and stimulating the ones on the apical site for lower frequency sounds (located deeper into the ST). There are two types of stimulation of these arrays of electrodes: 1) bipolar stimulation where a pair of electrodes is activated and 2) monopolar stimulation where currents are passed through intracochlear electrodes one by one. The latter one is the most common type of stimulation because it is equally as good as the bipolar stimulation, has a better long lasting battery, and makes the speech processer more comprehensive since the threshold is lower for loudness detection.
The accuracy of electrodes for activating a specific subpopulation of neurons in the cochlea depends on the geometric position of electrodes during insertion, the proximity of arrays to the neurons of interest, and the overlapping electrical field of neighboring electrodes. Originally, the standard length electrodes (Nucleus CI512) were used with a straight shape structure that could only go into 1 turn of the cochlea (360°) (Figure2). A less traumatic shortened implant with a higher preservation of hearing was developed (Hybrid L24) with 16mm length, 22 electrodes, and 250° turn in the cochlea. Overtime, the hybrid S12 was created with a reduced diameter and 195° turn in the cochlea that had a titanium marker for directing electrodes insertions.
|Examples of electrode arrays used in CI|
|Fig2. Adapted from Soken et al. An example of different sizes and diameters for various electrode arrays|
1.2 Surgical procedures for implantation
Cochlear Implantation surgery is usually done under general anesthesia and it takes about two hours. As a preparatory task, prophylactic antibiotics are administrated 30 minutes before any skin incision. Antibiotics such as cephalosporin are used to prevent the contamination of bacteria located on the skin with the site of surgery. Since the site of the implant insertion is very proximate to the facial nerve, all surgeons are required to follow a facial recess approach .Facial recess is an extension of the middle ear cavity and is confined by facial nerve laterally and chorda-tympani nerve medially. Therefore, surgeons need to monitor the facial nerve constantly. Then, methylene blue is used to mark the position of an inverted J-shaped skin flap before the surgeon makes any incisions . After the creation of incision, the mastoid bones are exposed and ready for mastoidectomy which is the opening of the mastoid bones to remove hair cells and some of the middle ear bones (Figure3.B). The recess created from mastoidectomy is a good site for positioning the receiver-stimulator piece of CI . To insert the electrodes, the insertions can be done on either scala tympani or scala vestibule ,however, it has been shown that placement of electrodes on scala tympani reduces the postoperative risks, increases hearing preservation, and reduces vertigo compared to patients with electrodes inserted on scala vestibuli . There is a controversy over the two ways that can open the Scala Tympani (ST) for the insertion of electrodes: 1) directly via cochleostomy or 2) indirectly through the round window membrane.
|Fig3. Adapted from Witte et al. Surgical techniques used in CI: A) a skin flap J-shaped incision is done behind the ear. B) an antromastoidectomy is performed and afterwards, the facial recess approach is carries out between C(Chorda Tympani nerve) and F(facial nerve). C) Cochleostomy: Arrow indicates the drilling from R(round window) into the cochlea where the electrode arrays would be inserted.|
This method, which is the more common way of opening the scala tympani, is done by drilling into the basal side of the cochlea located anteriorly to the round window. Then with a help of an introducer, the electrode array is inserted into the scala tympani. As the insertion happens, surgeon has to directly visualize the insertion to minimize the surgery-induced trauma to the hair cells and the membranes. The axial direction of insertion is also a critical factor:it should be maintained as parallel to the scala tympani otherwise the implant can penetrate into the basilar membrane and lead to trauma .
1.2.b Round Window Insertion (RWI)
In RWI, the overhang bone covering round window is removed and RW is exposed for incision. Following the incision of RW, the electrode is gently inserted into the cochlea with the same direction of the curved cochlea circumferentially. Then, the round window is closed using a gel foam and the temporalis muscle.
According to a survey in 2006, less than 20% of the surgeons perform RWI in the OR . However, this method is argued by some researchers to be less traumatic and more effective in preservation of hearing and speech perception when compared to cochlosteomy. When introduced in 1973 as an effective and safe method, round window insertion became a dominant technique during cochlear implantation using single channel electrode arrays. However, due to the development of multichannel arrays, a deeper placement of electrodes was needed and this method was not efficient and could traumatize the cochlea. This led to the invention of cochleostomy, which is now the more dominant method even though controversy between these two techniques still exists.
An example of a CI surgery:
1.2.c Local anesthesia vs. general anesthesia
CI surgery is always done under general anesthesia ,however, some researchers have proposed a possible alternative of using local anesthesia and sedation during surgery. The goal is to reduce the cost of the surgery, length of stay in the hospital, length of the surgery itself, and all the postoperative side effects of general anesthesia (hypotension, nausea, pain, dizziness).
1.3 Implantation for special population of patients
In some patients, lack of hearing is caused by factors such as meningitis and other pathologies that can change the shape of the cochlea (Table.1). This leads to labyrinthitis ossification and cochlear duct obstruction . At this point, specialized CI with specific electrode arrays might not be as effective as Auditory Brainstem Implant(ABI). Some researchers argue that CI is a better choice since the pathways to brainstem stay untouched. Precise different surgeries are performed depending on the degree of ossification and the newly formed bone is drilled to allow the electrode insertion . Imaging techniques such as MRI and HRTC can help the surgeons to evaluate the position and the onset of the ossifications and determine whether the patient is better off going under CI or ABI.
|Table 1. Causes of cochlear ossification. Adapted from Smullen et al. |
|Chronic otitis media|
2.1 Hearing preservation by drug therapy
Beside the imaging techniques that help the insertion of electrodes and regardless of the newer less traumatic electrode designs and surgical methods, implants still lead to hair cell trauma in the patients. Studies in rat and guinea pig models have shown that comparing to control animals, the cochlea of implanted animals lose hearing as the damaged hair cells undergo apoptosis . These researchers also observed chromatin condensation, genome fragmentation,and oxidative stress in the hair cells which indicates program cell death due to surgery-induced trauma.
|The caspase apoptosis pathway|
|Fig4. Adapted from Hakan et al.. The apoptosis pathway caused by activation of different caspases. Caspase 8,9,and 3 are confirmed to be activated by physical damage.|
As hair cells die, they undergo necrosis and apoptosis. Necrosis, caused by electrode insertion damage leads to swelling of the hair cell, lysis, and a subsequent inflammatory response leading to loss of hearing . On the other hand, apoptosis (type 1 PCD) is an active program leading to automatic cell death due to intramolecular trafficking events (Fig4). In the damaged cochlea, this program cell death leads to nuclear condensation and mitochondrial aggregation forming apoptotic bodies . There are two proposed mechanisms for this program cell death:1) activation of Caspases that are a family of cysteine-aspartic proteases (Fig5) . 2) Activation of MAPK/JNK cell death signalling pathway, c-jun, and AP1 transcription complex in response to oxidative stress (Fig6). c-Jun N terminal Kinase (JNK) is a type of MAPK that phosphorylates c-Jun to activate the transcription factors on the target gene. Blocking the second pathway is more commonly used for the development of preventive drugs. This is helpful in preserve hearing loss after the trauma induced disruption of organ of corti. Also another method to prevent this overwhelming stress is to use hair cell regeneration . The preventive drugs are  : I) c-Jun N terminal Kinase (JNK) inhibitor. II) caspase inhibitor z-VAD-FMK(carbobenzoxyvalyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone). III) Glucocorticoids (dexamethasone) acting as an anti-oxidants reducing inflammatory response .
|the JNK/MAPK cell death pathway|
|Fig5. Adapted from Hakan et al..|